Colloidal gelatin microgels with tunable elasticity support the viability and differentiation of mesenchymal stem cells under pro‐inflammatory conditions

Despite a promising potential for mesenchymal stem cells (MSCs) in tissue regeneration, a major challenge in MSC-based therapy has been associated with poor cell survival and low levels of cell integration into host tissue following transplantation. The objective of this study was to develop a gelatin-based colloidal microgel platform that enables the encapsulation of viable MSCs as well as confer fine-tuning of mechanical stiffness and low cytotoxicity. In this study, we report a facile method of fabricating gelatin-based microgel spheres for the encapsulation of MSCs using a water-in-oil mini-emulsification method, which is covalently crosslinked by genipin. At a given seeding cell number, there was a positive correlation between the size of the microsphere and the number of encapsulated MSCs. Controlling the crosslinking degree of gelatin matrix enabled a fine-tuning of mechanical stiffness of gel microsphere. MSCs within softer microgel exhibit more spread morphology than the cells in the stiffer matrix, while cells within stiffer matrix become more elongated morphology. Importantly, we show that the colloidal gelatin microgel could support the viability and differentiation of encapsulated MSCs in a pro-inflammatory environment. This study demonstrates the feasibility of using genipin-crosslinked gelatin gel microspheres as an injectable carrier of MSCs for tissue engineering applications, which can be further explored for MSC-based cell therapy for tissue repair.