Near-infrared light driven photodynamic therapy by hyaluronic acid encapsulated ionic polymer integrated with oxygen self-supply and high acetate supplement for chronic wound healing.

Hypoxia, persistent inflammation, excessive reactive oxygen species (ROS), bacterial infection, immune regulation disorder, and impaired angiogenesis are critical factors hindering diabetic wound healing. So far, clinical treatment still lacks comprehensive solutions to address these challenges. The main objective of this study is to develop and evaluate a novel multifunctional nanomaterial (Gen-BioCa/i-ZnPPOPs@HA) for enhancing the treatment of bacterial-infected diabetic wounds through a combination of photodynamic therapy, oxygen self-supply, and acetate supplementation. When infection occurs, Hyaluronic Acid (HA) shells are initially decomposed by hyaluronidase (HAase) secreted by the bacteria, releasing Gen, biomass Calcium peroxide (BioCa) and ionic porphyrin-based polyporous organic polymer (i-ZnPPOPs). BioCa decomposes to oxygen and Ca(OH)2, which alleviates the hypoxia in diabetes wounds and neutralize lactic acid released by the damaged blood vessels. Under NIR irradiation, cationic i-ZnPPOPs combined with Gen showed bacteria-targeting capacity, rapid and high-efficient microbicidal activity. The vitro/vivo experiments results revealed that Gen-BioCa/i-ZnPPOPs@HA could promote macrophages toward M2 polarization, accelerating angiogenesis, collagen deposition and tissues remodeling. In addition, further introduction of acetate supplement shorten the inflammatory period and accelerated wound healing process. This study provides a new strategy for the treatment of chronic bacterial infectious diseases, indicating the important potential of multifunctional nanomaterials in chronic wounds treatment.