Resveratrol-Loaded <i>Dendrobium Officinale</i> Polysaccharide Hydrogel Developed via Dynamic Covalent Bonding for Improved Diabetic Wound Healing

Excessive reactive oxygen species (ROS) accumulation and an imbalance in M1/M2 macrophage polarization are major contributors to impaired diabetic wound healing. Based on these findings, we developed an injectable hydrogel dressing capable of modulating the wound microenvironment. 1,4-Butanediol diglycidyl ether (BDDE) was linked to Dendrobium officinale polysaccharide (DOP) and sodium polyacrylate (PAAS) via ether bonds to form the DOP-BDDE-PAAS (DBP). 3-Aminophenylboronic acid (PBA) was linked to hyaluronic acid (HA) via amide bonds and to resveratrol (Res) via boronate bonds, yielding the HA-PBA-Res (HPR). The DBP and HPR components were then combined to form the DBPHPR hydrogel network. The hydrogel exhibited suitable injectability and self-healing properties. In vitro experiments demonstrated that the hydrogel released Res in response to high ROS or glucose concentrations. Through the synergistic effects of DOP and Res, the hydrogel promoted fibroblast proliferation and migration, effectively scavenged excessive ROS, and regulated macrophage polarization toward the M2 phenotype. In a full-thickness skin defect model in mice, the DBPHPR hydrogel reduced inflammation, promoted wound epithelialization, accelerated collagen deposition, and enhanced overall wound healing. In summary, the plant polysaccharide-bioactive small-molecule hydrogel developed via dynamic covalent bonding offers a strategy for diabetic wound dressings and has promising potential for clinical application.