A rapidly degrading methacrylated hyaluronic acid-gelatin hydrogel for injectable, short-term cell support in bone tissue engineering.

Abstract

Effective cell transplantation for bone regeneration requires rapidly degrading biomaterials that can temporarily encapsulate cells, facilitating early release and minimizing prolonged contact that might reduce responsiveness to the native tissue environment. Injectable hydrogels that mimic the extracellular matrix offer a promising platform for localized cell delivery, yet achieving both mechanical integrity and rapid degradation remains a challenge. In this study, we developed a methacrylated hyaluronic acid (MeHA)-gelatin hydrogel with tunable crosslinking and bioactivity for short-term support of transplanted cells. By modulating crosslinking density and gelatin content, the hydrogel exhibited controllable stiffness, high swelling capacity, and enzymatic degradation within hours. The low-crosslinking formulation significantly enhanced encapsulated cell activities, including viability, spreading, and early proliferation in vitro. Although fewer cells were retained in vivo due to faster degradation, those recovered maintained metabolic function and demonstrated enhanced osteogenic differentiation potential compared to cells from more rigid hydrogels. These findings suggest that the MeHA-gelatin hydrogel offers a transient yet bioactive environment suitable for injectable cell-based therapies in bone tissue engineering.