3D Bioplotter Research Papers

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Remote triggering of TGF-β/Smad2/3 signaling in human adipose stem cells laden on magnetic scaffolds synergistically promotes tenogenic commitmen

Acta Biomaterialia 2020 Volume 113, Pages 488-500

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…

Kinetics of alloy formation and densification in Fe-Ni-Mo microfilaments extruded from oxide- or metal-powder inks

Acta Materialia 2020 Volume 193, Pages 51-60

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

Shape memory epoxy composites with high mechanical performance manufactured by multi-material direct ink writing

Composites Part A: Applied Science and Manufacturing 2020 Volume 135, Article 105903

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…

3D bioprinted multiscale composite scaffolds based on gelatin methacryloyl (GelMA)/chitosan microspheres as a modular bioink for enhancing 3D neurite outgrowth and elongation

Journal of Colloid and Interface Science 2020 Volume 574, Pages 162-173

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 high thermal cycling stability created by Ag infiltration of 3D ink-extruded SnO2 microlattices

Applied Materials Today 2020 Volume 21, Article 100794

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…

3D printing of clay for decorative architectural applications: Effect of solids volume fraction on rheology and printability

Additive Manufacturing 2020 Volume 35, Article 101335

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…

3D-Printing with precise layer-wise dose adjustments for paediatric use via pressure-assisted microsyringe printing

European Journal of Pharmaceutics and Biopharmaceutics 2020 Volume 157, Pages 59-65

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

Microfabricated and 3-D printed electroconductive hydrogels of PEDOT:PSS and their application in bioelectronics

Biosensors and Bioelectronics 2020 Volume 168, Article 112568

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°,…

Engineering hiPSC-CM and hiPSC-EC laden 3D nanofibrous splenic hydrogel for improving cardiac function through revascularization and remuscularization in infarcted heart

Bioactive Materials 2021 Volume 6, Issue 12, Pages 4415-4429

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

Highly Conductive Silicone Elastomers via Environment-Friendly Swelling and In Situ Synthesis of Silver Nanoparticles

Advanced Materials Interfaces 2021 Volume 8, Issue 9, Article 2100137

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

The effect of induced membranes combined with enhanced bone marrow and 3D PLA-HA on repairing long bone defects in vivo

Journal of Tissue Engineering and Regenerative Medicine 2020 Volume 14, Issue 10, Pages 1403-1414

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…

Paper-Based, Chemiresistive Sensor for Hydrogen Peroxide Detection

Advanced Materials Technologies 2021 Volume 6, Issue 4, Article 2001148

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

Experimental investigation of esophageal reconstruction with electrospun polyurethane nanofiber and 3D printing polycaprolactone scaffolds using a rat model

Head & Neck 2021 Volume 43, Issue 3, Pages 833-848

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

The performance of 3D bioscaffolding based on a human periodontal ligament stem cell printing technique

Journal of Biomedical Materials Research Part A 2021 Volume 109, Issue 7, Pages 1209-1219

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

Mechanical Properties Tailoring of 3D Printed Photoresponsive Nanocellulose Composites

Advanced Functional Materials 2020 Volume 30, Issue 35, Article 2002914

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…

Freeform 3D printing using a continuous viscoelastic supporting matrix

Biofabrication 2020 Volume 12, Number 3, Article 035017

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…

Digestion degree is a key factor to regulate the printability of pure tendon decellularized extracellular matrix bio-ink in extrusion-based 3D cell printing

Biofabrication 2020 Volume 12, Number 4, Article 045011

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)…

Dual-crosslinked 3D printed gelatin scaffolds with potential for temporomandibular joint cartilage regeneration

Biomedical Materials 2021 Volume 16, Number 3, Article 035026

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

Hierarchical patterning via dynamic sacrificial printing of stimuli-responsive hydrogels

Biofabrication 2020 Volume 12, Number 3, Article 035007

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…

In vitro characterization of hierarchical 3D scaffolds produced by combining additive manufacturing and thermally induced phase separation

