3D Bioplotter Research Papers
Constructing a Wireless Nerve Electrical Stimulation System to Repair Peripheral Nerve Defects
Purpose: The repair effect of peripheral nerve injury mainly depends on rapid regeneration of proximal axons, accurate docking, and effective nerve re-innervation of target organs. Accordingly, identifying effective methods to protect the functional state of target organs and realize rapid regeneration of proximal nerve fibers is of great significance. The purpose of this study is to build a nervous electrical stimulation system powered by electromagnetic induction and evaluate its repair effect on a rat sciatic nerve defect model. Methods: Biodegradable materials [magnesium (Mg), polylactic acid (PLLA), chitosan, and silk fibroin] were chosen to build thein vivo part of the wireless…
3-Dimensional Bioprinting of a Tendon Stem Cell–Derived Exosomes Loaded Scaffold to Bridge the Unrepairable Massive Rotator Cuff Tear
Background: Unrepairable massive rotator cuff tears (UMRCTs) are challenging to surgeons owing to the severely retracted rotator cuff musculotendinous tissues and extreme defects in the rotator cuff tendinous tissues. Purpose: To fabricate a tendon stem cell–derived exosomes loaded scaffold (TSC-Exos-S) and investigate its effects on cellular bioactivity in vitro and repair in a rabbit UMRCT model in vivo. Study Design: Controlled laboratory study. Methods: TSC-Exos-S was fabricated by loading TSC-Exos and type 1 collagen (COL-I) into a 3-dimensional bioprinted and polycaprolactone (PCL)–based scaffold. The proliferation, migration, and tenogenic differentiation activities of rabbit bone marrow stem cells (BMSCs) were evaluated in…
Double-network structure sponge with enhanced mechanical properties, procoagulant potential, and 3D printability for acute hemorrhage
In pre-hospital care, achieving rapid and effective hemostasis for arterial rupture and visceral perforation wounds remains a critical challenge. Herein, we have developed a macroporous sponge with double-network structure using foaming technique, chemical and physical crosslinking reactions, and lyophilization. The prepared sponge not only demonstrates outstanding water absorption and water-triggered shape recovery capacity, but also exhibits significantly enhanced mechanical properties due to the construction of double-network structure. Simultaneously, the sponge shortens blood clotting time (from 1354.3 ± 41 s to 473.0 ± 28 s) by concentrating blood components and regulating coagulation pathways. Particularly, the sponge possesses excellent 3D printability and…
Performance of Mg stabilised Na-β’’-alumina solid electrolytes prepared by direct ink writing
Mg-stabilised Na-β’’-alumina solid electrolyte (Mg-BASE) for Na-ion batteries was synthesised and fabricated into 3D structures via direct ink writing (DIW), an extrusion-based additive manufacturing process. To produce a water-based ink with optimum viscoelastic properties and supreme printing quality, a comprehensive investigation of ink formulation and printing parameters was conducted. The sintered 3D structures of Mg-BASE, fabricated via direct ink writing, achieved relative density of 98.0 ± 1.1 % with β’’ phase fraction of 99.7 wt% whilst bulk ionic conductivity of 0.081 S⋅cm−1 at 350 °C was obtained. XRD results indicated that Mg-BASE fabricated via DIW may have different c-axis orientation than conventional dry-pressed pellets, leading to…
Polycaprolactone strengthening gelatin/nano-hydroxyapatite composite biomaterial inks for potential application in extrusion-based 3D printing bone scaffolds
Extrusion-based three-dimensional (3D) printing of gelatin (Gel) is crucial for fabricating bone tissue engineering scaffolds via additive manufacturing. However, the thermal instability of Gel remains a persistent challenge, as it tends to collapse at mild temperatures. Current approaches often involve simply mixing Gel particles with various materials, resulting in biomaterial inks that lack uniformity and have inconsistent degradation characteristics. In this study, acetic acid was used to dissolve Gel and polycaprolactone (PCL) separately, producing homogeneous Gel/PCL dispersions with optimal pre-treatment performance. These dispersions were then combined and hybridized with nano-hydroxyapatite (n-HA) to create a composite printing ink. By evaluating the…
Cav3.3-mediated endochondral ossification in a three-dimensional bioprinted GelMA hydrogel
The growth plate (GP) is a crucial tissue involved in skeleton development via endochondral ossification (EO). The bone organoid is a potential research model capable of simulating the physiological function, spatial structure, and intercellular communication of native GPs. However, mimicking the EO process remains a key challenge for bone organoid research. To simulate this orderly mineralization process, we designed an in vitro shCav3.3 ATDC5-loaded gelatin methacryloyl (GelMA) hydrogel model and evaluated its bioprintability for future organoid construction. In this paper, we report the first demonstration that the T-type voltage-dependent calcium channel (T-VDCC) subtype Cav3.3 is dominantly expressed in chondrocytes and…
Robust design optimization of Critical Quality Indicators (CQIs) of medical-graded polycaprolactone (PCL) in bioplotting
Polycaprolactone (PCL), either in its pure grade or as a polymeric matrix for bio-composites, plays a key role in the biomedical and bioengineering industries. It is also considered a multifunctional and versatile polymer for bioprinting and bioplotting purposes, especially in tissue engineering. Herein, an undiscovered yet valuable aspect of PCL extrusion-based bioprinting, such as the predictability of Critical Quality Indicators (CQIs), is investigated in depth. With the aid of the robust L25 orthogonal matrix design, the six most generic and device-independent control factors proved their impact on quality metrics such as global porosity, dimensional conformity, and surface roughness, determined with…
Optimization of the engineering response of medical-graded polycaprolactone (PCL) over multiple generic control parameters in bioplotting
Bioplotting has high potential for the 3D printing of scaffolds and cellular structures. Medical-grade poly(ε-caprolactone) (PCL) is characterized by low 3D printing temperatures and strengths compared to those of common polymers. Thus far, research on PCL in bioplotting has mainly focused on improving its performance through the development of composites. In this study, the quantitative impact of six common 3D plotting settings on the engineering strength of PCL parts was evaluated. Three modeling approaches were implemented: linear regression modeling (LRM), reduced quadratic regression modeling, and quadratic regression modeling. The LRM results were not as accurate as those obtained using the…
Biobased hydrogel bioinks of pectin, nanocellulose and lysozyme nanofibrils for the bioprinting of A375 melanoma cell-laden 3D in vitro platforms
Melanoma is one of the most aggressive types of skin cancer, and the need for advanced platforms to study this disease and to develop new treatments is rising. 3D bioprinted tumor models are emerging as advanced tools to tackle these needs, with the design of adequate bioinks being a fundamental step to address this challenging process. Thus, this work explores the synergy between two biobased nanofibers, nanofibrillated cellulose (NFC) and lysozyme amyloid nanofibrils (LNFs), to create pectin nanocomposite hydrogel bioinks for the 3D bioprinting of A375 melanoma cell-laden living constructs. The incorporation of LNFs (5, 10 or 15 wt%) on a…
Novel 3D-printing bilayer GelMA-based hydrogel containing BP, β-TCP and exosomes for cartilage–bone integrated repair
The integrated repair of cartilage and bone involves the migration and differentiation of cells, which has always been a difficult problem to be solved. We utilize the natural biomaterial gelatin to construct gelatin methacryloyl (GelMA), a hydrogel scaffold with high cell affinity. GelMA is mixed with different components to print a bi-layer porous hydrogel scaffold with different modulus and composition in upper and lower layers through three-dimensional (3D) printing technology. The upper scaffold adds black phosphorus (BP) and human umbilical cord mesenchymal stem cells (hUMSCs) exosomes (exos) in GelMA, which has a relatively lower elastic modulus and is conducive to…
Assessing design-induced elasticity of 3D printed auxetic scaffolds for tissue engineering applications
Auxetic scaffolds fabricated via additive manufacturing can enable cyclic mechanical stimulation to promote the biomechanical functionalization of engineered tissues. Typical designs of additively manufactured scaffolds used in tissue engineering literature (e.g., 0/90˚ strand laydown) are not amenable to cyclic loading due to their rigidity, which is in part due to the high stiffness of biopolymers such as polycaprolactone (PCL). Auxetic scaffolds can help overcome this due to their design-induced elasticity while recapitulating negative Poisson’s ratios seen in various natural tissues. In this study, we investigated the effects of auxetic design patterns and unit cell sizes on the mechanical properties of…
