A mesenchymal stem cell-derived nanovesicle-biopotentiated bovine serum albumin-bridged gelatin hydrogel for enhanced diabetic wound therapy

The application of gelatin hydrogels is hampered by their poor mechanical properties, which are unfavorable for debridement and diabetic wound healing. Herein, bovine serum albumin (BSA)-bridged gelatin hydrogels biopotentiated by bone marrow mesenchymal stem cell (BMSC)-derived nanovesicles (NV), named NV@BSA-GEL, were fabricated by reinforcement of gelatin hydrogels with genipin and BSA in a one-pot, low-cost green approach based on amide bonding-guided crosslinking. Genipin introduction endowed the crosslinking of gelatin hydrogels with weak mechanical properties that were reinforced by BSA bridging to realize suitable mechanical properties for wound dressing, including excellent flexibility and appropriate rigidity. The bioactivity of NV released by the hydrogels resulted in efficient ROS scavenging and favorable immunomodulatory activity as well as promoted cell proliferation and migration of fibroblasts and vascular endothelial cells. Proteomic analysis confirmed that NV harbors a variety of growth factors that can promote wound healing. In vivo, the NV@BSA-GEL hydrogel had superior wound healing effects compared to BSA-GEL, including faster wound healing, stimulation of angiogenesis, contributing to an anti-inflammatory extracellular matrix, and promoting skin maturation, with no systemic toxicity. Thus, the combined merits of NV@BSA-GEL suggest that it has high potential as a new hydrogel dressing for the safe and efficient treatment of diabetic wounds.