A dual-network <i>Bletilla striata</i> polysaccharide hydrogel for PPAR-mediated macrophage polarization and accelerated diabetic wound healing

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 photopolymerization of carboxymethyl chitosan methacrylate (CMCMA), <i>Bletilla striata</i> 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 <i>Bletilla striata</i> polysaccharide is mediated <i>via</i> the PPAR signaling pathway. <i>In vivo</i> 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.