FRESH 3D Bioprinting of Alginate – Cellulose – Gelatin Constructs for Soft Tissue Biofabrication
The fabrication of three-dimensional (3D) bioprinted free-standing, low viscous, cell-laden hydrogels with good resolution, low cytotoxicity, and mechanical properties, comparable to native soft tissues, is a current challenge in tissue engineering. Recently, a new syringe extrusion approach, called Freeform Reversible Embedding of Suspended Hydrogels (FRESH), has been introduced to enhance 3D-bioprinting of soft hydrogels. Printing is conducted with the material embedded in a thermo-reversible gelatin bath, which acts as supporting material and can also initiate in-situ crosslinking when proper crosslinker agents are added. This work is the first to develop a 3D FRESH printable, low-cost, polymeric hydrogel composed of sodium…
Synergistic Coassembly of Folic Acid-Based Supramolecular Polymer with a Covalent Polymer Toward Fabricating Functional Antibacterial Biomaterials
Supramolecular biomaterials can recapitulate the structural and functional facets of the native extracellular matrix and react to biochemical cues, leveraging the unique attributes of noncovalent interactions, including reversibility and tunability. However, the low mechanical properties of supramolecular biomaterials can restrict their utilization in specific applications. Combining the advantages of supramolecular polymers with covalent polymers can lead to the fabrication of tailor-made biomaterials with enhanced mechanical properties/degradability. Herein, we demonstrate a synergistic coassembled self-healing gel as a multifunctional supramolecular material. As the supramolecular polymer component, we chose folic acid (vitamin B9), an important biomolecule that forms a gel comprising one-dimensional (1D)…
Evaluating osteogenic potential of a 3D-printed bioceramic-based scaffold for critical-sized defect treatment: an in vivo and in vitro investigation
The integration of precision medicine principles into bone tissue engineering has ignited a wave of research focused on customizing intricate scaffolds through advanced 3D printing techniques. Bioceramics, known for their exceptional biocompatibility and osteoconductivity, have emerged as a promising material in this field. This article aims to evaluate the regenerative capabilities of a composite scaffold composed of 3D-printed gelatin combined with hydroxyapatite/tricalcium phosphate bioceramics (G/HA/TCP), incorporating human dental pulp–derived stem cells (hDPSCs). Using 3D powder printing, we created cross-shaped biphasic calcium phosphate scaffolds with a gelatin layer. The bone-regenerating potential of these scaffolds, along with hDPSCs, was assessed through in…
Femtosecond laser ablation of 3D-printed PCL Scaffolds as a strategy to enhance bone tissue regeneration efficacy
New photonic techniques need to be developed to improve personalised medicine methods in tissue engineering. In the case of severe bone injuries, difficulties arise when creating platforms where cells required to be efficiently adhered. Femtosecond laser ablation appears as a versatile technique for modifying the surface of materials with high precision and neat outcomes. Thus, a strategy combining 3D printing of biopolymeric scaffolds and femtosecond laser ablation is proposed to design a device with enhanced material properties in terms of cell growth for bone tissue regeneration. Three different patterns were proposed, and it was proven that cell adhesion improvements rely…
Sr-Incorporated Bioactive Glass Remodels the Immunological Microenvironment by Enhancing the Mitochondrial Function of Macrophage via the PI3K/AKT/mTOR Signaling Pathway
The repair of critical-sized bone defects continues to pose a challenge in clinics. Strontium (Sr), recognized for its function in bone metabolism regulation, has shown potential in bone repair. However, the underlying mechanism through which Sr2+ guided favorable osteogenesis by modulating macrophages remains unclear, limiting their application in the design of bone biomaterials. Herein, Sr-incorporated bioactive glass (SrBG) was synthesized for further investigation. The release of Sr ions enhanced the immunomodulatory properties and osteogenic potential by modulating the polarization of macrophages toward the M2 phenotype. In vivo, a 3D-printed SrBG scaffold was fabricated and showed consistently improved bone regeneration by…
Hybrid biofabricated blood vessel for medical devices testing
Current in vitro and in vivo tests applied to assess the safety of medical devices retain several limitations, such as an incomplete ability to faithfully recapitulate human features, and to predict the response of human tissues together with non-trivial ethical aspects. We here challenged a new hybrid biofabrication technique that combines bioprinting and Fast Diffusion-induced Gelation strategy to generate a vessel-like structure with the attempt to spatially organize fibroblasts, smooth-muscle cells, and endothelial cells. The introduction of Fast Diffusion-induced Gelation minimizes the endothelial cell mortality during biofabrication and produce a thin endothelial layer with tunable thickness. Cell viability, Von Willebrand…
3D printing modality effect: Distinct printing outcomes dependent on selective laser sintering (SLS) and melt extrusion
A direct and comprehensive comparative study on different 3D printing modalities was performed. We employed two representative 3D printing modalities, laser- and extrusion-based, which are currently used to produce patient-specific medical implants for clinical translation, to assess how these two different 3D printing modalities affect printing outcomes. The same solid and porous constructs were created from the same biomaterial, a blend of 96% poly-ε-caprolactone (PCL) and 4% hydroxyapatite (HA), using two different 3D printing modalities. Constructs were analyzed to assess their printing characteristics, including morphological, mechanical, and biological properties. We also performed an in vitro accelerated degradation study to compare…
Large artificial bone from 3D printed polycaprolactone/β-tricalcium phosphate (3D PCL/β-TCP) effectively promoting MC3T3-E1 cell adhesion, proliferation, and new bone formation
The use of 3D printing technology has advanced the bone tissue engineering, and constructing large artificial bones for repairing large-scale bone defects is highly significant. This study aimed to construct large artificial bones in a precise and controllable manner, focusing on repairing critical-sized bone defects. The researchers used 3D printing technology to synthesize 3D PCL/β-TCP, and then evaluated its ability to promote MC3T3-E1 cell adhesion, proliferation, and new bone formation through a series of characterizations. The results confirmed that 3D PCL/β-TCP, presented as a lattice structure similar to natural bone, could be used to prepare personalized artificial bone blocks based…
Smart Design for Hybrid Bioprinting of Scalable and Viable Tissue Constructs
Hybrid bioprinting uses sequential printing of melt-extruded biodegradable thermoplastic polymer and cell-encapsulated bioink in a predesigned manner using high- and low-temperature print heads for the fabrication of robust three-dimensional (3D) biological constructs. However, the high-temperature print head and melt-extruded polymer cause irreversible thermal damage to the bioprinted cells, and it affects viability and functionality of 3D bioprinted biological constructs. Thus, there is an urgent need to develop innovative approaches to protect the bioprinted cells, coming into contact or at close proximities to the melt-extruded thermoplastic polymer and the high-temperature print head during hybrid bioprinting. Therefore, this study investigated the potential…
Printable Poly(3,4-ethylenedioxythiophene)-Based Conductive Patches for Cardiac Tissue Remodeling
Myocardial cardiopathy is one of the highest disease burdens worldwide. The damaged myocardium has little intrinsic repair ability, and as a result, the distorted muscle loses strength for contraction, producing arrhythmias and fainting, and entails a high risk of sudden death. Permanent implantable conductive hydrogels that can restore contraction strength and conductivity appear to be promising candidates for myocardium functional recovery. In this work, we present a printable cardiac hydrogel that can exert functional effects on networks of cardiac myocytes. The hydrogel matrix was designed from poly(vinyl alcohol) (PVA) dynamically cross-linked with gallic acid (GA) and the conductive polymer poly(3,4-ethylenedioxythiophene)…
Alveolar bone regeneration using a 3D-printed patient-specific resorbable scaffold for dental implant placement: A case report
