3D Bioplotter Research Papers

Background Bone tissue engineering, based on three-dimensional (3D) printing technology, has emerged as a promising approach to treat bone defects using scaffolds. The objective of this study was to investigate the influence of porosity and internal structure on the mechanical properties of scaffolds. Methods We fabricated composite scaffolds (which aimed to replicate trabecular bone) from polycaprolactone (PCL) reinforced with 30% (wt.) nano-hydroxyapatite (nHAp) by extrusion printing. Scaffolds with various porosities were designed and fabricated with and without an interlayer offset, termed as staggered and lattice structure, respectively. Mechanical compressive testing was performed to determine scaffold elastic modulus and yield strength.…

Background Scaffolds are of great importance in tissue engineering applications as they provide a mechanically supportive environment for cellular activity, which is particularly necessary for hard tissues such as bone. Notably, the mechanical properties of a scaffold vary with differing design parameters such as those related to scaffold height and internal structure. Thus, the present study aimed to explore the relationship between design parameters and mechanical properties of composite polycaprolactone (PCL) and nano-hydroxyapatite (nHAp) scaffolds fabricated by three-dimensional (3D) printing. Methods We designed and printed scaffolds with different internal structures (lattice and staggered) and varying heights (4, 6, 8 and…

Scaffolds play a key role in bone tissue engineering (BTE) as they provide a mechanically and biologically supportive template to treat bone defects. Yet, the ideal scaffold structures are far from certain, leaving a lot to be discovered in terms of the scaffold structure–performance relationships. In this study, we investigated the influence of pore size and internal structure on osteoblast performance in vitro. Three-dimensional (3D) scaffolds were printed from polycaprolactone (PCL) reinforced with 30% (wt.) nano-hydroxyapatite (nHAp), with two different internal structures (lattice and staggered) and four pore sizes (0.280, 0.380, 0.420, and 0.550 mm). Scaffolds were seeded with pre-osteoblast…

Excellent electrical performance of assemblies of 1D silver nanowires (AgNWs) has been demonstrated in the past years. Up to now, however, there are limited approaches to realize simultaneously deterministic assembly with dense arrangement of AgNWs and desired functional layouts. Herein, an assembly strategy from compressed air-modulated alignment of AgNWs to heterogeneous integration of stretchable sensing devices through printing transfer is proposed. In this process, a convective flow induced by compressed air brings the AgNWs to the air–droplet interface, where the AgNWs are assembled with excellent alignment and packing due to the surface flow, van der Waals, and capillary interactions. Compared…

Combined photothermal-hygroscopic effects enable novel materials actuation strategies based on renewable and sustainable energy sources such as sunlight. Plasmonic nanoparticles have gained considerable interest as photothermal agents, however, the employment in sunlight-driven photothermal-hygroscopic actuators is still bounded, mainly due to the limited absorbance once integrated into nanocomposite actuators and the restricted plasmonic peaks amplitude (compared to the solar spectrum). Herein, the design and fabrication of an AgNPs-based plasmonic photothermal-hygroscopic actuator integrated with printed cellulose tracks are reported (bioinspired to Geraniaceae seeds structures). The nanocomposite is actuated by sunlight power density (i.e., 1 Sun = 100 mW cm−2). The plasmonic AgNPs…

Hydrogel-based scaffolds have been widely used in soft tissue regeneration due to their biocompatible and tissue-like environment for maintaining cellular functions and tissue regeneration. Understanding the mechanical properties and internal microstructure of hydrogel-based scaffold, once implanted, is imperative in many tissue engineering applications and longitude studies. Notably, this has been challenging to date as various conventional characterization methods by, for example, mechanical testing (for mechanical properties) and microscope (for internal microstructure) are destructive as they require removing scaffolds from the implantation site and processing samples for characterization. Synchrotron propagation-based imaging – computed tomography (PBI-CT) is feasible and promising for non-destructive…

Articular cartilage tissue engineering is being considered an alternative treatment strategy for promoting cartilage damage repair. Herein, we proposed a modular hydrogel-based bioink containing microsphere-embedded chondrocytes for 3D printing multiscale scaffolds integrating the micro and macro environment of the native articular cartilage. Gelatin methacryloyl (GelMA)/alginate microsphere was prepared by a microfluidic approach, and the chondrocytes embedded in the microspheres remained viable after being frozen and resuscitated. The modular hydrogel bioink could be printed via the gel-in-gel 3D bioprinting strategy for fabricating the multiscale hydrogel-based scaffolds. Meanwhile, the cells cultured in the scaffolds showed good proliferation and differentiation. Furthermore, we also found that…

Meniscus is a complex and crucial fibrocartilaginous tissue within the knee joint. Meniscal regeneration remains to be a scientific and translational challenge. We clarified that mesenchymal stem cells (MSCs) participated in meniscal maturation and regeneration using MSC-tracing transgenic mice model. Here, inspired by meniscal natural maturational and regenerative process, we developed an effective and translational strategy to facilitate meniscal regeneration by three-dimensionally printing biomimetic meniscal scaffold combining autologous synovium transplant, which contained abundant intrinsic MSCs. We verified that this facilitated anisotropic meniscus–like tissue regeneration and protected cartilage from degeneration in large animal model. Mechanistically, the biomechanics and matrix stiffness up-regulated…

Tissue-engineered articular cartilage constructs are currently not able to equal native tissues in terms of mechanical and biological properties. A major cause lies in the deficiency in engineering the biomechanical microenvironment (BMME) of articular chondrocytes. In this work, to engineer the BMME of articular chondrocytes, heterogeneous hydrogel structures of gelatin methacrylated (GelMA) containing differential-stiffness domains were first fabricated, and then periodic dynamic mechanical stimulations were applied to the hydrogel structures. The chondrocyte phenotype of ATDC5 cells was enhanced as the spatial differentiation in stiffness was increased in the hydrogel structures and was further strengthened by dynamic mechanical stimulation. It was…

Metabolic energy to steer osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) could be a promising therapeutic target for bone tissue engineering (BTE), but prior knowledge of this issue is limited. To address bone defects with BTE, we customized a three-dimensional (3D)-printed composite scaffold (Cur@MS) to allow the controlled release of curcumin, which could facilitate the “switch-on” mode of Glucose transporter 1 (GLUT1) in BMSCs. Consequently, bioenergetic channels, i.e. glucose uptake, were “switched on” to activate GLUT1-RUNX2 crosstalk, which was closely orchestrated with bone regeneration. Furthermore, curcumin-induced cholesterol/lipid raft (Cho/LR) was a “sensor” to trigger the “switch” (GLUT1) by…

The use of bioabsorbable and biodegradable composites in the medical field has experienced significant growth. Cellulose nanofibers (CNF) have been employed to reinforce medical-grade poly[ε-caprolactone], enhancing both its load-bearing capacity and stiffness compared to pure polycaprolactone PCL. The manufacturing process involved a series of steps applied to five different grades of PCL/CNF filaments. Initially, melt extrusion and pelletization were performed on the filament, followed by 3D bioplotting to create the specimens. The influence of CNF reinforcement on poly[ε-caprolactone] was evaluated through a range of tests, including rheological, thermomechanical, and in situ micromechanical assessments. To further characterize the samples, Micro-Computed Tomography…

Acetabular cups, which are among the most important implants in total hip arthroplasty, are usually made from titanium alloys with high porosity and adequate mechanical properties. The current three-dimensional (3D) printing approaches to fabricate customized acetabular cups have some inherent disadvantages such as high cost and energy consumption, residual thermal stress, and relatively low efficiency. Thus, in this work, a direct ink writing method was developed to print a cup structure at room temperature, followed by multi-step heat treatment to form microscale porous structure within the acetabular cup. Our method is facilitated by the development of a self-supporting titanium-6 aluminum-4…

Bioinks for 3D bioprinting of tumor models should not only meet printability requirements but also accurately maintain and support phenotypes of tumor surrounding cells to recapitulate key tumor hallmarks. Collagen is a major extracellular matrix protein for solid tumors, but low viscosity of collagen solution has made 3D bioprinted cancer models challenging. This work produces embedded, bioprinted breast cancer cells and tumor organoid models using low-concentration collagen I based bioinks. The biocompatible and physically crosslinked silk fibroin hydrogel is used to generate the support bath for the embedded 3D printing. The composition of the collagen I based bioink is optimized…

CO2 sensing is important in many applications ranging from air-quality monitoring to food packaging. In this study, an amine-functionalized copolymer, poly(N-[3-(dimethylamino)propyl]-methacrylamide-co-2-N-morpholinoethyl methacrylate) (p(D-co-M)) is synthesized, offering moderate basicity suitable for a wide CO2 detection range. Taking advantage of this characteristic of p(D-co-M), this polymer is used for designing a chemiresistive, low-cost, flexible, and reversible CO2 sensor. The p(D-co-M)-based sensors show a noticeable decrease in their direct current resistance and alternating current impedance upon exposure to a wide range of CO2 concentration (1–100%) at room temperature with a response and a recovery time of 6 and 14 min, respectively. Additionally, the…

Polysaccharide based hydrogels have been predominantly utilized as ink materials for 3D bioprinting due to biocompatibility and cell responsive features. However, most hydrogels require extensive crosslinking due to poor mechanical properties leading to limited printability. To improve printability without using cytotoxic crosslinkers, thermoresponsive bioinks could be developed. Agarose is a thermoresponsive polysaccharide with upper critical solution temperature (UCST) for sol-gel transition at 35–37 °C. Therefore, we hypothesized that a triad of carboxymethyl cellulose(C)–agarose(A)–gelatin(G) could be a suitable thermoresponsive ink for printing since they undergo instantaneous gelation without any addition of crosslinkers after bioprinting. The blend of agarose-carboxymethyl cellulose was mixed with…

Background There is a great clinical need and it remains a challenge to develop artificial soft tissue constructs that can mimic the biomechanical properties and bioactivity of natural tissue. This is partly due to the lack of suitable biomaterials. Hydrogels made from human placenta offer high bioactivity and represent a potential solution to create animal-free 3D bioprinting systems that are both sustainable and acceptable, as placenta is widely considered medical waste. A combination with silk and gelatin polymers can bridge the biomechanical limitations of human placenta chorion extracellular matrix hydrogels (hpcECM) while maintaining their excellent bioactivity.   Method In this…

Hydrogels show promise in cartilage tissue engineering (CTE) by supporting chondrocytes and maintaining their phenotype and extracellular matrix (ECM) production. Under prolonged mechanical forces, however, hydrogels can be structurally unstable, leading to cell and ECM loss. Furthermore, long periods of mechanical loading might alter the production of cartilage ECM molecules, including glycosaminoglycans (GAGs) and collagen type 2 (Col2), specifically with the negative effect of stimulating fibrocartilage, typified by collagen type 1 (Col1) secretion. Reinforcing hydrogels with 3D-printed Polycaprolactone (PCL) structures offer a solution to enhance the structural integrity and mechanical response of impregnated chondrocytes. This study aimed to assess the…

The development of new biomaterials for bone tissue regeneration with high bioactivity abilities and antibacterial properties is being intensively investigated. We have synthesized nanocomposites formed by mesoporous bioactive glasses (MBGs) in the ternary SiO2, CaO and P2O5 system doped with metallic silver nanoparticles (AgNPs) that were homogenously embedded in the MBG matrices. Ag/MBG nanocomposites have been directly synthesized and silver species were spontaneously reduced to metallic AgNPs by high temperatures (700 °C) obtained of last MBG synthesis step. Three-dimensional silver-containing mesoporous bioactive glass scaffolds were fabricated showing uniformly interconnected ultrapores, macropores and mesopores. The manufacture method consisted of a combination…

Engineered grafts constitute an alternative to autologous transplant for repairing severe peripheral nerve injuries. However, current clinically available solutions have substantial limitations and are not suited for the repair of long nerve defects. A novel design of nerve conduit is presented here, which consists of a chitosan porous matrix embedding a 3D-printed poly-ε-caprolactone mesh. These materials are selected due to their high biocompatibility, safe degradability, and ability to support the nerve regeneration process. The proposed design allows high control over geometrical features, pores morphology, compression resistance, and bending stiffness, yielding tunable and easy-to-manipulate grafts. The conduits are tested in chronic…

Three Dimensional (3D) bioprinting is one of the most recent additive manufacturing technologies and enables the direct incorporation of cells within a highly porous 3D-bioprinted construct. While the field has mainly focused on developing methods for enhancing printing resolution and shape fidelity, little is understood about the biological impact of bioprinting on cells. To address this shortcoming, this study investigated the in vitro and in vivo response of human osteoblasts subsequent to bioprinting using gelatin methacryloyl (GelMA) as the hydrogel precursor. First, bioprinted and two-dimensional (2D) cultured osteoblasts were compared, demonstrating that the 3D microenvironment from bioprinting enhanced bone-related gene…

Breath analysis is a non-invasive tool used in medical diagnosis. However, the current generation of breath analyzers is expensive, time-consuming, and requires sample gas separation. In this work, a simple, yet effective, low-cost ammonia gas sensor based on poly(2-acrylamido-2-methyl-1-propanesulfonic acid) is presented for non-invasive medical diagnosis. The designed sensor has a broad detection range to ammonia gas up to 1000 ppm with a limit of detection of 30 ppb. This is a robust sensor, which functions at high relative humidity (RH) (>90%) and exhibits consistent electrical responses under different test conditions. The result of a blind test validates the sensor’s…

Self-setting calcium phosphate cement (CPC) scaffold with interconnected macropores is hard to prepare without compromising its hydration reaction. Herein, an indirect 3D printing method is using to prepare CPC scaffolds. Detailedly, polycaprolactone (PCL)-sacrificed models with different strut sizes are first printed by 3D plotting technique, and then the CPC pastes are perfused into the PCL models and then self-setting. After the removal of the PCL models, the CPC scaffolds with different pore sizes are obtained. It is showed in the results that the prepared CPC scaffolds had uniform shape and 3D interconnected macropore structure. Meanwhile, the compressive strength of CPC…

Distributed sensing of environmental parameters is going towards solutions that are more efficient by taking inspiration from flying plant seeds. Yet, present technologies mostly rely on electronics, and they are often heavy and not biodegradable. Here, we develop a biodegradable and porous material, based on cellulose acetate and lignin, and characterize its degree of porosity. We use this material to 3D print lightweight and porous artificial fliers inspired by Ailanthus altissima seeds. By 3D printing, we can tailor in a precise way the morphology of the artificial flier that strongly influences its aerodynamic behavior. We add a cellulose-based photonic crystal…

Nerve conduits may represent a valuable alternative to autograft for the regeneration of long-gap damages. However, no NCs have currently reached market approval for the regeneration of limiting gap lesions, which still represents the very bottleneck of this technology. In recent years, a strong effort has been made to envision an engineered graft to tackle this issue. In our recent work, we presented a novel design of porous/3D-printed chitosan/poly-ε-caprolactone conduits, coupling freeze drying and additive manufacturing technologies to yield conduits with good structural properties. In this work, we studied genipin crosslinking as strategy to improve the physiochemical properties of our…

Bulk Ni samples were additively manufactured using particle-based ink extrusion. Three samples were characterized for thermoelectric transport properties including electrical resistivity, thermal conductivity, Seebeck coefficient, and thermoelectric figure of merit. Sample-to-sample deviations in transport were small but observable; these were attributed to stochastic porosity from the manufacturing method. Transport results were compared to previously published results in both porous and dense Ni, indicating that the salient features in the traditionally manufactured Ni samples are maintained in their additively manufactured counterparts. These results are offered as evidence of the feasibility of using particle-based ink extrusion additive manufacturing for thermoelectric applications.

The repair of nasal cartilage lesions and defects is still a difficult problem in nasal surgery, and nasal cartilage tissue engineering will be an effective way to solve this problem. Hydrogel has excellent application potential in tissue engineering. In order to produce a 3D printable scaffold for cartilage regeneration, we prepared gelatin methacryloyl (GelMA)/hyaluronic acid methacryloyl (HAMA)/bacterial cellulose (BC) composite hydrogel. The composite hydrogel was characterized by swelling, mechanical properties, and printing performance test. Compared with GelMA/HAMA hydrogel, the addition of BC not only significantly enhanced the mechanical properties of the hydrogels, but also improved the printing fidelity. At the…

Decellularized extracellular matrices (ECMs) are being extensively used for tissue engineering purposes and detergents are predominantly used for this. A facile detergent-free decellularization method is developed for dermal matrix and compared it with the most used detergent-based decellularization methods. An optimized, single-step, cost-effective Hypotonic/Hypertonic (H/H) Sodium Chloride (NaCl) solutions-based method is employed to decellularize goat skin that resulted in much higher yield than other methods. The ECM composition, mechanical property, and cytocompatibility are evaluated and compared with other decellularization methods. Furthermore, this H/H-treated decellularized dermal ECM (ddECM) exhibits a residual DNA content of <50 ng mg−1 of dry tissue. Moreover, 85.64 ± 3.01% of glycosaminoglycans…

Large size bone defects affect human health and remain a worldwide health problem that needs to be solved immediately. 3D printing technology has attracted substantial attention for preparing penetrable multifunctional scaffolds to promote bone reconditioning and regeneration. Inspired by the spongy structure of natural bone, novel porous degradable scaffolds have been printed using polymerization of lactide and caprolactone (PLCL) and bioactive glass 45S5 (BG), and polydopamine (PDA) was used to decorate the PLCL/BG scaffolds. The physicochemical properties of the PLCL/BG and PLCL/BG/PDA scaffolds were measured, and their osteogenic and angiogenic effects were characterized through a series of experiments both in…

3D bioprinting enables the fabrication of biomimetic cell-laden constructs for cartilage regeneration, offering exclusive strategies for precise pharmacological screenings in osteoarthritis (OA). Synovial inflammation plays a crucial role in OA’s early stage and progression, characterized by the increased of the synovial pro-inflammatory mediators and cytokines and chondrocyte apoptosis. Therefore, there is an urgent need to develop solutions for effectively managing the primary events associated with OA. To address these issues, a phenolic-based biocompatible ionic liquid approach, combining alginate (ALG), acemannan (ACE), and cholinium caffeate (Ch[Caffeate]), was used to produce easily printable bioinks. Through the use of this strategy 3D constructs…

Objective. The objective of this study was to compare the host inflammatory response of our previously described hyperelastic, 3D-printed (3DP) hydroxyapatite (HA)-demineralized bone matrix (DBM) composite scaffold to the response elicited with the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a preclinical rat posterolateral lumbar fusion model. Summary of Background Data. Our group previously found that this 3D-printed HA-DBM composite material shows promise as a bone graft substitute in a preclinical rodent model, but its safety profile had yet to be assessed. Methods. Sixty female Sprague-Dawley rats underwent bilateral posterolateral intertransverse lumbar spinal fusion using with the following…

Fibrosis is shared in multiple diseases with progressive tissue stiffening, organ failure and limited therapeutic options. This unmet need is also due to the lack of adequate pre-clinical models to mimic fibrosis and to be challenged novel by anti-fibrotic therapeutic venues. Here using bioprinting, we designed a novel 3D model where normal human healthy fibroblasts have been encapsulated in type I collagen. After stimulation by Transforming Growth factor beta (TGFβ), embedded cells differentiated into myofibroblasts and enhanced the contractile activity, as confirmed by the high level of α − smooth muscle actin (αSMA) and F-actin expression. As functional assays, SEM…

A modular reinforced bone scaffold with enhanced mechanical properties has recently been developed by our group. It includes: 1) A load-bearing module: a skeleton which is made of a slowly degradable material, undertaking mechanical necessities of the scaffold, and 2) A bio-reactive module: a porous and biodegradable component undertaking biological necessities of the scaffold. The load-bearing module is placed into the bio-reactive module to reinforce it. This paper is dedicated to optimizing the load-bearing module for a certain customized alveolar bone defect. More specifically, a 3D-printed skeleton, made of polycaprolactone (PCL), is optimized based on the boundary conditions of the…

Critical-sized bone defects, caused by congenital disorders or trauma, are defects that will not heal spontaneously and require surgical intervention. Recent advances in biomaterial design for the treatment of such defects focus on improving their osteoinductive properties. Here, we propose a bioactive composite with high ceramic content composed of poly(ethyleneoxide terephthalate)/poly(butylene terephthalate) (1000PEOT70PBT30, PolyActive, PA) and 50 % beta-tricalcium phosphate (β-TCP) with the addition of zinc in a form of a coating on the TCP particles. Due to its essential role in bone homeostasis, we hypothesised that the addition of zinc to the polymer-ceramic composite will further enhance its osteogenic…

Cellulose is a promising candidate for the fabrication of superinsulating materials, which would be of great interest for thermal management applications as well as for the scientific community. Until now, the production of strong cellulose-based aerogels has been dominated by traditional manufacturing processes, which have limited the possibilities to achieve the structural control and mechanical properties seen in natural materials such as wood. In this work, we show a simple but versatile method to fabricate cellulose aerogels in intricate geometries. We take advantage of the 3D printing technique direct ink writing to control both the shape and the thermal-mechanical properties…

Fibre alignment technology is crucial in various emerging applications, such as drug delivery systems, tissue engineering, and scaffold fabrication. However, conventional methods have limitations when it comes to incorporating aligned fibres into 3D printed structures in situ. This research demonstrates the use of custom-designed templates made with conductive ink to control the alignment of drug-loaded polymer fibres on a 3D printed microscale structure. Three different geometries were designed, and the effects of the template on fibre diameter and pattern were investigated. The hybrid structure demonstrated successful control of aligned fibres on printed structures using grounded conductive ink geometric electrodes, as…

Corneal transplantation remains gold standard for the treatment of severe cornea diseases, however, scarcity of donor cornea is a serious bottleneck. 3D bioprinting holds tremendous potential for cornea tissue engineering (TE). One of the key technological challenges is to design bioink compositions with ideal printability and cytocompatibility. Photo-crosslinking and ionic crosslinking are often used for the stabilization of 3D bioprinted structures, which can possess limitations on biological functionality of the printed cells. Here, we developed a hyaluronic acid-based dopamine containing bioink using hydrazone crosslinking chemistry for the 3D bioprinting of corneal equivalents. First, the shear thinning property, viscosity, and mechanical…

Tissue engineering offers a great potential in regenerative dentistry and to this end, three dimensional (3D) bioprinting has been emerging nowadays to enable the incorporation of living cells into the biomaterials (such a mixture is referred as a bioink in the literature) to create scaffolds. However, the bioinks available for scaffold bioprinting are limited, particularly for dental tissue engineering, due to the complicated, yet compromised, printability, mechanical and biological properties simultaneously imposed on the bioinks. This paper presents our study on the development of a novel bioink from carboxymethyl chitosan (CMC) and alginate (Alg) for bioprinting scaffolds for enamel tissue…

Polarized THz time domain spectroscopy was used to study the anisotropic properties of wood-based materials for potential optical elements in the THz range, such as half-wave and quarter-wave plates. Wood samples of different species and sample thickness were studied experimentally showing high birefringence but rather high absorption. We elaborate on two approaches to optimize the optical properties for use as wave plates and assess them based on a figure of merit describing their efficiency as a function of birefringence and absorption. The first approach is to dry the wood samples, which significantly improves the efficiency of wave plates. The second…

