3D Bioplotter Research Papers

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…

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…

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…

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,…

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°,…

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…

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)…

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…

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…

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…

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…

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…

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…

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…

Repairing massive rotator cuff tendon defects remains a challenge due to the high retear rate after surgical intervention. 3D printing has emerged as a promising technique that enables the fabrication of engineered tissues with heterogeneous structures and mechanical properties, as well as controllable microenvironments for tendon regeneration. In this study, we developed a new strategy for rotator cuff tendon repair by combining a 3D printed scaffold of polylactic-co-glycolic acid (PLGA) with cell-laden collagen-fibrin hydrogels. We designed and fabricated two types of scaffolds: one featuring a separate layer-by-layer structure and another with a tri-layered structure as a whole. Uniaxial tensile tests…

Bone scaffold for aiding bone regeneration in large bone defects should have following ideal characteristics; biocompatibility, biodegradability, bio-activity, high porous and interconnected-pore architecture, as well as, mechanical characteristics similar to the cortical bone for supporting loads. 3D printed Sr–HT (Sr–Ca2ZnSi2O7)–gahnite scaffold with hexagonal pore structure is an interesting bone scaffold meeting most of these ideal features. To explain, biocompatible, osteoinductive, and osteoconductive properties as well as unique high compressive strength are obtained from Sr–HT–gahnite, glass-ceramic, material. With hexagonal pore structure, the scaffold has compressive strength comparable to cortical bone balancing with high porosity and large pore size. Nonetheless, the scaffold…

Sutures are one of the most widely used medical devices with employment in over 12 million procedures per year globally.1 Yet, the ideal suture material does not exist. Over the years scientists and surgeons alike have set out to find a suture material that is biocompatible, easy to handle, does not cause unnecessary tissue damage and creates an optimal environment for wound healing.2 This has led to the discovery of numerous suture materials ranging from silk and catgut in the early 1800s to synthetic polymers such as polylactic acid and polyglycolide that are currently in use.3 Sutures on the market…

The use of composite materials, processed as 3D tissue-like scaffolds, has been widely investigated as a promising strategy for bone tissue engineering applications. Also, additive manufacturing technologies such as fused deposition modelling (FDM) have greatly contributed to the manufacture of patient-specific scaffolds with predefined pore structures and intricate geometries. However, conventional FDM techniques require the use of materials exclusively in the form of filaments, which in order to produce composite scaffolds lead to additional costs for the fabrication of precursor filaments as well as multi-step production methods. In this study, we propose the use of an advantageous extrusion-based printing technology,…

With the increasing applications of 3D printing technology in biomedical field, the composition or additives of the related materials has become critical for the next development. In the current study, we have prepared 3D printed polycaprolactone-hydroxyapatite (PCL-HA) porous scaffolds with loaded heparan sulfate (HS), in order to reveal the reparative effect of different concentrations of HS on the healing of bone defects. As a result, the scaffold itself showed sound compression resistance, air porosity and good biocompatibility. From both in vitro and in vivo experiments, the scaffold with low concentration of HS led to positive effects in promoting osteoblast maturation…

Thermal management is of importance to microelectronic industry. Owing to both excellent thermal conduction and electrical insulation, hexagonal boron nitride (BN) platelets are the widely-used thermal conductive fillers in polymers. Adding high content of BN can endow polymers high thermal conductivity, but in most cases, destroy the flexibility, failure strength as well as processability of the polymers significantly. Here, we report a multi-material 3D printing technique to prepare high thermal conductive epoxy based composites, by which BN platelets were assembled together in heat-conducting phase to form the dense, continuous thermal pathway. The BN platelets show excellent alignment along printing direction…

Reproducing the advanced complexity of native tissue by means of the 3D multi-functional construct is a promising tissue engineering approach to osteochondral tissue regeneration. In this study, we present a porous 3D construct composed of three zones responsible for the regeneration of non-calcified cartilage, calcified cartilage and subchondral bone. These three zones of the hybrid were composed of modified biopolymers: (i) alginate (Alg) reinforced by short polylactide (PLA) fibres, (ii) alginate and gelatine methacrylate (GelMA) combined with ß-tricalcium phosphate particles (TCP), (iii) 3D printed polycaprolactone scaffold subsequently modified with the use of an innovative solvent treatment method based on acetone…

