Acholinebio-ionicliquid-functionalized gelatin methacryloyl hydrogel for chronic wound healing

Chronic wounds present a major healthcare challenge due to delayed healing, risk of infection, and limited treatment options. Current biomaterials-based chronic wound treatment strategies lack the multifunctional at- tributes necessary for tackling a myriad of pathophysiological complexities presented by chronic wounds. Here, we introduce a choline-based bio-ionic liquid (BIL)-functionalized gelatin methacryloyl (GelMA) hydrogel (BioGel) formulated for treating diabetic chronic wounds in a unique mouse model that recapitulates chronic wounds in humans. We tested the in vitro angiogenic potential of BioGel using human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs). Finally, we applied the BioGel hydrogel on chronic wounds in db/db-/- mice, twice weekly for 21 days or until wound closure. BioGel improved angiogenesis in co- cultures of HUVECs and hMSCs as evidenced by a significantly increased number of intact vascular tube for- mations compared to GelMA, highlighting the pro-angiogenic function of choline in BioGel. The application of BioGel accelerated wound closure, reduced biofilm, and promoted hair regrowth, in our human-relevant diabetic chronic wound model. These results suggest that BioGel offers a multifunctional, effective solution for chronic wound management, surpassing the limitations of current treatments.