Journal of Biomaterials Science, Polymer Edition 2021 Volume 32, Issue 4, Pages 454-476

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

A powerful combination in designing polymeric scaffolds: 3D bioprinting and cryogelation

International Journal of Polymeric Materials and Polymeric Biomaterials 2020

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…

Edible meta-atoms

arXiv 2021 Condensed Matter > Soft Condensed Matter, Article 2103.14909

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

Control Delivery of Multiple Growth Factors to Actively Steer Differentiation and Extracellular Matrix Protein Production

Advanced Biology 2021 Volume 5, Issue 4, Article 2000205

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

3D printed silk-gelatin hydrogel scaffold with different porous structure and cell seeding strategy for cartilage regeneration

Bioactive Materials 2021 Volume 6, Issue 10, Pages 3396-3410

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

Bioprinting and In Vitro Characterization of an Egg White-Based Cardiac Patch for Myocardial Infarction

University of Saskatchewan 2021 Dissertation
Y. Delkash

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

3D porous Ti6Al4V-beta-tricalcium phosphate scaffolds directly fabricated by additive manufacturing

Acta Biomaterialia 2021 Volume 126, Pages 496-510

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

Interfacial Piezoelectric Polarization Locking in Printable Ti3C2Tx MXene-Fluoropolymer Composites

arXiv 2021 Condensed Matter > Materials Science, Article 2101.12211

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

3D printing of shape-morphing and antibacterial anisotropic nanocellulose hydrogels

Carbohydrate Polymers 2021 Volume 259, Article 117716

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

3D printing PCL/nHA bone scaffolds: exploring the influence of material synthesis techniques

Biomaterials Research 2021 Volume 25, Article number 3

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

A 3D printed graphene electrode device for enhanced and scalable stem cell culture, osteoinduction and tissue building

Materials & Design 2021 Volume 201, Article 109473

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

3D bioprinting dermal-like structures using species-specific ulvan

Biomaterials Science 2021 Volume 9, Pages 2424-2438

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

3D-printable zwitterionic nano-composite hydrogel system for biomedical applications

Journal of Tissue Engineering 2020 Volume 11, Pages 1-11

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…

The Effect Of Multi-Material Printing To Flexibility

Acta Tecnología 2020 Volume 6, Pages 85-88

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.

Three-dimensional biofabrication of an aragonite-enriched self-hardening bone graft substitute and assessment of its osteogenicity in vitro and in vivo

Biomaterials Translational 2020 Volume 1, Issue 1, Pages 69-81

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…

Cryo‐3D Printing of Hierarchically Porous Polyhydroxymethylene Scaffolds for Hard Tissue Regeneration

Macromolecular Materials and Engineering 2021 Volume 306, Issue 1, Article 2000541

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

Osteogenic differentiation of adipose-derived mesenchymal stem cells using 3D-Printed PDLLA/ β-TCP nanocomposite scaffolds

Bioprinting 2021 Volume 21, Article e00117

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

Breast cancer patient‐derived scaffolds as a tool to monitor chemotherapy responses in human tumor microenvironments

Journal of Cellular Physiology 2021 Volume 236, Issue 6, Pages 4709-4724

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

Fabrication and characterization of mechanically competent 3D printed polycaprolactone-reduced graphene oxide scaffolds

Scientific Reports 2020 Volume 10, Article number 22210

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…

Development of novel chitosan / guar gum inks for extrusion-based 3D bioprinting: Process, printability and properties

Bioprinting 2021 Volume 21, Article e00122

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

A tri-component knee plug for the 3rd generation of autologous chondrocyte implantation

Scientific Reports 2020 Volume 10, Article number: 17048

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…

Direct Ink Writing of Fully Bio-Based Liquid Crystalline Lignin/ Hydroxypropyl Cellulose Aqueous Inks: Optimization of Formulations and Printing Parameters