The aim of this study was to develop and validate a semi-automated segmentation approach that identifies the round window niche (RWN) and round window membrane (RWM) for use in the development of patient individualized round window niche implants (RNI) to treat inner ear disorders. Twenty cone beam computed tomography (CBCT) datasets of unilateral temporal bones of patients were included in the study. Defined anatomical landmarks such as the RWM were used to develop a customized 3D Slicer™ plugin for semi-automated segmentation of the RWN. Two otolaryngologists (User 1 and User 2) segmented the datasets manually and semi-automatically using the developed…

Implant-associated infections are not easy to diagnose and very difficult to treat, due to the ability of major pathogens, such as Staphylococcus aureus, to develop biofilms and escape the immune response and antibiotic treatment. We, therefore, aimed to develop a 3D-printed dual rifampicin (Rif)- and vancomycin (Van)-loaded polylacticco-glycolic acid (PLGA) nanoparticles (NPs) delivery system based on hydrogels made of gelatin methacrylate (GelMA). The release of Rif and Van from NPs manufactured from different PLGA molecular weights was studied in phosphate-buffered saline for 21 days. Low molecular weight PLGA NPs exhibited the fastest release of Rif and Van within the first…

Three-dimensional (3D) bioprinting has brought new promising strategies for the regeneration of cartilage with specific shapes. In cartilage bioprinting, chondrocyte-laden hydrogels are the most commonly used bioinks. However, the dispersion of cells and the dense texture of the hydrogel in the conventional bioink may limit cell–cell/ cell–extracellular matrix (ECM) interactions, counting against cartilage regeneration and maturation. To address this issue, in this study, we developed a functional bioink for cartilage bioprinting based on chondrocyte spheroids (CSs) and microporous hydrogels, in which CSs as multicellular aggregates can provide extensive cell– cell/cell–ECM interactions to mimic the natural cartilage microenvironment, and microporous hydrogels…

Recent studies on osteosarcoma and matrix stiffness are still mostly performed in a 2D setting, which is distinct from in vivo conditions. Therefore, the results from the 2D models may not reflect the real effect of matrix stiffness on cell phenotype. Here, we employed a 3D bioprinted osteosarcoma model, to study the effect of matrix stiffness on osteosarcoma cells. Through density adjustment of GelMA, we constructed three osteosarcoma models with distinct matrix stiffnesses of 50, 80, and 130 kPa. In this study, we found that osteosarcoma cells proliferated faster, migrated more actively, had a more stretched morphology, and a lower…

The healing of meniscus injuries poses a significant challenge, as prolonged failure to heal can lead to osteoarthritis, which presents a therapeutic dilemma in the field of sports medicine. Decellularized extracellular matrix (MdECM) derived from natural meniscus, and the incorporated growth factors have been used for potential fibrochondrocyte induction and meniscus regeneration. However, homogeneous MdECM is difficult to achieve region-specific biomimetic microenvironment for tissue regeneration. In this study, we successfully prepared a region-specific MdECM, which were then mixed with an ultraviolet responsible Gelatin Methacryloyl (GelMA)/hyaluronic acid Methacryloy (HAMA) hydrogel incorporated with bioactive factors, faciliatated a functional region-specific bioink. The 3D…

More relevant human tissue models are needed to produce reliable results when studying disease mechanisms of genetic diseases and developing or testing novel drugs in cardiac tissue engineering (TE). Three-dimensional (3D) bioprinting enables physiologically relevant positioning of the cells inside the growth matrix according to the detailed digital design. Here we combined human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) with methacrylated gelatin (GelMA) and collagen I-based bioink and 3D extrusion bioprinted a cardiac in vitro model for disease modeling and drug screening. Bioprinted constructs were characterized for their rheological properties, swelling behavior, degradation, as well as shape fidelity. The…

Myocardial infarction (MI) is a lethal cardiac disease that causes most of the mortality across the world. MI is a consequence of plaque in the arterial walls of heart, which eventually result in occlusion and ischemia to the myocardial tissues due to inadequate nutrient and oxygen supply. As an efficient alternative to the existing treatment strategies for MI, 3D bioprinting has evolved as an advanced tissue fabrication technique where the cell–laden bioinks are printed layer–by–layer to create functional cardiac patches. In this study, a dual crosslinking strategy has been utilized towards 3D bioprinting of myocardial constructs by using a combination…

The development of suitable bioinks is an important research topic in the field of three-dimensional (3D) bioprinting. Herein, novel hydrogel-based bioinks composed of nanofibrillated cellulose (NFC) and gellan gum (GG) in different NFC/GG mass proportions (90:10, 80:20, 70:30, and 60:40) were developed and characterized. The increase in the content of GG, as well as its combination with NFC, enhanced their rheological properties, increasing both storage (G’) and loss (G”) moduli and the G’ recovery capacity of the hydrogels (from 70.05 ± 3.06 % (90:10) to 82.63 ± 1.21 % (60:40)), as well as their mechanical properties, increasing the compressive stiffness…

Extrusion-based three-dimensional (3D) printing of gelatin is important for additive manufactured tissue engineering scaffolds, but gelatin’s thermal instability has remained an ongoing challenge. The gelatin tends to suddenly collapse at mild temperatures, which is a significant limitation for using it at physiological temperature of 37 °C. Hence, fabrication of a thermo-processable gelatin hydrogel adapted for extrusion-based additive manufacturing is still a challenge. To achieve this, a self-healing nanocomposite double-network (ncDN) gelatin hydrogel was fabricated with high thermo-processability, shear-thinning, mechanical strength, self-healing, self-recovery, and biocompatibility. To do this, amino group-rich gelatin was first created by combining gelatin with carboxyl methyl chitosan.…

The regular way to determine the in vitro release rates of drugs from implantable drug delivery systems consists of the complete immersion of the implant into a medium. The medium surrounds the implant, and the diffusion of the drugs occurs across the whole implant surface directly into the medium. This method does not accurately model the release rates if the real diffusion only happens across only one part of the surface of the implant, through a membrane, and into a small volume of medium. It also does not address the anatomical shape of the studied structure. One example for this…

Background To investigate the effect of low-intensity pulsed ultrasound (LIPUS) combined with lipid microbubbles on the proliferation and bone regeneration of bone marrow mesenchymal stem cells (BMSCs) in poly (lactic-glycolic acid copolymer) (PLGA)/α-tricalcium phosphate (TCP) 3D-printed scaffolds. Methods BMSCs were irradiated with different LIPUS parameters and microbubble concentrations, and the best acoustic excitation parameters were selected. The expression of type I collagen and the activity of alkaline phosphatase were detected. Alizarin red staining was used to evaluate the calcium salt production during osteogenic differentiation. Results BMSCs proliferation was the most significant under the condition of 0.5% (v/v) lipid microbubble concentration,…

Calcific aortic valve disease (CAVD) is a frequent cardiac pathology in the aging society. Although valvular interstitial cells (VICs) seem to play a crucial role, mechanisms of CAVD are not fully understood. Development of tissue-engineered cellular models by 3D-bioprinting may help to further investigate underlying mechanisms of CAVD. VIC were isolated from ovine aortic valves and cultured in Dulbecco’s modified Eagle’s Medium (DMEM). VIC of passages six to ten were dissolved in a hydrogel consisting of 2% alginate and 8% gelatin with a concentration of 2 × 106 VIC ml−1. Cell-free and VIC-laden hydrogels were printed with an extrusion-based 3D-bioprinter…

Reconstruction of segmental defects are popularly approached with surface engineered additively manufactured scaffolds owing to its enhanced post-surgery tissue integration properties. The present work is aimed at fabrication of Ti lattice structures using 3D printing, with a novel approach of silane chemistry-based surface modification of those Ti-surfaces with osteogenic peptides (OGP). The lattice structures with 0.6 mm strut-diameter having 0.5 mm inter-strut distance were chosen for fabrication using an extrusion-based 3D printing. Based on the evidence, it could be concluded that extrusion-based 3D printing is an optimal alternative as compared to those high cost incurring additive manufacturing processes. Therefore, OGP…

Extrusion additive manufacturing is widely used to fabricate polymer-based 3D bone scaffolds. However, the insight views of crystal growths, scaffold features and eventually cell-scaffold interactions are still unknown. In this work, melt and solvent extrusion additive manufacturing techniques are used to produce scaffolds considering highly analogous printing conditions. Results show that the scaffolds produced by these two techniques present distinct physiochemical properties, with melt-printed scaffolds showing stronger mechanical properties and solvent-printed scaffolds showing rougher surface, higher degradation rate, and faster stress relaxation. These differences are attributed to the two different crystal growth kinetics, temperature-induced crystallization (TIC) and strain-induced crystallization (SIC),…

Surgery is the most frequent treatment for patients with brain tumors. The construction of full-scale human brain models, which is still challenging to realize via current manufacturing techniques, can effectively train surgeons before brain tumor surgeries. This paper aims to develop a set of three-dimensional (3D) printing approaches to fabricate customized full-scale human brain models for surgery training as well as specialized brain patches for wound healing after surgery. First, a brain patch designed to fit a wound’s shape and size can be easily printed in and collected from a stimuli-responsive yield-stress support bath. Then, an inverse 3D printing strategy,…

Polyvinyl alcohol (PVA) is a biodegradable polymer having applications in several industries, such as textiles and paper manufacturing. Due to the water solubility, it is also a useful solvent in 3D dispensing to extrude printable solutions at a low temperature. However, its hydrophilicity is a drawback when considering the property of the end-use material if water contact is required. Using the water solubility of PVA as a benefit during 3D dispensing but avoiding the hydrophilicity in the printed material is tricky and unresolved. This study proposes a technique to achieve this phenomenon by taking advantage of the natural hydrophobicity of…

Self-healable degradable networks encounter a growing popularity for biomedical applications due to their ability to recover their properties after damage. Self-healable hydrogels dominate with applications in tissue engineering and drug delivery. On the opposite and despite their potential for medical devices, self-healable elastomers remain scarce, especially if they must be compatible with fused deposition modeling (FDM) 3D-printing and self-heal at physiological temperature under a hydrated state. These unmet challenges are addressed in this work with degradable elastomeric networks based on dynamic imine bonds prepared from multi(aldehyde) and multi(amine) hydrophobic PEG-PLA star-shaped copolymers. The star topology of these copolymers is the…

The parathyroid glands are localized at the back of the thyroid glands in the cervical region and are responsible for regulation of the calcium level in the blood, through specialized cells that sense Ca2+ and secrete parathyroid hormone (PTH) in response to a decline in its serum level. PTH stimulates the skeleton, kidneys and intestines and controls the level of Ca2+ through specialized activities. Iatrogenic removal of the parathyroid gland, as well as damage to its vascular integrity during cauterization are some of the common complications of thyroid surgery. Therefore, regeneration and/or replacement of malfunctioning parathyroid tissue is required. Tissue…

Partial-thickness thermal burn wounds are characterized by a prolonged inflammatory response, oxidative stress, tissue damage, and secondary necrosis. An optimal dressing for burn wounds would reduce inflammation and oxidative stress while providing a moist, absorbent, and protective cover. We have developed an extract from unfertilized salmon roe containing components with potential anti-inflammatory and antioxidative properties, called HTX. HTX has been combined with alginate from brown algae and nanocellulose from tunicates, and 3D printed into a solid hydrogel wound dressing called Collex. Here, Collex was tested on partial thickness burn wounds in Göttingen minipigs compared to Jelonet, and a variant of…

In this work, artificial bones composed of hydroxyapatite (HA)/polyacrylonitrile (PAN) and polylactic acid (PLA) were prepared as a potential replacement for natural bone. The cylindrical specimens included an auxetic system with artificial osteons. HA/PAN and PLA were used to fabricate composite filaments by fused deposition modeling three-dimensional (3D) printing, and the obtained filaments were applied to produce reentrant artificial bone materials. Scanning electron microscopy was used to analyze the scaffold morphology and functional groups. Energy-dispersive X-ray spectroscopy was used for elemental analysis. The compressive properties of the samples were studied to determine the optimal scaffolding prototype. Compressive tests were also…

Bioprinting is one of the newest but mostly studied additive manufacturing processes of the last decade. Despite the huge amount of literature on this topic, a huge amount of aspects still have to be fully investigated. Precisely, each 3D printing process is characterized by a low stability and difficult replicability, in relation to conventional processes. For this reason, research on process control and optimization is one of the trending aspects nowadays. In this work, the Response Surface Methodology (RSM) approach is applied to 3D printing of hydrogel for biomedical applications and specifically of biocompatible hydrogels for cell-laden direct bioprinting purposes.…

Damping mechanical resonances is a formidable challenge in an increasing number of applications. Many passive damping methods rely on using low stiffness, complex mechanical structures or electrical systems, which render them unfeasible in many of these applications. Herein, a new method for passive vibration damping, by allowing buckling of the primary load path in mechanical metamaterials and lattice structures, is introduced, which sets an upper limit for vibration transmission: the transmitted acceleration saturates at a maximum value in both tension and compression, no matter what the input acceleration is. This nonlinear mechanism leads to an extreme damping coefficient tanδ ≈ 0.23…

Visualization of low-density tissue scaffolds made from hydro­gels is important yet challenging in tissue engineering and regenerative medicine (TERM). For this, synchrotron radiation propagation-based imaging computed tomography (SR-PBI-CT) has great potential, but is limited due to the ring artifacts commonly observed in SR-PBI-CT images. To address this issue, this study focuses on the integration of SR-PBI-CT and helical acquisition mode (i.e. SR-PBI-HCT) to visualize hydro­gel scaffolds. The influence of key imaging parameters on the image quality of hydro­gel scaffolds was investigated, including the helical pitch (p), photon energy (E) and the number of acquisition projections per rotation/revolution (Np), and, on…

Osteochondral defects pose a great challenge and a satisfactory strategy for their repair has yet to be identified. In particular, poor repair could result in the generation of fibrous cartilage and subchondral bone, causing the degeneration of osteochondral tissue and eventually leading to repair failure. Herein, taking inspiration from the chemical elements inherent in the natural extracellular matrix (ECM), we proposed a novel ECM-mimicking scaffold composed of natural polysaccharides and polypeptides for osteochondral repair. By meticulously modifying natural biopolymers to form reversible guest–host and rigid covalent networks, the scaffold not only exhibited outstanding biocompatibility, cell adaptability, and biodegradability, but also…

Geraniaceae seeds represent a role model in soft robotics thanks to their ability to move autonomously across and into the soil driven by humidity changes. The secret behind their mobility and adaptivity is embodied in the hierarchical structures and anatomical features of the biological hygroscopic tissues, geometrically designed to be selectively responsive to environmental humidity. Following a bioinspired approach, the internal structure and biomechanics of Pelargonium appendiculatum (L.f.) Willd seeds are investigated to develop a model for the design of a soft robot. The authors exploit the re-shaping ability of 4D printed materials to fabricate a seed-like soft robot, according…

3D bioprinting is a versatile technique that allows the fabrication of living tissue analogs through the layer-by-layer deposition of cell-laden biomaterials, viz. bioinks. In this work, composite alginate hydrogel-based bioinks reinforced with curcumin-loaded particles of cellulose esters (CEpCUR) and laden with human keratinocytes (HaCaT) are developed. The addition of the CEpCUR particles, with sizes of 740 ± 147 nm, improves the rheological properties of the inks, increasing their shear stress and viscosity, while preserving the recovery rate and the mechanical and viscoelastic properties of the resulting fully cross-linked hydrogels. Moreover, the presence of these particles reduces the degradation rate of…

Treatment of critical size defects is quite challenging, often requiring autologous bone grafts for bone regeneration. A massive volume of autologous bone is essential during this process to fill the defect leading to donor site morbidity. Although 3D printed PCL scaffolds are frequently utilised for bone correction procedures, there have been reports of delayed PCL biodegradation and inadequate bone tissue formation. To enhance the regenerative potential, in this study, silk in the form of silk fibroin microfibers are reinforced into the PCL matrix to form the composite. Two silk variations were used: Antheraea mylitta and Bombyx mori, and has been…

For the treatment of bone defects, biodegradable, compressive biomaterials are needed as replacements that degrade as the bone regenerates. The problem with existing materials has either been their insufficient mechanical strength or the excessive differences in their elastic modulus, leading to stress shielding and eventual failure. In this study, the compressive strength of CPC ceramics (with a layer thickness of more than 12 layers) was compared with sintered β-TCP ceramics. It was assumed that as the number of layers increased, the mechanical strength of 3D-printed scaffolds would increase toward the value of sintered ceramics. In addition, the influence of the…

The composite, thermoplastic material composed of polyhydroxybutyrate (PHB) and polylactic acid (PLA) was seeded with stem cells in the experiment. Tests of the polymer were oriented towards biocompatibility in vitro using mesenchymal stem cells isolated from the chorion. PHB/PLA is a currently tested biopolymer for applications in and medicine. Using additive technology, 3D forms of scaffolds in the form of a grid were prepared, which were seeded with stem cells and cultivated in suitable conditions. After an interval of 5 days, the proliferation and viability of the mesenchymal stem cells was tested by the proliferation test. From the results, it…

With the increasing need for architectural sustainability, biodesign offers a new approach to incorporating living organisms in building materials. Bacteria hold a range of biological activities that impact their environment, and which could enable the solidification of inorganic materials; this has already been seen with microbially-induced carbonate precipitation that strengthens bonds between sand particles. This paper describes the novel development of an additive co-fabrication manufacturing process, demonstrating an interdisciplinary approach of architecture and microbiology. Specifically, the activity of a biological deposition (i.e., cyanobacterial calcium carbonate precipitation) and its integration with that of a robotic deposition (i.e., a sand-based biomixture) within…

Microlattices with orthogonal 0-90° architecture are 3D-extrusion printed from inks containing a blend of oxide powders (Co3O4, CuO, Fe2O3, and NiO) and metal powder (Cr). Equiatomic CoCrCuFeNi microlattices with ∼170 µm diameter struts are then synthesized by H2-reduction of the oxides followed by sintering and interdiffusion of the resulting metals. These process steps are studied by in-situ synchrotron X-ray diffraction on single extruded microfilaments (lattice struts) with ∼250 µm diameter. After reduction and partial interdiffusion at 600 ˚C for 1 h under H2, filaments consist of lightly-sintered metallic particles with some unreduced Cr2O3. A reduced, nearly fully densified (porosity: 1.6 ± 0.7%)…

Polymer blend system has been commonly applied in a wide variety of applications. Herein, we propose to introduce sugar particles to polymer matrix, which results in a controllable polymer swelling under the action of osmotic pressure upon soaking in water. Taking advantage of this economic and environment-friendly, water-induced polymer swelling process, we have fabricated wrinkled conductive films and 3D structures by depositing conductive materials on the swollen polymer substrates for stretchable strain sensing devices. Several commercial silicone elastomers were utilized in the study. Key processing factors affecting the polymer swelling were investigated, including film thickness, sugar concentration, and temperature of…

As an engineering frontier, highly stretchable sensors are widely applied in many fields, such as human motion detection, personal healthcare monitoring, and human-machine interactions. In this study, novel silver nanowire (AgNW)-based stretchable sensors with hierarchical wrinkled structures were fabricated through a two-step process, namely water-induced swelling and AgNW deposition. As highly soluble additives, sodium chloride particles were incorporated into the elastomer matrix. Upon soaking in dopamine aqueous solution, significant swelling was introduced onto the elastomer substrate. The dopamine deposition is accompanied with the swelling process, which endows the sample surface with ultra-hydrophilicity. Additionally, the dopamine-modified swollen samples “capture” the nanowires…

Polyelectrolyte complex (PEC) hydrogels are advantageous as therapeutic agent and cell carriers. However, due to the weak nature of physical crosslinking, PEC swelling and cargo burst release are easily initiated. Also, most current cell-laden PEC hydrogels are limited to fibers and microcapsules with unfavorable dimensions and structures for practical implantations. To overcome these drawbacks, alginate (Alg)/poly-L-ornithine (PLO) PEC hydrogels are fabricated into microcapsules, fibers, and bulk scaffolds to explore their feasibility as drug and cell carriers. Stable Alg/PLO microcapsules with controllable shapes are obtained through aqueous electrospraying technique, which avoids osmotic shock and prolongs the release time. Model enzyme and…

Poly (lactic-co-glycolic acid) (PLGA) is a star biodegradable polymer widely studied and applied in the biomedical field. Improving the acidic microenvironment caused by its degradation products and regulating its degradation behavior are still urgent scientific and technological problems to be solved. In this study, to regulate the degradation behaviors of PLGA and improve its bioactivity, hydroxyapatite (HA) and magnesium oxide (MgO) were incorporated into PLGA substrate in different proportions and a series of 3D-printing PLGA/HA/MgO (PHM) composite porous scaffolds were prepared. Then the physicochemical properties, degradation behaviors, in vitro and in vivo biological performance of fabricated scaffolds were systematically studied.…

4D printing of shape memory polymers (SMPs) endows the 3D printed structures with tunable shape-changing behavior and functionalities that opens up new avenues towards intelligent devices. Multiple-SMPs, specially, could memorize more than two shapes that have greatly extended the performance of 4D printed structures. However, the actuation to trigger the shape change of 4D printed multiple-SMPs is usually by direct heating to different temperatures. It hasn’t brought the full superiority of the programmability of multiple-SMPs with distinct responsive regions that could be sequentially and selectively actuated by various stimuli. Besides, the functionality of multi-material based additive manufacturing is another area…

Background Poly(3-caprolactone) (PCL)/β-tricalcium phosphate (β-TCP) composite scaffolds fabricated by three-dimensional (3D) printing are one of the common scaffolds for bone tissue regeneration. However, the main challenge of these 3D printed PCL/β-TCP scaffolds is the fact that many cells pass from porosities during in vitro cell seeding, leading to poor initial cell attachment. This study aimed to demonstrate the fabrication of a new collagen coating process for optimizing the hydrophilic property and cell-substrate interactions. This method may be used for coating collagen on any relevant biomedical constructs made of synthetic polymers to increase their biocompatibility and cell attachment. Materials and methods…

People with neurological deficits face difficulties perceiving their surroundings, resulting in an urgent need for wearable electronic skin (e-skin) that can monitor external stimuli and temperature changes. However, the monolithic structure of e-skin is not conducive to breathability and hinders hair growth, limiting its wearing comfort. In this work, we prepared fully three-dimensional (3D) printed e-skin that allowed hair penetration and growth. This e-skin also achieved simultaneous pressure and temperature detection and a high tactile resolution of 100 cm–2, which is close to that of human fingertips. The temperature sensor maintained linear measurements within 10–60 °C. The pore microstructure prepared…

Objectives There are complications in applying regenerative strategies at the interface of hard and soft tissues due to the limited designs of constructs that can accommodate different cell types in different sites. The problem originates from the challenges in the adhesion of dissimilar materials, such as polymers and hydrogels, that can be suitable for regenerating different tissues such as bone and soft tissues. This paper presents a design of a new hybrid construct in which a polymer (polycaprolactone (PCL)) membrane firmly adheres to a layer of hydrogen (gelatin). Methods PCL membranes with defined size and porosity were fabricated using 3D…

Using three-dimensional (3D) printing technology, a 3D calcium alginate/graphene oxide (3D CA/GO) adsorbent, with a hierarchical macroporous structure, was successfully constructed. Owing to the optimized construction process, the 3D CA/GO showed an enhanced adsorption capacity (490.2 mg/g at pH = 3.0) for lead (Pb(II)) in aqueous solution, which was two times higher than reported in the literature). Meanwhile, the selective adsorption ratio of 3D CA/GO for Pb(II) reached 99.8% when positive ions occurred. In addition, after eight adsorption–desorption cycles, the adsorption capacity did not experience a significant decrease and the structure remained stable. Meanwhile, the adsorbed Pb(II) could be eluted…

3D Bioprinting plays an irreplaceable role in bone tissue engineering. Shellac and curcumin are two natural compounds that are widely used in the food and pharmaceutical sectors. In this study, a new composite scaffold with good biocompatibility and antibacterial ability was manufactured by adding shellac and curcumin into the traditional bone scaffold through low-temperature three-dimensional printing (LT-3DP), and its impact on the osteoimmune microenvironment was evaluated.

