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      Synthesis and Properties of Gelatin Methacryloyl (GelMA) Hydrogels and Their Recent Applications in Load-Bearing Tissue

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          Abstract

          Photocrosslinked gelatin methacryloyl (GelMA) hydrogels have attracted great concern in the biomedical field because of their good biocompatibility and tunable physicochemical properties. Herein, different approaches to synthesize GelMA were introduced, especially, the typical method using UV light to crosslink the gelatin-methacrylic anhydride (MA) precursor was introduced in detail. In addition, the traditional and cutting-edge technologies to characterize the properties of GelMA hydrogels and GelMA prepolymer were also overviewed and compared. Furthermore, the applications of GelMA hydrogels in cell culture and tissue engineering especially in the load-bearing tissue (bone and cartilage) were summarized, followed by concluding remarks.

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          Most cited references80

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          A simple and high-resolution stereolithography-based 3D bioprinting system using visible light crosslinkable bioinks.

          Bioprinting is a rapidly developing technique for biofabrication. Because of its high resolution and the ability to print living cells, bioprinting has been widely used in artificial tissue and organ generation as well as microscale living cell deposition. In this paper, we present a low-cost stereolithography-based bioprinting system that uses visible light crosslinkable bioinks. This low-cost stereolithography system was built around a commercial projector with a simple water filter to prevent harmful infrared radiation from the projector. The visible light crosslinking was achieved by using a mixture of polyethylene glycol diacrylate (PEGDA) and gelatin methacrylate (GelMA) hydrogel with eosin Y based photoinitiator. Three different concentrations of hydrogel mixtures (10% PEG, 5% PEG + 5% GelMA, and 2.5% PEG + 7.5% GelMA, all w/v) were studied with the presented systems. The mechanical properties and microstructure of the developed bioink were measured and discussed in detail. Several cell-free hydrogel patterns were generated to demonstrate the resolution of the solution. Experimental results with NIH 3T3 fibroblast cells show that this system can produce a highly vertical 3D structure with 50 μm resolution and 85% cell viability for at least five days. The developed system provides a low-cost visible light stereolithography solution and has the potential to be widely used in tissue engineering and bioengineering for microscale cell patterning.
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            Gelatin as a delivery vehicle for the controlled release of bioactive molecules.

            Gelatin is a commonly used natural polymer which is derived from collagen. The isoelectric point of gelatin can be modified during the fabrication process to yield either a negatively charged acidic gelatin, or a positively charged basic gelatin at physiological pH. This theoretically allows electrostatic interactions to take place between a charged biomolecule and gelatin of the opposite charge, forming polyion complexes. Various forms of gelatin carrier matrices can be fabricated for controlled-release studies, and characterization studies have been performed which show that gelatin carriers are able to sorb charged biomolecules such as proteins and plasmid DNA through polyion complexation. The crosslinking density of gelatin hydrogels has been shown to affect their degradation rate in vivo, and the rate of biomolecule release from gelatin carriers has been shown to have a similar profile, suggesting that complexed gelatin/biomolecule fragments are released by enzymatic degradation of the carrier in vivo. This review will emphasize how biomolecules released from gelatin controlled-release systems are able to retain their biological activity, allowing for their use in tissue engineering, therapeutic angiogenesis, gene therapy, and drug delivery applications.
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              Bioprinted Osteogenic and Vasculogenic Patterns for Engineering 3D Bone Tissue.

              Fabricating 3D large-scale bone tissue constructs with functional vasculature has been a particular challenge in engineering tissues suitable for repairing large bone defects. To address this challenge, an extrusion-based direct-writing bioprinting strategy is utilized to fabricate microstructured bone-like tissue constructs containing a perfusable vascular lumen. The bioprinted constructs are used as biomimetic in vitro matrices to co-culture human umbilical vein endothelial cells and bone marrow derived human mesenchymal stem cells in a naturally derived hydrogel. To form the perfusable blood vessel inside the bioprinted construct, a central cylinder with 5% gelatin methacryloyl (GelMA) hydrogel at low methacryloyl substitution (GelMALOW ) was printed. We also develop cell-laden cylinder elements made of GelMA hydrogel loaded with silicate nanoplatelets to induce osteogenesis, and synthesized hydrogel formulations with chemically conjugated vascular endothelial growth factor to promote vascular spreading. It was found that the engineered construct is able to support cell survival and proliferation during maturation in vitro. Additionally, the whole construct demonstrates high structural stability during the in vitro culture for 21 days. This method enables the local control of physical and chemical microniches and the establishment of gradients in the bioprinted constructs.

                Author and article information

                Journal
                Polymers (Basel)
                Polymers (Basel)
                polymers
                Polymers
                MDPI
                2073-4360
                21 November 2018
                November 2018
                : 10
                : 11
                : 1290
                Affiliations
                [1 ]School of Fundamental Sciences, China Medical University, Shenyang 110122, China; smilesmy@ 123456foxmail.com (M.S.); xtsun@ 123456cmu.edu.cn (X.S.)
                [2 ]The Queen’s University of Belfast Joint College, China Medical University, Shenyang 110122, China; zwang19@ 123456qub.ac.uk (Z.W.); Sguo04@ 123456qub.ac.uk (S.G.); gyu01@ 123456qub.ac.uk (G.Y.)
                Author notes
                [* ]Correspondence: hzyang@ 123456cmu.edu.cn ; Tel.: +86-189-0091-1486
                [†]

                These authors contribute equally to this work.

                Author information
                https://orcid.org/0000-0003-3177-6517
                Article
                polymers-10-01290
                10.3390/polym10111290
                6401825
                30961215
                84d350d3-7e8f-4656-adea-f27e24daeed3
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 October 2018
                : 16 November 2018
                Categories
                Review

                gelma,photocrosslink,cell culture,load-bearing tissue
                gelma, photocrosslink, cell culture, load-bearing tissue

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