Genetically\nEncoded Incorporation of IFN‑α\ninto Collagen-like Protein–Hyaluronic Acid Hydrogels for Diabetic\nChronic Wound Healing

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