3D Bioplotter Research Papers

Displaying all papers about Gelatin (42 results)

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…

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…

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…

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…

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…

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…

3D printing of silk fibroin-based hybrid scaffold treated with platelet rich plasma for bone tissue engineering

Bioactive Materials 2019 Volume 4, Pages 256-260

3D printing/bioprinting are promising techniques to fabricate scaffolds with well controlled and patient-specific structures and architectures for bone tissue engineering. In this study, we developed a composite bioink consisting of silk fibroin (SF), gelatin (GEL), hyaluronic acid (HA), and tricalcium phosphate (TCP) and 3D bioprinted the silk fibroin-based hybrid scaffolds. The 3D bioprinted scaffolds with dual crosslinking were further treated with human platelet-rich plasma (PRP) to generate PRP coated scaffolds. Live/Dead and MTT assays demonstrated that PRP treatment could obviously promote the cell growth and proliferation of human adipose derived mesenchymal stem cells (HADMSC). In addition, the treatment of PRP…

Design of a new 3D‐printed joint plug

Asia‐Pacific Journal of Chemical Engineering 2019 Volume 14, Issue 6, Article e2360

This paper introduces a kit of parts as a novel three‐dimensional (3D)–printed joint plug, in which each of the parts function cooperatively to treat cartilage damage in joints of the human body (e.g., hips, wrists, elbow, knee, and ankle). Three required and one optional parts are involved in this plug. The first part is a 3D‐printed hard scaffold (bone portion) to accommodate bone cells, and the second is a 3D‐printed soft scaffold (cartilage portion) overlying the bone portion to accommodate chondrocytes. The third part of joint plug is a permeable membrane, termed film, to cover the entire plug to provide…

Employing PEG crosslinkers to optimize cell viability in gel phase bioinks and tailor post printing mechanical properties

Acta Biomaterialia 2019 Volume 99, Pages 121-132

The field of 3D bioprinting has rapidly grown, yet the fundamental ability to manipulate material properties has been challenging with current bioink methods. Here, we change bioink properties using our PEG cross-linking (PEGX) bioink method with the objective of optimizing cell viability while retaining control of mechanical properties of the final bioprinted construct. First, we investigate cytocompatible, covalent cross-linking chemistries for bioink synthesis (e.g. Thiol Michael type addition and bioorthogonal inverse electron demand Diels-Alder reaction). We demonstrate these reactions are compatible with the bioink method, which results in high cell viability. The PEGX method is then exploited to optimize extruded…

3D printed HUVECs/MSCs cocultures impact cellular interactions and angiogenesis depending on cell-cell distance

Biomaterials 2019 Volume 222, Article 119423

Vascularization is a crucial process during the growth and development of bone 1, yet it remains one of the main challenges in the reconstruction of large bone defects. The use of in vitro coculture of human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) has been one of the most explored options. Both cell types secrete specific growth factors that are mutually beneficial, and studies suggested that cell-cell communication and paracrine secretion could be affected by a number of factors. However, little is known about the effect of cell patterning and the distance between cell populations on…

An investigation into the relationship between inhomogeneity and wave shapes in phantoms and ex vivo skeletal muscle using Magnetic Resonance Elastography and finite element analysis

Journal of the Mechanical Behavior of Biomedical Materials 2019 Volume 98, Pages 108-120

Soft biological tissues such as skeletal muscle and brain white matter can be inhomogeneous and anisotropic due to the presence of fibers. Unlike biological tissue, phantoms with known microstructure and defined mechanical properties enable a quantitative assessment and systematic investigation of the influence of inhomogeneities on the nature of shear wave propagation. This study introduces a mathematical measure for the wave shape, which the authors call as the 1-Norm, to determine the conditions under which homogenization may be a valid approach. This is achieved through experimentation using the Magnetic Resonance Elastography technique on 3D printed inhomogeneous fiber phantoms as well…

Bacterial cellulose nanofibers promote stress and fidelity of 3D-printed silk based hydrogel scaffold with hierarchical pores