Background: This case report demonstrates the effective clinical application of a 3D-printed, patient-specific polycaprolactone (PCL) resorbable scaffold for staged alveolar bone augmentation. Objective: To evaluate the effectiveness of a 3D-printed PCL scaffold in facilitating alveolar bone regeneration and subsequent dental implant placement. Materials and Methods: A 46-year-old man with a missing tooth (11) underwent staged alveolar bone augmentation using a patient-specific PCL scaffold. Volumetric bone gain and implant stability were assessed. Histological analysis was conducted to evaluate new bone formation and graft integration. Results: The novel approach resulted in a volumetric bone gain of 364.69 ± 2.53 mm3, sufficient to reconstruct the original…
A heparin-functionalized bioink with sustained delivery of vascular endothelial growth factor for 3D bioprinting of prevascularized dermal constructs
Skin tissue engineering faces challenges due to the absence of vascular architecture, impeding the development of permanent skin replacements. To address this, a heparin-functionalized 3D-printed bioink (GH/HepMA) was formulated to enable sustained delivery of vascular endothelial growth factor (VEGF), comprising 0.3 % (w/v) hyaluronic acid (HA), 10 % (w/v) gelatin methacrylate (GelMA), and 0.5 % (w/v) heparin methacrylate (HepMA). The bioink was then used to print dermal constructs with angiogenic functions, including fibroblast networks and human umbilical vein endothelial cell (HUVEC) networks. GH/HepMA, with its covalently cross-linked structure, exhibits enhanced mechanical properties and heparin stability, allowing for a 21-day sustained…
Meniscal repair with additive manufacture of bioresorbable polymer: From physicochemical characterization to implantation of 3D printed poly (L-co-D, L lactide-co-trimethylene carbonate) with autologous stem cells in rabbit
Three-dimensional (3D) structures are actually the state-of-the-art technique to create porous scaffolds for tissue engineering. Since regeneration in cartilage tissue is limited due to intrinsic cellular properties this study aims to develop and characterize three-dimensional porous scaffolds of poly (L-co-D, L lactide-co-trimethylene carbonate), PLDLA-TMC, obtained by 3D fiber deposition technique. The PLDLA-TMC terpolymer scaffolds (70:30), were obtained and characterized by scanning electron microscopy, gel permeation chromatography, differential scanning calorimetry, thermal gravimetric analysis, compression mechanical testing and study on in vitro degradation, which showed its amorphous characteristics, cylindrical geometry, and interconnected pores. The in vitro degradation study showed significant loss of…
Release Rates of Prednisolone-21-Hydrogen- Succinate from 3D-Printed Silicone as Material for Patient-Individualized Drug Releasing Implants
For treating idiopathic sudden sensorineural hearing loss, prednisolone is commonly used. However, systemic or middle ear injections often lead to insufficient drug delivery to the inner ear, causing ineffective treatment and systemic side effects. An implant inserted into the middle ear and delivering the drug directly to the inner ear offers a promising solution, providing controlled, long-term drug release with potentially better efficacy and fewer side effects. Individualized implants made of prednisolone-containing silicone can optimize inner ear treatment by fitting the patient’s middle ear anatomy. To gauge the properties of prednisolone-21-hydrogen succinate containing silicone, samples with different geometries and drug…
The induction of bone formation by 3D-printed PLGA microsphere scaffolds in a calvarial orthotopic mouse model: a pilot study
Polymeric biodegradable microspheres are readily utilized to support targeted drug delivery for various diseases clinically. 3D printed tissue engineering scaffolds from polymer filaments with embedded microspheres or nanoparticles, as well as bulk microsphere scaffolds, have been investigated for regenerative medicine and tissue engineering. However, 3D printed scaffolds consisting only of a homogenous microsphere size with an optimized architecture that includes a unique micro- and macroporosity, have been challenging to produce and hence, have not been assessed in the literature yet. Utilizing our recently established 3D-MultiCompositional Microsphere-Adaptive Printing (3D-McMap) method, the present study evaluated the effectiveness of 3D-printed poly (lactic-co-glycolic acid)…
3D Bioprinting-Based Dopamine-Coupled Flexible Material for Nasal Cartilage Repair
Introduction Since 3D printing can be used to design implants according to the specific conditions of patients, it has become an emerging technology in tissue engineering and regenerative medicine. How to improve the mechanical, elastic and adhesion properties of 3D-printed photocrosslinked hydrogels is the focus of cartilage tissue repair and reconstruction research. Materials and Methods We established a strategy for toughening hydrogels by mixing GelMA-DOPA (GD), which is prepared by coupling dopamine (DA) with GelMA, with HAMA, bacterial cellulose (BC) to produce composite hydrogels (HB–GD). HB–GD hydrogel scaffolds were characterized in vitro by scanning electron microscopy (SEM), Young’s modulus, swelling…
A Novel Strategy for Fabrication of Polyamide 66/Nanohydroxyapatite Composite Bone Repair Scaffolds by Low-Temperature Three-Dimensional Printing
Due to the decomposition temperature of Polyamide 66 (PA66) in the environment is close to its thermoforming temperature, it is difficult to construct porous scaffolds of PA66/nanohydroxyapatite (PA66/HAp) by fused deposition modeling (FDM) three-dimensional (3D) printing. In this study, we demonstrated for the first time a method for 3D printing PA66/HAp composites at room temperature, prepared PA66/HAp printing ink using a mixed solvent of formic acid/dichloromethane (FA/DCM), and constructed a series of composite scaffolds with varying HAp content. This printing system can print composite materials with a high HAp content of 60 wt %, which is close to the mineral…
Advancing knee cartilage repair with 3D printed GelMA/SF/Haps composite hydrogels for enhanced chondrocyte regeneration
The repair of cartilage injuries and defects in the knee presents a significant challenge in the field of human joint surgery. A promising solution involves the synergy of three-dimensional printing and articular cartilage tissue engineering. This research primarily focuses on the formulation of composite hydrogels comprising gelatin methacryloyl (GelMA), silk fibroin (SF) and hydroxyapatites (Haps), with a thorough examination of their morphology and mechanical properties. We also conducted tests on stacking height and grid area to assess the 3D printability of GM/SF/Haps inks. To evaluate the suitability of GM/SF/Haps scaffolds in cartilage regeneration, we performed 2D culture with mouse chondrocytes…
Characterization of a conductive hydrogel@Carbon fibers electrode as a novel intraneural interface
Peripheral neural interfaces facilitate bidirectional communication between the nervous system and external devices, enabling precise control for prosthetic limbs, sensory feedback systems, and therapeutic interventions in the field of Bioelectronic Medicine. Intraneural interfaces hold great promise since they ensure high selectivity in communicating only with the desired nerve fascicles. Despite significant advancements, challenges such as chronic immune response, signal degradation over time, and lack of long-term biocompatibility remain critical considerations in the development of such devices. Here we report on the development and benchtop characterization of a novel design of an intraneural interface based on carbon fiber bundles. Carbon fibers…
3D-Printed Hydrogels as Photothermal Actuators
Thermoresponsive hydrogels were 3D-printed with embedded gold nanorods (GNRs), which enable shape change through photothermal heating. GNRs were functionalized with bovine serum albumin and mixed with a photosensitizer and poly(N-isopropylacrylamide) (PNIPAAm) macromer, forming an ink for 3D printing by direct ink writing. A macromer-based approach was chosen to provide good microstructural homogeneity and optical transparency of the unloaded hydrogel in its swollen state. The ink was printed into an acetylated gelatin hydrogel support matrix to prevent the spreading of the low-viscosity ink and provide mechanical stability during printing and concurrent photocrosslinking. Acetylated gelatin hydrogel was introduced because it allows for…
Co3O4@SiO2 3D Monolith Catalysts, Additive Manufactured Structures for Propane Oxidation Reaction
In this study, we successfully fabricated a three-dimensional Co3O4@SiO2 3D Monolith catalyst. This process allowed for the effective and straightforward anchoring of Co3O4 nanoparticles onto SiO2 3D Monoliths. The active Co3O4 phase was primarily identified through XRD and XPS analyses, complemented by Co3O4 loading measurements (1.7 %). This innovative catalyst displayed remarkable proficiency in selectively converting propane to carbon dioxide. Additionally, it was demonstrated that the catalytic activity remained unimpaired even upon the catalyst’s reuse in 5 successive reaction cycles. This performance was observed across various heating ramps, showcasing the catalyst’s stability over time.
