Sprayable EGCG-Grafted Alginate Hydrogels Embedded with Platelet Exosomes: Functional Synergy of Immunomodulation and Angiogenesis for Accelerating Burn Wound Healing

Abstract Burn wounds were often entrapped in inflammatory cascades and highly vulnerable to bacterial infection. Meanwhile, accumulated necrotic tissue and impaired vessels further aggravated local ischemia, thereby impeding the wound healing process. Herein, a sprayable hydrogel based on EGCG-grafted oxidized alginate/carboxymethyl chitosan/platelet exosomes (AECP hydrogel) was fabricated. Covalent grafting of EGCG onto alginate endowed an AECP hydrogel with a controllable release profile for a sustained functional effect of EGCG. Due to the inherent bioactivity of EGCG, the AECP hydrogel could eliminate bacteria, scavenge intracellular ROS, and promote macrophage polarization. Moreover, the introduced platelet exosomes significantly upregulated angiogenesis-related gene expression in HUVECs. 3D cell encapsulation demonstrated that the AECP hydrogel supported cell proliferation and spreading, conducive to exerting the biological functions of cells recruited to the wound site. Additionally, an AECP hydrogel precursor could be conveniently sprayed onto irregular wounds and in situ form a protective barrier via dynamic hydrogen bond interactions and Schiff base reactions. In vivo experiments confirmed that sprayable AECP hydrogel accelerated burn wound closure through enhanced collagen deposition, granulation tissue formation, macrophage polarization, and neovascularization. Overall, this work presents a sprayable EGCG-grafted, platelet exosome-incorporated alginate hydrogel with integrated immunoregulatory and proangiogenic properties, holding substantial potential for clinical burn wound management.