A Dual-Network Bletilla Striata Polysaccharide Hydrogel for PPAR-Mediated Macrophage Polarization and Accelerated Diabetic Wound Healing

Abstract

Chronic diabetic wounds remain difficult to heal due to persistent inflammation and impaired macrophage polarization. Herein, we developed an immunoregulatory dressing using a hybrid hydrogel (C-B-S) synthesized from natural polysaccharides through the photo-polymerization of carboxymethyl chitosan methacrylate (CMCMA), Bletilla striata polysaccharide methacrylate (BSPMA), and thiolated hyaluronic acid (HA-SH). The hydrogel demonstrated dual functionality by promoting hemostasis and inducing macrophage polarization toward the M2 phenotype. RNA sequencing analysis revealed that the immunomodulatory effect of Bletilla striata polysaccharide is mediated via the PPAR signaling pathway. In vivo studies demonstrated the C-B-S hydrogel enhanced angiogenesis, re-epithelialization, and collagen deposition, leading to the fastest wound closure among all groups. This study offers a transformative therapeutic strategy to restore immune balance and accelerate diabetic tissue repair, highlighting its potential for clinical translation in treating chronic diabetic wounds.