A 3D bioprinted pseudo-bone drug delivery scaffold was fabricated to display matrix strength, matrix resilience, as well as porous morphology of healthy human bone. Computer-aided design (CAD) software was employed for developing the 3D bioprinted scaffold. Further optimization of the scaffold was undertaken using MATLAB® software and artificial neural networks (ANN). Polymers employed for formulating the 3D scaffold comprised of polypropylene fumarate (PPF), free radical polymerized polyethylene glycol- polycaprolactone (PEG-PCL-PEG), and pluronic (PF127). Simvastatin was incorporated into the 3D bioprinted scaffolds to further promote bone healing and repair properties. The 3D bioprinted scaffold was characterized for its chemical, morphological, mechanical,…

The main aim of this paper is to achieve the suitable SA-GEL (sodium alginate and gelatin) porous cartilage scaffold by 3D printing technology with optimal prediction parameters. Firstly, the characteristics of SA-GEL were analyzed, the influence of calcium chloride on the gel was explored, and the optimal cross-linking concentration and gelation temperature were determined. Secondly, a prediction model of the extrusion line width of SA-GEL was established, in which the printing pressure, the moving speed of the needle and the fiber interval were the important parameters affecting the printing performance of the SA-GEL composite material. Thirdly, the SA-GEL composite scaffolds…

Bone defects are common and, in many cases, challenging to treat. Tissue engineering is an interdisciplinary approach with promising potential for treating bone defects. Within tissue engineering, three-dimensional (3D) printing strategies have emerged as potent tools for scaffold fabrication. However, reproducibility and quality control are critical aspects limiting the translation of 3D printed scaffolds to clinical use, which remain to be addressed. To elucidate the factors that yield to the generation of defects in bioprinting and to achieve reproducible biomaterial printing, the objective of this article is to frame a systematic approach for optimizing and validating 3D printing of poly(caprolactone)…

In this work, we describe a new 3D printing methodology for the fabrication of multimaterial scaffolds involving the combination of thermoplastic extrusion and low temperature extrusion of bioinks. A fiber engraving technique was used to create a groove on the surface of a thermoplastic printed fiber using a commercial 3D printer and a low viscosity bioink was deposited into this groove. In contrast to traditional extrusion bioinks that rely on increased viscosity to prevent lateral spreading, this groove creates a defined space for bioink deposition. By physically constraining bioink spreading, a broader range of viscosities can be used. As proof-of-concept,…

As scaffolds approach dimensions that are of clinical relevance, mechanical integrity and distribution becomes an important factor to the overall success of the implant. Hydrogels often lack the structural integrity and mechanical properties for use in vivo or handling. The inclusion of a structural support during the printing process, referred to as hybrid printing, allows the implant to retain structure and protect cells during maturation without needing to compromise its biological performance. In this study, scaffolds for the purpose of auricular cartilage reconstruction were evaluated via a hybrid printing approach using methacrylated Gelatin (GelMA) and Hyaluronic acid (HAMA) as the…

The meniscus has critical functions in the knee joint kinematics and homeostasis. Injuries of the meniscus are frequent, and the lack of a functional meniscus between the femur and tibial plateau can cause articular cartilage degeneration leading to osteoarthritis development and progression. Regeneration of meniscus tissue has outstanding challenges to be addressed. In the current study, novel Entrapped in cage (EiC) scaffolds of 3D-printed polycaprolactone (PCL) and porous silk fibroin were proposed for meniscus tissue engineering. As confirmed by micro-structural analysis the entrapment of silk fibroin was successful, and all scaffolds had excellent interconnectivity (≥99%). The EiC scaffolds had more…

The ability of boronic acids (BAs) to reversibly bind diols, such as sugars, has been widely studied in recent years. In solution, through the incorporation of additional fluorophores, the BA–sugar interaction can be monitored by changes in fluorescence. Ultimately, a practical realization of this technology requires a transition from solution‐based methodologies. Herein, the first example of 3D‐printed sugar‐sensing hydrogels, achieved through the incorporation of a BA–fluorophore pair in a gelatin methacrylamide‐based matrix is presented. Through optimization of monomeric cocktails, it is possible to use extrusion printing to generate structured porous hydrogels which show a measurable and reproducible linear fluorescence response…

