Plant-Derived B-CGT Hydrogel Accelerates Diabetic Wound Healing Through Multitarget Modulation of Inflammation, Angiogenesis, and Tissue Remodeling

Abstract

Diabetic wound healing presents significant challenges due to impaired angiogenesis, chronic inflammation, and cellular dysfunction. Building on previous research, this study further explores the potential of a plant-derived glucosyloxybenzyl 2-isobutylmalates (B-CGT) hydrogel in promoting diabetic wound healing. Network pharmacology and molecular docking analyses suggest that B-CGT may regulate key mechanisms, such as apoptosis, inflammation, and matrix remodeling, through core targets including SIRT1, CASP8, and MMP8. In vivo studies further demonstrated that B-CGT hydrogel significantly accelerated wound closure in diabetic mice, enhanced angiogenesis, promoted collagen deposition, and achieved immune balance by modulating macrophage polarization, thereby shifting the inflammatory environment toward a repair state. Moreover, B-CGT hydrogel significantly improved the wound microenvironment by upregulating VEGF expression and exerting antioxidant effects. By combining theoretical predictions with experimental validation, this study elucidates the multi-target synergistic regulatory mechanisms of B-CGT hydrogel. These findings provide new research directions for addressing immune imbalance and angiogenesis defects in diabetic wound healing and lay a scientific foundation for the optimization and application of chronic wound treatment strategies.