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

“Fusion peptide-functionalized amniotic membrane scaffold promotes diabetic burn repair by modulating neurovascular coupling. Xiao Z(1), Chen S(2), Luo H(3), Tong X(4), Zhou L(1), Liu W(5), Yang Y(6), Yang J(1), Tian H(7), Zhang Y(8). Author information: (1)Department of Medical Cosmetology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, 410028, China. (2)Department of Plastic and Laser Cosmetology, The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People's Hospital, Changsha, 410005, China. (3)Department of Plastic Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China. (4)Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. (5)Department of Orthopaedics, Third Xiangya Hospital, Central South University, Changsha, 410013, China. (6)Department of Research Development, Jiangxi Ruiji Biotechnology Engineering Co., Ltd., Nanchang, 330098, China; School of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China. (7)International Medical Department, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, 410013, China. Electronic address: 30440281@qq.com. (8)Department of Orthopedics, First Hospital of Shanxi Medical University, Taiyuan, 030001, China; Department of Orthopedic Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China. Electronic address: zhangyu171@126.com. 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. Copyright © 2026. Published by Elsevier B.V. Conflict of interest statement: Declaration of competing interest The authors state that there are no financial or personal competing interests to declare.”