Carbohydrate Polymers 2019 Volume 221, Pages 146-156

One of the latest trends in the regenerative medicine is the development of 3D-printing hydrogel scaffolds with biomimetic structures for tissue regeneration and organ reconstruction. However, it has been practically difficult to achieve a highly biomimetic hydrogel scaffolds with proper mechanical properties matching the natural tissue. Here, bacterial cellulose nanofibers (BCNFs) were applied to improve the structural resolution and enhance mechanical properties of silk fibroin (SF)/gelatin composite hydrogel scaffolds. The SF-based hydrogel scaffolds with hierarchical pores were fabricated via 3D-printing followed by lyophilization. Results showed that the tensile strength of printed sample increased significantly with the addition of BCNFs in…

Carbon Nanodots Doped Super-paramagnetic Iron Oxide Nanoparticles for Multimodal Bioimaging and Osteochondral Tissue Regeneration via External Magnetic Actuation

ACS Biomaterials Science & Engineering 2019 Volume 5, Issue 7, Pages 3549-3560

Super-paramagnetic iron oxide nanoparticles (SPIONs) have multiple theranostics applications such as T2 contrast agent in magnetic resonance imaging (MRI) and electromagnetic manipulations in biomedical devices, sensors, and regenerative medicines. However, SPIONs suffer from the limitation of free radical generation, and this has a certain limitation in its applicability in tissue imaging and regeneration applications. In the current study, we developed a simple hydrothermal method to prepare carbon quantum dots (CD) doped SPIONs (FeCD) from easily available precursors. The nanoparticles are observed to be cytocompatible, hemocompatible, and capable of scavenging free radicals in vitro. They also have been observed to be…

Effects of 3-dimensional Bioprinting Alginate/ Gelatin Hydrogel Scaffold Extract on Proliferation and Differentiation of Human Dental Pulp Stem Cells

Journal of Endodontics 2019 Volume 45, Issue 6, Pages 706-715

Abrasive flow machining (AFM) is a nontraditional surface finishing method that finishes complex surface by pushing the abrasive media flow through the workpiece surface. The entrance effect that the material removal increases at the entrance of changing the cross-sectional flow channel is a difficult problem for AFM. In this paper, the effects of media rheological properties on the entrance effect are discussed. To explore the effects of the media’s viscoelasticity on the entrance effect, two sets of media with different viscoelasticity properties are adopted to study their rheological and machining performances in the designed flow channel with a contraction area….

Printability and Cell Viability in Bioprinting Alginate Dialdehyde- Gelatin Scaffolds

ACS Biomaterials Science & Engineering 2019 Volume 5, Issue 6, Pages 2976-2987

Three-dimensional (3D) bioprinting is a promising technique used to fabricate scaffolds from hydrogels with living cells. However, the printability of hydrogels in bioprinting has not been adequately studied. The aim of this study was to quantitatively characterize the printability and cell viability of alginate dialdehyde (ADA)-gelatin (Gel) hydrogels for bioprinting. ADA-Gel hydrogels of various concentrations were synthesized and characterized using Fourier transform infrared spectroscopy, along with rheological tests for measuring storage and loss moduli. Scaffolds (with an area of 11 × 11 mm) of 1, 2, and 13 layers were fabricated from ADA-Gel hydrogels using a 3D-bioplotter under printing conditions…

Implantable Nanotube Sensor Platform for Rapid Analyte Detection

Macromolecular Bioscience 2019 Volume 19, Issue 6, Article 1800469

The use of nanoparticles within living systems is a growing field, but the long‐term effects of introducing nanoparticles to a biological system are unknown. If nanoparticles remain localized after in vivo implantation unanticipated side effects due to unknown biodistribution can be avoided. Unfortunately, stabilization and retention of nanoparticles frequently alters their function.1 In this work multiple hydrogel platforms are developed to look at long‐term localization of nanoparticle sensors with the goal of developing a sensor platform that will stabilize and localize the nanoparticles without altering their function. Two different hydrogel platforms are presented, one with a liquid core of sensors…

Indirect 3D bioprinting and characterization of alginate scaffolds for potential nerve tissue engineering applications

