纳米纤维
姜黄素
伤口愈合
化学
药理学
体内
炎症
透明质酸
细胞生物学
纳米技术
生物化学
材料科学
医学
免疫学
生物
解剖
生物技术
作者
Jibing He,Shasha Zhou,Jiaxing Wang,Binbin Sun,Dalong Ni,Jinglei Wu,Xiaochun Peng
标识
DOI:10.1186/s12951-024-02385-9
摘要
Abstract Background In the inflammatory milieu of diabetic chronic wounds, macrophages undergo substantial metabolic reprogramming and play a pivotal role in orchestrating immune responses. Itaconic acid, primarily synthesized by inflammatory macrophages as a byproduct in the tricarboxylic acid cycle, has recently gained increasing attention as an immunomodulator. This study aims to assess the immunomodulatory capacity of an itaconic acid derivative, 4-Octyl itaconate (OI), which was covalently conjugated to electrospun nanofibers and investigated through in vitro studies and a full-thickness wound model of diabetic mice. Results OI was feasibly conjugated onto chitosan (CS), which was then grafted to electrospun polycaprolactone/gelatin (PG) nanofibers to obtain P/G-CS-OI membranes. The P/G-CS-OI membrane exhibited good mechanical strength, compliance, and biocompatibility. In addition, the sustained OI release endowed the nanofiber membrane with great antioxidative and anti-inflammatory activities as revealed in in vitro and in vivo studies. Specifically, the P/G-CS-OI membrane activated nuclear factor-erythroid-2-related factor 2 (NRF2) by alkylating Kelch-like ECH-associated protein 1 (KEAP1). This antioxidative response modulates macrophage polarization, leading to mitigated inflammatory responses, enhanced angiogenesis, and recovered re-epithelization, finally contributing to improved healing of mouse diabetic wounds. Conclusions The P/G-CS-OI nanofiber membrane shows good capacity in macrophage modulation and might be promising for diabetic chronic wound treatment.
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