Protein-based functional hydrogel improves cutaneous nerve repair and diabetic wound healing

Cutaneous nerve regeneration in diabetic wounds remains a challenge for current clinical treatment. Herein, a natural protein-based functional hydrogel is developed using keratin as the sole matrix, and protocatechuic aldehyde (PA) and zinc ions as the building blocks through dual-dynamic crosslinking reactions of thiol-aldehyde addition and catechol-zinc ions coordination. The unique structural design endows the hydrogel with excellent injectability, skin adhesion, self-healing and antibacterial ability, and biocompatibility. In addition, this hydrogel acts as a drug carrier for the loading and sustained release of phellopterin (PP), a natural compound extracted from traditional Chinese medicine <i>Angelica dahurica</i>. Our findings demonstrate that the PP-loaded hydrogel promotes cutaneous nerve regeneration, angiogenesis and tissue remodeling in the full-thickness wounds in both db/db and streptozotocin-induced C57BL/6 diabetic mice, notably by the synergistic effect of zinc ions and PP, showing a great potential in diabetic wound therapy.