Journal of the Mechanical Behavior of Biomedical Materials 2019 Volume 93, Pages 183-193

Low-concentration hydrogels have favorable properties for many cell functions in tissue engineering but are considerably limited from a scaffold fabrication point of view due to poor three-dimensional (3D) printability. Here, we developed an indirect-bioprinting process for alginate scaffolds and characterized the potential of these scaffolds for nerve tissue engineering applications. The indirect-bioprinting process involves (1) printing a sacrificial framework from gelatin, (2) impregnating the framework with low-concentration alginate, and (3) removing the gelatin framework by an incubation process, thus forming low-concentration alginate scaffolds. The scaffolds were characterized by compression testing, swelling, degradation, and morphological and biological assessment of incorporated or…

Anisotropic composite material phantom to improve skeletal muscle characterization using magnetic resonance elastography

Journal of the Mechanical Behavior of Biomedical Materials 2019 Volume 89, Pages 199-208

The presence and progression of neuromuscular pathology, including spasticity, Duchenne’s muscular dystrophy and hyperthyroidism, has been correlated with changes in the intrinsic mechanical properties of skeletal muscle tissue. Tools for noninvasively measuring and monitoring these properties, such as Magnetic Resonance Elastography (MRE), could benefit basic research into understanding neuromuscular pathologies, as well as translational research to develop therapies, by providing a means of assessing and tracking their efficacy. Dynamic elastography methods for noninvasive measurement of tissue mechanical properties have been under development for nearly three decades. Much of the technological development to date, for both Ultrasound (US)-based and Magnetic Resonance…

Gelatin Imaging

Doping of Carbon Quantum Dots (CDs) in Calcium Phosphate Nanorods for Inducing Ectopic Chondrogenesis via Activation of the HIF-α/SOX‑9 Pathway

ACS Omega 2019 Volume 4, Issue 1, Pages 374-386

Calcium phosphate (CaPs)-based nanostructures are mostly known to induce osteogenic differentiation of mesenchymal stem cells (MSCs). However, in the current study, doping of carbon quantum dots into calcium phosphate nanorods (C-CaPs) has been observed to affect the differentiation pathway and enhanced the expression of chondrogenic genes instead of osteogenic ones. Here, we report a microwave-assisted single-step synthesis and doping of carbon dot into calcium phosphate nanorods and their ectopic chondrogenicity in a rodent subcutaneous model. High-resolution transmission electron microscopy, X-ray powder diffraction, and X-ray photoelectron spectroscopy studies show that the doping of carbon dots results in p-type semiconductor-like structure formation…

Anisotropic Composite Material Phantom Tested Using Magnetic Resonance Elastography

Proceedings of the Sixteenth International Tissue Elasticity Conference 2018 Page 22

Background: The presence and progression of neuromuscular pathologies, including spasticity, dystrophy and hyperthyroidism, have been correlated with changes in the intrinsic mechanical properties of skeletal muscle tissue. Tools of noninvasively measuring and monitoring these properties, such as Magnetic Resonance Elastography (MRE), could benefit basic research into understanding neuromuscular pathologies, as well as translational research to develop therapies, by providing a means of assessing and tracking their efficacy. While various approaches have been proposed in the literature [1,2], there is not yet an accepted standard for the identification of the mechanical properties of anisotropic and viscoelastic tissues through MRE; advances in…

Gelatin Imaging

Mechanically robust cryogels with injectability and bioprinting supportability for adipose tissue engineering

Acta Biomaterialia 2018 Volume 74, Pages 131-142

Bioengineered adipose tissues have gained increased interest as a promising alternative to autologous tissue flaps and synthetic adipose fillers for soft tissue augmentation and defect reconstruction in clinic. Although many scaffolding materials and biofabrication methods have been investigated for adipose tissue engineering in the last decades, there are still challenges to recapitulate the appropriate adipose tissue microenvironment, maintain volume stability, and induce vascularization to achieve long-term function and integration. In the present research, we fabricated cryogels consisting of methacrylated gelatin, methacrylated hyaluronic acid, and 4arm poly(ethylene glycol) acrylate (PEG-4A) by using cryopolymerization. The cryogels were repeatedly injectable and stretchable, and…