The membrane based on receptor functionalization provides a new paradigm for the development of mechanical biosensors. However, improvement of sensitivity and test accuracy is still a challenge for mechanical biosensors in practical application. Herein, a surface stress mechanical biosensor (MBioS) based on double-side-gold nanoparticale (AuNP)-coated grid-type polydimethylsiloxane (PDMS) membrane (D-G-MBioS) and 3D printing for human serum albumin (HSA) detection is developed. The surface stress is amplified by the grid coupling sandwich immune structure to improve the sensitivity of the MbioS, successfully reducing limite of detection (LOD) by two orders of magnitude. By self-assembly of AuNPs, the double-side-coated PDMS membrane is…

Tissue-engineered ear cartilage scaffold based on three-dimensional (3D) bioprinting technology presents a new strategy for ear reconstruction in individuals with microtia. Natural hydrogel is a promising material due to its excellent biocompatibility and low immunogenicity. However, insufficient mechanical property required for cartilage is one of the major issues pending to be solved. In this study, the gelatin methacryloyl (GelMA) hydrogel reinforced with bacterial nanocellulose (BNC) was developed to enhance the biomechanical properties and printability of the hydrogel. The results revealed that the addition of 0.375% BNC significantly increased the mechanical properties of the hydrogel and promoted cell migration in the…

High-density polyethylene (HDPE) is a promising material for the development of scaffold implants for auricle reconstruction. However, preparing a personalized HDPE auricle implant with favorable bioactive and antibacterial functions to promote skin tissue ingrowth is challenging. Herein, we present 3D-printed HDPE auricle scaffolds with satisfactory pore size and connectivity. The layer-by-layer (LBL) approach was applied to achieve the improved bioactive and antibacterial properties of these 3D printed scaffolds. The HDPE auricle scaffolds were fabricated using an extrusion 3D printing approach, and the individualized macrostructure and porous microstructure were both adjusted by the 3D printing parameters. The polydopamine (pDA) coating method…

Poor fiber orientation and mismatched bone–ligament interface fusion have plagued the regeneration of periodontal defects by cell-based scaffolds. A 3D bioprinted biomimetic periodontal module is designed with high architectural integrity using a methacrylate gelatin/decellularized extracellular matrix (GelMA/dECM) cell-laden bioink. The module presents favorable mechanical properties and orientation guidance by high-precision topographical cues and provides a biochemical environment conducive to regulating encapsulated cell behavior. The dECM features robust immunomodulatory activity, reducing the release of proinflammatory factors by M1 macrophages and decreasing local inflammation in Sprague Dawley rats. In a clinically relevant critical-size periodontal defect model, the bioprinted module significantly enhances the…

Introduction The use of scaffolds in tissue engineering is becoming increasingly important as solutions need to be found to preserve human tissues such as bone or cartilage. Various factors, including cells, biomaterials, cell and tissue culture conditions, play a crucial role in tissue engineering. The in vivo environment of the cells exerts complex stimuli on the cells, thereby directly influencing cell behavior, including proliferation and differentiation. Therefore, to create suitable replacement or regeneration procedures for human tissues, the conditions of the cells’ natural environment should be well mimicked. Therefore, current research is trying to develop 3-dimensional scaffolds (scaffolds) that can…

Decellularized extracellular matrix hydrogel (dECM-G) has demonstrated its significant tissue-specificity, high biocompatibility, and versatile utilities in tissue engineering. However, the low mechanical stability and fast degradation are major drawbacks for its application in three-dimensional (3D) printing. Herein, we report a hybrid hydrogel system consisting of dECM-Gs and photocrosslinkable gelatin methacrylate (GelMA), which resulted in significantly improved printability and structural fidelity. These premixed hydrogels retained high bioactivity and tissue-specificity due to their containing dECM-Gs. More specifically, it was realized that the hydrogel containing dECM-G derived from porcine peripheral nerves (GelMA/pDNM-G) effectively facilitated neurite growth and Schwann cell migration from two-dimensional cultured…

Purpose Drug release from hypromellose-based tablets involves the formation of characteristic dry cores surrounded by outer gel layers in aqueous media. The aim of this study was to investigate the effect of perforation sizes on the dissolution of repaglinide from three-dimensionally (3D) printed tablets with two viscosity grades of hypromellose as rate-controlling polymer. Methods Printing pastes of appropriate consistency were developed and fed into a bioplotter cartridge to extrude strands/filaments. Tablets were printed in a crisscross pattern with 1.0, 1.3, and 1.6 mm of inter-strand distances. Printed tablets were characterized and repaglinide dissolution data were evaluated mathematically. Results Scanning electron…

Nonunion bone fractures can impact the quality of life and represent a major economic burden. Scaffold-based tissue engineering has shown promise as an alternative to bone grafting. Achieving desirable bone reconstruction requires appropriate surface properties, together with optimizing the internal architecture of 3D scaffolds. This study presents the surface modification of poly(lactic-co-glycolic acid) (PLGA), collagen, and PLGA-collagen via an argon plasma treatment. Argon plasma can modify the surface chemistry and topography of biomaterials and improve in vivo integration. Solvent-cast films were prepared using 1,1,1,3,3,3-hexafluoro-2-propanol and characterized via differential scanning calorimetry, thermogravimetric analysis, contact angle measurement, and critical surface tension analysis.…

With more than 1.5 million total knee and hip implants placed each year, there is an urgent need for a drug delivery system that can effectively support the repair of bone infections. Scaffolds made of natural biopolymers are widely used for this purpose due to their biocompatibility, biodegradability, and suitable mechanical properties. However, the poor processability is a bottleneck, as highly customizable scaffolds are desired. The aim of the present research is to develop a scaffold made of thermoplastic collagen (TC) using 3D printing technology. The viscosity of the material was measured using a rheometer. A 3D bioplotter was used…

Objectives: The current study aimed to perform an in vivo examination using a critical-size periodontal canine model to investigate the capability of a 3D-printed soft membrane for guided tissue regeneration (GTR). This membrane is made of a specific composition of gelatin, elastin, and sodium hyaluronate that was fine-tuned and fully characterized in vitro in our previous study. The value of this composition is its potential to be employed as a suitable replacement for collagen, which is the main component of conventional GTR membranes, to overcome the cost issue with collagen. Methods: Critical-size dehiscence defects were surgically created on the buccal…

Human brain organoids present a new paradigm for modeling human brain organogenesis, providing unprecedented insight to the molecular and cellular processes of brain development and maturation. Other potential applications include in vitro models of disease and tissue trauma, as well as three-dimensional (3D) clinically relevant tissues for pharmaceuticals development and cell or tissue replacement. A key requirement for this emerging technology in both research and medicine is the simple, scalable, and reproducible generation of organoids using reliable, economical, and high-throughput culture platforms. Here we describe such a platform using a defined, clinically compliant, and readily available hydrogel generated from gelatin…

The inevitable gap between in vitro and in vivo degradation rate of biomaterials has been a challenging factor in the optimal designing of scaffold’s degradation to be balanced with new tissue formation. To enable non-/minimum-invasive tracking of in vivo scaffold degradation, chemical modifications have been applied to label polymers with fluorescent dyes. However, the previous approaches may have limited expandability due to complicated synthesis processes. Here, we introduce a simple and efficient method to fluorescence labeling of polymeric scaffolds via blending with near-infrared (NIR) quantum dots (QDs), semiconductor nanocrystals with superior optical properties. QDs-labeled, 3D-printed PCL scaffolds showed promising efficiency…

Gelatin methacrylate (GelMA) is a widely used biomaterial in tissue engineering and regenerative medicine. GelMA is a chemically modified form of gelatin. Researchers have employed various methods to synthesize GelMA, such as the conventional method (Bulcke et al. 2000), the sequential method (Lee et al. 2015), and facile one-pot (Shirahama et al. 2016) methods to achieve GelMA hydrogels with a wide range of degree of functionalization or methacrylation. However, the impact of these different synthesis methods and their reac- tion parameters on GelMA hydrogels and scaffolds remains to be investigated concerning bioink formulation and 3D printing application. In this study,…

The poor interfacial adhesion between silk fiber and polyester species remains a critical problem for the optimal mechanical performance of silk-reinforced polyester composites. Here, we investigated in quantitative terms the interfacial properties between natural silk fibers and polycaprolactone (PCL) at nano-, micro-, and macroscales and fabricated continuous silk-PCL composite filaments by melt extrusion and drawing processing of PCL melt at 100, 120, and 140 °C. Bombyx mori (Bm) silk, Antheraea pernyi (Ap) silk, and polyamide6 (PA6) fiber were compared to the composite with PCL. The Ap silk exhibited the highest surface energy, the best wettability, and the largest interfacial shear…

Magnetic refrigeration is an energy-efficient, sustainable, environmentally-friendly alternative to the conventional vapor-compression cooling technology. There are several magnetic refrigerator device designs in existence today that are predicted to be highly energy-efficient, on condition that suitable working materials can be developed. This challenge in manufacturing magnetocaloric devices is unresolved, mainly due to issues related to shaping the mostly brittle magnetocaloric alloys into thin-walled channeled regenerator structures to facilitate efficient heat transfer between the solid refrigerant and the heat exchange fluid in an active magnetic regenerator (AMR) cooling device. To address this challenge, a novel extrusion-based additive manufacturing (AM) method has been…

Amine-functionalized polymers (AFPs) are able to react with carbon dioxide (CO2) and are therefore useful in CO2 capture and sensing. To develop AFP-based CO2 sensors, it is critical to examine their electrical responses to CO2 over long periods of time, so that the device can be used consistently for measuring CO2 concentration. To this end, we synthesized poly(N-[3-(dimethylamino)propyl] methacrylamide) (pDMAPMAm) by free radical polymerization and tested its ability to behave as a CO2-responsive polymer in a transducer. The electrical response of this polymer to CO2 upon long exposure times was measured in both the aqueous and solid phases. Direct current…

3D bioprinting technology has gained increased attention in the regenerative medicine and tissue engineering communities over the past decade with their attempts to create functional living tissues and organs de novo. While tissues such as skin, bone, and cartilage have been successfully fabricated using 3D bioprinting, there are still many technical and process driven challenges that must be overcome before a complete tissue engineered solution is realized. Although there may never be a single adopted bioprinting process in the scientific community, adherence to optimized bioprinting protocols could reduce variability and improve precision with the goal of ensuring high quality printed…

A modular design composed of 3D-printed polycaprolactone (PCL) as the load-bearing module, and dual porosity gelatin foam as the bio-reactive module, was developed and characterized in this study. Surface treatment of the PCL module through aminolysis-aldehyde process was found to yield a stronger interface bonding compared to NaOH hydrolysis, and therefore was used in the fabrication procedure. The modular scaffold was shown to significantly improve the mechanical properties of the gelatin foam. Both compressive modulus and ultimate strength was found to increase over 10 times when the modular design was employed. The bio-reactive module i.e., gelatin foam, presented a dual…

Postoperative restenosis in patients with external ear canal (EEC) atresia or stenosis is a common complication following canaloplasty. Our aim in this study was to explore the feasibility of using a three dimensionally (3D)-printed, patient-individualized, drug ((dexamethasone (DEX)), and ciprofloxacin (cipro))-releasing external ear canal implant (EECI) as a postoperative stent after canaloplasty. We designed and pre-clinically tested this novel implant for drug release (by high-performance liquid chromatography), biocompatibility (by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay), bio-efficacy (by the TNF-α (tumor necrosis factor-alpha)-reduction test (DEX) and inhibition zone test (for cipro)), and microbial contamination (formation of turbidity or sediments in culture medium).…

This work presents the first example of an imidazolium ionene containing aromatic ether-ketone-ether linkages inspired by poly(ether ether ketone) (PEEK), a well-known ultrahigh-performance (UHP) engineering polymer. The requisite starting materials for this “PEEK ionene” were efficiently synthesized in good yields and then polymerized through condensation (Menshutkin reaction), followed by anion metathesis to form the final polymer product, which had a number-average molecular weight (Mn) of ∼90 kDa. The properties of the PEEK-ionene were thoroughly characterized, and its potential utility was demonstrated by analyzing this material as a gas separation membrane and 3D-printing this ionic UHP polymer. Thin films of this…

Photoresponsive soft liquid crystalline elastomers (LCEs) transform light’s energy into dynamic shape changes and are considered promising candidates for production of soft robotic or muscle-like devices. 3D printing allows access to elaborated geometries as well as control of the photoactuated movements; however, this development is still in its infancy and only a limited choice of LCE is yet available. Herein, we propose to introduce biocompatible and sustainable cellulose nanocrystals (CNC) into an LCE in order to facilitate the printing process by direct ink writing (DIW) and to benefit from the anisotropic mechanical properties resulting from the extrusion-induced alignment of such…

Impedance-matched acoustic materials were developed to improve ultrasound penetration through the aberration layer. The traditional ultrasound layer matching material is called a couplant, which can only enhance ultrasound transmission to soft biological media such as the cartilage and muscle but cannot penetrate hard media such as the bone. Here, we propose a phase-modulated complementary acoustic metamaterial based on the principle of impedance matching, which enables ultrasound to penetrate the bone, and use the equivalent parameter technology of acoustic metamaterials for parameter design. Ultrasonic layer adjustment is performed through 3D printing and corrects bone aberrations. Several configurations were investigated through numerical…

Cultivated meat harnesses tissue engineering (TE) concepts to create sustainable, edible muscle tissues, for addressing the rising meat product demands and their global consequences. As 3D-printing is a promising method for creating thick and complex structures, two plant-protein-enriched scaffolding compositions were primarily assessed in our work as 3D-printable platforms for bovine satellite cells (BSC) maturation. Mixtures of pea protein isolate (PPI) and soy protein isolate (SPI) with RGD-modified alginate (Alginate(RGD)) were evaluated as prefabricated mold-based and 3D-printed scaffolds for BSC cultivation, and ultimately, as potential bioinks for cellular printing. Mold-based protein enriched scaffolds exhibited elevated stability and stiffness compared to…

Presented here is the synthesis of a 3D printable nano-polysaccharide self-healing hydrogel for flexible strain sensors. Consisting of three distinct yet complementary dynamic bonds, the crosslinked network comprises imine, hydrogen, and catecholato-metal coordination bonds. Self-healing of the hydrogel is demonstrated by macroscopic observation, rheological recovery, and compression measurements. The hydrogel was produced via imine formation of carboxyl methyl chitosan, oxidized cellulose nanofibers, and chitin nanofibers followed by two subsequent crosslinking stages: immersion in tannic acid (TA) solution to create hydrogen bonds, followed by soaking in FeIII solution to form catecholato-metal coordination bonds between TA and FeIII. The metal coordination bonds…

Bacterial infection is an important challenge when repairing bone defects with implant materials. The development of functional scaffolds with an intelligent antibacterial function that can be used for bone repair are of great significance. In this study, we used vancomycin (VAN) as a model antibiotic drug and proposed the fabrication of VAN-loaded zeolite imidazole framework-8-functionalized bioglass (ZIF-8@VAN@BG) scaffolds with a pH-responsive antibacterial effect for use in potentially infected bone repair applications. The physicochemical properties, in vitro biological properties and antibacterial properties of the scaffolds were studied. The results showed that the ZIF-8@VAN@BG scaffolds had a 3D porous structure and exhibited…

The lack of an effective printable ink preparation method and the usual mechanically weak performance obstruct the functional 3D printing hydrogel exploitation and application. Herein, we propose a gentle pre-cross-linking strategy to enable a loosely cross-linked cellulose network for simultaneously achieving favorable printability and a strong hydrogel network via mediating the cellulose self-assembly. A small amount of epichlorohydrin is applied to (i) slightly pre-cross-link the cellulose chains for forming the percolating network to regulate the rheological properties and (ii) form the loosely cross-linked points to mediate the cellulose chains’ self-assembly for achieving superior mechanical properties. The fabrication of the complex…

In this work, nanoparticles of a luminescent metal–organic framework were embedded in a photopolymerized methacrylated gelatin. Steady-state and time-resolved luminescence spectroscopy was used to explore the drying and the photopolymerization processes, as well as the effect the methacrylated gelatin had on the quantum yield and decay time of the nanoparticles. A drying time of 27.5 min was needed for a 20 µL droplet, and the proposed intensity ratio analysis resulted in a minimum irradiation time of 18.6 min, at a lamp intensity of 2.7 W/m2, for the photopolymerization process to end. The presence of the methacrylated gelatin decreased the quantum yield of the…

Critical bone defects with a sluggish rate of auto-osteoconduction and imperfect reconstruction are motivators for the development of an alternate innovative approach for the regeneration of bone. Tissue engineering for bone regeneration signifies an advanced way to overcome this problem by creating an additional bone tissue substitute. Among different fabrication techniques, the 3D printing technique is obviously the most efficient and advanced way to fabricate an osteoconductive scaffold with a controlled porous structure. In the current article, the polycarbonate and polyester diol based polyurethane–urea (P12) was synthesized and 3D porous nanohybrid scaffolds (P12/TP-nHA) were fabricated using the 3D printing technique…

Hip dysplasia is a developmental disorder that resulted in insufficient acetabular coverage. Current surgical treatments are technically demanding, complex, invasive, and often lead to associated complications. Therefore, the development of regenerative implants that fit to the bone and induce osteogenesis and chondrogenesis is in high demand. In this study, an implant was developed in which the osteogenic part was 3D printed using polycaprolactone (PCL), crosslinked with dopamine, and subjected to surface mineralization; while the chondrogenic part was prepared using silk fibroin (SF) and bone morphogenetic protein 2. Physical and chemical characterization of the implant was conducted using energy dispersive spectrometry…

Regeneration of the gradient structure of the tendon-to-bone interface is still a significant clinical challenge. This study reports a novel therapeutic method combining three-dimensional (3D) bioprinting and melt electrospinning writing techniques to regenerate a functional tendon-to-bone interface. We generated biomimetic multilayered scaffolds with 3D-bioprinted pre-differentiated autologous adipose-derived mesenchymal stem cells (ADMSC), which recapitulated compositional and cellular structures of the interface. The hydrogel-based bioinks offered high cell viability and proliferative capability for rabbit ADMSCs. The hydrogels with pre-differentiated (into tenogenic, chondrogenic, and osteogenic lineages) or undifferentiated rabbit ADMSCs were 3D-bioprinted into zonal-specific constructs to mimic the structure of the tendon-to-bone interface.…

Osteoarthritis is a highly prevalent rheumatic musculoskeletal disorder that commonly affects many joints. Repetitive joint overloading perpetuates the damage to the affected cartilage, which undermines the structural integrity of the osteochondral unit. Various tissue engineering strategies have been employed to design multiphasic osteochondral scaffolds that recapitulate layer-specific biomechanical properties, but the inability to fully satisfy mechanical demands within the joint has limited their success. Through computational modeling and extrusion-based bioprinting, we attempted to fabricate a biphasic osteochondral scaffold with improved shear properties and a mechanically strong interface. A 3D stationary solid mechanics model was developed to simulate the effect of…

4D printing is an advanced manufacturing technology combining additive manufacturing with smart materials. Based on light-active shape memory composites, smart medical structures with remote control capability, therapeutic function, and biocompatibility are hopefully fabricated by 4D printing. Here, a multifunctional composite with good mechanical properties, biocompatibility, and light-active shape memory performance is prepared by incorporating gold nanoparticles into a shape memory polyurethane matrix. The composites demonstrate a rapid and stable light-thermal effect, which can achieve localized and controlled breast tumor ablation, providing an approach to hyperthermia treatment for cancer cells. By directly bioprinting the composite melt, a series of 4D-printed structures…

Currently, the implants used for enophthalmic invagination have the disadvantages of precise filling difficulty, weak filling ability, large surgical wounds, and lack of CT development. Here, a CT-developable orbital stent was manufactured via 4D printing of a shape memory polyurethane composite for enophthalmos treatment. The composite was endowed with good CT development properties via incorporation of gold nanoparticles and nano-hydroxyapatite. Based on the bionic idea and CT reconstruction technique, a 4D printed orbital stent with a bionic honeycomb pore structure and an outer contour matching the orbital coloboma was designed to support the orbital tissue more accurately and stably. CT…

The cultured meat is the solution to reduce resources using in a traditional meat production. It helps produce meat without killing livestock and decrease residue products. The method could also integrate with scaffold’s material which does not derive from animal products. This study aims to investigate the effects of carboxymethyl cellulose (CMC) and apple powder on printability and cytotoxicity as additives in alginate/agarose-based hydrogel. 3D structures of them were printed to find a proper printing condition. From our experiments, the structure could maintain their shapes and uniform line sizes for carboxylmethyl cellulose, but not for apple powder at the 2%…

Cellulose nanocrystals (CNCs), a type of natural photonic crystal, have been used to develop various optical materials owing to their chiral nematic organization, renewability, sustainability, and abundance. However, scaling up the production of CNC-based photonic materials remains challenging because of their long self-assembly time, inevitable assembly defects, static optical properties, and brittle nature. To address these drawbacks, the current study introduces flexible photonic hydrogels with chromatic patterns that are 3D printed using CNC-based inks. These viscoelastic inks were composed of photopolymerizable monomers and CNCs that harbored high aspect ratios. The luminance and color difference of the patterns in the photonic…

Regenerative biomaterials play a crucial role in the success of maxillofacial reconstructive procedures. Yet today, limited options are available when choosing polymeric biomaterials to treat critical size bony defects. Further, there is a requirement for 3D printable regenerative biomaterials to fabricate customized structures confined to the defect site. We present here a 3D printable composite formulation consisting of polycaprolactone (PCL) and silk fibroin microfibers and have established a robust protocol for fabricating customized 3D structures of complex geometry with the composite. The 3D printed composite scaffolds demonstrated higher compressive modulus than 3D printed scaffolds of PCL alone. Furthermore, the compressive…