Objectives This study investigates the design, workflow, and manufacture of highly porous, resorbable additively manufactured, 3‐dimensional (3D) custom scaffolds for the regeneration of large volume alveolar bone defects. Materials and Methods Computed tomography (CT) scans of 5 posterior mandibular vertical bone defects were obtained. Surface masks (3D surface contours) of the recipient site were first isolated using a contrast threshold, transformed into 3D objects, and used to guide the formation of custom implant template models. To determine model accuracy and fit, the gap and overlap between the patient geometry models and the idealized template 3D models were quantified. Models were…

Engineering substantia propria (or stroma of cornea) that mimics the function and anatomy of natural tissue is vital for in vitro modelling and in vivo regeneration. There are, however, few examples of bioengineered biomimetic corneal stroma. Here we describe the construction of an orthogonally oriented 3D corneal stroma model (3D-CSM) using pure electro-compacted collagen (EC). EC films comprise aligned collagen fibrils and support primary human corneal stromal cells (hCSCs). Cell-laden constructs are analogous to the anatomical structure of native human cornea. The hCSCs are guided by the topographical cues provided by the aligned collagen fibrils of the EC films. Importantly,…

Articular cartilage disease can cause pain, mobility issues, and disability. Clinical treatment includes microfracture, subchondral drilling, graft transplantation, and eventually total joint replacement implant. However, these approaches can present specific problems and limitations. Three-dimensional (3D) bioprinted scaffolds utilising hydrogels can provide a suitable 3D biochemical and biophysical environment, thus is a promising strategy for cartilage tissue therapy and regeneration. This study aims to develop a new hydrogel bioink with improved printability, mechanical, and biological properties for cartilage regeneration. A photocrosslinkable methacrylated methylcellulose (MCMA) and gelatin (GelMA) hybrid bioink is evaluated in this preliminary investigation. The results showed that methylcellulose and…

Background Biological composite scaffolds are increasingly being used in abdominal wall reconstruction but still have certain shortcomings. The present study describes here a novel three-dimensional (3D) scaffold fabricated by combining 3D printing (3DP) and electrospinning (ESP). Methods Biological composite scaffolds are composed of integrated 3DP interconnected macrofiber and random ESP microfiber networks. The 3DP scaffold retains intact 3D architecture and mechanical properties, while the ESP network serves as a cell entrapment system at the extracellular matrix (ECM) scale. Biological composite scaffolds are implanted in a defective rat abdominal wall to detect if it could induce early vascularization and reconstruction of…

Improving bone regeneration is one of the most pressing problems facing bone tissue engineering (BTE) which can be tackled by incorporating different biomaterials into the fabrication of the scaffolds. The present study aims to apply the 3D-printing and freeze-drying methods to design an ideal scaffold for improving the osteogenic capacity of Dental pulp stem cells (DPSCs). To achieve this purpose, hybrid constructs consisted of 3D-printed Beta-tricalcium phosphate (β-TCP)-based scaffolds filled with freeze-dried gelatin/reduced graphene oxide-Magnesium-Arginine (GRMA) matrix were fabricated through a novel green method. The effect of different concentrations of Reduced graphene oxide-Magnesium-Arginine (RMA) (0, 0.25% and 0.75%wt) on the…

Silicon-substituted hydroxyapatite (SiHA) macroporous scaffolds have been prepared by robocasting. In order to optimize their bone regeneration properties, we have manufactured these scaffolds presenting different microstructures: nanocrystalline and crystalline. Moreover, their surfaces have been decorated with vascular endothelial growth factor (VEGF) to evaluate the potential coupling between vascularization and bone regeneration. In vitro cell culture tests evidence that nanocrystalline SiHA hinders pre-osteblast proliferation, whereas the presence of VEGF enhances the biological functions of both endothelial cells and pre-osteoblasts. The bone regeneration capability has been evaluated using an osteoporotic sheep model. In vivo observations strongly correlate with in vitro cell culture…

