Leak-free encapsulation of EGF-expressing yeast in a hyaluronic acid-based hydrogel for diabetes wound healing

The integration of living cells into hydrogels offers a promising approach to enhance functionality of biomaterials for biomedical applications while protecting the encapsulated cells. In this study, we developed a living yeast-based system for in situ production of epidermal growth factor (EGF) to address the challenges associated with diabetic wound healing. Our approach involves surface-initiated polymerization of hyaluronic acid methacrylate (HAMA) from the engineered yeast surface, followed by photo-crosslinking to form a living hydrogel embedded with viable yeast cells. These cells function both as bioactive components and structural anchors within the hydrogel. We demonstrate that the yeast cells remain fully encapsulated for at least 7 days, maintaining high viability and sustained EGF expression with controlled release in vitro. In vitro assays showed that the hydrogel significantly promotes the proliferation and migration of human umbilical vein endothelial cells (HUVECs), resulting in a ~ 20 % increase in proliferation and a ~ 30 % enhancement in migration rate compared to control groups. In vivo evaluation using a diabetic mouse model confirmed that the hydrogel accelerates chronic wound healing, as indicated by improved tissue regeneration and reduced healing time. Specifically, wounds treated with the ELH treated wounds reached a ~ 96 % closure rate by day 14, outperforming a commercially dressing. This leak-free, living-hydrogel platform provides a versatile route to localized, cell-based therapy and holds promise for regenerative medicine and advanced wound care.