Three-dimensional (3D) printed hydrogel scaffolds enhanced with ceramics have shown potential applications for cartilage regeneration, but leaving biological and mechanical properties to be desired. This paper presents our study on the development of chitosan /alginate scaffolds with nano hydroxyapatite (nHA) by combining 3D printing and impregnating techniques, forming a hybrid, yet novel, structure of scaffolds for potential cartilage regeneration. First, we incorporated nHA into chitosan scaffold printing and studied the printability by examining the difference between the printed scaffolds and their designs. Then, we impregnated alginate with nHA into the printed chitosan scaffolds to forming a hybrid structure of scaffolds;…

Urinary tract disorders come at great discomfort to the patients suffering from them. To treat them, several potent drug substances are available but unfortunately, systemic drug therapy often comes along with undesired adverse effects. Previous work has therefore been conducted aiming at a local drug release in the urinary bladder. However, whether a therapeutically relevant drug concentration may be reached at the target site is not easy to determine when applying common compendial dissolution methods. Therefore, the aim of this study was to develop a biorelevant dissolution model able to take physiological conditions into consideration, i.e. urine flow rates, urination…

Discontinued treatment and non-adherence are oftentimes weaknesses of common first-line drug therapy against bladder conditions due to their negative side-effects. To overcome these limitations and increase patients’ quality of life, intravesical therapies are continuously being explored. 3D-printing offers the possibility of freely tailoring drug delivery systems to manufacture indwelling devices that may administer drugs locally over an extended time and avoiding frequently repeated administrations while minimizing systemic side-effects. In the present work, pressure-assisted micro syringe printing has been used to develop flexible drug-loaded inserts applicable via common urinary catheter that can remain up to several weeks inside the urinary bladder.…

In the field of orthopedics, an infected bone defect is a refractory disease accompanied by bone infection and defects as well as aggravated circulation. There are currently no personalized scaffolds that can treat bone infections using local stable and sustained-release antibiotics while providing mechanical support and bone induction to promote bone repair in the process of absorption in vivo. In our previous study, rifampicin/moxifloxacin-poly lactic-co-glycolic acid (PLGA) microspheres were prepared and tested for sustained release and antibacterial activity. The composite scaffold of poly-L-lactic acid (PLLA)/Pearl had a positive effect on mechanics supports and promoted osteogenesis. Therefore, in this study, the…

The efficiency of nerve guide conduits (NGCs) in repairing peripheral nerve injury is not high enough yet to be a substitute for autografts and is still insufficient for clinical use. To improve this efficiency, 3D electrospun scaffolds (3D/E) of poly(l-lactide-co-ε-caprolactone) (PLCL) and poly(l-lactide-co-glycolide) (PLGA) were designed and fabricated by the combination of 3D printing and electrospinning techniques, resulting in an ideal porous architecture for NGCs. Polypyrrole (PPy) was deposited on PLCL and PLGA scaffolds to enhance biocompatibility for nerve recovery. The designed pore architecture of these “PLCL-3D/E” and “PLGA-3D/E” scaffolds exhibited a combination of nano- and microscale structures. The mean…

Conventional manufacturing techniques allow the production of photoresponsive cellulose nanocrystals (CNC)-based composites that can reversibly modify their optical, mechanical, or chemical properties upon light irradiation. However, such materials are often limited to 2D films or simple shapes and do not benefit from spatial tailoring of mechanical properties resulting from CNC alignment. Herein, we propose the direct ink writing (DIW) of 3D complex structures that combine CNC reinforcement effects with photoinduced responses. After grafting azobenzene photochromes onto the CNC surfaces, up to 15 wt % of modified nanoparticles can be introduced into a polyurethane acrylate matrix. The influence of CNC on…

Personalised drug delivery systems with the ability to offer real-time imaging and control release are an advancement in diagnostic and therapeutic applications. This allows for a tailored drug dosage specific to the patient with a release profile that offers the optimum therapeutic effect. Coupling this application with medical imaging capabilities, real-time contrast can be viewed to display the interaction with the host. Current approaches towards such novelty produce a drug burst release profile and contrasting agents associated with side effects as a result of poor encapsulation of these components. In this study, a 3D-printed drug delivery matrix with real-time imaging…

Epigenetic approaches using the histone deacetylase 2 and 3 inhibitor-MI192 have been reported to accelerate stem cells to form mineralised tissues. Gelatine methacryloyl (GelMA) hydrogels provide a favourable microenvironment to facilitate cell delivery and support tissue formation. However, their application for bone repair is limited due to their low mechanical strength. This study aimed to investigate a GelMA hydrogel reinforced with a 3D printed scaffold to support MI192-induced human bone marrow stromal cells (hBMSCs) for bone formation. Cell culture: The GelMA (5 wt%) hydrogel supported the proliferation of MI192-pre-treated hBMSCs. MI192-pre-treated hBMSCs within the GelMA in osteogenic culture significantly increased…

A full PDMS micro-droplet chip for 3D cell culture was prepared by using SLA light-curing 3D printing technology. This technology can quickly customize various chips required for experiments, saving time and capital costs for experiments. Moreover, an injection molding method was used to prepare the full PDMS chip, and the convex mold was prepared by light-curing 3D printing technology. Compared with the traditional preparation process of micro-droplet chips, the use of 3D printing technology to prepare micro-droplet chips can save manufacturing and time costs. The different ratios of PDMS substrate and cover sheet and the material for making the convex…

Current in vitro models for osteosarcoma investigation and drug screening, including two-dimensional (2D) cell culture and tumour spheroids (i.e. cancer stem-like cells), lack extracellular matrix (ECM). Therefore, results from traditional models may not reflect real pathological processes in genuine osteosarcoma histological structures. Here, we report a three-dimensional (3D) bioprinted osteosarcoma model (3DBPO) that contains osteosarcoma cells and shrouding ECM analogue in a 3D frame. Photo-crosslinkable bioinks composed of gelatine methacrylamide and hyaluronic acid methacrylate mimicked tumour ECM. We performed multi-omics analysis, including transcriptomics and DNA methylomics, to determine differences between the 3DBPO model and traditional models. Compared with 2D models…

Protein delivery and release from synthetic scaffold materials are major challenges within the field of bone tissue engineering. In this study, 13-93B1.5 borosilicate bioactive glass (BSG) base paste was 3D printed to produce BSG-based scaffolds with high porosity (59.85 ± 6.04%) and large pore sizes (350–400 μm) for functionalization with a sodium alginate (SA)/calcitonin gene-related peptide (CGRP) hydrogel mixture. SA/CGRP hydrogel was uniformly filled into the interconnected pores of 3D printed BSG constructs to produce BSG-SA/CGRP scaffolds which were subject to bioactivity and biocompatibility analysis. BSG scaffolds filled with SA hydrogel underwent dissolution in simulated body fluid (SBF), resulting in…

High-dose methotrexate (HDMTX) is one of the chemotherapeutic agents used to treat a variety of cancers in both adults and children. However, the toxicity associated with HDMTX has resulted in the spread of infections and treatment interruption. Further, poor bioavailability due to efflux pump activities mediated by P-glycoprotein has also been linked to poor therapeutic effects of methotrexate following oral administrations. D-α-Tocopheryl poly-ethylene glycol 1000 succinate (TPGS) is known to improve the bioavailability of poorly soluble drugs by inhibiting P-gp efflux activities, thus enhancing cellular uptake. Therefore, to achieve improved bioavailability for MTX, this study aimed to design and develop…

3D printed ceramics have received much attention of late due to the ability to manufacture complex near net shapes with a range of structures across multiple length scales. The introduction of hierarchical features offers a wider array of properties, yet with this comes additional unknowns as to their limits including the mechanisms behind failures. The present work applies in-situ Synchrotron micro X-ray computed tomography (μXCT) with 4-point flexural testing to study and further understand the failure pattern of 3D printed hierarchical porous ultra-high temperature ceramics. Samples were imaged at incremental load steps to observe the propagation of defects until final…

Tissue engineering provides a promising strategy for auricular reconstruction. Although the first international clinical breakthrough of tissue-engineered auricular reconstruction has been realized based on polymer scaffolds, this approach has not been recognized as a clinically available treatment because of its unsatisfactory clinical efficacy. This is mainly since reconstruction constructs easily cause inflammation and deformation. In this study, we present a novel strategy for the development of biological auricle equivalents with precise shapes, low immunogenicity, and excellent mechanics using auricular chondrocytes and a bioactive bioink based on biomimetic microporous methacrylate-modified acellular cartilage matrix (ACMMA) with the assistance of gelatin methacrylate (GelMA),…

Fluoropolymers are amongst the most common polymers used for the fabrication of filtration membranes. Despite this, commercial production of these membranes remains dominated by simple casting and solvent phase separation. Herein, we show a rapid, simple approach to produce fluoropolymer membranes, with a porous patterned surface, via immersion precipitation printing (ipP). The patterns can act as a permeate spacer, which are traditionally added to a membrane separately to induce turbulent flow and subsequently decreasing membrane fouling. The direct phase inversion of the permeate spacer during membrane production induces a porous morphology. Further, intimate mechanical connection between the membrane surface and…

Self-bending actuators have time and cost reduction benefits for applications like self-assembly and self-deployable structures. Three-dimensional (3D) printing is a promising rapid and accurate manufacturing method for controlling spatial self-bending actuation in custom-designed soft structures. This paper studies the features merely imparted by 3D printing fabrication in control of self-folding actuators. It is shown that 3D printing control parameters such as different spatial patterns of hinges affect the response time and bending angle of the actuator. A polystyrene (PS) pane as a representative of thermo-responsive shape memory polymers is used as the main material for being remotely stimulated via light…

Introduction The use of scaffolds in tissue engineering is becoming increasingly important as solutions need to be found for the problem of preserving human tissue, such as bone or cartilage. In this work, scaffolds were printed from the biomaterial known as polycaprolactone (PCL) on a 3D Bioplotter. Both the external and internal geometry were varied to investigate their influence on mechanical stability and biocompatibility. Materials and Methods: An Envisiontec 3D Bioplotter was used to fabricate the scaffolds. First, square scaffolds were printed with variations in the strand width and strand spacing. Then, the filling structure was varied: either lines, waves,…

Yield-stress support bath-enabled three-dimensional (3D) printing has been widely used in recent years for diverse applications. However, current yield-stress fluids usually possess single microstructures and still face the challenges of on-demand adding and/or removing support bath materials during printing, constraining their application scope. This study aims to propose a concept of stimuli-responsive yield-stress fluids with an interactive dual microstructure as support bath materials. The microstructure from a yield-stress additive allows the fluids to present switchable states at different stresses, facilitating an embedded 3D printing process. The microstructure from stimuli-responsive polymers enables the fluids to have regulable rheological properties upon external…

Direct ink writing (DIW) is a promising extrusion-based 3D printing technology, which employs an ink-deposition nozzle to fabricate 3D scaffold structures with customizable ink formulations for tissue engineering applications. However, determining the optimal DIW process parameters such as temperature, pressure, and speed for the specific ink is essential to achieve high reproducibility of the designed geometry and subsequent mechano-biological performance for different applications, particularly for porous scaffolds of finite sizes (total volume > 1000 mm3) and controlled pore size and porosity. The goal of this study was to evaluate the feasibility of fabricating Polycaprolactone (PCL) and bio-active glass (BG) composite-based…

Background To support bone regeneration, 3D-printed templates function as temporary guides. The preferred materials are synthetic polymers, due to their ease of processing and biological inertness. Poly(lactide-co-trimethylene carbonate) (PLATMC) has good biological compatibility and currently used in soft tissue regeneration. The aim of this study was to evaluate the osteoconductivity of 3D-printed PLATMC templates for bone tissue engineering, in comparison with the widely used 3D-printed polycaprolactone (PCL) templates. Methods The printability and physical properties of 3D-printed templates were assessed, including wettability, tensile properties and the degradation profile. Human bone marrow-derived mesenchymal stem cells (hBMSCs) were used to evaluate osteoconductivity and…

Three-dimensional printing (3D printing) is a promising technique for producing scaffolds for bone tissue engineering applications. Porous scaffolds can be printed directly, and the design, shape and porosity can be controlled. 3D synthetic biodegradable polymeric scaffolds intended for in situ bone regeneration must meet stringent criteria, primarily appropriate mechanical properties, good 3D design, adequate biocompatibility and the ability to enhance bone formation. In this study, healing of critical-sized (5 ​mm) femur defects of rats was enhanced by implanting two different designs of 3D printed poly(l-lactide-co-ε-caprolactone) (poly(LA-co-CL)) scaffolds seeded with rat bone marrow mesenchymal stem cells (rBMSC), which had been pre-differentiated…

The generation of monoclonal antibodies using an in vitro immunization approach is a promising alternative to conventional hybridoma technology. As recently published, the in vitro approach enables an antigen-specific activation of B lymphocytes within 10–12 d followed by immortalization and subsequent selection of hybridomas. This in vitro process can be further improved by using a three-dimensional surrounding to stabilize the complex microenvironment required for a successful immune reaction. In this study, the suitability of Geltrex as a material for the generation of monoclonal antigen-specific antibodies by in vitro immunization was analyzed. We could show that dendritic cells, B cells, and…

In this project, different calcification methods for collagen and collagen coatings were compared in terms of their applicability for 3D printing and production of collagen-coated scaffolds. For this purpose, scaffolds were printed from polycaprolactone PCL using the EnvisionTec 3D Bioplotter and then coated with collagen. Four different coating methods were then applied: hydroxyapatite (HA) powder directly in the collagen coating, incubation in 10× SBF, coating with alkaline phosphatase (ALP), and coating with poly-L-aspartic acid. The results were compared by ESEM, µCT, TEM, and EDX. HA directly in the collagen solution resulted in a pH change and thus an increase in…

The development of a well-designed tissue-engineered blood vessel (TEBV) still remains a challenge. In recent years, approaches in which the host response to implanted biomaterials is used to generate vascular constructs within the patient’s body have gained increasing interest. The delivery of growth factors to these in situ-engineered vascular grafts might enhance myofibroblast recruitment and the secretion of essential extracellular matrix proteins, thereby optimizing their functional properties. Layer-by-layer (LbL) coating has emerged as an innovative technology for the controlled delivery of growth factors in tissue engineering applications. In this study, we combined the use of surface-etched polymeric rods with LbL…

Carbon-based materials are promising candidates for enhancing thermal properties of phase change materials (PCMs) without lowering its energy storage capacity. Nowadays, researchers are trying to find a proper porous structure as PCMs support for thermal energy storage applications. In this context, the main novelty of this paper consists in using a ZnO-CNT-based nanocomposite powder, prepared by an own hydrothermal method at high pressure, to obtain porous 3D printed support structures with embedding capacity of PCMs. The morphology of 3D structures, before and after impregnation with three PCMs inorganic salts (NaNO3, KNO3 and NaNO3:KNO3 mixture (1:1 vol% saturated solution) was investigated…

This study aimed to fabricate biodegradable substrate with colorimetric humidity indicator for detective moisture in food packaging. The poor properties of poly(lactic acid) (PLA) were enhanced by melt blending PLA with non-toxic poly(ethylene oxide) PEO at 180 °C. Specifically, three-dimensional (3D) substrates of PLA/PEO blends were fabricated by solvent-cast 3D printing. Furthermore, cobalt chloride (CoCl2) solution was printed onto the substrate with an inkjet printer to serve as a colorimetric humidity sensing indicator. It found that the flexibility and thermal stability of the PLA were improved and the hydrophilicity was increased with an increase in PEO content. Color changes and…

In the literature, many studies have described the 3D printing of ceramic-based scaffolds (e.g., printing with calcium phosphate cement) in the form of linear structures with layer rotations of 90°, although no right angles can be found in the human body. Therefore, this work focuses on the adaptation of biological shapes, including a layer rotation of only 1°. Sample shapes were printed with calcium phosphate cement using a 3D Bioplotter from EnvisionTec. Both straight and wavy spokes were printed in a round structure with 12 layers. Depending on the strand diameter (200 and 250 µm needle inner diameter) and strand…

An ideal artificial bone implant should have similar mechanical properties and biocompatibility to natural bone, as well as an internal structure that facilitates stomatal penetration. In this work, 3D printing was used to fabricate and investigate artificial bone composites based on HA-ZrO2-PVA. The composites were proportionally configured using zirconia (ZrO2), hydroxyapatite (HA) and polyvinyl alcohol (PVA), where the ZrO2 played a toughening role and PVA solution served as a binder. In order to obtain the optimal 3D printing process parameters for the composites, a theoretical model of the extrusion process of the composites was first established, followed by the optimization…

Cardiac tissue engineering has emerged as a promising strategy to treat infarcted cardiac tissues by replacing the injured region with an ex vivo fabricated functional cardiac patch. Nevertheless, integration of the transplanted patch with the host tissue is still a burden, limiting its clinical application. Here, a bi-functional, 3D bio-printed cardiac patch (CP) design is proposed, composed of a cell-laden compartment at its core and an extracellular vesicle (EV)-laden compartment at its shell for better integration of the CP with the host tissue. Alginate-based bioink solutions were developed for each compartment and characterized rheologically, examined for printability and their effect…

Liquid ink-printing followed by sintering is used to fabricate WC-Co microlattices and cutting tools. The microstructure of WC-xCo (x=0.5-20 wt.%) is studied for a range of carbide-to-binder ratios and for various sintering temperatures. For 0.5≤Co≤5 wt.%, struts in microlattices exhibit residual porosity due to incomplete densification, even at the highest sintering temperature of 1650 °C. With 10 wt.% Co, fully dense lattice struts are achieved after sintering at 1450 °C for 1 h. For 1450-1650 °C sintering temperatures, the hardness of WC-xCo struts initially increases (due to increasing densification with increased Co) and then gradually decreases (due to an increase…

As an alternative to beam-based additive manufacturing, 3D ink-extrusion additive manufacturing is studied here for thermoelectric Bi2Te3, starting from Bi2O3+TeO2 oxide precursor powders. In situ synchrotron XRD in flowing H2 at elevated temperatures reveals the complex phase evolution upon co-reduction leading to the formation of Bi2Te3, Bi2TeO5 and Bi2TeO2. Sintering trials performed using optimal temperatures identified by in situ XRD show that low heating rates and extensive holding times are required to achieve full co-reduction to pure Bi2Te3. The formation of liquid Bi at the temperatures required for oxide reduction leads to local transient-liquid-phase sintering, creating a coarse-grained porous structure.…

Hydrogel materials are being investigated for application as scaffolds in tissue engineering owing to their many advantages, such as high water content, softness and flexibility similar to many soft tissues, tuneable physical, chemical, and biological properties, excellent biocompatibility and biodegradability, and extensive framework for cell proliferation and survival. During the past decade, because of the great versatility offered in terms of processing approach, material selection, and customization, 3D printing has become a leading technology used to fabricate hydrogel scaffolds. Furthermore, high reproducibility and unparalleled control over structural and compositional characteristics make additive manufacturing the preferred technology for the fabrication of…

The 3D printing has become important in drug development for patient-centric therapy by combining multiple drugs with different release characteristics in a single polypill. This study explores the critical formulation and geometric variables for tailoring the release of Atorvastatin and Metoprolol as model drugs in a polypill when manufactured via pressure-assisted-microextrusion 3D printing technology. The effects of these variables on the extrudability of printing materials, drug release and other quality characteristics of polypills were studied employing a definitive screening design. The extrudability of printing materials was evaluated in terms of flow pressure, non-recoverable strain, compression rate, and elastic/plastic flow. The…

In the field of regenerative medicine and tissue engineering, the use of such materials has been included for a short time, serving not only as a replacement for damaged or missing tissue, but also as a support for the surrounding tissues and cells. Such materials should not only be passively tolerated by the cell, but should also actively promote the growth, differentiation and other processes involved in tissue regeneration. The latest approach is the use and development of bioresorbable and biodegradable polymeric materials. Such materials, with their biocompatibility, degradability and suitable mechanical properties, support the overgrowth of new tissue. The…

Porous materials, including foams and lattice structures, are used in many applications such as biomedical implants, heat exchangers, catalysts, and batteries due to their light weight, high surface area and energy absorption properties. Lattice structures, specifically, are of great interest since their properties can be tailored by employing various design methodologies (e.g., topology optimization). On the other hand, Ni-based superalloys are used in many applications where high-temperature and oxidation/corrosion resistance are important such as in gas turbine components. The advantageous properties of these Ni-Cr-Al-based alloys with the geometry and tailored mechanical properties of lattice structures can be combined through a…

The emergence of four-dimensional (4D) printing and bioprinting in additive manufacturing (AM), which require knowledge of multi-physics, chemistry, and engineering skills, are bringing many engineering applications in biomedical devices, wearables, and robotics. This newly emerging technology has become a feasible commercial proposition because of lower costs, more design freedom, and more rapid production methods. This serves as a significant multidisciplinary research and training platform for both academia and the professional world. This work aims at enhancing researchers’ interest, knowledge, and skills in the emerging field of 4D printing and bioprinting. A greater knowledge of 4D printing and promotion of its…

Flowable photocurable resins can be printed effectively by stereolithographic 3D printing for dental applications; however, the 3D-printed objects’ mechanical properties cannot meet the requirements for the dental restorative materials. In this study, a strong customized crown for tooth repair was first prepared via direct ink writing 3D printing from a high-viscosity hybrid paste of acrylic monomer and multi-scale inorganic particles. The results showed that the hybrid resin-based composites (RBCs) could be printed successfully and smoothly through a metal nozzle with a gradually shrinking channel. The theoretical simulation of finite element methods was consistent with the experiment results. The printed objects…

A 3D printed scaffold consisting of a composite with very high volume fraction of particulate hydroxyapatite (hAp, 74 vol.%) and small volume fraction of poly-lactic-co-glycolic acid (26 vol.%) was loaded in compression, and the internal strains in the hAp phase were measured by high-energy x-ray diffraction. Diffraction patterns were recorded at multiple positions in the scaffold at cross-head displacements of 0, -0.52 and -0.62 mm (2.0 mm total scaffold height). The 00.2 and 21.0 hAp strains never exceeded 2 × 10−4, and most positions showed strains ≤ 1 × 10−4, which was the magnitude of the experimental uncertainty.

