Multifunctional bioactive peptide-laden and adhesion-switchable dual-crosslinked hydrogel for accelerated healing of infected deep burn wounds.

Abstract

Infected deep burn wounds represent a severe clinical challenge due to microbial invasion, persistent inflammation, impaired tissue regeneration, and subsequent scar formation. To address these issues, we developed stimuli-responsive and on-demand removable hydrogel dressing (AMP@GPQCD) with injectability, antibacterial, antioxidant, anti-inflammatory, and pro-angiogensis capacities for comprehensive management of deep burn wounds. The AMP@GPQCD hydrogel was composed of phenylboronic acid-modified gelatin methacrylate (GelMA-PBA), catechol-decorated chitosan (CS-DA), vinyl-terminated VEGF-mimetic peptide (QKMA), and an ultrashort antimicrobial lipopeptide (AMP, C₁₂-RFKFRF-NH₂). The dual crosslinking GPQCD hydrogel was fabricated through the dynamic phenylborate bonds between GelMA-PBA and CS-DA, and UV-initiated polymerization of GelMA and QKMA. The acidic and oxidative microenvironment at the infected burn wounds triggered the dissociation of phenylborate bonds, leading to the rapid release of the encapsulated AMP. Notably, the on-demand and painless removal of the hydrogel dressing could be achieved by applying glucose solution through competition with the catechol groups on CS-DA for binding to phenylboronic acid. In vivo studies demonstrated advanced burn wound healing via hemostasis, antibacterial, antioxidant, anti-inflammation, angiogenesis, and tissue regeneration, promoting the formation of a healthier basket-weave collagen network, thereby reducing the tendency towards fibrosis. This study provides a transformative therapeutic solution for infected deep burn wounds. STATEMENT OF SIGNIFICANCE: A dual-crosslinked smart hydrogel (AMP@GPQCD) with multi-stimuli responsiveness was constructed. The dynamic borate network of AMP@GPQCD hydrogels in response to acidic pH and high ROS level could rapidly release ultrashort antimicrobial lipopeptides and scavenge excess ROS, followed by effective macrophages polarization into M2 phenotype for comprehensive anti-infection and inflammation regulation. AMP@GPQCD hydrogels can continuously promote fibroblast proliferation/migration and angiogenesis through covalently grafted VEGF mimetic peptides, capable of enhancing collagen remodeling for reducing fibrosis tendency. In addition, the glucose-responsive AMP@GPQCD hydrogel can be painlessly removed on demand, avoiding secondary damage to the wound.