A multifunctional Dihydromyricetin-loaded hydrogel for the sequential modulation of diabetic wound healing and Glycemic control

• DOI: 10.1093/burnst/tkaf024
• Publication Date: 2025-03-19T19:33:29Z
• Authors: Hongyi Li; Huiyun Wen; He Zhang; Xiang Cao; Li Li; Xiaowen Hu; Yanmei Zhang; Xinkun Shen; Quazi T H Shubhra; Hong Yang; Xiaojun Cai

Abstract Background The management of chronic diabetic wounds remains a formidable challenge in clinical practice. Persistent hyperglycemia triggers vasculopathy, neuropathy, and immune dysfunction, critically impeding wound repair. We developed multifunctional hydrogel (DPFI) engineered for sequential therapeutic actions, including antibacterial, anti-inflammatory, antioxidant, pro-vascularization/epithelialization, glycemic-regulating properties, to address these complications. Methods DPFI hydrogels were prepared by encapsulating dihydromyricetin (DMY) into aldehyde-functionalized Pluronic F127 micelles (DMY@PF127-CHO), followed Schiff base reaction with amine-rich polyethyleneimine (PEI), resulting the formation controlled drug release. antimicrobial, pro-cellular proliferative, angiogenic properties evaluated using various techniques, structural characterization, bacterial live/dead staining, reactive oxygen species (ROS) assays, antioxidant enzyme reverse transcription–polymerase chain (RT–PCR), cellular immunofluorescence scratch healing angiogenesis assays. In vivo, effects on glycemic control assessed MRSA-infected mice streptozotocin-induced diabetes. Results exhibits exceptional injectability, bioadhesion, self-healing facilitating controlled, sustained release DMY, which synergistically enhances antimicrobial combination PEI. activity DMY is remarkable; it effectively scavenges induces expression enzymes while promoting phenotypic switch M1 macrophages M2 mitigate inflammation. Critically, also contributes regulation, reducing hyperglycemia-associated complications creating microenvironment conducive Comprehensive vitro vivo analyses corroborate multifaceted capabilities DPFI, its antibacterial abilities clear ROS, reduce inflammation, promote angiogenesis, epithelialization, modulate blood glucose levels. Conclusions represents promising, integrative strategy enhanced management, meriting further exploration application.