Li Hongyi, Wen Huiyun, Zhang He, Cao Xiang, Li Li, Hu Xiaowen, Zhang Yanmei, Shen Xinkun, Shubhra Quazi T H, Yang Hong, Cai Xiaojun
Department of Chemical Engineering, Northwest University, No. 229, Taibai North Road, Beilin District, Xi'an City, Xi'an 710069, China.
School and Hospital of Stomatology, Wenzhou Medical University, No. 268, Xueyuan West Road, Lucheng District, Wenzhou 325027, China.
Burns Trauma. 2025 Mar 19;13:tkaf024. doi: 10.1093/burnst/tkaf024. eCollection 2025.
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 a multifunctional hydrogel (DPFI) engineered for sequential therapeutic actions, including antibacterial, anti-inflammatory, antioxidant, pro-vascularization/epithelialization, and glycemic-regulating properties, to address these complications.
DPFI hydrogels were prepared by encapsulating dihydromyricetin (DMY) into aldehyde-functionalized Pluronic F127 micelles (DMY@PF127-CHO), followed by a Schiff base reaction with amine-rich polyethyleneimine (PEI), resulting in the formation of a hydrogel for controlled drug release. The antimicrobial, antioxidant, anti-inflammatory, pro-cellular proliferative, and angiogenic properties of the hydrogels were evaluated using various techniques, including structural characterization, bacterial live/dead staining, reactive oxygen species (ROS) assays, antioxidant enzyme assays, reverse transcription-polymerase chain reaction (RT-PCR), cellular immunofluorescence staining, scratch wound healing assays, and angiogenesis assays. , the effects of the hydrogel on wound healing and glycemic control were assessed in methicillin-resistant -infected mice with streptozotocin-induced diabetes.
The hydrogel exhibits exceptional injectability, bioadhesion, and self-healing properties, facilitating the controlled, sustained release of DMY, which synergistically enhances antimicrobial effects in combination with PEI. The antioxidant activity of DMY is remarkable; it effectively scavenges ROS and induces the expression of antioxidant enzymes while promoting the phenotypic switch of M1 macrophages to M2 macrophages to mitigate inflammation. Critically, DPFI also contributes to glycemic regulation, reducing hyperglycemia-associated complications and creating a microenvironment conducive to wound repair. Comprehensive and analyses corroborate the multifaceted therapeutic capabilities of DPFI, including its antibacterial activity and abilities to clear ROS, reduce inflammation, promote angiogenesis, promote epithelialization, and modulate blood glucose levels.
DPFI represents a promising, integrative strategy for enhanced diabetic wound management, meriting further exploration for clinical application.
慢性糖尿病伤口的管理在临床实践中仍然是一项艰巨的挑战。持续的高血糖会引发血管病变、神经病变和免疫功能障碍，严重阻碍伤口修复。我们开发了一种多功能水凝胶（DPFI），其设计用于连续的治疗作用，包括抗菌、抗炎、抗氧化、促血管生成/上皮形成和血糖调节特性，以解决这些并发症。
通过将二氢杨梅素（DMY）封装到醛功能化的普朗尼克F127胶束（DMY@PF127-CHO）中，然后与富含胺的聚乙烯亚胺（PEI）进行席夫碱反应，制备DPFI水凝胶，从而形成用于药物控释的水凝胶。使用各种技术评估水凝胶的抗菌、抗氧化、抗炎、促细胞增殖和血管生成特性，包括结构表征、细菌活/死染色、活性氧（ROS）测定、抗氧化酶测定、逆转录-聚合酶链反应（RT-PCR）、细胞免疫荧光染色、划痕伤口愈合测定和血管生成测定。此外，在链脲佐菌素诱导的糖尿病且感染耐甲氧西林金黄色葡萄球菌的小鼠中评估水凝胶对伤口愈合和血糖控制的影响。
该水凝胶具有出色的可注射性、生物粘附性和自愈特性，有助于DMY的可控、持续释放，与PEI联合可协同增强抗菌效果。DMY的抗氧化活性显著；它能有效清除ROS并诱导抗氧化酶的表达，同时促进M1巨噬细胞向M2巨噬细胞的表型转换以减轻炎症。至关重要的是，DPFI还有助于血糖调节，减少与高血糖相关的并发症，并创造有利于伤口修复的微环境。全面的体外和体内分析证实了DPFI的多方面治疗能力，包括其抗菌活性以及清除ROS、减轻炎症、促进血管生成、促进上皮形成和调节血糖水平的能力。
DPFI是一种有前景的、综合的增强糖尿病伤口管理的策略，值得进一步探索其临床应用。