Human bone marrow stromal cells (hBMSCs) have been extensively utilised for bone tissue engineering applications. However, they are associated with limitations that hinder their clinical utility for bone regeneration. Cell fate can be modulated via altering their epigenetic functionality. Inhibiting histone deacetylase (HDAC) enzymes have been reported to promote osteogenic differentiation, with HDAC3 activity shown to be causatively associated with osteogenesis. Therefore, this study aimed to investigate the potential of using an HDAC2 & 3 selective inhibitor – MI192 to induce epigenetic reprogramming of hBMSCs and enhance its therapeutic efficacy for bone formation. Treatment with MI192 caused a time-dose dependant…

We report herein the fabrication of a pectin-based scaffold (6 wt% pectin, 3 wt% alginate) with high resolution (small-diameter rods), small pores, and interconnected porosity using a low temperature 3D printing process known as freeze-printing. The ability to successfully print natural polymers has been a long-standing challenge in the field of additive manufacturing of polymeric tissue scaffolds. This is due to the slow evaporation rate of the aqueous solvent, which leads to unstable structures. This problem has been addressed by utilizing the fast solidification rate of the freeze-printing process. Scaffolds with a hgresolution (rod-diameter of 83 ± 14 µm), small…

3D printing has become a promising and revolutionary pill-making technique for the pharmaceutical industry, enabling a relatively low-cost personalized medicine. Fused deposition modelling, also known by its initials FDM, is the most affordable technology for this goal, printing the material by a layer-by-layer deposition. However, the pressure assisted microsyringe technique is more adequate for working with drug containing inks as it does not need high temperatures, preventing the drug degradation. However, to make this goal possible, high accuracy and reproducibility is required, avoiding trial and error procedures. Thus, a correlation between rheology, printing parameters and the printed object was investigated.…

The emergence of four-dimensional (4D) printing in additive manufacturing (AM), which requires knowledge in multi-physics, chemistry, and engineering skills, is bringing many applications in biomedical, robotics, aerospace, and food industries. The increased usage of AM technology and smart materials in industry means that companies are seeking to develop and manage production system for academics with the multidisciplinary abilities and knowledge. This enables a high interdisciplinary platform for research and project modules suitable to be used in the academic environment for hands-on students training. This paper proposed an easy to implement and follow 4D bio/printing module well designed for students and…

In bone tissue engineering, 3D printing technology represents a promising means to obtain complex architectures with the possibility to control precisely the pore size.Diopside (CaMgSi2O6) is a biomaterial which has the ability to induce in vitro apatite formation and in vivo growth and differentiation of the osteoblast. CaMgSi2O6 is a biocompatible material that possesses good bending strength and fracture toughness, bioactivity and slow degradation rate. Due to its outstanding properties diopside has tremendous potential in medical applications.

Additive manufacturing is becoming an increasingly attractive method for the fabrication of devices in both industry applications and materials science research. Comparatively, conventional synthesis methods are often more time-intensive and provide geometric constraints. This is true for the fabrication of thermoelectric devices, where additive manufacturing is being further explored to improve cost and design flexibility. Currently, little work has been conducted on the direct effects between additive manufacturing fabrication methods and if or how thermoelectric transport properties are altered from these methods. This work focuses on the process development of constructing bulk Ni samples via particle-based ink extrusion printing, where…

The excellent rheological property has legitimated the suitability of starch hydrogel for extrusion-based 3D printing. However, the inability to promote cell attachment and migration has precluded the non-modified starch hydrogel from direct applications in the biomedical field. Herein, a novel 3D printable nanocomposite starch hydrogel is developed with highly enhanced biocompatibility for promoting 3D cell growth, by formulating with gelatin nanoparticles and collagen. The rheological evaluation reveals the shear-thinning and thixotropic properties of the starch-based hydrogel, as well as the combinatorial effect of collagen and gelatin nanoparticles on maintaining printability and 3D shape fidelity. The homogeneous microporous structure with abundant…

Extrusion-based bioprinting is an emerging and most frequently used technique for the fabrication of cell-laden constructs. A suitable hydrogel-based bioink for cell encapsulation and protection is critical for printability, structural stability, and post-printing cell viability. The thiol–ene chemistry-based gelatin-norbornene (GelNB) hydrogels have drawn much attention as a promising substitution of gelatin methacryloyl (GelMA), owing to the fast and controllable step-growth polymerization mechanism, as well as a significant reduction in reactive oxygen species (ROS) accumulation. Herein, thiolated heparin (HepSH) was synthesized and used as a macromolecular crosslinker for GelNB-based bioprinting, so that GelNB gelation became less sensitive to the thiol/ene ratio.…

Intensively studied 3D printing technology is frequently hindered by the effective printable ink preparation method. Herein, we propose an elegant and gentle solvent consumption strategy to slowly disrupt the thermodynamic stability of the biopolymer (polysaccharide: cellulose, chitin, and chitosan) solution to slightly induce the molecule chains to in situ self-assemble into nanostructures for regulating the rheological properties, eventually achieving the acceptable printability. The polysaccharides are dissolved in the alkali/urea solvent. The weak Lewis acid fumed silica (as solvent mediator) is used to (i) slowly and partially consume the alkali/urea solvent to induce the polysaccharide chains to self-assemble into nanofibers to…

Repair of large bone defects represents a major challenge for orthopedic surgeons. The newly formed microvessels inside grafts play a crucial role in successful bone tissue engineering. Previously, an active role for mesenchymal stem cell (MSC)-derived exosomes in blood vessel development and progression was suggested in the repair of multiple tissues. However, the reports on the application of MSC-derived exosomes in the repair of large bone defects are sparse. In this study, we encapsulated umbilical MSC-derived exosomes (uMSCEXOs) in hyaluronic acid hydrogel (HA-Gel) and combined them with customized nanohydroxyapatite/poly-ε-caprolactone (nHP) scaffolds to repair cranial defects in rats. Imaging and histological…

Complex-shaped, finely-featured, ultra-high-melting ZrC/W composite structures were produced by coupling, for the first time, three-dimensional (3D) ink-extrusion printing with shape/size-preserving reactive melt infiltration (the Displacive Compensation of Porosity, DCP, process). Inks containing sub-micron WC powders were printed at ambient temperature into either fine-scale structures (sub-millimeter filaments) or into a larger-scale, finely-featured 3D structure (a centimeter-scale nozzle with a sub-millimeter-thick wall). After organic binder removal, the printed structures were sintered at 1650 °C for 1 h to achieve a porosity of 50%. The porous, rigid WC structures then underwent ambient pressure infiltration and reaction with Zr-Cu liquid at up to 1350…

Massive oral and maxillofacial bone defect regeneration remains a major clinical challenge due to the absence of functionalized bone grafts with ideal mechanical and proregeneration properties. In the present study, Laponite (LAP), a synthetic nanosilicate, is incorporated into polycaprolactone (PCL) to develop a biomaterial for bone regeneration. It is explored whether LAP-embedded PCL would accelerate bone regeneration by orchestrating osteoblasts to directly and indirectly induce bone regeneration processes. The results confirmed the presence of LAP in PCL, and LAP is distributed in the exfoliated structure without aggregates. Incorporation of LAP in PCL slightly improved the compressive properties. LAP-embedded PCL is…

This article reports tunable crosslinking, reversible phase transition, and three-dimensional printing (3DP) of hyaluronic acid (HyA) hydrogels via dynamic coordination of Fe3+ ions with their innate carboxyl groups for the first time. The concentrations of Fe3+ and H+ ions and the reaction time determine the tunable ratios of mono-, bi-, and tridentate coordination, leading to the low-to-high crosslinking densities and reversible solid–liquid phase transition of HyA hydrogels. At the monodentate-dominant coordination, the liquid hydrogels have low crosslinking densities (HyA_L). At the mixed coordination of mono-, bi-, and tridentate bonding, the solid hydrogels have medium crosslinking densities (HyA_M). At the tridentate-dominant…

Critical oral-maxillofacial bone defects, damaged by trauma and tumors, not only affect the physiological functions and mental health of patients but are also highly challenging to reconstruct. Personalized biomaterials customized by 3D printing technology have the potential to match oral-maxillofacial bone repair and regeneration requirements. Laponite (LAP) nanosilicates have been added to biomaterials to achieve biofunctional modification owing to their excellent biocompatibility and bioactivity. Herein, porous nanosilicate-functionalized polycaprolactone (PCL/LAP) was fabricated by 3D printing technology, and its bioactivities in bone regeneration were investigated in vitro and in vivo. In vitro experiments demonstrated that PCL/LAP exhibited good cytocompatibility and enhanced the…

Three-dimensional (3D) printing technology has been applied to fabricate bone tissue engineering scaffolds for a wide range of materials with precisely control over scaffold structures. Coral is a potential bone repair and bone replacement material. Due to the natural source limitation of coral, we developed a fabrication protocol for 3D printing of calcium carbonate (CaCO3) nanoparticles for coral replacement in the application of bone tissue engineering. Up to 80% of CaCO3 nanoparticles can be printed with high resolution using poly-l-lactide as a blender. The scaffolds were subjected to a controlled hydrothermal process for incomplete conversion of carbonate to phosphate to…

Pressure-assisted coating (PAC) is introduced to coat 3D-printed polymeric scaffolds with β-tricalcium phosphate (β-TCP) for tissue engineering applications. The method consists of four steps: infiltration of ceramic particles into the porous structure of the polymeric scaffold, dehydration of the slurry, compaction of ceramic particles around the scaffold, and heat treatment. The optimal coating is obtained at an infiltration speed of 400 mm/min followed by complete dehydration, compaction under ca. 8 MPa pressure, and subsequent heat treatment at 65 °C. The outcome is a uniformly coated scaffold with no deformation or structural defects, as confirmed by micro-CT analysis and laser and…

The field of 3D cell cultures is currently emerging, and material development is essential in striving toward mimicking the microenvironment of a native tissue. By using the response of reporter cells to a 3D environment, a comparison between materials can be assessed, allowing optimization of material composition and microenvironment. Of particular interest, the response can be different in a normoxic and hypoxic culturing conditions, which in turn may alter the conclusion regarding a successful recreation of the microenvironment. This study aimed at determining the role of such environments to the conclusion of a better resembling cell culture model to native…

The development of 3D printing techniques has provided a promising platform to study tissue engineering and mechanobiology; however, the pursuit of printability limits the possibility of tailoring scaffolds’ mechanical properties. The brittleness of those scaffolds also hinders potential clinical application. To overcome these drawbacks, a double-network ink composed of only natural biomaterials is developed. A shear-thinning hydrogel made of silk fibroin (SF) and methacrylated hyaluronic acid (MAHA) presents a high mechanical modulus with a low concentration of macromers. The physical cross-linking due to protein folding further increases the strength of the scaffolds. The proposed SF/MAHA scaffold exhibits a storage modulus…

The capacity for a soft material to combine remote sensing and remote actuation is highly desirable for many applications in soft robotics and wearable technologies. This work presents a silicone elastomer with a suspension of a small weight fraction of ferromagnetic nickel nanorods, which is capable of both sensing deformation and altering stiffness in the presence of an external magnetic field. Cylinders composed of silicone elastomer and 1% by weight nickel nanorods experience large increases in compressive modulus when exposed to an external magnetic field. Incremental compressions totaling 600 g of force applied to the same silicone–nanorod composites increase the…

In the past decade, cartilage tissue engineering has arisen as a promising therapeutic option for degenerative joint diseases, such as osteoarthritis, in the hope of restoring the structure and physiological functions. Hydrogels are promising biomaterials for developing engineered scaffolds for cartilage regeneration. However, hydrogel-delivered mesenchymal stem cells or chondrocytes could be exposed to elevated levels of reactive oxygen species (ROS) in the inflammatory microenvironment after being implanted into injured joints, which may affect their phenotype and normal functions and thereby hinder the regeneration efficacy. To attenuate ROS induced side effects, a multifunctional hydrogel with an innate anti-oxidative ability was produced…

The use of porous 3D scaffolds for the repair of bone nonunion and osteoporotic bone is currently an area of great interest. Using a combination of thermally-induced phase separation (TIPS) and 3D-plotting (3DP), we have generated hierarchical 3DP/TIPS scaffolds made of poly(lactic-co-glycolic acid) (PLGA) and nanohydroxyapatite (nHA). A full factorial design of experiments was conducted, in which the PLGA and nHA compositions were varied between 6‒12% w/v and 10‒40% w/w, respectively, totaling 16 scaffold formulations with an overall porosity ranging between 87%‒93%. These formulations included an optimal scaffold design identified in our previous study. The internal structures of the scaffolds…

Emerging technologies such as smart packaging are shifting the requirements on electronic components, notably regarding service life, which counts in days instead of years. As a result, standard materials are often not adapted due to economic, environmental or manufacturing considerations. For instance, the use of metal conductive tracks in disposable electronics is a waste of valuable resources and their accumulation in landfills is an environmental concern. In this work, we report a conductive ink made of carbon particles dispersed in a solution of shellac. This natural and water-insoluble resin works as a binder, favourably replacing petroleum-derived polymers. The carbon particles…

Advances in 3D bioprinting allows not only controlled deposition of cells or cell-laden hydrogels but also flexibility in creating constructs that match the anatomical features of the patient. This is especially the case for reconstructing the pinna (ear), which is a large feature of the face and made from elastic cartilage that primarily relies on diffusion for nutrient transfer. The selection of cell lines for reconstructing this cartilage becomes a crucial step in clinical translation. Chondrocytes and mesenchymal stem cells are both studied extensively in the area of cartilage regeneration as they are capable of producing cartilage in vitro. However,…

Micropores are essential for tissue engineering to ensure adequate mass transportation for embedded cells. Despite the considerable progress made by advanced 3D bioprinting technologies, it remains challenging to engineer micropores of 100 µm or smaller in cell-laden constructs. Here, a microgel-templated porogel (MTP) bioink platform is reported to introduce controlled microporosity in 3D bioprinted hydrogels in the presence of living cells. Templated gelatin microgels are fabricated with varied sizes (≈10, ≈45, and ≈100 µm) and mixed with photo-crosslinkable formulations to make composite MTP bioinks. The addition of microgels significantly enhances the shear-thinning and self-healing viscoelastic properties and thus the printability of bioinks…

There is a need for the development of effective treatments for focal articular cartilage injuries. We previously developed a multiphasic 3D-bioplotted osteochondral scaffold design that can drive site-specific tissue formation when seeded with adipose-derived stem cells (ASC). The objective of this study was to evaluate this scaffold in a large animal model. Osteochondral defects were generated in the trochlear groove of Yucatan minipigs and repaired with scaffolds that either contained or lacked an electrospun tidemark and were either unseeded or seeded with ASC. Implants were monitored via computed tomography (CT) over the course of 4 months of in vivo implantation and…

The three-dimensional (3D)-printing processes reach increasing recognition as important fabrication techniques to meet the growing demands in tissue engineering. However, it is imperative to fabricate 3D tissue units, which contain cells that have the property to be regeneratively active. In most bio-inks, a metabolic energy-providing component is missing. Here a formulation of a bio-ink is described, which is enriched with polyphosphate (polyP), a metabolic energy providing physiological polymer. The bio-ink composed of a scaffold (N,O-carboxymethyl chitosan), a hydrogel (alginate) and a cell adhesion matrix (gelatin) as well as polyP substantially increases the viability and the migration propensity of mesenchymal stem…

Polymeric systems displaying spontaneous formation of surface wrinkling patterns are useful for a wide range of applications, such as diffraction gratings, flexible electronics, smart adhesives, optical devices, and cell culture platforms. Conventional fabrication techniques for wrinkling patterns involves multitude of processing steps and impose significant limitations on fabrication of hierarchical patterns, creating wrinkles on 3D and nonplanar structures, the scalability of the manufacturing process, and the integration of wrinkle fabrication process into a continuous manufacturing process. In this work, 4D printing of surface morphing hydrogels enabling direct fabrication of wrinkling patterns on curved and/or 3D structures with user-defined and spatially…

The development of synthetic structures that mimic mechanical actuation in living matter such as autonomous translation and shape changes remains a grand challenge for materials science. In living systems the integration of supramolecular structures and covalent polymers contributes to the responsive behaviour of membranes, muscles and tendons, among others. Here we describe hybrid light-responsive soft materials composed of peptide amphiphile supramolecular polymers chemically bonded to spiropyran-based networks that expel water in response to visible light. The supramolecular polymers form a reversibly deformable and water-draining skeleton that mechanically reinforces the hybrid and can also be aligned by printing methods. The noncovalent…

Controlled release of drugs from medical implants is an effective approach to reducing foreign body reactions and infections. We report here on a one-step 3D printing strategy to create drug-eluting polymer devices with a drug-loaded bulk and a drug-free coating. The spontaneously formed drug-free coating dramatically reduces the surface roughness of the implantable devices and serves as a protective layer to suppress the burst release of drugs. A high viscosity liquid silicone that can be extruded based on its shear-thinning property and quickly vulcanize upon exposure to ambient moisture is used as the ink for 3D printing. S-Nitrosothiol type nitric…

Emulsion gels have a wide range of applications. We report on a facile and versatile method to produce stable emulsion gels with tunable rheological properties. Gel formation is triggered by subjecting a mixture containing aqueous colloidal particle (CP) suspensions and water-immiscible liquids to intense turbulence, generated by low frequency (20 kHz) ultrasound or high-pressure homogenization. Through systematic investigations, requisite gel formation criteria are established with respect to both formulation and processing, including ratio/type of liquid pairs, CP properties, and turbulence conditions. Based on the emulsion microstructure and rheological properties, inter-droplet bridging and CP void-filling are proposed as universal stabilization mechanisms.…

Organ-on-a-chip (OOC) is now becoming a potential alternative to the classical preclinical animal models, which reconstitutes in vitro the basic function of specific human tissues/organs and dynamically simulates physiological or pathological activities in tissue and organ level. Despite of the much progress achieved so far, there is still an urgent need to explore new biomaterials to construct a reliable and efficient tissue–tissue interface and a general fabrication strategy to expand from single-organ OOC to multi-organ OOC in an easy manner. In this paper, we propose a novel strategy to prepare double-compartment organ-on-a-chip (DC-OOC) using electrospun poly(l-lactic acid)/collagen I (PLLA/Col I)…

Growth factors such as bone morphogenetic protein-2 (BMP-2) are potent tools for tissue engineering. Three-dimensional (3D) printing offers a potential strategy for delivery of BMP-2 from polymeric constructs; however, these biomolecules are sensitive to inactivation by the elevated temperatures commonly employed during extrusion-based 3D printing. Therefore, we aimed to correlate printing temperature to the bioactivity of BMP-2 released from 3D printed constructs composed of a model polymer, poly(propylene fumarate). Following encapsulation of BMP-2 in poly(dl-lactic-co-glycolic acid) particles, growth factor-loaded fibers were fabricated at three different printing temperatures. Resulting constructs underwent 28 days of aqueous degradation for collection of released BMP-2.…

Pb0.99(Zr0.95Ti0.05)0.98Nb0.02O3 ferroelectric ceramics with porous structure of periodic distribution were fabricated successfully via Direct Ink Writing, a type of 3D printing technique. The effect of periodically distributed porous microstructure on the dielectric, ferroelectric, as well as hydrostatic-pressure-induced depolarization properties of PZT95/5 ferroelectric ceramics, was investigated. The printed porous ceramics exhibit relatively good viscoelasticity to retain the periodic structure during 3D printing and drying. In contrast with dense PZT95/5 ferroelectric ceramics prepared by conventional solid-state sintering, low bulk density of the periodically distributed porous PZT95/5 ceramics leads to a decreased remanent polarization of 22.9 µC/cm2 under 2 kV/mm. As the hydrostatic pressure…

Gelatin has emerged as a biocompatible polymer with high printability in scaffold-based tissue engineering. The aim of the current study was to investigate the potential of genipin-crosslinked 3D printed gelatin scaffolds for temporomandibular joint (TMJ) cartilage regeneration. Crosslinking with genipin increased the stability and mechanical properties, without any cytotoxic effects. Chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSC) on the scaffolds were compared to cell pellets and spheres. Although hBMSC seeded scaffolds showed a lower expression of chondrogenesis-related genes compared to cell pellets and spheres, they demonstrated a significantly reduced expression of collagen (COL) 10, suggesting a decreased…

Effective skeletal muscle tissue engineering relies on control over the scaffold architecture for providing muscle cells with the required directionality, together with a mechanical property match with the surrounding tissue. Although recent advances in 3D printing fulfill the first requirement, the available synthetic polymers either are too rigid or show unfavorable surface and degradation profiles for the latter. In addition, natural polymers that are generally used as hydrogels lack the required mechanical stability to withstand the forces exerted during muscle contraction. Therefore, one of the most important challenges in the 3D printing of soft and elastic tissues such as skeletal…

The 3D printability of poly(l-lysine-ran–l-alanine) and four-arm poly(ethylene glycol) (P(KA)/4-PEG) hydrogels as 3D biomaterial inks was investigated using two approaches to develop P(KA)/4-PEG into 3D biomaterial inks. Only the “composite microgel” inks were 3D printable. In this approach, P(KA)/4-PEG hydrogels were processed into microparticles and incorporated into a polymer solution to produce a composite microgel paste. Polymer solutions composed of either 4-arm PEG-acrylate (4-PEG-Ac), chitosan (CS), or poly(vinyl alcohol) (PVA) were used as the matrix material for the composite paste. The three respective composite microgel inks displayed good 3D printability in terms of extrudability, layer-stacking ability, solidification mechanism, and 3D…

Articular cartilage has unique load-bearing properties but has minimal capacity for intrinsic repair. Here, we used three-dimensional weaving, additive manufacturing, and autologous mesenchymal stem cells to create a tissue-engineered, bicomponent implant to restore hip function in a canine hip osteoarthritis model. This resorbable implant was specifically designed to function mechanically from the time of repair and to biologically integrate with native tissues for long-term restoration. A massive osteochondral lesion was created in the hip of skeletally mature hounds and repaired with the implant or left empty (control). Longitudinal outcome measures over 6 months demonstrated that the implant dogs returned to…

Tailor-made polymers are needed to fully exploit the possibilities of additive manufacturing, constructing complex, and functional devices in areas such as bioelectronics. In this paper, the synthesis of a conducting and biocompatible graft copolymer which can be 3D printed using direct melting extrusion methods is shown. For this purpose, graft copolymers composed by conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and a biocompatible polymer polylactide (PLA) are designed. The PEDOT-g-PLA copolymers are synthesized by chemical oxidative polymerization between 3,4-ethylenedioxythiophene and PLA macromonomers. PEDOT-g-PLA copolymers with different compositions are obtained and fully characterized. The rheological characterization indicates that copolymers containing below 20 wt% of…

Three-dimensional (3D) printing has emerged as a valuable tool in medicine over the past few decades. With a growing number of applications using this advanced processing technique, new polymer libraries with varied properties are required. Herein, we investigate tyrosol-based poly(ester-arylate)s as biodegradable inks in fused deposition modeling (FDM). Tyrosol-based polycarbonates and polyesters have proven to be useful biomaterials due to their excellent tunability, nonacidic degradation components, and the ability to be functionalized. Polymers are synthesized by polycondensation between a custom diphenol and commercially available diacids. Thermal properties, degradation rates, and mechanical properties are all tunable based on the diphenol and…

Fabrication of scaffolds using polymers and then cell seeding is a routine protocol of tissue engineering applications. Synthetic polymers have adequate mechanical properties to substitute for some bone tissue, but they are generally hydrophobic and have no specific cell recognition sites, which leads to poor cell affinity and adhesion. Some natural polymers, have high cell affinity but are mechanically weak and do not have the strength required as a bone supporting material. In the present study, 3D printed hybrid scaffolds were fabricated using PCL and GelMA carrying dental pulp stem cells (DPSCs), which is printed in the gaps between the…