ACS Applied Bio Materials 2020 Volume 3, Issue 10, Pages 6897–6907

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…

Three dimensional printed bioglass/gelatin/alginate composite scaffolds with promoted mechanical strength, biomineralization, cell responses and osteogenesis

Journal of Materials Science: Materials in Medicine 2020 Volume 31, Article 77

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…

Inclusion of a 3D-printed Hyperelastic Bone mesh improves mechanical and osteogenic performance of a mineralized collagen scaffold

Acta Biomaterialia 2021 Volume 121, Pages 224–236

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

Benefits of Polydopamine as Particle/Matrix Interface in Polylactide/PD-BaSO4 Scaffolds

International Journal of Molecular Sciences 2020 Volume 21, Issue 15, Article 5480

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…

Engineering 3D degradable, pliable scaffolds toward adipose tissue regeneration; optimized printability, simulations and surface modification

Journal of Tissue Engineering 2020 Volume 11, Pages 1-17

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…

Expanding and optimizing 3D bioprinting capabilities using complementary network bioinks

Science Advances 2020 Volume 6, Article eabc5529

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)….

Towards 3D Multi-Layer Scaffolds for Periodontal Tissue Engineering Applications: Addressing Manufacturing and Architectural Challenges

Polymers 2020 Volume 12, Issue 10, Article 2233

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…

Additive manufacturing of silica aerogels

Nature 2020 Volume 584, Pages 387–392

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…

Influence of Geometry and Architecture on the In Vivo Success of 3D-Printed Scaffolds for Spinal Fusion

Tissue Engineering Part A 2021 Volume 27, Issue 1-2, Pages 26-36

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

Topology-Optimized 4D Printing of a Soft Actuator

Acta Mechanica Solida Sinica 2020 Volume 33, Pages 418–430

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….

Endothelial/Mesenchymal Stem Cell Crosstalk within Bioprinted Cocultures

Tissue Engineering: Part A 2020 Volume: 26 Issue 5-6, Pages 339-349

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…

3D-Printed Ceramic-Demineralized Bone Matrix Hyperelastic Bone Composite Scaffolds for Spinal Fusion

Tissue Engineering: Part A 2020 Volume: 26 Issue 3-4, Pages 157-166

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…

Bioprinting of an osteocyte network for biomimetic mineralization

Biofabrication 2020 Volume 12, Number 4, Article 045013

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…

Polyhydroxymethylenes as Multifunctional High Molecular Weight Sugar Alcohols Tailored for 3D Printing and Medical Applications

Macromolecular Chemistry and Physics 2020 Volume 221, Issue 15, Article 2000132

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…

A novel vehicle-like drug delivery 3D printing scaffold and its applications for a rat femoral bone repairing in vitro and in vivo

International Journal of Biological Sciences 2020 Volume 16, Issue 11, Pages 1821-1832

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…

Cellular, Mineralized, and Programmable Cellulose Composites Fabricated by 3D Printing of Aqueous Pastes Derived from Paper Wastes and Microfibrillated Cellulose

Macromolecular Materials and Engineering 2020 Volume 305, Issue 4, Article 1900740

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…

Functional reconstruction of injured corpus cavernosa using 3D-printed hydrogel scaffolds seeded with HIF-1α-expressing stem cells

Nature Communications 2020 Volume 11, Article 2687

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…

Fabrication of forsterite scaffolds with photothermal-induced antibacterial activity by 3D printing and polymer-derived ceramics strategy

Ceramics International 2020 Volume 46, Issue 9, Pages 13607-13614
T. Zhu M. Zhu Y. Zhu

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….

