Fusion peptide-functionalized amniotic membrane scaffold promotes diabetic burn repair by modulating neurovascular coupling

Diabetic wounds are a severe complication of diabetes, characterized by impaired neurovascular regeneration and chronic inflammation, which leads to high rates of amputation and a diminished quality of life. To overcome this challenge, we engineered a biofunctional composite scaffold by immobilizing a rationally designed fusion peptide (FP) onto a decellularized amniotic membrane (dAM) matrix. The FP integrates the neuroactive IKVAV sequence and the angiogenic QK motif through a specific collagen-binding domain (CBD), enabling stable and uniform anchoring within the dAM's collagen network. Comprehensive in vitro evaluations demonstrated that the dAM-FP scaffold significantly outperformed control scaffolds (dAM alone or modified with single peptides) in promoting the migration of endothelial progenitor cells and rat schwann cells, fostering capillary-like tube formation, and stimulating robust neurite outgrowth from PC12 cells. In a diabetic mouse full-thickness burn wound model, treatment with the dAM-FP scaffold resulted in markedly accelerated wound closure kinetics. Most importantly, histological and immunofluorescence analyses confirmed its superior dual functionality: the scaffold simultaneously and synergistically enhanced the regeneration of both microvascular networks and sensory nerve fibers within the healing wound bed. This study suggests that CBD-mediated co-presentation of neurogenic and angiogenic cues on a natural ECM scaffold may contribute to neurovascular regeneration in diabetic burn wound repair. The dAM-FP scaffold thus represents a promising biomaterial strategy for refractory diabetic wounds, while further validation is still required before clinical translation.