Low-Concentration Gelatin Methacryloyl Hydrogel with Tunable 3D Extrusion Printability and Cytocompatibility: Exploring Quantitative Process Science and Biophysical Properties
Three-dimensional (3D) bioprinting of hydrogels with a wide spectrum of compositions has been widely investigated. Despite such efforts, a comprehensive understanding of the correlation among the process science, buildability, and biophysical properties of the hydrogels for a targeted clinical application has not been developed in the scientific community. In particular, the quantitative analysis across the entire developmental path for 3D extrusion bioprinting of such scaffolds is not widely reported. In the present work, we addressed this gap by using widely investigated biomaterials, such as gelatin methacryloyl (GelMA), as a model system. Using extensive experiments and quantitative analysis, we analyzed how…
Development of a drug delivering round window niche implant for cochlear pharmacotherapy
Background There exists an unfulfilled requirement for effective cochlear pharmacotherapy. Controlled local drug delivery could lead to effective bioavailability. The round window niche (RWN), a cavity in the middle ear, is connected to the cochlea via a membrane through which drug can diffuse. We are developing individualized drug-eluting RWN implants (RNIs). To test their effectiveness in guinea pigs, a commonly used model in cochlear pharmacology studies, it is first necessary to develop guinea pig RNIs (GP-RNI). Methods Since guinea pigs do not have a RWN such as it is present in humans and to reduce the variables in in vivo…
Mechanical and Physical Characterization of a Biphasic 3D Printed Silk-Infilled Scaffold for Osteochondral Tissue Engineering
Osteochondral tissue damage is a serious concern, with even minor cartilage damage dramatically increasing an individual’s risk of osteoarthritis. Therefore, there is a need for an early intervention for osteochondral tissue regeneration. 3D printing is an exciting method for developing novel scaffolds, especially for creating biological scaffolds for osteochondral tissue engineering. However, many 3D printing techniques rely on creating a lattice structure, which often demonstrates poor cell bridging between filaments due to its large pore size, reducing regenerative speed and capacity. To tackle this issue, a novel biphasic scaffold was developed by a combination of 3D printed poly(ethylene glycol)-terephthalate-poly(butylene-terephthalate) (PEGT/PBT)…
3D Printing of a Chitosan and Tamarind Gum Ink: a Two-Step Approach
3D bioprinting stands out as one of the most promising innovations in the field of high technologies for personalized biomedicine, enabling the fabrication of biomaterial-based scaffolds designed to repair, restore, or regenerate tissues and organs in the body. Among the various materials used as inks, hydrogels play a critical role due to their unique characteristics, including excellent biocompatibility, adjustable mechanical properties, and high solvent retention. This versatility makes them ideal for various applications such as biomedical devices, drug delivery, or flexible electronics. Although chitosan is a promising material for such applications, when used alone, it does not possess the necessary…
Impact of Porosity and Stiffness of 3D Printed Polycaprolactone Scaffolds on Osteogenic Differentiation of Human Mesenchymal Stromal Cells and Activation of Dendritic Cells
Despite the potential of extrusion-based printing of thermoplastic polymers in bone tissue engineering, the inherent nonporous stiff nature of the printed filaments may elicit immune responses that influence bone regeneration. In this study, bone scaffolds made of polycaprolactone (PCL) filaments with different internal microporosity and stiffness was 3D-printed. It was achieved by combining three fabrication techniques, salt leaching and 3D printing at either low or high temperatures (LT/HT) with or without nonsolvent induced phase separation (NIPS). Printing PCL at HT resulted in stiff scaffolds (modulus of elasticity (E): 403 ± 19 MPa and strain: 6.6 ± 0.1%), while NIPS-based printing…
Algal protein-based 3D-printed fish-analogs as a new approach for sustainable seafood
Rising global demand for animal-products exceeds human-population growth. This unsustainable trend causes harmful ecological effects. Overfishing causes extinction of aquatic animals and a dangerous biodiversity loss harming aquatic ecosystems. Hence, replacing animal-based food, particularly beef and fish, with sustainable alternatives is an urgent vital global mission. Analogs of animal-based products include plant-based, tissue-culture-based and fermentation-based products. Fish analogs have mainly been based on plant-protein, fungi, tissue-culture, but to our knowledge, fish analogs made of algae, particularly macroalgae, as the major component and protein-source have not been reported. 3D-food-printing is a fast-developing technology, enabling formation of complex three-dimensional structures with various…
Fabricating Multiphasic Angiogenic Scaffolds Using Amyloid/Roxadustat-Assisted High-Temperature Protein Printing
Repairing multiphasic defects is cumbersome. This study presents new soft and hard scaffold designs aimed at facilitating the regeneration of multiphasic defects by enhancing angiogenesis and improving cell attachment. Here, the nonimmunogenic, nontoxic, and cost-effective human serum albumin (HSA) fibril (HSA-F) was used to fabricate thermostable (up to 90 °C) and hard printable polymers. Additionally, using a 10.0 mg/mL HSA-F, an innovative hydrogel was synthesized in a mixture with 2.0% chitosan-conjugated arginine, which can gel in a cell-friendly and pH physiological environment (pH 7.4). The presence of HSA-F in both hard and soft scaffolds led to an increase in significant…
A framework for digital twin integration in biofabrication and a scaffold 3D bioplotting case study
Biofabrication, which integrates biological sciences with advanced manufacturing, is vital for innovations in tissue engineering and regenerative medicine. One primary consideration in this domain is ensuring consistent, scalable, and adaptable processes that are amenable to clinical translation. Toward this, this paper introduces a new framework for digital twin integration in biofabrication. Digital twins, which are real-time virtual replicas of physical systems, can facilitate comprehensive monitoring, accurate prediction, and effective optimization to enable robust biofabrication processes and systems. The proposed framework incorporates major building blocks for implementing digital twins for biofabrication, including comprehensive data acquisition and analysis using sophisticated sensors to…
Biocompatibility and bio-efficacy of 3D printed dexamethasone loaded implants after autoclaving: Comparison of three different silicone brands
Introduction: For the treatment of sudden sensorineural hearing loss (SSNHL), dexamethasone (DEX) delivery via silicone implants, customized to individual patient anatomy through 3D printing, may be used. To ensure safety, the sterility of these implants must be verified. Autoclaving was employed as a potential sterilization method, and the biocompatibility and bio-efficacy of 3D-printed, DEX-loaded implants, using three different medical-grade silicones, were assessed post-autoclaving. Methods: UV-Silicone 60A MG (Momentive, Niskayuna, USA), Nusil Med-4960 (Avantor, Radnor, USA), and Amsil Silbione 24503-50 A (Elkem, Oslo, Norway) loaded with 0, 1, 10, or 20 (w/w) % DEX (caelo, Hilden, Germany) were 3D printed…
Extrusion-based Additive Manufacturing of Magnetic Heat Exchange Structures for Caloric Applications
Currently, the commercial building sector accounts for 18% of total U.S. end-use energy consumption, of which almost a third was from on-site combustion of fossil fuels for space and water heating. Magnetic heat pumping (MHP) technology is an energy-efficient, sustainable, environmentally-friendly alternative to conventional vapor-compression cooling technology. Several MHP designs today are predicted to be highly energy efficient, on condition that suitable working materials can be developed. This materials challenge has proven to be daunting due to issues associated with intricate synthesis/post-processing protocols and complications related to shaping the mostly brittle magnetocaloric alloys into thin-walled channeled regenerator structures to facilitate…
Optimization of Biomanufacturing process for Tissue Engineering applications
In recent years, tissue engineering has experienced significant advancements, mostly driven by the emergence of additive manufacturing technologies and the integration of biomaterials and cells. This advanced technique enables the creation of intricate structures with diverse components and properties, specifically designed for use in biomedical applications. The primary benefit of this technology is its ability to be customised, which helps minimise post-operative difficulties for patients with orthopaedic diseases and those undergoing tissue transplants. For this purpose, the essential components can be synthesised by the patient’s own cells. However, there are still other obstacles that need to be addressed in order…
Artificial Stimuli-responsive constructs through 4D fabrication
In the ever-evolving landscape of bioengineering, the current research effort to push the boundaries of biomedical engineering through a multidisciplinary effort using advanced 4D fabrication techniques. This study represents a pioneering effort to create artificial constructs, such as skin, and muscles by leveraging knowledge from material science, mechanical engineering, biomedical engineering and advanced manufacturing. By seamlessly integrating these domains, our approach aims to overcome the inherent complexities associated with tissue engineering. The utilisation of 4D fabrication techniques introduces a dynamic dimension to the fabrication process, allowing for the creation of tissues with intricate spatial and temporal characteristics. The central focus…
