Cell‐Delivering Injectable Hydrogels with Tunable Microporous Structures Improve Therapeutic Efficacy for Volumetric Muscle Loss

Abstract Volumetric muscle loss (VML) is a traumatic or surgical injury to the skeletal muscles that causes irrecoverable functional loss, leading to chronic deficits and long‐term disability. Although cell transplantation is a potent therapeutic approach, treating VML remains challenging because of the poor graft survival of cell suspensions injected into defects. Here, the development of tunable micropore‐forming injectable hydrogels is reported to deliver mesenchymal stem cells (MSCs) for VML treatment. The molecular modification of gelatin with hydrogen‐bonding functional groups induces liquid–liquid phase separation when mixed with chemically crosslinkable gelatin to form injectable hydrogels with tunable microporous structures. MSCs encapsulated in porous hydrogels show higher cell adhesion, spreading, proliferation, and secretion of paracrine signals than those encapsulated in non‐porous hydrogels. Porous hydrogels enhance cell infiltration and myoblast differentiation. Additionally, porous hydrogels improve the graft survival of transplanted MSCs in VML mouse models and ameliorate therapeutic efficiency. This controlled microstructure‐containing injectable hydrogel may serve as a cell‐delivering scaffold to improve the efficacy of cell transplantation therapies in regenerative medicine.