Stable gelatin-based phantom materials with tunable x-ray attenuation properties and 3D printability for x-ray imaging

Physics in Medicine & Biology 2018 Volume 63, Number 9, Article 09NT01

We report a novel method for developing gelatin-based phantom materials for transmission x-ray imaging with high stability at room temperature and tunable x-ray attenuation properties. This is achieved by efficiently cross-linking gelatin in a glycerin solution with only 10% water by volume and systematically decreasing their x-ray attenuation coefficients by doping with microbubbles that are originally designed to be used as lightweight additives for paints and crack fillers. For demonstration, we mimic breast glandular and adipose tissues by using such gelatin materials and also study the feasibility of 3D printing them based on the extrusion-based technique. Results from x-ray spectroscopy…

3D-printed thick structured gelatin membrane for engineering of heterogeneous tissues

Materials Letters 2018 Volume 217, Pages 39-43

Although biological membranes may look like a 2D assembly, they often have complex structures in their 3rd dimension. Using layer-by-layer assembly, 3D-printing can offer an advanced and unique approach for the fabrication of such models. However, printing of some widely used hydrogels, such as gelatin, encounters experimental difficulties due to their rheological properties. In this paper, we (a) discuss the complexities involved in printing gelatin, (b) offer a reproducible approach to overcome such difficulties, and (c) present the detailed design criteria and the production process of such 3D-printed gelatin membranes by exemplifying scaffolds suitable for growth of full-thickness oral mucosa…

3D-printed gelatin scaffolds of differing pore geometry modulate hepatocyte function and gene expression

Acta Biomaterialia 2018 Volume 69, Pages 63-70

Three dimensional (3D) printing is highly amenable to the fabrication of tissue-engineered organs of a repetitive microstructure such as the liver. The creation of uniform and geometrically repetitive tissue scaffolds can also allow for the control over cellular aggregation and nutrient diffusion. However, the effect of differing geometries, while controlling for pore size, has yet to be investigated in the context of hepatocyte function. In this study, we show the ability to precisely control pore geometry of 3D-printed gelatin scaffolds. An undifferentiated hepatocyte cell line (HUH7) demonstrated high viability and proliferation when seeded on 3D-printed scaffolds of two different geometries….

Effects of tunable, 3D-bioprinted hydrogels on human brown adipocyte behavior and metabolic function

Acta Biomaterialia 2018 Volume 71, Pages 486-495

Obesity and its related health complications cause billions of dollars in healthcare costs annually in the United States, and there are yet to be safe and long-lasting anti-obesity approaches. Using brown adipose tissue (BAT) is a promising approach, as it uses fats for energy expenditure. However, the effect of the microenvironment on human thermogenic brown adipogenesis and how to generate clinically relevant sized and functioning BAT are still unknown. In our current study, we evaluated the effects of endothelial growth medium exposure on brown adipogenesis of human brown adipose progenitors (BAP). We found that pre-exposing BAP to angiogenic factors promoted…

[Gelatin/alginate hydrogel scaffolds prepared by 3D bioprinting promotes cell adhesion and proliferation of human dental pulp cells in vitro]

Nan Fang Yi Ke Da Xue Xue Bao (Journal of Southern Medical University) 2017 Volume 37, Issue 5, Pages 668-672

OBJECTIVE: To evaluate the cytotoxicity of gelatin/alginate hydrogel scaffolds prepared by 3D bioprinting in human dental pulp cells (HDPCs) and compare the cell adhesion and proliferation of the cells seeded in the biomaterial using two different methods. METHODS: HDPCs isolated by tissue block culture and enzyme digestion were cultured and passaged. Gelatin/alginate hydrogel scaffolds were printed using a bioplotter, and the cytotoxicity of the aqueous extracts of the scaffold material was tested in the third passage of HDPCs using cell counting kit-8. Scanning electron microscopy and trypan blue were used to assess the adhesion and proliferation of the cells seeded…