Bioprinting and in vitro characterization of alginate dialdehyde–gelatin hydrogel bio-ink

Bio-Design and Manufacturing 2020 Volume 3, Pages 48–59

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…

Experiments on Flexible Filaments in Air Flow for Aeroelasticity and Fluid-Structure Interaction Models Validation

Fluids 2020 Volume 5, Issue 2, Article 90

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…

Three-dimensional printing of chemically crosslinked gelatin hydrogels for adipose tissue engineering

Biofabrication 2020 Volume 12, Number 2, Article 025001

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…

A multilayered valve leaflet promotes cell-laden collagen type I production and aortic valve hemodynamics

Biomaterials 2020 Volume 240, Article 119838

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…

Biomechanically, structurally and functionally meticulously tailored polycaprolactone/silk fibroin scaffold for meniscus regeneration

Theranostics 2020 Volume 10, Issue 11, Pages 5090-5106

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…

3D printing of multilayered scaffolds for rotator cuff tendon regeneration

Bioactive Materials 2020 Volume 5, Issue 3, Pages 636-643

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…

Toughening 3D-printed Sr–HT–Gahnite caffold through natural and synthetic polymer coating

International Journal of Applied Biomedical Engineering 2020 Volume 13, number 1, Pages 18-22

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…

An advanced 3D monofilament biosuture

South African Pharmaceutical Journal 2020 Volume 87, Number 1, Cum Laude

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…

3D printed Sr-containing composite scaffolds: Effect of structural design and material formulation towards new strategies for bone tissue engineering

Composites Science and Technology 2020 Volume 191, Article 108069

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,…

Heparan sulfate loaded polycaprolactone-hydroxyapatite scaffolds with 3D printing for bone defect repair

International Journal of Biological Macromolecules 2020 Volume 148, Pages 153-162

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…

High thermal conductive epoxy based composites fabricated by multi-material direct ink writing

Composites Part A: Applied Science and Manufacturing 2020 Volume 129, Article 105684

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…

Mechanical properties of hybrid triphasic scaffolds for osteochondral tissue engineering

Materials Letters 2020 Volume 261, Article 126893

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 for Bone Tissue Engineering

Pharmaceutics 2020 Volume 12, Issue 2, Article 166

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,…

Experimental Investigation and Optimal 3D Bioprinting Parameters of SA-Gel Porous Cartilage Scaffold

Applied Sciences 2020 Volume 10, Article 768

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…

Process–Structure–Quality Relationships of Three-Dimensional Printed Poly(Caprolactone)-Hydroxyapatite Scaffolds

Tissue Engineering Part A 2020 Volume 26, Number 5-6, Pages 279-291

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)…

Fiber engraving for bioink bioprinting within 3D printed tissue engineering scaffolds

Bioprinting 2020 Volume 18, Article e00076

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,…

3D hybrid printing platform for auricular cartilage reconstruction

Biomedical Physics & Engineering Express 2020 Volume 6, Number 3, Article 035003

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…

Entrapped in cage (EiC) scaffolds of 3D-printed polycaprolactone and porous silk fibroin for meniscus tissue engineering

Biofabrication 2020 Volume 12, Number 2, Article 025028

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…

3D Printed Sugar‐Sensing Hydrogels

Macromolecular Rapid Communications 2020 Volume 41, Issue 9, Article 1900610

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…

Workflow for highly porous resorbable custom 3D printed scaffolds using medical grade polymer for large volume alveolar bone regeneration

Clinical Oral Implants Research 2020 Volume 31, Issue 5, Pages 431-441

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…

Biomimetic corneal stroma using electro-compacted collagen

Acta Biomaterialia 2020 Volume 113, Pages 360-371

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,…

Development of a Photocrosslinkable Methacrylated Methylcellulose and Gelatin bioink for Cartilage Tissue Regeneration

MACE PGR Conference 2020

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…

A smart scaffold composed of three-dimensional printing and electrospinning techniques and its application in rat abdominal wall defects

Stem Cell Research & Therapy 2020 Volume 11, Article number 533

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…

Incorporation of functionalized reduced graphene oxide/magnesium nanohybrid to enhance the osteoinductivity capability of 3D printed calcium phosphate-based scaffolds

Composites Part B: Engineering 2020 Volume 185, Article 107749

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/VEGF scaffolds stimulate bone regeneration in osteoporotic sheep

Acta Biomaterialia 2020 Volume 101, Pages 544-553

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…

Aminated 3D Printed Polystyrene Maintains Stem Cell Proliferation and Osteogenic Differentiation

Tissue Engineering Part C: Methods 2020 Volume 26, Number 2, Pages 118-131

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….