The present study sought to demonstrate the swelling behavior of hydrogel-microcarrier composite constructs to inform their use in controlled release and tissue engineering applications. In this study, gelatin methacrylate (GelMA) and GelMA-gelatin microparticle (GMP) composite constructs were three-dimensionally printed, and their swelling and degradation behavior was evaluated over time and as a function of the degree of crosslinking of included GMPs. GelMA-only constructs and composite constructs loaded with GMPs crosslinked with 10 mM (GMP-10) or 40 mM (GMP-40) glutaraldehyde were swollen in phosphate-buffered saline for up to 28 days to evaluate changes in swelling and polymer loss. In addition, scaffold reswelling capacity…

Objective Alveolar bone defects can be highly variable in their morphology and, as the defect size increases, they become more challenging to treat with currently available therapeutics and biomaterials. This investigation sought to devise a protocol for fabricating customized clinical scale and patient-specific, bioceramic scaffolds for reconstruction of large alveolar bone defects. Methods Two types of calcium phosphate (CaP)-based bioceramic scaffolds (alginate/β-TCP and hydroxyapatite/α-TCP, hereafter referred to as hybrid CaP and Osteoink™, respectively) were designed, 3D printed, and their biocompatibility with alveolar bone marrow stem cells and mechanical properties were determined. Following scaffold optimization, a workflow was developed to use…

With the development of the internet-of-things for applications such as wearables and packaging, a new class of electronics is emerging, characterized by the sheer number of forecast units and their short service-life. Projected to reach 27 billion units in 2021, connected devices are generating an exponentially increasing amount of electronic waste (e-waste). Fueled by the growing e-waste problem, the field of sustainable electronics is attracting significant interest. Today, standard energy-storage technologies such as lithium-ion or alkaline batteries still power most of smart devices. While they provide good performance, the nonrenewable and toxic materials require dedicated collection and recycling processes. Moreover,…

Osteochondral defects affect both of cartilage and subchondral areas, thus it poses a significant challenge to simultaneously regenerate two parts in orthopedics. Tissue engineering strategy is currently regarded as the most promising way to repair osteochondral defects. This study focuses on developing a multilayered scaffold with enhanced interface bonding through 3D printing. One-shot printing process enables control over material composition, pore structure, and size in each region of the scaffold, while realizes seamlessly integrated construct as well. The scaffold was designed to be triphasic: a porous bone layer composed of alginate sodium (SA) and mesoporous bioactive glasses (MBG), an intermediate…

A three-dimensional (3D) printed biodegradable hydrogel scaffold with a strong self-expanding ability to conform to the contour of irregular bone defects and be closely adjacent to host tissues is reported herein. The scaffold has a triple cross-linked network structure consisting of photo-cross-linked polyacrylamide (PAAM) and polyurethane (PU) as the primary IPN network and chemical cross-linked gelatin (Gel) as the secondary network, which confers the scaffold with good mechanical properties. The addition of PU in the polymerization process of acrylamide (AAM) can improve the ultraviolet (UV) photocuring efficiency of the hydrogel and incorporate abundant hydrogen bonds between the PAAM copolymer chain…

Although bioinks with both high printability and shape fidelity while maintaining high cell viability are developed, the biofunctionality of the resulting bioprinted construct is often overlooked. To address this, a methacrylated gelatin (GelMA)-based bioink biofunctionalized with bone particles (BPs) is developed as a personalized treatment strategy for bone regeneration. The bioink consists of incorporating BPs of various sizes (0–500 µm) in GelMA at various concentrations (ranging from 5 to 15% w/v). The printability of the bioink is systematically investigated and it is demonstrated that a 15% w/v BP-loading results in high print quality for 10% and 12.5% GelMA concentrations. Rheological…

The current standard for cell encapsulation platforms is enveloping cells in semipermeable membranes that physically isolate transplanted cells from the host while allowing for oxygen and nutrient diffusion. However, long-term viability and function of encapsulated cells are compromised by insufficient oxygen and nutrient supply to the graft. To address this need, a strategy to achieve enhanced vascularization of a 3D-printed, polymeric cell encapsulation platform using platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) is investigated. The study is conducted in rats and, for clinical translation relevance, in nonhuman primates (NHP). Devices filled with PRP, MSCs, or vehicle hydrogel are subcutaneously…

Herein, we demonstrate 3D printing of an elastomeric imidazolium polyamide-ionene which exhibits intrinsic shape-memory (SM) and self-healing (SH) character, reporting optimized printing conditions and rheological properties. This study shows the suitability of this material for 3D-printing via fused deposition modeling. The 3D-printed objects retain elasticity and SM when external force is applied, and the elastomeric character is quantified via mechanical testing. This work highlights the benefits of SH behavior as a design feature combatting inherent material weaknesses or insufficient adhesion at seams and layer junctions. DFT calculations confirmed the importance of ionic interactions and H-bonding in the SH process.

Blends of polycaprolactone (PCL) and poly(3-hydroxyoctanoate) P(3HO) were prepared by melt compounding. These immiscible blends exhibited droplet-matrix morphology at compositions up to 30 wt% P(3HO). Even though the addition of amorphous P(3HO) decreased the crystallinity of PCL, the crystallization temperature of the blends increased by 6 to 7 8C. Blends containing up to 30 wt% P(3HO) had higher crystallization rates, and lower crystallization half-times compared to neat PCL. The viscosity of PCL decreased upon addition of P(3HO), making the blends suitable for processing using a 3D bioplotter. Compositions with 10 to 30 wt% P(3HO) were ideal for processing, because of…

The flow-induced supramolecular arrangement, or band texture, present in water-soluble anisotropic films prepared from blend solutions of hydroxypropyl cellulose and organosolv lignin is locked via esterification with bio-based polycarboxylic acids. Subsequent to shear casting of the blend solutions, the chemical cross-linking with citric acid-based cross-linkers and a dimerized fatty acid yields water-insoluble, anisotropic films prone to swelling in water. The liquid crystalline networks are analyzed by means of polarized optical microscopy, tensile testing, Fourier transform infrared, and swelling experiments. Depending on the cross-linker, the dry “banded” films reach up to 3.5 GPa in tensile modulus, 80 MPa in tensile strength…

3D printing of soft-tissue like cytocompatible single material constructs with appropriate mechanical properties remains a challenge. Hybrid printing technology provides an attractive alternative as it combines a cell-free ink for providing mechanical support with a bioink for housing embedded cells. Several hybrid printed structures have been developed, utilizing thermoplastic polymers such as polycaprolactone as structural support. These thermoplastics demonstrated limited structural integration with the cell-laden components, and this may compromise the overall performance. In this work, a hybrid printing platform is presented using two distinct hydrogel inks that share the same photo-crosslinking chemistry to enable simple fabrication and seamless structural…

In this study, we describe the additive manufacturing of porous three-dimensionally (3D) printed ceramic scaffolds prepared with hydroxyapatite (HA), β-tricalcium phosphate (β-TCP), or the combination of both with an extrusion-based process. The scaffolds were printed using a novel ceramic-based ink with reproducible printability and storability properties. After sintering at 1200°C, the scaffolds were characterized in terms of structure, mechanical properties, and dissolution in aqueous medium. Microcomputed tomography and scanning electron microscopy analyses revealed that the structure of the scaffolds, and more specifically, pore size, porosity, and isotropic dimensions were not significantly affected by the sintering process, resulting in scaffolds that…

Bio-inspired multi-scaled (hierarchical) porous structures have remarkable strength and stiffness-to-density properties. Direct ink writing (DIW) or robocasting, an additive manufacturing (or also commonly known as 3D printing) material extrusion technique is able to create near-net-shaped complex geometries. A new approach of combining DIW, colloidal particle-stabilized emulsion paste inks and partial densification to create tailored architectures of hierarchical porosity on three scales has been demonstrated. The printed and sintered ceramic lattice structures possess relatively high overall porosity of 78.7% (on average), comprising mainly (64.7%) open porosity. The effects of formulation (surfactant and oil concentrations, solids particle size, and mixing speed) on…

The use of three-dimensional (3D) printable hydrogels for biomedical applications has attracted considerable attention as a consequence of the ability to precisely define the morphology of the printed object, allowing patients’ needs to be targeted. However, the majority of hydrogels do not possess suitable mechanical properties to fulfill an adequate rheological profile for printability, and hence, 3D printing of cross-linked networks is challenging and normally requires postprinting modifications to obtain the desired scaffolds. In this work, we took advantage of the crystallization process of poly(ethylene glycol) to print non-isocyanate poly(hydroxyurethane) hydrogels with tunable mechanical properties. As a consequence of the…

Engineering hierarchical vasculatures is critical for creating implantable functional thick tissues. Current approaches focus on fabricating mesoscale vessels for implantation or hierarchical microvascular in vitro models, but a combined approach is yet to be achieved to create engineered tissue flaps. Here, millimetric vessel-like scaffolds and 3D bioprinted vascularized tissues interconnect, creating fully engineered hierarchical vascular constructs for implantation. Endothelial and support cells spontaneously form microvascular networks in bioprinted tissues using a human collagen bioink. Sacrificial molds are used to create polymeric vessel-like scaffolds and endothelial cells seeded in their lumen form native-like endothelia. Assembling endothelialized scaffolds within vascularizing hydrogels incites…

The current study introduces two novel, smart polymer three-dimensional (3D)-printable interpenetrating polymer network (IPN) hydrogel biomaterials with favorable chemical, mechanical, and morphological properties for potential applications in traumatic brain injury (TBI) such as potentially assisting in the restoration of neurological function through closure of the wound deficit and neural tissue regeneration. Additionally, removal of injury matter to allow for the appropriate scaffold grafting may assist in providing a TBI treatment. Furthermore, due to the 3D printability of the IPN biomaterials, complex structures can be designed and fabricated to mimic the native shape and structure of the injury sight, which can…

The fabrication of 3D ink-printed and sintered porous Si scaffolds as electrode material for lithium-ion batteries is explored. A hierarchically-porous architecture consisting of channels (~220 μm in diameter) between microporous Si struts is created to accommodate the large volume change from Si (de)lithiation during electrochemical (dis)charging. The influence of sintering parameters on Si strut porosity and the resulting mechanical and electrochemical properties of the scaffolds are studied experimentally and computationally. Varying sintering temperatures (1150–1300 °C) and sintering times (1–16 h) the open porosity within the Si filaments can be tailored between 46 and 60%. Pore size (3–6 μm) and wall…

Although allogeneic islet transplantation has been proposed as a therapy for type 1 diabetes, its success rate remains low. Disruption of both extracellular matrix (ECM) and dense vascular network during islets isolation are referred to as some of the main causes of their poor engraftment. Therefore, the recapitulation of the native pancreatic microenvironment and its prompt revascularization should be beneficial for long-term islet survival. In this study, we developed novel bioinks suitable for the microfluidic-assisted multi-material biofabrication of 3D porous pancreatic and vascular structures. The tissue-specific bioactivity was introduced by blending alginate either with pancreatic decellularized extracellular matrix powder (A_ECM)…

The central theme of this dissertation is the observation that mechanical waves propagate and scatter at different velocities in biological tissues due to a difference in local material properties (such as viscosity and stiffness), due to the presence of inhomogeneities such as a blood vessel, an axon or a muscle filament. These scattered waves contain information about the characteristic stiffness, viscosity and the mechanical property inhomogeneity of the tissues through which they propagate; this information can aid in non-invasive diagnosis of disease and injury using novel quantitative techniques such as Insonification, Percussion and 1-Norm using Magnetic Resonance Elastography (MRE). The…

The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone, most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells. Human umbilical vein endothelial cell-derived decellularized extracellular matrix (HdECM), which contains a collection of angiocrine biomolecules, has recently been demonstrated to mediate endothelial cells(ECs) – osteoprogenitors(OPs) crosstalk. We employed the HdECM to create a PCL (polycaprolactone)/fibrin/HdECM (PFE) hybrid scaffold. We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk, resulting in vascularized bone regeneration. Following implantation in a…

Beta-tricalcium phosphate (β-TCP)-based bioinks were developed to support direct-ink 3D printing-based manufacturing of macroporous scaffolds. Binding of the gelatin:β-TCP ink compositions was optimized by adding carboxymethylcellulose (CMC) to maximize the β-TCP content while maintaining printability. Post-sintering, the gelatin:β-TCP:CMC inks resulted in uniform grain size, uniform shrinkage of the printed structure, and included microporosity within the ceramic. The mechanical properties of the inks improved with increasing β-TCP content. The gelatin:β-TCP:CMC ink (25:75 gelatin:β-TCP and 3% CMC) optimized for mechanical strength was used to 3D print several architectures of macroporous scaffolds by varying the print nozzle tip diameter and pore spacing during…

Three-dimensional (3D) bioprinting is an emerging fabrication technique to create 3D constructs with living cells. Notably, bioprinting bioinks are limited due to the mechanical weakness of natural biomaterials and the low bioactivity of synthetic peers. This paper presents the development of a natural bioink from chicken eggwhite and sodium alginate for bioprinting cell-laden patches to be used in endothelialized tissue engineering applications. Eggwhite was utilized for enhanced biological properties, while sodium alginate was used to improve bioink printability. The rheological properties of bioinks with varying amounts of sodium alginate were examined with the results illustrating that 2.0–3.0% (w/v) sodium alginate…

Many drugs show promising results in laboratory research but eventually fail clinical trials. We hypothesize that one main reason for this translational gap is that current cancer models are inadequate. Most models lack the tumor-stroma interactions, which are essential for proper representation of cancer complexed biology. Therefore, we recapitulated the tumor heterogenic microenvironment by creating fibrin glioblastoma bioink consisting of patient-derived glioblastoma cells, astrocytes, and microglia. In addition, perfusable blood vessels were created using a sacrificial bioink coated with brain pericytes and endothelial cells. We observed similar growth curves, drug response, and genetic signature of glioblastoma cells grown in our…

Background: Traditionally, the iliac crest has been the most common harvesting site for autologous bone grafts; however, it has some limitations, including poor bone availability and donor-site morbidity. This study sought to explore the effect of enhanced bone marrow (eBM) in conjunction with three-dimensional (3D)-printed polylactide–hydroxyapatite (PLA-HA) scaffolds in the repair of critical-sized bone defects in a rabbit model. Methods: First, 3D-printed PLA-HA scaffolds were fabricated and evaluated using micro-computed tomography (µCT) and scanning electron microscopy (SEM). Twenty-seven New Zealand white rabbits were randomly divided into 3 groups (n=9 per group), and the defects were treated using 3D-printed PLA-HA scaffolds…

Composites are promising candidates for treating bone defects, but manufacturing of composite scaffolds is challenging. This study aimed to fabricate composite scaffolds based on polycaprolactone (PCL) and doped Hydroxyapatite (HA) via a single step melt extrusion additive manufacturing technique. Starting from the raw powder forms, the printed scaffolds were produced and then characterized for morphology, mechanical behavior and in vitro mineralization. MicroCT revealed the homogenous dispersion of ceramic particles in the PCL matrix. Also, SEM showed the ceramic particles on the surfaces of printed scaffolds. Furthermore, bioactivity assays confirmed the enhanced apatite deposit formation on composite scaffolds compared to PCL…

Auricle reconstruction is a routine surgery in the field of Otolaryngology but the design of the reconstruction is based on the clinicians guess of the correct previous anatomy. Using additive manufacturing processes to build a model the surgeon can refer to may be a good substitute for conventional surgery. The quality of the framework replicating the three-dimensional architecture of the ear and precise sculpting of the anatomical structures are necessary in order to reach a desired outcome. In this work we present the workflow to produce an individualized 3D outer ear model for use in auricle reconstruction surgery and report…

Bone defects remain a major threat to human health and bone tissue regeneration has become a prominent clinical demand worldwide. The combination of microRNA (miRNA) therapy with 3D printed scaffolds has always posed a challenge. It can mimic physiological bone healing processes, in which a biodegradable scaffold is gradually replaced by neo-tissue, and the sustained release of miRNA plays a vital role in creating an optimal osteogenic microenvironment, thus achieving promising bone repair outcomes. However, the balance between two key factors – scaffold degradation behavior and miRNA release profile – on osteogenesis and bone formation is still poorly understood. Herein,…

The cancer microenvironment influences tumor progression and metastasis and is pivotal to consider when designing in vivo-like cancer models. Current preclinical testing platforms for cancer drug development are mainly limited to 2D cell culture systems that poorly mimic physiological environments and traditional, low throughput animal models. The aim of this work was to produce a tunable testing platform based on 3D printed scaffolds (3DPS) with a simple geometry that, by extracellular components and response of breast cancer reporter cells, mimics patient-derived scaffolds (PDS) of breast cancer. Here, the biocompatible polysaccharide alginate was used as base material to generate scaffolds consisting…

Rupture of the scapholunate interosseous ligament can cause the dissociation of scaphoid and lunate bones, resulting in impaired wrist function. Current treatments (e.g., tendon-based surgical reconstruction, screw-based fixation, fusion, or carpectomy) may restore wrist stability, but do not address regeneration of the ruptured ligament, and may result in wrist functional limitations and osteoarthritis. Recently a novel multiphasic bone-ligament-bone scaffold was proposed, which aims to reconstruct the ruptured ligament, and which can be 3D-printed using medical-grade polycaprolactone. This scaffold is composed of a central ligament-scaffold section and features a bone attachment terminal at either end. Since the ligament-scaffold is the primary…

Soft-ionic materials with biocompatibility and 3D printability are needed to develop next-generation devices to interface between electronic and biological signals. Herein, thermoreversible and biocompatible ionic liquid gels or iongels, which can be processed by direct ink writing are reported. The iongels are designed by taking advantage of polyvinyl alcohol/phenol interactions to gelify biocompatible cholinium carboxylate ionic liquids. The obtained iongels are stable, soft, and flexible materials (Young modulus between 14 and 70 kPa) with high ionic conductivity (1.8 × 10–2 S cm–1). Interestingly, they presented thermoreversible properties with gel–sol transitions ranging from 85 and 110 °C, which allows the iongel…

Three-dimensional cell culture platforms based on decellularised patient-based microenvironments provide in vivo-like growth conditions allowing cancer cells to interact with intact structures and components of the surrounding tissue. A patient-derived scaffold (PDS) model was therefore evaluated as a testing platform for the endocrine therapies (Z)-4-Hydroxytamoxifen (4OHT) and fulvestrant as well as the CDK4/6-inhibitor palbociclib, monitoring the treatment responses in breast cancer cell lines MCF7 and T47D adapted to the patient-based microenvironments. MCF7 cells growing in PDSs showed increased resistance to 4OHT and fulvestrant treatment (100- and 20-fold) compared to 2D cultures. Quantitative PCR analyses of endocrine treated cancer cells in…

Skeletal muscle is an electrically and mechanically active tissue that contains highly oriented, densely packed myofibrils. The tissue has self-regeneration capacity upon injury, which is limited in the cases of volumetric muscle loss. Several regenerative therapies have been developed in order to enhance this capacity, as well as to structurally and mechanically support the defect site during regeneration. Among them, biomimetic approaches that recapitulate the native microenvironment of the tissue in terms of parallel-aligned structure and biophysical signals were shown to be effective. In this study, we have developed 3D printed aligned and electrically active scaffolds in which the electrical…

Stable and predictive neural cell culture models are a necessary premise for many research fields. However, conventional 2D models lack 3D cell-material/-cell interactions and hence do not reflect the complexity of the in vivo situation properly. Here two alginate/gellan gum/laminin (ALG/GG/LAM) hydrogel blends are presented for the fabrication of human induced pluripotent stem cell (hiPSC)-based 3D neural models. For hydrogel embedding, hiPSC-derived neural progenitor cells (hiNPCs) are used either directly or after 3D neural pre-differentiation. It is shown that stiffness and stress relaxation of the gel blends, as well as the cell differentiation strategy influence 3D model development. The embedded…

Piezoelectric ceramics, such as BaTiO3, have gained considerable attention in bone tissue engineering applications thanks to their biocompatibility, ability to sustain a charged surface as well as improve bone cells’ adhesion and proliferation. However, the poor processability and brittleness of these materials hinder the fabrication of three-dimensional scaffolds for load bearing tissue engineering applications. For the first time, this study focused on the fabrication and characterisation of BaTiO3 composite scaffolds by using a multi-material 3D printing technology. Polycaprolactone (PCL) was selected and used as dispersion phase for its low melting point, easy processability and wide adoption in bone tissue engineering.…

3D bioprinting, a paradigm shift in tissue engineering holds a promising perspective for regenerative medicine and disease modelling. 3D scaffolds are fabricated for subsequent cell seeding or incorporated directly to the bioink to create cell-laden 3D constructs. A plethora of factors relating to bioink properties, printing parameters and post print curing play a significant role in the optimisation of the printing process. Although qualitative evaluation of printability has been investigated largely, there is a paucity of studies on quantitative approaches to assess printability. Hence, this study explores machine learning as a novel tool to evaluate printability quantitatively and to fast…

3D ink-extrusion of powders followed by sintering is an emerging additive manufacturing method capable of creating metallic microlattices. Here, we study the creation of hierarchically porous Fe or Ni scaffolds by 3D extrusion of 0/90° lattices from inks consisting of fine oxide powders (Fe2O3 or NiO, < 3 µm), coarse space-holder particles (CuSO4, < 45 µm) and a polymer binder within a solvent. After space-holder leaching and debinding of the lattices, a sintering step densifies the metallic Fe or Ni powders created by oxide reduction with H2, while maintaining the larger pores templated by the space-holder particles within the printed…

3D printing, an advent from rapid prototyping technology is emerging as a suitable solution for various regenerative engineering applications. In this study, blended gelatin-sodium alginate 3D printed scaffolds with different pore geometries were developed by altering the spatial alignment of even layered struts in the scaffolds. A significant difference in compression modulus and osteogenic expression due to the difference in spatial printing was demonstrated. Pore geometry was found to be more dominant than the compressive modulus of the scaffold in regulating osteogenic gene expression. A shift in pore geometry by at least 45° was critical for significant increase in osteogenic…

Malignant bone tumors have caused great obstacles and serious illnesses for tumor recurrence and difficulty in reconstructing and repairing large defects after tumorectomy. Additionally, long-term efficacy, satisfactory biocompatibility and excellent properties for anti-tumor agents are necessary in the biomedical field. To solve these problems, a novel idea has been proposed on building an integrative anti-tumor/bone repairing scaffold by covering photothermal therapy (PTT) composite MoS2-PLGA film on the surface of borosilicate bioactive glass (BG). In our study, the MoS2-integrated composite BG (BGM) scaffolds can rapidly and effectively elevate temperature, and they exhibited excellent photothermal stability, under 808 nm laser irradiation. Notably,…