A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice

Nature Communications 2017 Volume 88, Article number 15261

Emerging additive manufacturing techniques enable investigation of the effects of pore geometry on cell behavior and function. Here, we 3D print microporous hydrogel scaffolds to test how varying pore geometry, accomplished by manipulating the advancing angle between printed layers, affects the survival of ovarian follicles. 30° and 60° scaffolds provide corners that surround follicles on multiple sides while 90° scaffolds have an open porosity that limits follicle–scaffold interaction. As the amount of scaffold interaction increases, follicle spreading is limited and survival increases. Follicle-seeded scaffolds become highly vascularized and ovarian function is fully restored when implanted in surgically sterilized mice. Moreover,…

Osteogenic Differentiation of Three-Dimensional Bioprinted Constructs Consisting of Human Adipose-Derived Stem Cells In Vitro and In Vivo

PloS One 2016 Volume 11, Issue 6, e0157214

Here, we aimed to investigate osteogenic differentiation of human adipose-derived stem cells (hASCs) in three-dimensional (3D) bioprinted tissue constructs in vitro and in vivo. A 3D Bio-plotter dispensing system was used for building 3D constructs. Cell viability was determined using live/dead cell staining. After 7 and 14 days of culture, real-time quantitative polymerase chain reaction (PCR) was performed to analyze the expression of osteogenesis-related genes (RUNX2, OSX, and OCN). Western blotting for RUNX2 and immunofluorescent staining for OCN and RUNX2 were also performed. At 8 weeks after surgery, osteoids secreted by osteogenically differentiated cells were assessed by hematoxylin-eosin (H&E) staining,…

[Osteogenesis of human adipose-derived mesenchymal stem cells-biomaterial mixture in vivo after 3D bio-printing]

Journal of Peking University. Health Sciences 2016 Volume 48, Issue 1, Pages 45-50

To construct human adipose-derived mesenchymal stem cells (hASCs)-biomaterial mixture 3D bio-printing body and detect its osteogenesis in vivo, and to establish a guideline of osteogenesis in vivo by use of 3D bio-printing technology preliminarily.P4 hASCs were used as seed cells, whose osteogenic potential in vitro was tested by alkaline phosphatase (ALP) staining and alizarin red staining after 14 d of osteogenic induction. The cells were added into 20 g/L sodium alginate and 80 g/L gelatin mixture (cell density was 1×10(6)/mL), and the cell-sodium alginate-gelatin mixture was printed by Bioplotter 3D bio-printer (Envision company, Germany), in which the cells’survival rate was…

3D Printing of Porous Alginate/gelatin Hydrogel Scaffolds and Their Mechanical Property Characterization

International Journal of Polymeric Materials and Polymeric Biomaterials 2016 Volume 66, Issue 6, Pages 299-306

Hydrogel scaffolds with well-defined internal structure and interconnected porosity are important for tissue engineering. 3D Bioplotting technique supplemented with thermal/submerged ionic crosslinking process was used to fabricate hydrogel scaffolds. Six scaffold geometries were fabricated and their influence on mechanical performance was investigated. 0/90-0.8 group with the lowest porosity showed the highest Young’s modulus while the Shift group showed the lowest Young’s modulus. Same trend has also been observed for the dynamic modulus of each group. Results demonstrated that the mechanical performance of hydrogel scaffolds can be tuned by changing the internal structure parameters including strands orientation and spacing between strands.

Alginate Gelatin

3D Bioplotting of Gelatin/Alginate Scaffolds for Tissue Engineering: Influence of Crosslinking Degree and Pore Architecture on Physicochemical Properties

Journal of Materials Science & Technology 2016 Volume 32, Issue 9, Pages 889–900

Gelatin/Alginate hydrogels were engineered for bioplotting in tissue engineering. One major drawback of hydrogel scaffolds is the lack of adequate mechanical properties. In this study, using a bioplotter, we constructed the scaffolds with different pore architectures by deposition of gelatin/alginate hydrogels layer-by-layer. The scaffolds with different crosslinking degree were obtained by post-crosslinking methods. Their physicochemical properties, as well as cell viability, were assessed. Different crosslinking methods had little influence on scaffold architecture, porosity, pore size and distribution. By contrast, the water absorption ability, degradation rate and mechanical properties of the scaffolds were dramatically affected by treatment with various concentrations of…