As 3D printing becomes more common and the technique is used to build culture platforms, it is imperative to develop surface treatments for specific responses. The advantages of aminating and oxidizing polystyrene (PS) for human mesenchymal stem cell (hMSC) proliferation and osteogenic differentiation are investigated. We find that ammonia (NH3) plasma incorporates amines while oxygen plasma adds carbonyl and carboxylate groups. Across 2D, 3D, and 3D dynamic culture, we find that the NH3- treated surfaces encouraged cell proliferation. Our results show that the NH3-treated scaffold was the only treatment allowing dynamic proliferation of hMSCs with little evidence of osteogenic differentiation.…

In this study of three-dimensional (3D) printed composite β-tricalcium phosphate (β-TCP)-/hydroxyapatite/poly(ɛ-caprolactone)-based constructs, the effects of vertical compositional ceramic gradients and architectural porosity gradients on the osteogenic differentiation of rabbit bone marrow-derived mesenchymal stem cells (MSCs) were investigated. Specifically, three different concentrations of β-TCP (0, 10, and 20 wt%) and three different porosities (33% ± 4%, 50% ± 4%, and 65% ± 3%) were examined to elucidate the contributions of chemical and physical gradients on the biochemical behavior of MSCs and the mineralized matrix production within a 3D culture system. By delaminating the constructs at the gradient transition point, the spatial separation of cellular phenotypes could be specifically…

Cellulose is an attractive material resource for the fabrication of sustainable functional products, but its processing into structures with complex architecture and high cellulose content remains challenging. Such limitation has prevented cellulose‐based synthetic materials from reaching the level of structural control and mechanical properties observed in their biological counterparts, such as wood and plant tissues. To address this issue, a simple approach is reported to manufacture complex‐shaped cellulose‐based composites, in which the shaping capabilities of 3D printing technologies are combined with a wet densification process that increases the concentration of cellulose in the final printed material. Densification is achieved by…

The implementation of tailor-made dosage forms is currently one of the biggest challenges in the health sector. Over the last years, different approaches have been introduced to provide an individual and precise dispensing of the appropriate dose of an active pharmaceutical ingredient (API). A more recent approach, which has been intensively researched in the last years, is 3D-printing of medicines. The aim of this work was to develop printing formulations free of organic solvents for a pressure-assisted microsyringe printing method (PAM), which should also be printable over several days of storage. Furthermore, the printed dosage forms should provide a sustained…

Background The anatomical properties of the enthesis of the rotator cuff are hardly regained during the process of healing. The tendon-to-bone interface is normally replaced by fibrovascular tissue instead of interposition fibrocartilage, which impairs biomechanics in the shoulder and causes dysfunction. Tissue engineering offers a promising strategy to regenerate a biomimetic interface. Here, we report heterogeneous tendon-to-bone interface engineering based on a 3D-printed multiphasic scaffold. Methods A multiphasic poly(ε-caprolactone) (PCL)–PCL/tricalcium phosphate–PCL/tricalcium phosphate porous scaffold was manufactured using 3D printing technology. The three phases of the scaffold were designed to mimic the graded tissue regions in the tendon-to-bone interface—tendon, fibrocartilage, and…

Synthetic polycaprolactone (PCL) was modified with various concentrations of gelatin (GL) to enhance its physical properties and biological activity for bone regeneration. A novel trisolvent mixture has been used to mix PCL and GL that were fabricated as scaffolds using 3D plotting. The scaffolds were characterized for their mechanical properties, hydrophilicity and swelling ability. In addition, the structure and morphology of the printed scaffolds were analyzed by Fourier-Transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and microcomputed tomography (μCT). Attachment, proliferation and osteogenic differentiation of rat bone marrow stromal cells (BMSC) cultured on the printed scaffolds were…