Synthesis of Alginate/Collagen Bioink for Bioprinting Respiratory Tissue Models
Synthesis of bioinks for bioprinting of respiratory tissue requires considerations related to immunogenicity, mechanical properties, printability, and cellular compatibility. Biomaterials can be tailored to provide the appropriate combination of these properties through the synergy of materials with individual pros and cons. Sodium alginate, a water-soluble polymer derived from seaweed, is a cheap yet printable biomaterial with good structural properties; however, it lacks physiological relevance and cell binding sites. Collagen, a common component in the extra cellular matrix of many tissues, is expensive and lacks printability; however, it is highly biocompatible and exhibits sites for cellular binding. This paper presents our…
Ink-Extrusion 3D Printing and Silicide Coating of HfNbTaTiZr Refractory High-Entropy Alloy for Extreme Temperature Applications
An oxygen-resistant refractory high-entropy alloy is synthesized in microlattice or bulk form by 3D ink-extrusion printing, interdiffusion, and silicide coating. Additive manufacturing of equiatomic HfNbTaTiZr is implemented by extruding inks containing hydride powders, de-binding under H2, and sintering under vacuum. The sequential decomposition of hydride powders (HfH2+NbH+TaH0.5+TiH2+ZrH2) is followed by in situ X-ray diffraction. Upon sintering at 1400 °C for 18 h, a nearly fully densified, equiatomic HfNbTaTiZr alloy is synthesized; on slow cooling, both α-HCP and β-BCC phases are formed, but on quenching, a metastable single β-BCC phase is obtained. Printed and sintered HfNbTaTiZr alloys with ≈1 wt.% O shows excellent mechanical properties…
3D-ink-printing of monocrystalline YBCO superconductor
Single-crystal microstructure can bring high performance for many materials including piezoelectrics, semiconductors, and cuprate superconductors. Unlike single-crystal metals that can be machined into complex components, most single-crystal ceramics are limited to the shape of thin films or plates due to their brittleness. However, more designs of advanced devices need to break these geometric limitations. 3D-ink-printing can efficiently fabricate complex architectured ceramics, but the microstructure is polycrystals. Here, for the first time, we demonstrate a route to grow single-crystal on 3D printed ceramic-YBa2 Cu 3 O7-x (YBCO) superconductors that can simultaneously have complex architectures and high critical current density. An ink…
Targeting micromotion for mimicking natural bone healing by using NIPAM/Nb2C hydrogel
Natural fracture healing is most efficient when the fine-tuned mechanical force and proper micromotion are applied. To mimick this micromotion at the fracture gap, a near-infrared-II (NIR–II)–activated hydrogel was fabricated by integrating two-dimensional (2D) monolayer Nb2C nanosheets into a thermally responsive poly(N-isopropylacrylamide) (NIPAM) hydrogel system. NIR–II–triggered deformation of the NIPAM/Nb2C hydrogel was designed to generate precise micromotion for co-culturing cells. It was validated that micromotion at 1/300 Hz, triggering a 2.37-fold change in the cell length/diameter ratio, is the most favorable condition for the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Moreover, mRNA sequencing and verification revealed that…
[Performance of 3D-printed polylactic acid-nano-hydroxyapatite/chitosan/doxycycline antibacterial scaffold]
BACKGROUND: Polylactic acid has good biocompatibility and biodegradability, and has become a new orthopedic fixation material. However, the lack of cell recognition signal of this material is not conducive to cell adhesion and osteogenic differentiation, which limits its application in biomaterials. OBJECTIVE: 3D-printed polylactic acid-nano-hydroxyapatite (nHA)/chitosan (CS) scaffold to evaluate its drug sustained-release and biological properties
Carbon fiber reinforced liquid crystalline elastomer composites: a dual exploration in strength augmentation and transformation flexibility through 4D printing
Liquid Crystal Elastomers (LCEs) are renowned for their reversible deformation capabilities. Yet, enhancing their mechanical strength while retaining such flexibility has posed a considerable challenge. To overcome this, we utilized 4D printing to develop an innovative composite of LCE with carbon fiber fabric (LCEC). This approach has notably increased the tensile strength of LCE by eightfold, all the while maintaining its exceptional capacity for reversible deformation. By adjusting the alignment angle between carbon fiber and the LCE printing direction from 0° to 90°, the LCEC demonstrates an array of new deformation patterns, including bending, twisting, wrapping, and S-shaped transformations, which…
Extrusion bioprinting of elastin-containing bioactive double-network tough hydrogels for complex elastic tissue regeneration
Despite recent advances in extrusion bioprinting of cell-laden hydrogels, using naturally derived bioinks to biofabricate complex elastic tissues with both satisfying biological functionalities and superior mechanical properties is hitherto an unmet challenge. Here, we address this challenge with precisely designed biological tough hydrogel bioinks featuring a double-network structure. The tough hydrogels consisted of energy-dissipative dynamically crosslinked glycosaminoglycan hyaluronic acid (o-nitrobenzyl-grafted hyaluronic acid) and elastin through Schiff’s base reaction, and free-radically polymerized gelatin methacryloyl. The incorporation of elastin further improved the elasticity, stretchability (∼170% strain), and toughness (∼45 kJ m−3) of the hydrogels due to the random coiling structure. We used this novel…
A dual-crosslinking electroactive hydrogel based on gelatin methacrylate and dibenzaldehyde-terminated telechelic polyethylene glycol for 3D bio-printing
Gelatin was widely used as scaffold materials in 3D bio-printing due to its excellent bioactivity and availability and especially that their arginine–glycine–aspartic acid (RGD) sequences could efficiently promote cell adhesion and proliferation. In this study, an electroactive and 3D bio-printable hydrogel was prepared through a two-step chemical cross-linking process. Specifically, residual free amino groups of methacrylated gelatin (GelMA) were cross-linked with the aldehyde groups of dibenzaldehyde-terminated telechelic polyethylene glycol (DF-PEG) via Schiff base bonds, forming a gel at 37 °C. During the subsequent 3D bio-printing process, GelMA underwent UV curing, forming a secondary cross-linked network to the mechanical strength and stability…
3D Printing-Electrospinning Hybrid Nanofibrous Scaffold as LEGO-Like Bricks for Modular Assembling Skeletal Muscle-on-a-Chip Functional Platform
Organ-on-a-chip stands as a pivotal platform for skeletal muscle research while constructing 3D skeletal muscle tissues that possess both macroscopic and microscopic structures remains a considerable challenge. This study draws inspiration from LEGO-like assembly, employing a modular approach to construct muscle tissue that integrates biomimetic macroscopic and microscopic structures. Modular LEGO-like hybrid nanofibrous scaffold bricks were fabricated by the combination of 3D printing and electrospinning techniques. Skeletal muscle cells cultured on these modular scaffold bricks exhibited a highly orientated nanofibrous structure. A variety of construction of skeletal muscle tissues further enabled development by various assembling processes. Moreover, skeletal muscle-on-a-chip (SMoC)…
Cucurbit[8]uril Mediated Supramolecular and Photocrosslinked Interpenetrating Network Hydrogel Matrices for 3D-Bioprinting
Printing of biologically functional constructs is significant for applications in tissue engineering and regenerative medicine. Designing bioinks remains remarkably challenging due to the multifaceted requirements in terms of the physical, chemical, and biochemical properties of the three-dimensional matrix, such as cytocompatibility, printability, and shape fidelity. In order to promote matrix and materials stiffness, while not sacrificing stress relaxation mechanisms which support cell spreading, migration, and differentiation, this work reports an interpenetrating network (IPN) bioink design. The approach makes use of a chemically defined network, combining physical and chemical crosslinking units with a tunable composition and network density, as well as…
Optimization of cellulose nanocrystal (CNC) concentration in polycaprolactone bio-composites for bio-plotting: a robust interpretation of the reinforcement mechanisms
Bioabsorbable and biodegradable composites have experienced rapid growth, owing to their high demand in the biomedical sector. Polymer-cellulose nanocrystal (CNC) compounds were developed using a medical-grade poly (ε-caprolactone) (PCL) matrix to improve the stiffness and load-bearing capacity of pure PCL. Five PCL/CNCs filament grades were melt-extruded, pelletized, and fed into an industrial bioplotter to fabricate specimens. To assess the effects of CNCs on pure PCL, 14 tests were conducted, including rheological, thermomechanical, and in situ micro-mechanical testing, among others. The porosity and dimensional accuracy of the samples were also documented using micro-computed tomography while scanning electron microscopy was employed for…
Additive Manufacturing of Nanocellulose Aerogels with Structure-Oriented Thermal, Mechanical, and Biological Properties
