Genetically Encoded Incorporation of IFN-α into Collagen-like Protein–Hyaluronic Acid Hydrogels for Diabetic Chronic Wound Healing

The role of interferon-alpha is critical in modulating immune responses and the wound healing process. However, the rapid degradation and short lifespan of IFN-α in the body limit its therapeutic efficacy in wound management. This study presents an innovative approach to enhancing diabetic wound repair through the incorporation of IFN-α into double network hydrogels composed of hyaluronic acid and collagen-like protein (CLP). Two incorporation methods were evaluated: genetic fusion and spy-chemistry ligation. Our results demonstrate that IFN-α incorporated via spy-chemistry significantly outperformed genetic fusion in terms of cell viability, migration, and protein expression. In vivo studies further confirmed that spy-chemistry ligated IFN-α HA-CLP hydrogels markedly improved wound healing, as evidenced by elevated levels of COL-1α, CK-14, and α-SMA, compared to blank HA-CLP hydrogels and saline-treated controls. These findings underscore the potential of spy-chemistry ligated IFN-α-HA-CLP hydrogels as a promising therapeutic strategy for promoting effective wound healing in diabetic patients.