Conventional tough hydrogels offer enhanced mechanical properties and high toughness. Their application scope however is limited by their lack of processability. Here, a new porous tough hydrogel system is introduced which is processable via gel fiber spinning and 3D printing. The tough hydrogels are produced by rehydrating processable organogels developed by induced phase separation between two linear polymer chains capable of intermolecular hydrogen bonding. Through a slow sol–gel phase separation, highly porous gel networks made of hydrogen bonded polymer chains is formed. These organogels can be easily transformed to 3D printed multimaterial constructs or gel fibers, and after rehydration produce…

Scaffolds based on bioconjugated hydrogels are attractive for tissue engineering because they can partly mimic human tissue characteristics. For example, they can further increase their bioactivity with cells. However, most of the hydrogels present problems related to their processability, consequently limiting their use in 3D printing to produce tailor-made scaffolds. The goal of this work is to develop bioconjugated hydrogel nanocomposite inks for 3D printed scaffold fabrication through a micro-extrusion process having improved both biocompatibility and processability. The hydrogel is based on a photocrosslinkable alginate bioconjugated with both gelatin and chondroitin sulfate in order to mimic the cartilage extracellular matrix,…

Various 3D printing techniques currently use degradable polymers such as aliphatic polyesters to create well-defined scaffolds. Even though degradable polymers are influenced by the printing process, and this subsequently affects the mechanical properties and degradation profile, degradation of the polymer during the process is not often considered. Degradable scaffolds are today printed and cell–material interactions evaluated without considering the fact that the polymer change while printing the scaffold. Our methodology herein was to vary the printing parameters such as temperature, pressure, and speed to define the relationship between printability, polymer microstructure, composition, degradation profile during the process, and rheological behavior.…

We investigate the key 3D bioplotting processing parameters, including needle diameter and dispensing pressure, on the shear rates, shear stresses, pressure drops, and swell ratios of extruded miscible polycaprolactone (PCL) blends having a range of viscosities. Assuming simple capillary flow, we construct flow curves and we estimate that the shear stresses inside the needle of the bioplotter range from 2500 to 20,000 Pa and the corresponding shear rates from 2 to 25 s−1, depending upon the viscosity of the blend. We further identify relevant dimensionless numbers that reflect the material rheological properties and processing conditions; these include the capillary number…

Dynamic hydrogels are prepared by either dynamic covalent bonds or supramolecular chemistry. Herein, we develop a dynamic hydrogel by combining both dynamic covalent bonds and supramolecular chemistry that exhibits environmentally adaptive self-healing and pH-tuning properties. To do so, we prepared a gelatin–nanopolysaccharide mixed hydrogel containing pyrogallol/catechol groups and trivalent metal ions. The as-prepared hydrogels are able to heal damage inflicted on them under acidic (pH 3 and 6), neutral (pH 7), and basic (pH 9) environments. The mechanism of healing at acidic and neutral pHs is dominated by coordination bonds between pyrogallol/catechol groups of tannic acid and ferric ions, whilst…

In order to compare the influence of the manufacturing methods on the property of silicone samples, the latticed structure of sample are designed, the silicone material is prepared and the silicone sample are produced by 3D printing and injection molding respectively. Four performance indexes of latticed silicone parts including the error of line width, the error of quality, tensile strength at break and elongation at break are proposed and measured. A fuzzy comprehensive evaluation system for evaluating the optimal forming method of the parts is provided. The performance indexes are used as evaluation factors, and the importance degree of the…

Extrusion-based bioprinting of hydrogel scaffolds is challenging due to printing-related issues, such as the lack of capability to precisely print or deposit hydrogels onto three-dimensional (3D) scaffolds as designed. Printability is an index to measure the difference between the designed and fabricated scaffold in the printing process, which, however, is still under-explored. While studies have been reported on printing hydrogel scaffolds from one or more hydrogels, there is limited knowledge on the printability of hydrogels and their printing processes. This paper presented our study on the printability of 3D printed hydrogel scaffolds, with a focus on identifying the influence of…

Osteoarthritis is a degenerative joint disease that limits mobility of the affected joint due to the degradation of articular cartilage and subchondral bone. The limited regenerative capacity of cartilage presents significant challenges when attempting to repair or reverse the effects of cartilage degradation. Tissue engineered medical products are a promising alternative to treat osteochondral degeneration due to their potential to integrate into the patient’s existing tissue. The goal of this study was to create a scaffold that would induce site‐specific osteogenic and chondrogenic differentiation of human adipose‐derived stem cells (hASC) to generate a full osteochondral implant. Scaffolds were fabricated using…

