Small Intestinal Submucosa Membrane Modified by Fusion Peptide‐Mediated Extracellular Vesicles to Promote Tissue Regeneration

Abstract Tissue injury, which often occurs in daily life, remains challenging in clinical medicine. Developing a novel biomaterial with the capability to provide an ideal microenvironment and homeostasis around the wound is highly desirable for effective tissue regenerative medicine. The small intestinal submucosa (SIS) membrane possesses a precise spatial structure with excellent biocompatibility. Extracellular vesicles (EVs) derived from umbilical cord mesenchymal stem cells can achieve rapid cell proliferation and migration with little immune response by creating a satisfactory microenvironment. In this study, fusion peptide‐mediated EVs are able to modify the surface of the SIS membrane via specific combination. In vitro studies prove that modified SIS membranes can promote cell migration and spreading. This phenomenon may be because of the activation of TEADs, which regulate cell behavior. By constructing a rat abdominal wall defect model, it is further demonstrated that the modified SIS membrane is more conducive to tissue regeneration. Collectively, these results suggest that SIS membranes modified by fusion peptide‐mediated EVs achieve excellent biofunction and provide promising prospects for tissue regeneration.