East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 200241 Shanghai, China.
J Mater Chem B. 2019 Oct 16;7(40):6125-6138. doi: 10.1039/c9tb01327j.
The diabetic non-healing wound is one of the most common complications of diabetics. The long-term stimulus of oxidative stress, inflammation and infection caused by the hyperglycemic microenvironment in the wound site always leads to a delayed healing process of the diabetic wound. To address this issue, in this study, we prepared an asiatic acid (AA)-embedded aligned porous poly(l-lactic acid) (PLLA) electrospun fibrous scaffold (AA-PL) for accelerating diabetic wound healing. The results showed that the electrospun fibers with nanopores on the surfaces were aligned in a single direction, while the AA was well embedded in the fibers and can be continuously released from them. The in vitro results revealed that the AA-PL scaffolds can effectively alleviate the H2O2-induced oxidative stress damage to HaCat cells and downregulate the LPS-induced pro-inflammatory cytokine (IL-1β, TNF-α, IL6) gene expression in RAW 264.7 macrophage cells. Moreover, the growth of E. coli and S. aureus could be inhibited by the AA-PL scaffolds. The in vivo study further demonstrated that the AA-PL scaffolds can accelerate the re-epithelization, angiogenesis and extracellular matrix formation of a wound by relieving the high oxidative stress, inflammation and infection in the diabetic wound site. This study suggests that the combination of hierarchical structures (nanopores on the aligned fibers) with the controllable release of AA from the scaffolds is an efficient and innovative strategy for the treatment of diabetic non-healing wounds.
糖尿病不愈合创面是糖尿病患者最常见的并发症之一。高血糖微环境在创面处长期产生的氧化应激、炎症和感染刺激，总是导致糖尿病创面的愈合过程延迟。为了解决这个问题，在本研究中，我们制备了一种齐墩果酸（AA）嵌入的定向多孔聚（L-乳酸）（PLLA）静电纺丝纤维支架（AA-PL），以加速糖尿病创面愈合。结果表明，表面带有纳米孔的静电纺纤维呈单方向排列，而 AA 则很好地嵌入纤维中，并能从纤维中持续释放。体外结果表明，AA-PL 支架能有效缓解 H2O2 诱导的 HaCat 细胞氧化应激损伤，并下调 LPS 诱导的 RAW 264.7 巨噬细胞中促炎细胞因子（IL-1β、TNF-α、IL6）基因表达。此外，AA-PL 支架能抑制大肠杆菌和金黄色葡萄球菌的生长。体内研究进一步表明，AA-PL 支架通过缓解糖尿病创面处的高氧化应激、炎症和感染，能加速创面的再上皮化、血管生成和细胞外基质形成。本研究表明，具有分层结构（对齐纤维上的纳米孔）和 AA 从支架中可控释放的组合是治疗糖尿病不愈合创面的一种有效且创新的策略。