Modular Small Diameter Vascular Grafts with Bioactive Functionalities

PloS One 2015 Volume 10, Issue 7, Article e0133632

We report the fabrication of a novel type of artificial small diameter blood vessels, termed biomimetic tissue-engineered blood vessels (bTEBV), with a modular composition. They are composed of a hydrogel scaffold consisting of two negatively charged natural polymers, alginate and a modified chitosan, N,O-carboxymethyl chitosan (N,O-CMC). Into this biologically inert scaffold two biofunctionally active biopolymers are embedded, inorganic polyphosphate (polyP) and silica, as well as gelatin which exposes the cell recognition signal, Arg-Gly-Asp (RGD). These materials can be hardened by exposure to Ca2+ through formation of Ca2+ bridges between the polyanions, alginate, N,O-CMC, and polyP (alginate-Ca2+-N,O-CMC-polyP). The bTEBV are formed…

A Multimaterial Bioink Method for 3D Printing Tunable, Cell-Compatible Hydrogels

Advanced Materials 2015 Volume 27, Issue 9, Pages 1607–1614

A multimaterial bio-ink method using polyethylene glycol crosslinking is presented for expanding the biomaterial palette required for 3D bioprinting of more mimetic and customizable tissue and organ constructs. Lightly crosslinked, soft hydrogels are produced from precursor solutions of various materials and 3D printed. Rheological and biological characterizations are presented, and the promise of this new bio-ink synthesis strategy is discussed.

Fabrication of novel Si-doped Hydroxyapatite/Gelatine scaffolds by rapid prototyping for drug delivery and bone regeneration

Acta Biomaterialia 2015 Volume 15, Pages 200–209

Porous 3-D scaffolds consisting of gelatine and Si-doped hydroxyapatite were fabricated at room temperature by rapid prototyping. Microscopic characterization revealed a highly homogeneous structure, showing the pre-designed porosity (macroporosity) and a lesser in-rod porosity (microporosity). The mechanical properties of such scaffolds are close to those of trabecular bone of the same density. The biological behavior of these hybrid scaffolds is greater than that of pure ceramic scaffolds without gelatine, increasing pre-osteoblastic MC3T3-E1 cell differentiation (matrix mineralization and gene expression). Since the fabrication process of these structures was carried out at mild conditions, an antibiotic (vancomycin) was incorporated in the slurry…

Effect of Bioglass on Growth and Biomineralization of SaOS-2 Cells in Hydrogel after 3D Cell Bioprinting

PloS One 2014 Volume 9, Issue 11, Article e112497

We investigated the effect of bioglass (bioactive glass) on growth and mineralization of bone-related SaOS-2 cells, encapsulated into a printable and biodegradable alginate/gelatine hydrogel. The hydrogel was supplemented either with polyphosphate (polyP), administered as polyP•Ca2+-complex, or silica, or as biosilica that had been enzymatically prepared from ortho-silicate by silicatein. These hydrogels, together with SaOS-2 cells, were bioprinted to computer-designed scaffolds. The results revealed that bioglass (nano)particles, with a size of 55 nm and a molar ratio of SiO2∶CaO∶P2O5 of 55∶40∶5, did not affect the growth of the encapsulated cells. If silica, biosilica, or polyP•Ca2+-complex is co-added to the cell-containing alginate/gelatin…

Engineering a morphogenetically active hydrogel for bioprinting of bioartificial tissue derived from human osteoblast-like SaOS-2 cells

Biomaterials 2014 Volume 35, Issue 31, Pages 8810–8819

Sodium alginate hydrogel, stabilized with gelatin, is a suitable, biologically inert matrix that can be used for encapsulating and 3D bioprinting of bone-related SaOS-2 cells. However, the cells, embedded in this matrix, remain in a non-proliferating state. Here we show that addition of an overlay onto the bioprinted alginate/gelatine/SaOS-2 cell scaffold, consisting of agarose and the calcium salt of polyphosphate [polyP·Ca2+-complex], resulted in a marked increase in cell proliferation. In the presence of 100 μm polyP·Ca2+-complex, the cells proliferate with a generation time of approximately 47–55 h. In addition, the hardness of the alginate/gelatin hydrogel substantially increases in the presence…