Additive manufacturing (AM) is widely recognized as a versatile tool for achieving complex geometries and customized functionalities in designed materials. However, the challenge lies in selecting an appropriate AM method that simultaneously realizes desired microstructures and macroscopic geometrical designs in a single sample. This study presents a direct ink writing method for 3D printing intricate, high-fidelity macroscopic cellulose aerogel forms. The resulting aerogels exhibit tunable anisotropic mechanical and thermal characteristics by incorporating fibers of different length scales into the hydrogel inks. The alignment of nanofibers significantly enhances mechanical strength and thermal resistance, leading to higher thermal conductivities in the longitudinal…
Chemiresistive Sensor for Enhanced CO2 Gas Monitoring
Carbon dioxide (CO2) gas sensing and monitoring have gained prominence for applications such as smart food packaging, environmental monitoring of greenhouse gases, and medical diagnostic tests. Although CO2 sensors based on metal oxide semiconductors are readily available, they often suffer from limitations such as high operating temperatures (>250 °C), limited response at elevated humidity levels (>60% RH), bulkiness, and limited selectivity. In this study, we designed a chemiresistive sensor for CO2 detection to overcome these problems. The sensing material of this sensor consists of a CO2 switchable polymer based on N-3-(dimethylamino)propyl methacrylamide (DMAPMAm) and methoxyethyl methacrylate (MEMA) [P(D-co-M)], and diethylamine.…
PDMS Microspheres as Rheological Additives for PDMS-Based DIW Inks
Direct Ink Writing holds vast potential for additive manufacturing with broad material compatibility as long as appropriate rheological properties are exhibited by the material of choice. Additives are often included to attain the desired rheological properties for printing, but these same additives can yield products with undesirable mechanical properties. For example, silica fillers are used to create silicone inks appropriate for printing but yield cured structures that are too stiff. In this work, we investigate the applicability of PDMS microspheres as a rheological and thixotropic additive for PDMS based DIW inks. We utilize a facile oil-in-water emulsion method to reproducibly…
3D-printed near-infrared-light-responsive on-demand drug-delivery scaffold for bone regeneration
Although several bioactive 3D-printed bone scaffolds loaded with multiple kinds of biomolecules for enhanced bone regeneration have been recently developed, the manipulation of on-demand release profiles of different biomolecules during bone regeneration remains challenging. Herein, a 3D-printed dual-drug-loaded biomimetic scaffold to regulate the host stem cell recruitment and osteogenic differentiation in a two-stage process for bone regeneration was successfully fabricated. First, a chemotactic small-molecule drug, namely, simvastatin (SIM) was directly incorporated into the hydroxyapatite/collagen bioink for printing and could be rapidly released during the early stage of bone regeneration. Further, near-infrared (NIR)-light-responsive polydopamine-coated hydroxyapatite nanoparticles were designed to deliver the…
Synergistic effects of calcium silicate/zinc silicate dual compounds and in-situ interconnected pores on promoting bone regeneration of composite scaffolds
Rapid bone regeneration in implants is important for successful transplantation. In this regard, we report the development of calcium silicate/zinc silicate (CS/ZS) dual-compound-incorporated calcium phosphate cement (CPC) scaffolds with a three-dimensional poly (lactic-co-glycolic acid) network that synergistically promote bone regeneration. In vitro results demonstrated that the incorporation of CS/ZS dual compounds into the CPC significantly promoted the osteogenic differentiation of stem cells compared to the addition of CS or ZS alone. Moreover, the bone-regeneration efficacy of the composite scaffolds was validated by filling in femur condyle defects in rabbits, which showed that the scaffolds with CS and ZS possessed a…
Self-setting calcium phosphate cement scaffolds with pre-forming and in-situ forming interconnected macropores: Comparative study in vitro and in vivo
Creating interconnected macropores in calcium phosphate cement (CPC) is an effective strategy to promote its degradation and osteogenesis. However, little attention has been given to the osteogenic effect of the CPC scaffolds with pre-forming and in-situ forming interconnected macropores. Herein, two types of CPC scaffolds were prepared by infiltrating CPC pastes into 3D-printed polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA) networks. Meanwhile, the sacrificial PCL network within CPC was dissolved to obtain the CPC scaffold with approximately 300 μm macropores, whereas the PLGA network was retained within the CPC to obtain the PLGA/CPC scaffold. The results indicated that the PLGA/CPC scaffold…
Cornea-Specific Human Adipose Stem Cell-Derived Extracellular Matrix for Corneal Stroma Tissue Engineering
Utilizing tissue-specific extracellular matrices (ECMs) is vital for replicating the composition of native tissues and developing biologically relevant biomaterials. Human- or animal-derived donor tissues and organs are the current gold standard for the source of these ECMs. To overcome the several limitations related to these ECM sources, including the highly limited availability of donor tissues, cell-derived ECM offers an alternative approach for engineering tissue-specific biomaterials, such as bioinks for three-dimensional (3D) bioprinting. 3D bioprinting is a state-of-the-art biofabrication technology that addresses the global need for donor tissues and organs. In fact, there is a vast global demand for human donor…
Combining direct ink writing with reactive melt infiltration to create architectured thermoelectric legs
We present a new additive-reactive synthesis method where inks – cast into molds or 3D-additively extruded into architectured shapes – are reacted into intermetallic thermoelectric compounds. The new method, as demonstrated for equiatomic TiNiSn, combines: (i) extrusion printing (or casting) of inks containing Ni and Ti powders, (ii) debinding and reactive sintering to form a porous NiTi network, (iii) network infiltration with liquid Sn and subsequent reaction to synthesize the TiNiSn phase. Thin plates, created through this method, show high phase purity and low residual porosity. A thermoelectric figure of merit = 0.47 ± 0.05 is achieved at 800 K, within the broad range…
3D Bioprinting of Biomimetic Alginate/Gelatin/Chondroitin Sulfate Hydrogel Nanocomposites for Intrinsically Chondrogenic Differentiation of Human Mesenchymal Stem Cells
3D-printed hydrogel scaffolds biomimicking the extracellular matrix (ECM) are key in cartilage tissue engineering as they can enhance the chondrogenic differentiation of mesenchymal stem cells (MSCs) through the presence of active nanoparticles such as graphene oxide (GO). Here, biomimetic hydrogels were developed by cross-linking alginate, gelatin, and chondroitin sulfate biopolymers in the presence of GO as a bioactive filler, with excellent processability for developing bioactive 3D printed scaffolds and for the bioprinting process. A novel bioink based on our hydrogel with embedded human MSCs presented a cell survival rate near 100% after the 3D bioprinting process. The effects of processing…
Towards sustainable, direct printed, organic transistors with biocompatible copolymer gate dielectrics
We have investigated the potential of three dielectric materials to meet the future demands of green dielectrics: Polycaprolactone (PCL) thermoplastic, polyvinyl alcohol (PVA)-carrageenan (CAR) crosslinked biopolymer, and boron nitride nanotubes (BNNTs) as a nano additive in PVA. Metal–insulator–metal (MIM) capacitors and organic thin film transistors (OTFT) were built with bilayer dielectric stacks of PVA-CAR, PVA-PCL, and PVA-BNNT materials to examine their electrical properties. The PVA-CAR layer uses a cyclic freeze thaw process to crosslink PVA and CAR for superior mechanical and electrical properties to either material alone. The PVA-CAR MIM capacitors showed a dielectric constant of 23, which was found…
Chondrogenesis of mesenchymal stromal cells on the 3D printed polycaprolactone/fibrin/decellular cartilage matrix hybrid scaffolds in the presence of piascledine
Nowadays, cartilage tissue engineering (CTE) is considered important due to lack of repair of cartilaginous lesions and the absence of appropriate methods for treatment. In this study, polycaprolactone (PCL) scaffolds were fabricated by three-dimensional (3D) printing and were then coated with fibrin (F) and acellular solubilized extracellular matrix (ECM). After extracting adipose-derived stem cells (ADSCs), 3D-printed scaffolds were characterized and compared to hydrogel groups. After inducing the chondrogenic differentiation in the presence of Piascledine and comparing it with TGF-β3 for 28 days, the expression of genes involved in chondrogenesis (AGG, COLII) and the expression of the hypertrophic gene (COLX) were examined…
The 3D-McMap Guidelines: Three-Dimensional Multicomposite Microsphere Adaptive Printing
Microspheres, synthesized from diverse natural or synthetic polymers, are readily utilized in biomedical tissue engineering to improve the healing of various tissues. Their ability to encapsulate growth factors, therapeutics, and natural biomolecules, which can aid tissue regeneration, makes microspheres invaluable for future clinical therapies. While microsphere-supplemented scaffolds have been investigated, a pure microsphere scaffold with an optimized architecture has been challenging to create via 3D printing methods due to issues that prevent consistent deposition of microsphere-based materials and their ability to maintain the shape of the 3D-printed structure. Utilizing the extrusion printing process, we established a methodology that not only…
3D printed PLGA scaffold with nano-hydroxyapatite carrying linezolid for treatment of infected bone defects
