An adhesive hydrogel enabling spatiotemporal delivery of umbilical cord exosomes for scarless skin regeneration through immunomodulation and ECM remodeling.

Abstract

The regenerative repair of full-thickness skin defects remains a formidable clinical challenge, often culminating in pathological scarring because conventional dressings lack the functionality to balance robust adhesion with mechanical compliance and actively direct tissue regeneration. To address this, we propose an adhesive dual-network hydrogel (GelMA-PBA/HANB/HepMA) via the synergistic integration of dynamic boronic ester bonds and photo-triggered imine crosslinking, while serving as a smart depot for sustained delivery of umbilical cord-derived exosomes (uExos). This system orchestrates a pro-regenerative niche by polarizing macrophages to a pro-healing phenotype and enhancing endothelial angiogenesis, thereby accelerating wound closure and re-epithelialization in a mouse full-thickness defect model. Crucially, in a rigorous rabbit ear hypertrophic scar model, treatment significantly reduces the Scar Elevation Index (SEI) and restores a physiological collagen architecture, evidenced by an increased Col III/I ratio and reduced bulge angle. Importantly, uExos promote scarless healing involved in extracellular matrix remodeling and balanced collagen deposition. By strategically combining smart adhesive materials with cell-free exosome therapy, this study offers a promising strategy for regenerative wound healing and scar prevention.