There is a growing interest in developing 3D porous scaffolds with tunable architectures for bone tissue engineering. Surface topography has been shown to control stem cell behavior including differentiation. In this study, we printed 3D porous scaffolds with wavy or linear patterns to investigate the effect of wavy scaffold architecture on human mesenchymal stem cell (hMSC) osteogenesis. Five distinct wavy scaffolds were designed using sinusoidal waveforms with varying wavelengths and amplitudes, and orthogonal scaffolds were designed using linear patterns. We found that hMSCs attached to wavy patterns, spread by taking the shape of the curvatures presented by the wavy patterns,…

The residual of malignant tumor cells and lack of bone‐tissue integration are the two critical concerns of bone‐tumor recurrence and surgical failure. In this work, the rational integration of 2D Ti3C2 MXene is reported with 3D‐printing bioactive glass (BG) scaffolds for achieving concurrent bone‐tumor killing by photonic hyperthermia and bone‐tissue regeneration by bioactive scaffolds. The designed composite scaffolds take the unique feature of high photothermal conversion of integrated 2D Ti3C2 MXene for inducing bone‐tumor ablation by near infrared‐triggered photothermal hyperthermia, which has achieved the complete tumor eradication on in vivo bone‐tumor xenografts. Importantly, the rational integration of 2D Ti3C2 MXene…

Two major challenges of 3D bioprinting are the retention of structural fidelity and efficient endothelialization for tissue vascularization. Both of these issues are addressed by introducing a versatile 3D bioprinting strategy, in which a templating bioink is deposited layer‐by‐layer alongside a matrix bioink to establish void‐free multimaterial structures. After crosslinking the matrix phase, the templating phase is sacrificed to create a well‐defined 3D network of interconnected tubular channels. This void‐free 3D printing (VF‐3DP) approach circumvents the traditional concerns of structural collapse, deformation, and oxygen inhibition, moreover, it can be readily used to print materials that are widely considered “unprintable.” By…

Tissue engineered heart valves (TEHV) provide several advantages over currently available aortic heart valve replacements. Bioprinting provides a patient-specific means of developing a TEHV scaffold from imaging data, and the capability to embed the patient’s own cells within the scaffold. In this work we investigated the remodeling capacity of a collagen-based bio-ink by implanting bioprinted disks in a rat subcutaneous model for 2, 4 and 12 weeks and evaluating the mechanical response using biaxial testing and subsequent finite element (FE) modeling. Samples explanted after 2 and 4 weeks showed inferior mechanical properties compared to native tissues while 12 week explants…

Tissue survival in regenerative tissue engineering requires rapid vascularization, which is influenced by scaffold material and seeded cell selection. Poly-l-lactide-co-glycolide (PLGA) and beta-tricalcium phosphate (β-TCP) are well-established biomaterials with angiogenic effects because of their material properties. Given the importance of the seeded cell type as a co-factor for vascularization, mesenchymal stem cells (MSCs) are known to have high angiogenic potential. We hypothesized that PLGA and β-TCP scaffolds seeded with MSCs would effectively induce a potent angiogenic response. Therefore, we studied the angiogenic effects after implanting PLGA and β-TCP scaffolds seeded with isogeneic MSCs in vivo. Fifty-six BALB/c mice were equally…

Three dimensional (3D) printing has been used to fabricate bioceramic scaffolds for treating the tumor-related defects in recent years, but the fabrication process and the introduction of anti-tumor agents are still challenging. In this study, porous free carbon-embedding larnite (larnite/C) scaffolds have been successfully fabricated by 3D printing of the silicone resin loaded with CaCO3 filler and high temperature treatment under an inert atmosphere. The fabricated larnite/C scaffolds had uniform interconnected macropores (ca. 400 μm), and exhibited excellent photothermal effect, which was able to kill human osteosarcoma cells (MNNG/HOS) and inhibit the tumor growth in nude mice. Moreover, the larnite/C scaffolds…