Layered Gradient Nonwovens of In Situ Crosslinked Electrospun Collagenous Nanofibers Used as Modular Scaffold Systems for Soft Tissue Regeneration

Advanced Functional Materials 2013 Volume 23, Issue 26, Pages 3277-3285

In a versatile modular scaffold system, gradient nonwovens of in situ crosslinked gelatin nanofibers (CGN), fabricated by reactive electrospinning, are laminated with perforated layers and nonwovens of thermoplastic non-crosslinked biodegradable polyesters. The addition of glyoxal to a gelatin solution in a non-toxic solvent mixture consisting of acetic acid, ethyl acetate, and water (5:3:2 w/w/w) enables the in situ crosslinking of gelatin nanofibers during electrospinning. The use of this fluorine-free crosslinking system eliminates the need of post-treatment crosslinking and purification steps typical for conventional CGN scaffolds. The slowly progressing crosslinking of the dissolved gelatin in the presence of glyoxal increases the…

Thermal imaging analysis of 3D biological agarose matrices

International Journal of Medical Engineering and Informatics 2011 Volume 3, Issue 2, Pages 167-179

Advances in rapid prototyping have allowed for the construction of biocompatible materials (hydrogels) to be used in regenerative medicine. Within this area of construction inherent problems arise due to the mechanical instability of such materials that are temperature dependent. This research paper describes a thermal imaging analysis used to circumvent needle blockage when using an RP technology called bioplotting, used for extruding high temperature hydrogels, where agarose was the experimental biomaterial. The investigation describes how we have overcome these inherent problems through thermal imaging analysis, allowing us to accurately construct 3D biological matrices that have satisfied the in-vitro cell requirements…

Construction of 3D biological matrices using rapid prototyping technology

Rapid Prototyping Journal 2009 Volume 15, Issue 3, Pages 204 - 210

Purpose Hydrogels with low viscosities tend to be difficult to use in constructing tissue engineering (TE) scaffolds used to replace or restore damaged tissue, due to the length of time it takes for final gelation to take place resulting in the scaffolds collapsing due to their mechanical instability. However, recent advances in rapid prototyping have allowed for a new technology called bioplotting to be developed, which aims to circumvent these inherent problems. This paper aims to present details of the process. Design/methodology/approach The paper demonstrates how by using the bioplotting technique complex 3D geometrical scaffolds with accurate feature sizes and…

Formed 3D Bio-Scaffolds via Rapid Prototyping Technology

IFMBE Proceedings 2009 Volume 22, Pages 2200-2204

The construction of biomaterial scaffolds for cell seeding is now seen as the most common approach for producing artificial tissue as compared with cell self-assembly and Acellular matrix techniques. This paper describes the use of synthetic and natural polymeric material shaped into 3D biological matrices by using Rapid Prototyping (RP) technology. Recent advances in RP technology have greatly enhanced the range of biomaterials that can now be constructed into scaffolds, also allowing for maximized control of the pore size and architecture. Bioplotting is one such method which allows the dispensing of various biomaterials into a media bath which has similar…

Rapid prototyping of scaffolds derived from thermoreversible hydrogels and tailored for applications in tissue engineering

Biomaterials 2002 Volume 23, Issue 23, Pages 4437-4447

In the year 2000 a new rapid prototyping (RP) technology was developed at the Freiburg Materials Research Center to meet the demands for desktop fabrication of scaffolds useful in tissue engineering. A key feature of this RP technology is the three-dimensional (3D) dispensing of liquids and pastes in liquid media. In contrast to conventional RP systems, mainly focused on melt processing, the 3D dispensing RP process (3D plotting) can apply a much larger variety of synthetic as well as natural materials, including aqueous solutions and pastes, to fabricate scaffolds for application in tissue engineering. For the first time, hydrogel scaffolds…