A ROS-Responsive Pectin/PVA Hydrogel Loaded with Ganoderma atrum Polysaccharide Accelerates Diabetic Wound Healing by Polarizing Macrophages toward the M2 Phenotype

Abstract Diabetic chronic wound healing is hindered by excessive reactive oxygen species (ROS) and dysregulated inflammation. To address this challenge, we developed a multifunctional hydrogel based on natural polymer. Specifically, an ROS-responsive hydrogel was fabricated via dynamic boronate ester bonds between phenylboronic acid-functionalized pectin (Pe-PBA) and poly(vinyl alcohol) (PVA), then loaded with Ganoderma atrum polysaccharide (PSG), termed Pe/PVA@PSG. The obtained hydrogel exhibited excellent mechanical properties and self-healing ability, enabling efficient PSG release triggered in response to high-glucose and -ROS conditions. In vitro, it showed excellent biocompatibility, significantly facilitated fibroblast proliferation and migration, and suppressed ROS accumulation and macrophage inflammatory responses. In a diabetic wound model, Pe/PVA@PSG markedly accelerated wound closure, achieving 93.42% closure on day 14, which enhanced collagen deposition and skin appendage regeneration, elevated IL-10, upregulated PD-L1, and drove macrophage polarization toward the M2 phenotype. Overall, the Pe/PVA@PSG hydrogel provides an innovative strategy for chronic diabetic wound management.