Hydrogel-Delivered Recombinant Fibronectin DK1 Promotes Diabetic Wound Healing by Boosting Cellular Responses

Diabetic wounds remain a major clinical challenge due to persistent inflammation, impaired angiogenesis, and delayed tissue regeneration. Fibronectin plays a crucial role in regulating cellular responses during wound repair, yet the therapeutic potential of recombinant fibronectin functional domains remains insufficiently explored. In this study, three recombinant fibronectin variants (D89, D8910, and DK1) were successfully designed, expressed, and purified. Among them, DK1 exhibited superior biological activity, significantly enhancing cell proliferation, adhesion, and migration in vitro. To improve its therapeutic efficacy, recombinant DK1 was incorporated into a biocompatible hydrogel delivery system. The DK1-loaded hydrogel demonstrated excellent cytocompatibility, antioxidant, and antibacterial properties. In a diabetic mouse wound model, hydrogel-mediated delivery of DK1 significantly accelerated wound closure. Histological and immunohistochemical analyses further revealed that DK1 promoted wound repair by enhancing re-epithelialization, improving collagen deposition and remodeling, reducing inflammatory responses, and stimulating angiogenesis. These findings demonstrate that recombinant fibronectin DK1 enhances cellular responses and effectively promotes diabetic wound healing, highlighting its potential as a promising biomolecular therapeutic strategy for chronic wound treatment.