Multimaterial Dual Gradient Three-Dimensional Printing for Osteogenic Differentiation and Spatial Segregation

Tissue Engineering Part A 2020 Volume 26, Number 5-6, Pages 239-252

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…

Complex‐Shaped Cellulose Composites Made by Wet Densification of 3D Printed Scaffolds

Advanced Functional Materials 2020 Volume 30, Issue 4, Article 1904127

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…

Investigation of semi-solid formulations for 3D printing of drugs after prolonged storage to mimic real-life applications

European Journal of Pharmaceutical Sciences 2020 Volume 146, Article 105266

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…

Three-dimensional printed multiphasic scaffolds with stratified cell-laden gelatin methacrylate hydrogels for biomimetic tendon-to-bone interface engineering

Journal of Orthopaedic Translation 2020 Volume 23, Pages 89-100

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…

3D printable Polycaprolactone-gelatin blends characterized for in vitro osteogenic potency

Reactive and Functional Polymers 2020 Volume 146, Article 104445

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…

Highly Porous, Biocompatible Tough Hydrogels, Processable via Gel Fiber Spinning and 3D Gel Printing

Advanced Materials Interface 2020 Volume 7, Issue 3, Article 1901770

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…

Chondroinductive Alginate-Based Hydrogels Having Graphene Oxide for 3D Printed Scaffold Fabrication

ACS Applied Materials & Interfaces 2020 Volume 12, Issue 4, Pages 4343-4357

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,…

Printability and Critical Insight into Polymer Properties during Direct-Extrusion Based 3D Printing of Medical Grade Polylactide and Copolyesters

Biomacromolecules 2020 Volume 21, Issue 2, Pages 388-396

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….


Investigation of thermoplastic melt flow and dimensionless groups in 3D bioplotting

Rheologica Acta 2020 Volume 59, Pages 83–93

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…


Double dynamic cellulose nanocomposite hydrogels with environmentally adaptive self-healing and pH-tuning properties

Cellulose 2020 Volume 27, Pages 1407–1422

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…

Fuzzy Evaluation of Rapid Prototyping Methods for Latticed Silicone Pieces

Silicon 2020 Volume 12, Pages 1995-2004

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…

Printability of 3D Printed Hydrogel Scaffolds: Influence of Hydrogel Composition and Printing Parameters

Applied Sciences 2020 Volume 10, Issue 1, Article 292

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…

Investigation of multiphasic 3D-bioplotted scaffolds for sitespecific chondrogenic and osteogenic differentiation of human adipose-derived stem cells for osteochondral tissue engineering applications

Journal of Biomedical Materials Research Part B: Applied Biomaterials 2020 Volume 108, Issue 5, Pages 2017-2030

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…

3D Printed Wavy Scaffolds Enhance Mesenchymal Stem Cell Osteogenesis

Micromachines 2020 Issue 11, Volume 1, Article 31

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,…

2D MXene‐Integrated 3D‐Printing Scaffolds for Augmented Osteosarcoma Phototherapy and Accelerated Tissue Reconstruction

Advanced Science 2020 Volume 7, Issue 2, Article 1901511

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…

Void‐Free 3D Bioprinting for In Situ Endothelialization and Microfluidic Perfusion

Advanced Functional Materials 2020 Volume 30, Issue 1, Article 1908349

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…

Mechanical and finite element evaluation of a bioprinted scaffold following recellularization in a rat subcutaneous model

Journal of the Mechanical Behavior of Biomedical Materials 2020 Volume 102, 103519

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…

Angiogenic effects of mesenchymal stem cells in combination with different scaffold materials

Microvascular Research 2020 Volume 127, Article 103925

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. There