Titanium metal matrix composite microlattices are fabricated using 3D ink extrusion printing and sintering. The inks consist of TiH2+TiB2 or TiH2+TiC powder blends to form (i) Ti-TiB composites by dehydrogenation and in situ reaction of Ti + TiB2 to form Ti + TiB and (ii) Ti-TiC composites, where TiC remains stable during the sintering process. Rapid densification of the printed powder blend is achieved during pressureless sintering in vacuum at 1200 °C between 1 and 4 h, due to the small Ti particle size available from dehydrogenation of micron-sized TiH2. Near-full density Ti-TiB and Ti-TiC is achieved within individual lattice…

Cobalt-based superalloy microlattices were created via (i) three-dimensional-extrusion printing of inks containing a suspension of Co-, Ni- and W-oxide particles, (ii) H2-reduction of the oxides and sintering to a homogenous Co-Ni-W alloy, (iii) Al pack-cementation to deposit Al on the microlattice struts, followed by Al-homogenization. The resulting Co-(18–20)Ni-(5–6)W-(10–13)Al (at.%) microlattices, with 27–30% relative density and 350 μm diameter struts, display a peak in yield strength at 750°C, consistent with their γ/γ′ aged microstructure. Oxidation resistance is strongly improved compared to Al-free printed Co-Ni-W lattices, via the formation of an Al2O3 surface layer. However, the resulting Al depletion within the struts…

Researchers have looked to cartilage tissue engineering to address the lack of cartilage regenerative capability related to cartilage disease/trauma. For this, a promising approach is extrusion-based three-dimensional (3D) printing technique to deliver cells, biomaterials, and growth factors within a scaffold to the injured site. This paper evaluates the printability of chitosan scaffolds for a cartilage tissue engineering, with a focus on identifying the influence of drying technique implemented before crosslinking on the improvement of chitosan printability. First, the printability of chitosan with concentrations of 8%, 10%, and 12% (w/v) was evaluated and 10% chitosan was selected for further studies. Then,…

Wounds impact millions of patients every year and represent a serious cause of morbidity and mortality worldwide, yet current treatment outcomes are far from ideal. Therapies based on delivery of multiple growth factors offer a promising approach for optimal wound management; however, their high production cost, low stability, and lack of effective delivery system limits their application in the clinic. Platelet lysate is a suitable, abundant and cost-effective source of growth factors that play an important role in the healing cascade. The aim of this current work is to develop an extrusion-based bioink consisting of platelet lysate (PL) and gelatin…

Liquid deposition modeling (LDM) is an evolving three-dimensional (3D) printing approach that mainly utilizes polymer solutions to enable the fabrication of biomedical scaffolds under mild conditions. A deep understanding of the rheological properties of polymer printing inks and the features of yielded scaffolds are critical for a successful LDM based fabrication of biomedical scaffolds. In this work, polymer printing inks comprised of Poly(epsilon-caprolactone) (PCL), sodium chloride (NaCl), and trichloromethane (CHCl3) were prepared. The rheological properties, including extrudability (shear stress, viscosity, and shear-thinning) and self-supporting ability (viscosity) of all printing inks were analyzed. Then printing performance was evaluated by measuring the…

3D printing of cell laden bioinks has the potential to recapitulate the hierarchical and spatial complexity of native tissues. However, the addition of cells can alter physical properties of printable resins, which in turn may impede or induce cellular sedimentation or affect the printability and shape fidelity of the final construct. In this study we investigated these considerations by bioprinting gelatin methacrylate (GelMA) bioinks, loaded with various concentrations of mouse fibroblast cells (L929), using extrusion-based direct-write 3D printing (EDP). The impact of various cellular concentrations on viscosity, and temperature-driven gelation of GelMA was examined with a rheometer. The effect of…

Poly(ε-caprolactone) (PCL) chain cleavage results in the formation of polar terminal species, comprising hydroxy and carboxyl groups that enhance surface hydrophilicity and enable subsequent biofunctionalization. However, the direct effects of various acidic and basic treatments on 3D printed PCL scaffolds have not been studied from a functional perspective. In this study, we comprehensively assessed the influence of acid (hydrochloric, HCl) and base (sodium hydroxide, NaOH) catalyzed hydrolysis across different conditions on various properties of 3D printed PCL scaffolds. Analyses included testing of physiochemical and mechanical properties, and assessment of rate and stability of surface-nucleating bioactive apatite-like minerals. HCl exposure resulted…

Calcium silicate (CS) composite bone tissue engineering scaffolds were three-dimensionally printed using titanium metallic powders as the second strengthening phase for overcoming the inherent brittleness and fast degradability. In order to promote the sintering process of all composite scaffolds, mesoporous structure was further introduced into sol-gel-derived CS powders obtaining mesoporous CS (MCS) with larger surface area. The influences of mesoporous structure, sintering temperature and Ti content have been investigated through comparisons of the final scaffold composition, microstructure, compressive strength and in vitro stability. Results showed that CS matrix materials reacted with Ti could form less degradable CaTiO3 and TiC ceramic…

Osteochondral repair remains a significant clinical challenge due to the multiple tissue phenotypes and complex biochemical milieu in the osteochondral unit. To repair osteochondral defects, it is necessary to mimic the gradation between bone and cartilage, which requires spatial patterning of multiple tissue-specific cues. To address this need, we have developed a facile system for the conjugation and patterning of tissue-specific peptides by melt extrusion of peptide-functionalized poly(ε-caprolactone) (PCL). In this study, alkyne-terminated PCL was conjugated to tissue-specific peptides via a mild, aqueous, and Ru(II)-catalyzed click reaction. The PCL-peptide composites were then 3D printed by multimaterial segmented printing to generate…

Here, a hybrid process for the fabrication of dehydrofluorinated PVDF (dPVDF) microfiltration (MF) membranes is presented. dPVDF was fabricated through the bulk modification of PVDF using ethylenediamine. To produce inks for direct ink writing (DIW), the dPVDF was dissolved in N,N-dimethyacetamide along with a pore-forming agent, poly(vinyl pyrrolidone) (PVP) (5–30 wt%, relative to dPVDF concentration). Membranes were produced by direct ink writing of the inks into continuous films – followed by non-solvent induced phase separation (NIPS). Attenuated total reflectance – Fourier transform infrared (ATR-FTIR) and Raman spectroscopies confirmed alkene moieties within the dPVDF polymer, resulting from the dehydrofluorination process. The…

Cobalt-based superalloy microlattices with γ/γ′ microstructure are manufactured by combining two additive methods: ink-extrusion 3D-printing and pack-cementation surface alloying. First, a microlattice green structure is 3D-printed at ambient temperature from inks comprised of Co3O4, NiO, and WO3 powders, an elastomeric binder and solvents. Organic removal followed by oxide reduction under Ar-5% H2, sintering and homogenization at 1250 °C lead to a metallic microlattice with dense struts with uniform γ (fcc)-Co–22Ni–8W (at.%) composition. Second, aluminum is deposited on the strut surfaces via pack-cementation at 1000 °C, diffused at 1300 °C through the strut volume to achieve a uniform composition (Co–20Ni–6W–10Al or…

We recently developed a recombinant growth factor-free bone regenerative scaffold composed of stoichiometric hydroxyapatite (HA) ceramic particles and human demineralized bone matrix (DBM) particles (HA-DBM). Here, we performed the first pre-clinical comparative evaluation of HA-DBM relative to the industry standard and established positive control, recombinant human bone morphogenetic protein-2 (rhBMP-2), using a rat posterolateral spinal fusion model (PLF). Female Sprague–Dawley rats underwent bilateral L4-L5 PLF with implantation of the HA-DBM scaffold or rhBMP-2. Fusion was evaluated using radiography and blinded manual palpation, while biomechanical testing quantified the segmental flexion-extension range-of-motion (ROM) and stiffness of the fused segments at 8-weeks postoperatively.…

Injuries affecting load bearing tendon tissues are a significant clinical burden and efficient treatments are still unmet. Tackling tendon regeneration, tissue engineering strategies aim to develop functional substitutes that recreate native tendon milieu. Tendon mimetic scaffolds capable of remote magnetic responsiveness and functionalized magnetic nanoparticles (MNPs) targeting cellular mechanosensitive receptors are potential instructive tools to mediate mechanotransduction in guiding tenogenic responses. In this work, we combine magnetically responsive scaffolds and targeted Activin A type II receptor in human adipose stem cells (hASCs), under alternating magnetic field (AMF), to synergistically facilitate external control over signal transduction. The combination of remote triggering…

3D ink-extrusion of powders followed by sintering is an emerging alternative to beam-based additive manufacturing, capable of creating 3D metallic objects from 1D-extruded microfilaments. Here, in situ synchrotron X-ray diffraction and tomography are combined to study the phase evolution, alloy formation and sinter-densification of Fe-20Ni-5Mo (at.%) microfilaments. The filaments are

Using 3D printing to manufacture shape memory polymers (SMPs) becomes popular, since the technique endows SMPs the ability to shape into desired structures according to their applications. Among various types of SMPs, epoxy-based shape memory polymer and their composites are known for their high modulus and strength. However, limited by their rheological behavior, it is still hard to prepare high-quality printable epoxy materials. Here, by carefully tuning of rheological properties, we can prepare printable ink showing good shape retention, excellent mechanical performances below and above the glass transition temperature of epoxy, as well as good shape memory effect. The prepared…

The integration of multiscale micro- and macroenvironment has been demonstrated as a critical role in designing biomimetic scaffolds for peripheral nerve tissue regeneration. While it remains a remarkable challenge for developing a biomimetic multiscale scaffold for enhancing 3D neuronal maturation and outgrowth. Herein, we present a 3D bioprinted multiscale scaffold based on a modular bioink for integrating the 3D micro- and macroenvironment of native nerve tissue. Gelatin methacryloyl (GelMA)/Chitosan Microspheres (GC-MSs) were prepared by a microfluidic approach, and the effect of these microspheres on enhancing neurite outgrowth and elongation of PC12 cells was demonstrated. The 3D multiscale composite scaffolds were…

SnO2-Ag composites with designed architectures with sub-millimeter feature sizes can provide enhanced functionality in electrical applications. SnO2-Ag composites consisting of a ceramic SnO2 micro-lattice filled with metallic Ag are created via a hybrid additive manufacturing method. The multistep process includes: (i) 3D extrusion printing of 0/90° cross-ply micro-lattices from SnO2-7%CuO nanoparticle-loaded ink; (ii) thermal treatment in air to burn the binders and sinter struts of the SnO2 micro-lattice to ~94% relative density; (iii) Ag melt infiltration of channels of sintered micro-lattices. Densification of the SnO2 struts during air-sintering is accelerated by CuO liquid phase forming at 1100°C. During the subsequent…

The effect of varying the solids volume fraction of an aqueous clay paste suspension on its printability via an Additive Manufacturing (AM) or 3D printing technique, Direct Ink Writing (DIW) or material extrusion, has been studied. DIW is a cost-effective and straightforward fabrication technology suitable for adoption at a larger scale by the traditional ceramics industry and the creative community. The pastes were prepared with volume fraction of solids ranging from 25–57 vol%. Their rheological properties (storage modulus and apparent yield stress) were measured by dynamic oscillatory rheometry. The relationships between solids content, rheological behaviour and print parameters were evaluated. An…

The establishment of 3D-printing as manufacturing process for oral solid dosage forms enables new options for the individualized medicine. The aim of this work was to develop a novel drug-printing model using pressure-assisted microsyringe (PAM) technology, which allows the precise dispensing of drug substances. Printed tablets with different numbers of layers, mimicking different doses for pediatric subgroups, were analyzed regarding mass variation, friability, thickness and disintegration time. Furthermore, the uniformity of dosage units and the dissolution behavior were investigated. Friability was

Biofabrication techniques such as microlithography and 3-D bioprinting have emerged in recent years as technologies capable of rendering complex, biocompatible constructs for biosensors, tissue and regenerative engineering and bioelectronics. While instruments and processes have been the subject of immense advancement, multifunctional bioinks have received less attention. A novel photocrosslinkable, hybrid bioactive and inherently conductive bioink formed from poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) nanomaterials within poly(2-hydroxyethyl methacrylate-co-polyethyleneglycol methacrylate) p(HEMA-co-EGMA) was used to render complex hydrogel constructs through microlithographic fabrication and 3-D printing. Constructs were directly compared through established metrics of acuity and fidelity, using side-by-side comparison of microarray grids, triangles incorporating angles 15–90°,…

Cell therapy has been a promising strategy for cardiac repair after myocardial infarction (MI), but a poor ischemic environment and low cell delivery efficiency remain significant challenges. The spleen serves as a hematopoietic stem cell niche and secretes cardioprotective factors after MI, but it is unclear whether it could be used for human pluripotent stem cell (hiPSC) cultivation and provide a proper microenvironment for cell grafts against the ischemic environment. Herein, we developed a splenic extracellular matrix derived thermoresponsive hydrogel (SpGel). Proteomics analysis indicated that SpGel is enriched with proteins known to modulate the Wnt signaling pathway, cell-substrate adhesion, cardiac…

Flexible and stretchable conductors are crucial components for next-generation flexible devices. Wrinkled structures often have been created on such conductors by depositing conductive materials on the pre-stretched or organic solvent swollen samples. Herein, water swelling is first proposed to generate the wrinkled structures on silicone elastomers. By immersing silicone/sugar hybrid in water, a significant amount of swelling occurs as a result of osmosis and capillary interactions with the sugar and silicone matrix. Considering the drastic swelling effect and controllable swelling ratio, water swelling is used to replace the conventional pre-stretching and organic solvent swelling to fabricate stretchable conductors. In situ…

The repair of large bone defects has always been a challenge, especially with respect to regeneration capacity and autogenous bone availability. To address this problem, we fabricated a 3D-printed polylactic acid (PLA) and hydroxyapatite (HA) scaffold (3D-printed PLA-HA, providing scaffold) loaded with enhanced bone marrow (eBM, providing seed cells) combined with induced membrane (IM, providing grow factors) to repair large radial defects in rabbits. in vitro assays, we demonstrated that 3D-printed PLA-HA had excellent biocompatibility, as shown by co-culturing with mesenchymal stem cells (MSCs); eBM-derived MSCs exhibited considerable differentiation potential, as shown in trilineage differentiation assays. To investigate bone formation…

Detecting hydrogen peroxide (H2O2) as the side product of enzymatic reactions is of great interest in food and medical applications. Despite the advances in this field, the majority of reported H2O2 sensors are bulky, expensive, limited to only one phase detection (either gas or liquid), and require multistep fabrications. This article aims to address some of these limitations by presenting a 3D printable paper-based sensor made from poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) decorated with horseradish peroxidase, an enzyme able to interact with H2O2. Unlike most electrochemical PEDOT:PSS-based H2O2 sensors with voltametric or potentiometric mechanisms, the sensing mechanism in this technology is impedimetric, significantly…

Background We evaluated the outcome of esophageal reconstructions using tissue-engineered scaffolds. Method Partial esophageal defects were reconstructed with the following scaffolds; animals were grouped (n = 7 per group) as follows: (a) normal rats; (b) rats implanted with three-dimensional printing (3DP) polycaprolactone (PCL) scaffolds; (c) with human adipose-derived mesenchymal stem cell (ADSC)-seeded 3DP PCL scaffolds; (d) with polyurethane (PU)-nanofiber(Nf) scaffolds; and (e) with ADSC-seeded PU-Nf scaffolds. Results The esophageal defects were successfully repaired; however, muscle regeneration was greater in the 3DP PCL + ADSC groups than in the PU-Nf + ADSC groups (P 

Bone tissue plays an important role in supporting and protecting the structure and function of the human body. Bone defects are a common source of injury and there are many reconstruction challenges in clinical practice. However, 3D bioprinting of scaffolds provides a promising solution. Hydrogels have emerged as biomaterials with good biocompatibility and are now widely used as cell-loaded materials for bioprinting. This study involved three steps: First, sodium alginate (SA), gelatin (Gel), and nano-hydroxyapatite (na-HA) were mixed into a hydrogel and its rheological properties assessed to identify the optimum slurry for printing. Second, SA/Gel/na-HA bioscaffolds were printed using 3D…

3D printing technologies allow control over the alignment of building blocks in synthetic materials, but compositional changes often require complex multimaterial printing steps. Here, 3D printable materials showing locally tunable mechanical properties are produced in a single printing step of Direct Ink Writing. These new inks consist of a polymer matrix bearing biocompatible photoreactive cinnamate derivatives and up to 30 wt% of anisotropic cellulose nanocrystals. The printed materials are mechanically versatile and can undergo further crosslinking upon illumination. When illuminating the material and controlling the irradiation doses, the Young’s moduli can be adjusted between 15 and 75 MPa. Moreover, spatially…

Embedded bio-printing has fostered significant advances toward the fabrication of soft complex tissue-like constructs, by providing a physical support that allows the freeform shape maintenance within the prescribed spatial arrangement, even under gravity force. Current supporting materials still present major drawbacks for up-scaling embedded 3D bio-printing technology towards tissue-like constructs with clinically relevant dimensions. Herein, we report a a cost-effective and widely available supporting material for embedded bio-printing consisting on a continuous pseudo-plastic matrix of xanthan-gum (XG). This natural polisaccharide exhibits peculiar rheological properties that have enabled the rapid generation of complex volumetric 3D constructs with out-of-plane features. The freedom…

Improving the printability of pure, decellularized extracellular matrix (dECM) bio-ink without altering its physiological components has been a challenge in three-dimensional (3D) cell printing. To improve the printability of the bio-ink, we first investigated the digestion process of the powdered dECM material obtained from porcine tendons. We manifested the digestion process of tendon derived dECM powders, which includes dissolution, gelatinization and solubilization. After a short dissolution period (around 10 min), we observed a ‘High viscosity slurry’ status (3 h) of the dECM precursors, i.e. the gelatinization process, followed by the solubilization processes, i.e. a ‘Medium viscosity slurry’ period (12 h)…

A promising alternative to current treatment options for degenerative conditions of the temporomandibular joint (TMJ) is cartilage tissue engineering, using 3D printed scaffolds and mesenchymal stem cells. Gelatin, with its inherent biocompatibility and printability has been proposed as a scaffold biomaterial, but because of its thermoreversible properties, rapid degradation and inadequate strength it must be crosslinked to be stable in physiological conditions. The aim of this study was to identify non-toxic and effective crosslinking methods intended to improve the physical properties of 3D printed gelatin scaffolds for cartilage regeneration. Dehydrothermal (DHT), ribose glycation and dual crosslinking with both DHT and…

Inspired by stimuli-tailored dynamic processes that spatiotemporally create structural and functional diversity in biology, a new hierarchical patterning strategy is proposed to induce the emergence of complex multidimensional structures via dynamic sacrificial printing of stimuli-responsive hydrogels. Using thermally responsive gelatin (Gel) and pH-responsive chitosan (Chit) as proof-of-concept materials, we demonstrate that the initially printed sacrificial material (Gel/Chit-H+ hydrogel with a single gelatin network) can be converted dynamically into non-sacrificial material (Gel/Chit-H+–Citr hydrogel with gelatin and an electrostatic citrate–chitosan dual network) under stimulus cues (citrate ions). Complex hierarchical structures and functions can be created by controlling either the printing patterns of…

This paper reports on the hybrid process we have used for producing hierarchical scaffolds made of poly(lactic-co-glycolic) acid (PLGA) and nanohydroxyapatite (nHA), analyzes their internal structures via scanning electron microscopy, and presents the results of our in vitro proliferation of MC3T3-E1 cells and alkaline phosphatase activity (ALP) for 0 and 21 days. These scaffolds were produced by combining additive manufacturing (AM) and thermally induced phase separation (TIPS) techniques. Slow cooling at a rate of 1.5 °C/min during the TIPS process was used to enable a uniform temperature throughout the scaffolds, and therefore, a relatively uniform pore size range. We produced ten different…

Three-dimensional (3D) bioprinting technologies have great attention in different researching areas such as tissue engineering, medicine, etc. due to its maximum mimetic property of natural biomaterials by providing cell combination, growth factors, and other biomaterials. Bioprinting of tissues, organs, or drug delivery systems emerged layer-by-layer deposition of bioinks. 3D bioprinting technique has some complexity such as choice of bioink combination, cell type, growth, and differentiation. In this study, a composite material in 3D bioprinting studies has been developed for biofabrication of the cell carrying scaffolds namely cryogenic scaffolds. Cryogenic scaffolds are highly elastic and have a continuous interconnected macroporous structure…

Metamaterials are artificial structures with unusual and superior properties that come from their carefully designed building blocks — also called meta-atoms. Metamaterials have permeated large swatches of science, including electromagnetics and mechanics. Although metamaterials hold the promise for realizing technological advances, their potential to enhance interactions between humans and materials has remained unexplored. Here, we devise meta-atoms with tailored fracture properties to control mouthfeel sensory experience. Using chocolate as a model material, we first use meta-atoms to control the fracture anisotropy and the number of cracks and demonstrate that these properties are captured in mouthfeel experience. We further use topology…

In tissue engineering, biomaterials have been used to steer the host response. This determines the outcome of tissue regeneration, which is modulated by multiple growth factors (GFs). Hence, a sustainable delivery system for GFs is necessary to control tissue regeneration actively. A delivery technique of single and multiple GF combinations, using a layer‐by‐layer (LBL) procedure to improve tissue remodeling, is developed. TGF‐β1, PDGF‐ββ, and IGF‐1 are incorporated on tailor‐made polymeric rods, which could be used as a tool for potential tissue engineering applications, such as templates to induce the formation of in situ tissue engineered blood vessels (TEBVs). Cell response…

Hydrogel scaffolds are attractive for tissue defect repair and reorganization because of their human tissue-like characteristics. However, most hydrogels offer limited cell growth and tissue formation ability due to their submicron- or nano-sized gel networks, which restrict the supply of oxygen, nutrients and inhibit the proliferation and differentiation of encapsulated cells. In recent years, 3D printed hydrogels have shown great potential to overcome this problem by introducing macro-pores within scaffolds. In this study, we fabricated a macroporous hydrogel scaffold through horseradish peroxidase (HRP)-mediated crosslinking of silk fibroin (SF) and tyramine-substituted gelatin (GT) by extrusion-based low-temperature 3D printing. Through physicochemical characterization,…

Myocardial infarction (MI) or heart attack occurs when the bloodstream to the heart is blocked, which may destroy a part of the heart muscle (or myocardium) and form perdurable scarred tissue. The infarcted myocardial muscle nowadays has no revival treatments, and also transplantation is limited as an option. Tissue engineering has the potential to restore myocardial function after an MI by fabricating tailored tissues for treatment. For tissue engineering, three-dimensional (3D) bioprinting is a fabrication method to create 3D constructs with living cells, which would be impossible by other traditional methods. Although various biomaterials, biologically-derived or synthetic, are available, only…

