3D Bioplotter Research Papers

Displaying all papers from 2020 (47 results)

Bioprinting of an osteocyte network for biomimetic mineralization

Biofabrication 2020

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

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,…

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

Tissue Engineering Part A 2020

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…

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…

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

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….

PLLA PCLA PLGA

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…

PCL

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…

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

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,…

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. 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…

Silicone resin derived larnite/C scaffolds via 3D printing for potential tumor therapy and bone regeneration

Chemical Engineering Journal 2020 Volume 382, Article 122928

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…