Electrospun Scaffold Co‐Modified with YIGSR Peptide and Heparin for Enhanced Skin Wound Healing

Abstract Angiogenesis is a critical step in biomaterial‐assisted skin tissue regeneration, as it ensures adequate oxygen and nutrient supply to the wound site, facilitating cellular proliferation and tissue remodeling. Electrospun polycaprolactone/gelatin (PG) scaffolds exhibit good biocompatibility and biodegradability; however, their bio‐inert nature limits their applications. To enhance the angiogenic properties of PG scaffolds, this study aimed to develop a novel biomaterial by co‐modifying electrospun PG scaffolds (PGHY) with YIGSR peptide and heparin. YIGSR, a laminin‐derived peptide, serves as an endothelial cell‐specific adhesion sequence, while heparin acts as a peptide reservoir, facilitating retention and controlled release. In vitro experiments demonstrated that among three peptide‐loading concentrations, PGHY 1.0 scaffold exhibited stable peptide release and promoted endothelial cell proliferation, migration, and tube formation via the FAK/MAPK/ERK1/2 signaling pathway. In vivo results further confirmed that the PGHY 1.0 scaffold enhanced angiogenesis in murine dorsal skin defects, accelerating wound healing. Overall, the PGHY 1.0 scaffold, with its excellent biocompatibility and pro‐angiogenic properties, presents a promising therapeutic strategy for skin tissue regeneration.