3D Ti6Al4V-beta-tricalcium phosphate (TCP) hybrid scaffolds with interconnected porous network and controllable porosity and pore size were successfully produced by three-dimensional fiber deposition (3DF). The macrostructure of scaffolds was determined by the 3D design, whereas the micro- and submicron structure were derived from the Ti6Al4V powder sintering and the crystalline TCP powder, respectively. Ti6Al4V-TCP slurry was developed for 3DF by optimizing the TCP powder size, Ti6Al4V-to-TCP powder ratio and Ti6Al4V-TCP powder content. Moreover, the air pressure and fiber deposition rate were optimized. A maximum achievable ceramic content in the Ti6Al4V-TCP slurry that enables 3DF manufacturing was 10 wt%. The chemical…

Piezoelectric fluoropolymers convert mechanical energy to electricity and are ideal for sustainably providing power to electronic devices. To convert mechanical energy, a net polarization must be induced in the fluoropolymer, which is currently achieved via an energy intensive electrical poling process. Eliminating this process will enable the low-energy production of efficient energy harvesters. Here, by combining molecular dynamics simulations, piezoresponse force microscopy, and electrodynamic measurements, we reveal a hitherto unseen polarization locking phenomena of poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE) perpendicular to the basal plane of two-dimensional (2D) Ti3C2Tx MXene nanosheets. This polarization locking, driven by strong electrostatic interactions enabled exceptional energy harvesting…

We report on a procedure for the preparation, printing and curing of antibacterial poly(N-isopropylacrylamide) nanocellulose-reinforced hydrogels. These composites present a highly anisotropic microstructure which allows to control and modulate the resulting mechanical properties. The incorporation of such nanoparticles enables us to modify both the strength and the humidity-dependent swelling direction of printed parts, offering a fourth-dimensional property to the resulting composite. Antibacterial properties of the hydrogels were obtained by incorporating the functionalized peptide ε-polylysine, modified with the addition of a methacrylate group to ensure UV-immobilization. We highlight the relevance of well-adapted viscoelastic properties of our material for 3D printing by…

Background It is known that a number of parameters can influence the post-printing properties of bone tissue scaffolds. Previous research has primarily focused on the effect of parameters associated with scaffold design (e.g., scaffold porosity) and specific scaffold printing processes (e.g., printing pressure). To our knowledge, no studies have investigated variations in post-printing properties attributed to the techniques used to synthesize the materials for printing (e.g., melt-blending, powder blending, liquid solvent, and solid solvent). Methods Four material preparation techniques were investigated to determine their influence on scaffold properties. Polycaprolactone/nano-hydroxyapatite 30% (wt.) materials were synthesized through melt-blending, powder blending, liquid solvent,…

Bone related diseases and disorders increasingly impact human health. Electrical stimulation (ES) has been shown to promote osteogenesis and healing of bone defects. Graphene, is an electrically conductive and biocompatible material with good mechanical properties (strength with flexibility), and therefore shows significant promise as a cell-compatible electrode for ES. Graphene-based scaffolds may therefore be used for 3D cell and tissue support, including 3D osteoinduction. We have fabricated 3D graphene electrode structures to provide ES to human adipose stem cells (ADSCs). The assemblies support ADSC growth and differentiation, with ES augmenting proliferation and osteogenesis. Our findings expand our previous work on…

3D bioprinting has been increasingly employed in skin tissue engineering for manufacturing living constructs with three-dimensional spatial precision and controlled architecture. There is however, a bottleneck in the tunability of bioinks to address specific biocompatibility challenges, functional traits and printability. Here we report on a traditional gelatin methacryloyl (GelMA) based bioink, tuned by addition of an ulvan type polysaccharide, isolated from a cultivated source of a specific Australian Ulvacean macroalgae (Ul84). Ul84 is a sulfate- and rhamnose-rich polysaccharide, resembling mammalian glycosaminoglycans that are involved in wound healing and tissue matrix structure and function. Printable bioinks were developed by addition of…

Herein, the cytotoxicity of a novel zwitterionic sulfobetaine hydrogel system with a nano-clay crosslinker has been investigated. We demonstrate that careful selection of the composition of the system (monomer to Laponite content) allows the material to be formed into controlled shapes using an extrusion based additive manufacturing technique with the ability to tune the mechanical properties of the product. Moreover, the printed structures can support their own weight without requiring curing during printing which enables the use of a printing-then-curing approach. Cell culture experiments were conducted to evaluate the neural cytotoxicity of the developed hydrogel system. Cytotoxicity evaluations were conducted…

Currently, 3D printing is one of the popular technological production methods, mainly because it offers various options that affect the resulting properties of prints. The aim of the presented work is to manufacture a prosthetic finger with a PIP and DIP joint using multi-material 3D printing, which will allow to mimic the flexion of a physiological finger. The subject of this research and testing is the design of a combination of solid and flexible material for a monolithic finger model, which will allow the required bending in selected areas of the print.

A self-hardening three-dimensional (3D)-porous composite bone graft consisting of 65 wt% hydroxyapatite (HA) and 35 wt% aragonite was fabricated using a 3D-Bioplotter®. New tetracalcium phosphate and dicalcium phosphate anhydrous/aragonite/gelatine paste formulae were developed to overcome the phase separation of the liquid and solid components. The mechanical properties, porosity, height and width stability of the end products were optimised through a systematic analysis of the fabrication processing parameters including printing pressure, printing speed and distance between strands. The resulting 3D-printed bone graft was confirmed to be a mixture of HA and aragonite by X-ray diffraction, Fourier transform infrared spectroscopy and energy…

High molecular weight polyhydroxymethylene (PHM) has a repeat unit identical to that of low molecular weight sugar alcohols and exhibits carbohydrate‐like properties. Herein, cryogenic extrusion‐based 3D printing is combined with a phase separation in water to fabricate hierarchically porous PHM scaffolds containing interconnected macro‐, micro‐, and nanopores. As PHM is infusible and insoluble in common solvents, its precursor polyvinylene carbonate (PVCA) dissolved in dimethylsulfoxide (DMSO) is used to 3D print hierarchically porous PVCA scaffolds that are converted into PHM by hydrolysis without impairing the pore architectures. Similar to low‐temperature deposition manufacturing, the PVCA/DMSO freezes on a build platform at −78…

Designing bone scaffolds containing both organic and inorganic composites simulating the architecture of the bone is the most important principle in bone tissue engineering. The objective of this study was to fabricate a composite scaffold containing poly (D, l)-lactide (PDLLA) and β-tricalcium phosphate (β-TCP) as a platform for osteogenic differentiation of adipose-derived mesenchymal stem cells. In this study, PDLLA/β-TCP scaffolds were fabricated using three-dimensional printing (3D) technology through melt excursion technique. The physicomechanical characteristics, including microstructure, mechanical properties, of the customized scaffolds were investigated. Further, the in vitro biological characteristics of manufactured scaffolds were evaluated in conjugation with buccal fat…

Breast cancer is a heterogeneous disease where the tumor microenvironment, including extracellular components, plays a crucial role in tumor progression, potentially modulating treatment response. Different approaches have been used to develop three‐dimensional models able to recapitulate the complexity of the extracellular matrix. Here, we use cell‐free patient‐derived scaffolds (PDSs) generated from breast cancer samples that were recellularized with cancer cell lines as an in vivo‐like culture system for drug testing. We show that PDS cultured MCF7 cancer cells increased their resistance against the front‐line chemotherapy drugs 5‐fluorouracil, doxorubicin and paclitaxel in comparison to traditional two‐dimensional cell cultures. The gene expression…

The ability to produce constructs with a high control over the bulk geometry and internal architecture has situated 3D printing as an attractive fabrication technique for scaffolds. Various designs and inks are actively investigated to prepare scaffolds for different tissues. In this work, we prepared 3D printed composite scaffolds comprising polycaprolactone (PCL) and various amounts of reduced graphene oxide (rGO) at 0.5, 1, and 3 wt.%. We employed a two-step fabrication process to ensure an even mixture and distribution of the rGO sheets within the PCL matrix. The inks were prepared by creating composite PCL-rGO films through solvent evaporation casting…

The major limitation of 3D bioprinting is the availability of inks. In order to develop new ink formulations, both their rheological behavior to obtain the best printability and the target bio-printed objects conformities must be studied. In this paper, for the first time in our knowledge, the preparation and the characterization of novel ink formulations based on two natural biocompatible polysaccharides, chitosan (CH) and guar gum (GG), are presented. Five ink formulations containing different proportions of CH and GG were prepared and characterized in terms of rheological properties and solvent evaporation. Their printability was assessed (by varying the nozzle diameter,…

Here, we report a newly designed knee plug to be used in the 3rd generation of Autologous Chondrocyte Implantation (ACI) in order to heal the damaged knee cartilage. It is composed of three components: The first component (Bone Portion) is a 3D printed hard scaffold with large pores (~ 850 µm), made by hydroxyapatite and β-tricalcium phosphate to accommodate the bony parts underneath the knee cartilage. It is a cylinder with a diameter of 20 mm and height of 7.5 mm, with a slight dome shape on top. The plug also comprises a Cartilage Portion (component 2) which is a 3D…

Following the recent demonstration of the potential to direct ink write lyotropic blends of organosolv lignin (OSL) and hydroxypropyl cellulose (HPC), this study aims to optimize the formulations and direct ink writing parameters for fully bio-based lignin/HPC inks. A prescreening identifies the theoretical window of printability for different compositions for formulations based on OSL solutions of 45, 47.5, and 50% solid contents and OSL/HPC wt %/wt % ratios of 30/70, 40/60, and 50/50. Measurements of shear–viscosity and recovery behavior evidence the shear-thinning contribution of HPC and the viscosity recovery contribution of lignin. Shape fidelity, morphology, and mechanical properties of printed…

In this study, porous bioglass/gelatin/alginate bone tissue engineering scaffolds were fabricated by three-dimensional printing. The compressive strength and in vitro biomineralization properties of the bioglass–gelatin–alginate scaffolds (BG/Gel/SA scaffolds) were significantly improved with the increase of bioglass content until 30% weight percentage followed by a rapid decline in strength. In addition, the cells attach and spread on the BG/Gel/SA scaffolds surfaces represents good adhesion and biocompatibility. Furthermore, the cells (rat bone marrow mesenchymal stem cells, mBMSCs) proliferation and osteogenic differentiation on the BG/Gel/SA scaffolds were also promoted with the increase of bioglass content. Overall, the adding of bioglass in Gel/SA scaffolds…

Regenerative repair of craniomaxillofacial bone injuries is challenging due to both the large size and irregular shape of many defects. Mineralized collagen scaffolds have previously been shown to be a promising biomaterial implant to accelerate craniofacial bone regeneration in vivo. Here we describe inclusion of a 3D-printed polymer or ceramic-based mesh into a mineralized collagen scaffold to improve mechanical and biological activity. Mineralized collagen scaffolds were reinforced with 3D-printed Fluffy-PLG (ultraporous polylactide-co-glycolide co-polymer) or Hyperelastic Bone (90wt% calcium phosphate in PLG) meshes. We show degradation byproducts and acidic release from the printed structures have limited negative impact on the viability…

This work reports the versatility of polydopamine (PD) when applied as a particle coating in a composite of polylactide (PLA). Polydopamine was observed to increase the particle–matrix interface strength and facilitate the adsorption of drugs to the material surface. Here, barium sulfate radiopaque particles were functionalized with polydopamine and integrated into a polylactide matrix, leading to the formulation of a biodegradable and X-ray opaque material with enhanced mechanical properties. Polydopamine functionalized barium sulfate particles also facilitated the adsorption and release of the antibiotic levofloxacin. Analysis of the antibacterial capacity of these composites and the metabolic activity and proliferation of human…

We present a solution to regenerate adipose tissue using degradable, soft, pliable 3D-printed scaffolds made of a medical-grade copolymer coated with polydopamine. The problem today is that while printing, the medical grade copolyesters degrade and the scaffolds become very stiff and brittle, being not optimal for adipose tissue defects. Herein, we have used high molar mass poly(L-lactide-co-trimethylene carbonate) (PLATMC) to engineer scaffolds using a direct extrusion-based 3D printer, the 3D Bioplotter®. Our approach was first focused on how the printing influences the polymer and scaffold’s mechanical properties, then on exploring different printing designs and, in the end, on assessing surface…

A major challenge in three-dimensional (3D) bioprinting is the limited number of bioinks that fulfill the physicochemical requirements of printing while also providing a desirable environment for encapsulated cells. Here, we address this limitation by temporarily stabilizing bioinks with a complementary thermo-reversible gelatin network. This strategy enables the effective printing of biomaterials that would typically not meet printing requirements, with instrument parameters and structural output largely independent of the base biomaterial. This approach is demonstrated across a library of photocrosslinkable bioinks derived from natural and synthetic polymers, including gelatin, hyaluronic acid, chondroitin sulfate, dextran, alginate, chitosan, heparin, and poly(ethylene glycol).…

Reduced periodontal support, deriving from chronic inflammatory conditions, such as periodontitis, is one of the main causes of tooth loss. The use of dental implants for the replacement of missing teeth has attracted growing interest as a standard procedure in clinical practice. However, adequate bone volume and soft tissue augmentation at the site of the implant are important prerequisites for successful implant positioning as well as proper functional and aesthetic reconstruction of patients. Three-dimensional (3D) scaffolds have greatly contributed to solve most of the challenges that traditional solutions (i.e., autografts, allografts and xenografts) posed. Nevertheless, mimicking the complex architecture and…

Owing to their ultralow thermal conductivity and open pore structure, silica aerogels are widely used in thermal insulation, catalysis, physics, environmental remediation, optical devices and hypervelocity particle capture. Thermal insulation is by far the largest market for silica aerogels, which are ideal materials when space is limited. One drawback of silica aerogels is their brittleness. Fibre reinforcement and binders can be used to overcome this for large-volume applications in building and industrial insulation, but their poor machinability, combined with the difficulty of precisely casting small objects, limits the miniaturization potential of silica aerogels. Additive manufacturing provides an alternative route to…

We previously developed a recombinant growth factor-free, three-dimensional (3D)-printed material comprising hydroxyapatite (HA) and demineralized bone matrix (DBM) for bone regeneration. This material has demonstrated the capacity to promote re-mineralization of the DBM particles within the scaffold struts and shows potential to promote successful spine fusion. Here, we investigate the role of geometry and architecture in osteointegration, vascularization, and facilitation of spine fusion in a preclinical model. Inks containing HA and DBM particles in a poly(lactide-co-glycolide) elastomer were 3D-printed into scaffolds with varying relative strut angles (90° vs. 45° advancing angle), macropore size (0 μm vs. 500 μm vs. 1000 μm), and strut…

Soft robots and actuators are emerging devices providing more capabilities in the field of robotics. More flexibility and compliance attributing to soft functional materials used in the fabrication of these devices make them ideal for delivering delicate tasks in fragile environments, such as food and biomedical sectors. Yet, the intuitive nonlinearity of soft functional materials and their anisotropic actuation in compliant mechanisms constitute an existent challenge in improving their performance. Topology optimization (TO) along with four-dimensional (4D) printing is a powerful digital tool that can be used to obtain optimal internal architectures for the efficient performance of porous soft actuators.…

The development of viable tissue surrogates requires a vascular network that sustains cell metabolism and tissue development. The coculture of endothelial cells (ECs) and mesenchymal stem cells (MSCs), the two key players involved in blood vessel formation, has been heralded in tissue engineering (TE) as one of the most promising approaches for scaffold vascularization. However, MSCs may exert both proangiogenic as well antiangiogenic role. Furthermore, it is unclear which cell type is responsible for the upregulation of angiogenic pathways observed in EC:MSC cocultures. There is disagreement on the proangiogenic action of MSCs, as they have also been shown to negatively…

Although numerous spinal biologics are commercially available, a cost-effective and safe bone graft substitute material for spine fusion has yet to be proven. In this study, “3D-Paints” containing varying volumetric ratios of hydroxyapatite (HA) and human demineralized bone matrix (DBM) in a poly(lactide-co-glycolide) elastomer were three-dimensional (3D) printed into scaffolds to promote osteointegration in rats, with an end goal of spine fusion without the need for recombinant growth factor. Spine fusion was evaluated by manual palpation, and osteointegration and de novo bone formation within scaffold struts were evaluated by laboratory and synchrotron microcomputed tomography and histology. The 3:1 HA:DBM composite…

Osteocytes, essential regulators of bone homeostasis, are embedded in the mineralized bone matrix. Given the spatial arrangement of osteocytes, bioprinting represents an ideal method to biofabricate a 3D osteocyte network with a suitable surrounding matrix similar to native bone tissue. Here, we reported a 3D bioprinted osteocyte-laden hydrogel for biomimetic mineralization in vitro with exceptional shape fidelity, a high cell density (107 cells per ml) and high cell viability (85–90%). The bioinks were composed of biomimetic modified biopolymers, namely, gelatine methacrylamide (GelMA) and hyaluronic acid methacrylate (HAMA), with or without type I collagen. The osteocyte-laden constructs were printed and cultured…

Common sugar alcohols used as artificial sweeteners and components of polymer networks represent low molecular weight polyhydroxymethylenes (PHMs) with the general formula [CH(OH)]n H2 but very low degree of polymerization (n = 2–6). Herein high molecular weight PHM (n >> 100) unparalleled in nature is tailored for 3D printing and medical applications by free radical polymerization of 1,3‐dioxol‐2‐one vinylene carbonate to produce polyvinylene carbonate (PVCA) which yields PHM by hydrolysis. Furthermore, PVCA is solution processable and enables PHM functionalization, membrane formation, and extrusion‐based 3D printing. Opposite to cellulose, amorphous PHM is plasticized by water and is readily functionalized via PVCA…

The high surface area ratio and special structure of mesoporous bioactive glass (MBG) endow it with excellent physical adsorption of various drugs without destroying the chemical activity. Silicate 1393 bioactive glass (1393) is famous for its fantastic biodegradability and osteogenesis. Herein, we have built a novel vehicle-like drug delivery 3D printing scaffold with multiplexed drug delivery capacity by coating MBG on the surface of 1393 (1393@MBG). Furthermore, we have applied DEX and BMP-2 on the 1393@MBG scaffold to endow it with antibacterial and osteogenic properties. Results indicated that this 1393@MBG scaffold could effectively load and controlled release BMP-2, DNA and…

Combining recycling of paper wastes (WPs) with extrusion‐based additive manufacturing represents a sustainable route to cellular cellulose composites tailored for lightweight construction. Particularly, shear mixing of shredded WPs with an aqueous solution of a polymer binder like polyvinyl alcohol (PVA) yields aqueous pastes suitable for 3D printing. As a shear thinning additive, both WP and microfibrillated cellulose account for enhanced shear thinning and dimensional stability. Opposite to the formation of dense WP/PVA composites by melt extrusion, 3D printing of aqueous pastes produces cellular cellulose/PVA composites exhibiting hierarchical pore architectures. In spite of low densities around 0.8 g cm−3, high Young’s…

Injury of corpus cavernosa results in erectile dysfunction, but its treatment has been very difficult. Here we construct heparin-coated 3D-printed hydrogel scaffolds seeded with hypoxia inducible factor-1α (HIF-1α)-mutated muscle-derived stem cells (MDSCs) to develop bioengineered vascularized corpora. HIF-1α-mutated MDSCs significantly secrete various angiogenic factors in MDSCs regardless of hypoxia or normoxia. The biodegradable scaffolds, along with MDSCs, are implanted into corpus cavernosa defects in a rabbit model to show good histocompatibility with no immunological rejection, support vascularized tissue ingrowth, and promote neovascularisation to repair the defects. Evaluation of morphology, intracavernosal pressure, elasticity and shrinkage of repaired cavernous tissue prove that…

Bacterial infection of the implanting materials is one of the greatest challenges in bone tissue engineering. In this study, porous forsterite scaffolds with antibacterial activity have been fabricated by combining 3D printing and polymer-derived ceramics (PDCs) strategy, which effectively avoided the generation of MgSiO3 and MgO impurities. Forsterite scaffolds sintered in an argon atmosphere can generate free carbon in the scaffolds, which exhibited excellent photothermal effect and could inhibit the growth of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) in vitro. In addition, forsterite scaffolds have uniform macroporous structure, high compressive strength (>30 MPa) and low degradation rate.…

Cell-laden cardiac patches have recently been emerging to renew cellular sources for myocardial infarction (MI, commonly know as a heart attack) repair. However, the fabrication of cell-laden patches with porous structure remains challenging due to the limitations of currently available hydrogels and existing processing techniques. The present study utilized a bioprinting technique to fabricate hydrogel patches and characterize them in terms of printability, mechanical and biological properties. Cell-laden hydrogel (or bio-ink) was formulated from alginate dialdehyde (ADA) and gelatin (GEL) to improve the printability, degradability as well as bioactivity. Five groups of hydrogel compositions were designed to investigate the influence…

Several problems in science and engineering are characterized by the interaction between fluid flows and deformable structures. Due to their complex and multidisciplinary nature, these problems cannot normally be solved analytically and experiments are frequently of limited scope, so that numerical simulations represent the main analysis tool. Key to the advancement of numerical methods is the availability of experimental test cases for validation. This paper presents results of an experiment specifically designed for the validation of numerical methods for aeroelasticity and fluid-structure interaction problems. Flexible filaments of rectangular cross-section and various lengths were exposed to air flow of moderate Reynolds…

Despite their outstanding potential and the success that has already been achieved with three-dimensional (3D) printed hydrogel scaffolds, there has been little investigation into their application in the regeneration of damaged or missing adipose tissue (AT). Due to their macroscopic shape, microarchitecture, extracellular matrix-mimicking structure, degradability and soft tissue biomimetic mechanical properties, 3D printed hydrogel scaffolds have great potential for use in aesthetic, structural and functional restoration of AT. Here, we propose a simple and cost-effective 3D printing strategy using gelatin-based ink to fabricate scaffolds suitable for AT engineering. The ink, successfully printed here for the first time, was prepared…

Patients with aortic heart valve disease are limited to valve replacements that lack the ability to grow and remodel. This presents a major challenge for pediatric patients who require a valve capable of somatic growth and at a smaller size. A patient-specific heart valve capable of growth and remodeling while maintaining proper valve function would address this major issue. Here, we recreate the native valve leaflet structure composed of poly-ε-caprolactone (PCL) and cell-laden gelatin-methacrylate/poly (ethylene glycol) diacrylate (GelMA/PEGDA) hydrogels using 3D printing and molding, and then evaluate the ability of the multilayered scaffold to produce collagen matrix under physiological shear…

Meniscus deficiency, the most common and refractory disease in human knee joints, often progresses to osteoarthritis (OA) due to abnormal biomechanical distribution and articular cartilage abrasion. However, due to its anisotropic spatial architecture, complex biomechanical microenvironment, and limited vascularity, meniscus repair remains a challenge for clinicians and researchers worldwide. In this study, we developed a 3D printing-based biomimetic and composite tissue-engineered meniscus scaffold consisting of polycaprolactone (PCL)/silk fibroin (SF) with extraordinary biomechanical properties and biocompatibility. We hypothesized that the meticulously tailored composite scaffold could enhance meniscus regeneration and cartilage protection. Methods: The physical property of the scaffold was characterized by…