Abstract
Chronic wounds, frequently arising from conditions like diabetes, trauma, or chronic inflammation, represent a significant medical challenge due to persistent inflammation, heightened infection risk, and limited treatment solutions. This study presents a novel bioengineered approach to promote tissue repair and improve the healing environment. We developed a bioactive hydrogel patch, encapsulated zeolitic imidazolate framework-8 (ZIF-8) into extracellular vesicles (EVs) derived from anti-inflammatory M2 macrophages, and synthesized ZIF@EV, then embedded it in the sodium alginate matrix. This hydrogel structure enables the controlled release of therapeutic agents directly into the wound site, where it stimulates endothelial cell proliferation and promotes new blood vessel formation. These processes are key components of effective tissue regeneration. Crucially, the EV-infused patch influences the immune response by polarizing macrophages towards an M2 phenotype, shifting the wound environment from inflammation toward regenerative healing. When applied in a murine model of chronic wounds, the EV hydrogel patch demonstrated notable improvements in healing speed, quality, and tissue integration compared to traditional approaches such as growth factor therapies and foam dressings. These promising findings suggest that this bioactive hydrogel patch could serve as a versatile, practical solution for chronic wound management, providing an adaptable platform that addresses both the biological and logistical needs of wound care in clinical settings.