Background Linezolid has been reported to protect against chronic bone and joint infection. In this study, linezolid was loaded into the 3D printed poly (lactic-co-glycolic acid) (PLGA) scaffold with nano-hydroxyapatite (HA) to explore the effect of this composite scaffold on infected bone defect (IBD). Methods PLGA scaffolds were produced using the 3D printing method. Drug release of linezolid was analyzed by elution and high-performance liquid chromatography assay. PLGA, PLGA-HA, and linezolid-loaded PLGA-HA scaffolds, were implanted into the defect site of a rabbit radius defect model. Micro-CT, H&E, and Masson staining, and immunohistochemistry were performed to analyze bone infection and bone…
3D bioprinting of thermosensitive inks based on gelatin, hyaluronic acid, and fibrinogen: reproducibility and role of printing parameters
Thermosensitive inks are considered an attractive option for the 3D bioprinting of different tissue types, yet comprehensive information on their reliability, preparation, and properties remains lacking. This paper addresses this gap by presenting a twofold aim: firstly, characterizing the preparation, rheology, and printing aspects of two inks that have demonstrated success in skeletal muscle tissue engineering both in vitro and in vivo. The first ink is composed of fibrinogen, gelatin, hyaluronic acid, and glycerol, while the second is a sacrificial ink made of gelatin, hyaluronic acid, and glycerol. Secondly, from this analysis, we demonstrate how thermosensitive and multicomponent inks can…
3D printed and smart alginate wound dressings with pH-responsive drug and nanoparticle release
The pH of a wound site can undergo a significant change from its normal range of 5.4–5.6 to a more alkaline environment of 7.2–8.9 after being infected by microorganisms. Therefore, the development of a smart material that can respond to this shift in pH and release antimicrobial agents for effective treatment of wound infections holds great promise for the future of wound care. In the present work, we produced 3D printed alginate wound dressings doped with calcium phosphate nanoparticles (CaP NPs), referred to as alginate-CaP nanocomposites hereafter. The CaP NPs enabled pH-responsive switching of the degradation and drug release of…
Multiscale embedded printing of engineered human tissue and organ equivalents
Creating tissue and organ equivalents with intricate architectures and multiscale functional feature sizes is the first step toward the reconstruction of transplantable human tissues and organs. Existing embedded ink writing approaches are limited by achievable feature sizes ranging from hundreds of microns to tens of millimeters, which hinders their ability to accurately duplicate structures found in various human tissues and organs. In this study, a multiscale embedded printing (MSEP) strategy is developed, in which a stimuli-responsive yield-stress fluid is applied to facilitate the printing process. A dynamic layer height control method is developed to print the cornea with a smooth…
Correlation between Ca Release and Osteoconduction by 3D-Printed Hydroxyapatite-Based Templates
The application of hydroxyapatite (HA)-based templates is quite often seen in bone tissue engineering since that HA is an osteoconductive bioceramic material, which mimics the inorganic component of mineralized tissues. However, the reported osteoconductivity varies in vitro and in vivo, and the levels of calcium (Ca) release most favorable to osteoconduction have yet to be determined. In this study, HA-based templates were fabricated by melt-extrusion 3D-printing and characterized in order to determine a possible correlation between Ca release and osteoconduction. The HA-based templates were blended with poly(lactide-co-trimethylene carbonate) (PLATMC) at three different HA ratios: 10, 30, and 50%. The printability…
Rapid manufacture of sodium polyaluminate electrolyte ceramics for solid state batteries via direct ink writing
Solid-state electrolyte structures using sodium polyaluminate ceramics, have been fabricated for the first time using direct ink writing; a material extrusion-based additive manufacturing process. A series of test samples were prepared using a high solids loading (80 wt%; 51.2 vol%) ceramic paste formulations with suitable rheological characteristics for 3D printing. Following optimum densification via conventional sintering at 1600 °C for 30 min, the additively manufactured electrolyte test samples exhibited an ionic conductivity of σ = 0.14 ± 0.019 S·cm−1 at 300 °C and density of ρ = 3.1 ± 0.02 g·cm−3 (relative density of 95%). These results suggest that direct ink writing of sodium polyaluminates…
Spatial Growth Factor Delivery for 3D Bioprinting of Vascularized Bone with Adipose-Derived Stem/Stromal Cells as a Single Cell Source
Encapsulating multiple growth factors within a scaffold enhances the regenerative capacity of engineered bone grafts through their localization and controls the spatiotemporal release profile. In this study, we bioprinted hybrid bone grafts with an inherent built-in controlled growth factor delivery system, which would contribute to vascularized bone formation using a single stem cell source, human adipose-derived stem/stromal cells (ASCs) in vitro. The strategy was to provide precise control over the ASC-derived osteogenesis and angiogenesis at certain regions of the graft through the activity of spatially positioned microencapsulated BMP-2 and VEGF within the osteogenic and angiogenic bioink during bioprinting. The 3D-bioprinted…
Silk fibroin/polyacrylamide-based tough 3D printing scaffold with strain sensing ability and chondrogenic activity
Cartilage tissue plays an important role in our life activities. The poor self-repair capacity makes cartilage tissue engineering an urgent clinical demand. Among them, the development of tissue engineering scaffolds with both biomimetic features and microenvironment signal sensing abilities could significantly promote the development of cartilage tissue engineering. While most of the reported cartilage scaffolds have no intelligent sensing features. Herein, a ternary composite 3D printing scaffold with both strain sensing ability and desired mechanical property was developed, by using regenerated silk fibroin (RSF) and polyacrylamide (PAM) as main matrixes, and oxidized bacterial cellulose nanofibers (OBC) as filler. Then, the…
Printable Single-Ion Polymer Nanoparticle Electrolytes for Lithium Batteries
New material solutions are searched for the manufacturing and safety of current batteries. Herein, an extrusion printable polymer separator for lithium batteries based on single-ion polymer electrolytes is presented. The polymer electrolytes are based on methacrylic polymeric nanoparticles (NPs) functionalized with a lithium sulfonamide group combined with different organic plasticizers such as sulfolane and carbonates. The synthesis of the polymer NPs is carried out by emulsion copolymerization of methyl methacrylate and lithium sulfonamide methacrylate in the presence of a crosslinker, resulting in particle sizes of less than 30 nm, as shown by electron microscopy. Then polymer electrolytes are prepared by mixing…
Magnetically Actuated GelMA-Based Scaffolds as a Strategy to Generate Complex Bioprinted Tissues
The 3D bioprinting of complex structures has attracted particular attention in recent years and has been explored in several fields, including dentistry, pharmaceutical technology, medical devices, and tissue/organ engineering. However, it still possesses major challenges, such as decreased cell viability due to the prolongation of the printing time, along with difficulties in preserving the print shape. The 4D bioprinting approach, which is based on controlled shape transformation upon stimulation after 3D bioprinting, is a promising innovative method to overcome these difficulties. Herein, the generation of skeletal muscle tissue-like complex structures is demonstrated by 3D bioprinting of GelMA-based C2C12 mouse myoblast-laden…
Sustainable highly stretchable and tough gelatin-alkali lignin hydrogels for scaffolding and 3D printing applications
Hydrogels and bioinks obtained from gelatin (Gel) generally present poor mechanical properties and require a series of time-consuming and stepwise chemical processes to exhibit improved elasticity and resistance to fatigue. Alkali lignin (AL) is an underutilized by-product of the paper and pulp industry. It is a widely available and inexpensive biomaterial that presents enormous potential for high-value applications owing to its ease of chemical modification and unique naturally occurring polyaromatic structure. This work aims to develop different GelAL hydrogel formulations with a single-step method that are innovative and sustainable. The results obtained from the mechanical, rheological, and degradation studies of…
Enhancing CAR Macrophage Efferocytosis Via Surface Engineered Lipid Nanoparticles Targeting LXR Signaling
The removal of dying cells, or efferocytosis, is an indispensable part of resolving inflammation. However, the inflammatory microenvironment of the atherosclerotic plaque frequently affects the biology of both apoptotic cells and resident phagocytes, rendering efferocytosis dysfunctional. To overcome this problem, a chimeric antigen receptor (CAR) macrophage that can target and engulf phagocytosis-resistant apoptotic cells expressing CD47 is developed. In both normal and inflammatory circumstances, CAR macrophages exhibit activity equivalent to antibody blockage. The surface of CAR macrophages is modified with reactive oxygen species (ROS)-responsive therapeutic nanoparticles targeting the liver X receptor pathway to improve their cell effector activities. The combination…
Microstructure and properties of high-entropy-superalloy microlattices fabricated by direct ink writing
