Abstract
Gelatin methacrylate (GelMA) hydrogels have been widely studied for biomedical applications, such as tissue engineering and drug delivery, because of their good biocompatibility and injectability. However, the quick degradation and low mechanical property of GelMA hydrogels need to be improved for further applications, especially for long-term implantation. In this study, a sequential double modification of gelatin was used to achieve high density of photocrosslinkable double bonds in gelatin derivatives. The amino groups in gelatin were first reacted with methacrylic anhydride. After this, the hydroxyl and carboxyl groups in gelatin were reacted with glycidyl methacrylate to obtain the double modified gelatin macromer. The double modified gelatin macromer was used to prepare gelatin hydrogels with high crosslinking density. The hydrogels exhibited high storage modulus and low degradation. Culture of bovine articular chondrocytes in the gelatin hydrogels showed that chondrocytes had round morphology and maintained a cartilaginous phenotype while cell proliferation was hampered. This method for increasing crosslinking density should be useful for preparation of stable hydrogels for cartilage tissue engineering.
Highlights
Cartilage tissue engineering has drawn a lot of attention due to the limited self-repairing capacity of avascular cartilage
Hydroxyl, and carboxyl groups that can be used for modification
After the reaction of the amino groups in gelatin molecules with methacrylic anhydride, the remaining hydroxyl and carboxyl groups can be used for further modification in an acidic environment [20]
Summary
Cartilage tissue engineering has drawn a lot of attention due to the limited self-repairing capacity of avascular cartilage. One crucial step of cartilage tissue engineering is in vitro expansion of chondrocytes, during which chondrocytes lose part of their chondrogenic phenotype due to the differences between the two-dimensional (2D) expansion culture microenvironment and the in vivo three-dimensional (3D) microenvironment. The loss of expression of cartilaginous matrices such as collagen type II and aggrecan is a process known as de-differentiation. De-differentiated chondrocytes should be re-differentiated in order to express cartilaginous matrices for functional cartilage tissue engineering [1]. Hydrogels have been frequently used for the 3D culturing of chondrocytes for re-differentiation and maintenance of chondrogenic phenotypes and for chondrogenic differentiation of stem cells [2,3,4]. Many reports have shown the re-differentiation of de-differentiated chondrocytes in hydrogels [6]. Gelatin hydrogels have many advantages such as good cell adhesion (RGD peptide), good biocompatibility and easy modification [7,8,9,10,11]
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