Ni-Co-Fe-based high-entropy superalloys (HESAs) are fabricated into microlattices via a three-step process: (i) layer-by-layer extrusion of inks containing elemental powders (Ni, Co, Fe, Cr, Ti) and TiAl3 powders; (ii) sintering to densify and homogenize the struts; (iii) aging to achieve a γ/γ’ microstructure. The struts of the microlattices show a nearly pore-free and fully-homogenized microstructure. Increasing the Ti concentration from 4 at% (Al9Co26Cr7Fe16Ni38Ti4) to 9 at% (Al8Co25Cr7Fe15Ni36Ti9) leads to a significant increase in the volume fraction of strengthening γ’ precipitates, from 51 to 78 %. Furthermore, in the Ti-rich composition, the γ’ precipitates exhibit a sharp-edged cubic morphology with larger…
Tailoring fractal structure via 3D printing to achieve flexible stretchable electrodes based on Ecoflex/CNT/CF
Flexible electrodes are crucial for the widespread application of flexible electronics. Flexible stretchable electrodes are a research hotspot for finding a solution for the inability of flexible electrodes to withstand large deformations. In this study, the suitability of silicone rubber (Ecoflex), carbon nanotube (CNT), and carbon fiber (CF) composite materials for flexible devices and their ratios were evaluated for the first time. 3D-printed electrodes based on fractal structures with tensile insensitivity and high linearity were prepared to achieve integrated stretching of flexible devices. To demonstrate the benefits and impact of fractal structures on electrode performance, we fabricated flexible stretchable electrodes…
3D printing of multi-scale porous β-tricalcium phosphate scaffolds: Mechanical properties and degradation
Processing-structure-property relationships of 3D-printed multi-scale porous ceramics were investigated. Direct ink writing (DIW) of oil-templated colloidal pastes produced hierarchically porous beta-tricalcium phosphate (TCP) scaffolds. Print architecture and microporosity within filaments were varied, mimicking bone structure. The scaffolds exhibited 60–70 % porosity with interconnected macropores 300–700 μm and microporosity within the filaments at the 10 micron-scale. Varying surfactant and oil concentrations created two micro-pore morphologies – bubble-like pores (emulsion) and channel-like pores (capillary suspension). Emulsion scaffolds were stronger, stiffer and more reliable than capillary suspension scaffolds under both compression and bending. Reducing nozzle diameter and inter-filament distance improved strength and stiffness,…
Tuning thermoresponsive properties of carboxymethyl cellulose (CMC)–agarose composite bioinks to fabricate complex 3D constructs for regenerative medicine
3D bioprinting has emerged as a viable tool to fabricate 3D tissue constructs with high precision using various bioinks which offer instantaneous gelation, shape fidelity, and cytocompatibility. Among various bioinks, cellulose is the most abundantly available natural polymer & widely used as bioink for 3D bioprinting applications. To mitigate the demanding crosslinking needs of cellulose, it is frequently chemically modified or blended with other polymers to develop stable hydrogels. In this study, we have developed a thermoresponsive, composite bioink using carboxymethyl cellulose (CMC) and agarose in different ratios (9:1, 8:2, 7:3, 6:4, and 5:5). Among the tested combinations, the 5:5…
3D bioprinted mesenchymal stem cell laden scaffold enhances subcutaneous vascularization for delivery of cell therapy
Subcutaneous delivery of cell therapy is an appealing minimally-invasive strategy for the treatment of various diseases. However, the subdermal site is poorly vascularized making it inadequate for supporting engraftment, viability, and function of exogenous cells. In this study, we developed a 3D bioprinted scaffold composed of alginate/gelatin (Alg/Gel) embedded with mesenchymal stem cells (MSCs) to enhance vascularization and tissue ingrowth in a subcutaneous microenvironment. We identified bio-ink crosslinking conditions that optimally recapitulated the mechanical properties of subcutaneous tissue. We achieved controlled degradation of the Alg/Gel scaffold synchronous with host tissue ingrowth and remodeling. Further, in a rat model, the Alg/Gel…
Manufacture dependent differential biodegradation of 3D printed shape memory polymers
In the field of tissue engineering, 3D printed shape memory polymers (SMPs) are drawing increased interest. Understanding how these 3D printed SMPs degrade is critical for their use in the clinic, as small changes in material properties can significantly change how they behave after in vivo implantation. Degradation of 3D printed acrylated poly(glycerol-dodecanedioate) (APGD) was examined via in vitro hydrolytic, enzymatic, and in vivo subcutaneous implantation assays. Three APGD manufacturing modalities were assessed to determine differences in degradation. Material extrusion samples showed significantly larger mass and volume loss at 2 months, compared to lasercut and vat photopolymerization samples, under both…
Bioprinted scaffolds assembled as synthetic skin grafts by natural hydrogels containing fibroblasts and bioactive agents
Hydrogel skin grafts provide a moist environment and act as a regenerative template to the newly formed tissue. In this study, we developed 3D-bio-printed hydrogels using methacrylated pectin and methacrylated gelatin together with an antibacterial agent (curcumin), a bioactive agent (Vitamin-C) and fibroblast cells. Curcumin release was almost 10 times higher at pH 7.4 than pH 5.0, and it demonstrated antimicrobial affinity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. The developed 3D-bio-printed hydrogels containing cells and bioactive agents demonstrated high cell viability, cell proliferation, and collagen production, and are promising skin graft candidates for the treatment of full-thickness problematic…
3D bioprinting of in vitro porous hepatoma models: establishment, evaluation, and anticancer drug testing
Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted drugs. To address this, this study describes the use of three-dimensional (3D) bioprinting technology to construct a 3D model with human hepatocarcinoma SMMC-7721 cells (3DP-7721) by combining gelatin methacrylate (GelMA) and poly(ethylene oxide) (PEO) as two immiscible aqueous phases to form a bioink and innovatively applying fluorescent carbon quantum dots for long-term tracking of cells. The GelMA (10%, mass fraction) and PEO (1.6%, mass fraction) hydrogel with 3:1 volume ratio offered distinct pore-forming characteristics,…
Influence of Polymeric Microparticle Size and Loading Concentration on 3D Printing Accuracy and Degradation Behavior of Composite Scaffolds
Successful employment of 3D printing for delivery of therapeutic biomolecules requires protection of their bioactivity on exposure to potentially inactivating conditions. Although intermediary encapsulation of the biomolecules in polymeric particulate delivery vehicles is a promising strategy for this objective, the inclusion of such particles in 3D printing formulations may critically impact the accuracy or precision of 3D printed scaffolds relative to their intended designed architectures, as well as the degradation behavior of both the scaffolds and the included particles. The present work aimed to elucidate the effect of poly(d,l-lactic-co-glycolic acid) particle size and loading concentration on material accuracy, machine precision,…
Optimization of 3D Printing Parameters of Polylactic-Co-Glycolic Acid-Based Biodegradable Antibacterial Materials Using Fused Deposition Modeling
A high incidence of ureteral diseases was needed to find better treatments such as implanting ureteral stents. The existing ureteral stents produced a series of complications such as bacterial infection and biofilm after implantation. The fused deposition modeling (FDM) of 3D printing biodegradable antibacterial ureteral stents had gradually become the trend of clinical treatment. But it was necessary to optimize the FDM 3D printing parameters of biodegradable bacteriostatic materials to improve the precision and performance of manufacturing. In this study, polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL), and nanosilver (AgNP) were mixed by the physical blending method, and the 3D printing parameters…
Polysiloxane Inks for Multimaterial 3d Printing of High-Permittivity Dielectric Elastomers
Dielectric elastomer transducers (DET) are promising candidates for electrically-driven soft robotics. However, the high viscosity and low yield stress of DET formulations prohibit 3D printing, the most common manufacturing method for designer soft actuators. DET inks optimized for direct ink writing (DIW) produce elastomers with high stiffness and mechanical losses, diminishing the utility of DET actuators. To address the antagonistic nature of processing and performance constraints, principles of capillary suspensions are used to engineer DIW DET inks. By blending two immiscible polysiloxane liquids with a filler, a capillary ink suspension is obtained, in which the ink rheology can be tuned…
3D Printing Process Research and Performance Tests on Sodium Alginate-Xanthan Gum-Hydroxyapatite Hybridcartilage Regenerative Scaffolds
Cartilage injury is a common occurrence in the modern world. Compared with traditional treatment methods, bio-3D printing technology features better utility in the field of cartilage repair and regeneration, but still faces great challenges. For example, there is currently no means to generate blood vessels inside the scaffolds, and there remains the question of how to improve the biocompatibility of the generated scaffolds, all of which limit the application of bio-3D printing technology in this area. The main objective of this article was to prepare sodium alginate-xanthan gum-hydroxyapatite (SA-XG-HA) porous cartilage scaffolds that can naturally degrade in the human body…
A Polymer-Based Chemiresistive Gas Sensor for Selective Detection of Ammonia Gas
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…
3D bioactive ionic liquid-based architectures: An anti-inflammatory approach for early-stage osteoarthritis
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…