Herbal micelles-loaded ROS-responsive hydrogel with immunomodulation and microenvironment reconstruction for diabetic wound healing

Xiaoyang Liang; Honggui Chen; Rui Zhang; Zhixuan Xu; Guo Zhang; Chen Xu; Yang Li; Lei Zhang; Fu-Jian Xu

doi:10.1016/j.biomaterials.2024.123076

Herbal micelles-loaded ROS-responsive hydrogel with immunomodulation and microenvironment reconstruction for diabetic wound healing

Biomaterials. 2024 Dec 30:317:123076. doi: 10.1016/j.biomaterials.2024.123076. Online ahead of print.

Authors

Xiaoyang Liang¹, Honggui Chen¹, Rui Zhang¹, Zhixuan Xu¹, Guo Zhang¹, Chen Xu¹, Yang Li², Lei Zhang³, Fu-Jian Xu⁴

Affiliations

¹ State Key Laboratory of Chemical Resource Engineering, Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology, Ministry of Education), Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China.
² State Key Laboratory of Chemical Resource Engineering, Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology, Ministry of Education), Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China. Electronic address: ly@mail.buct.edu.cn.
³ Department of Vascular Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China. Electronic address: zhanglei@shutcm.edu.cn.
⁴ State Key Laboratory of Chemical Resource Engineering, Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology, Ministry of Education), Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China. Electronic address: xufj@mail.buct.edu.cn.

PMID: 39805188
DOI: 10.1016/j.biomaterials.2024.123076

Abstract

Persistent inflammation is a major cause of diabetic wounds that are difficult to heal. This is manifested in diabetic wounds with excessive reactive oxygen clusters (ROS), advanced glycation end products (AGE) and other inflammatory factors, and difficulty in polarizing macrophages toward inhibiting inflammation. Berberine is a natural plant molecule that inhibits inflammation; however, its low solubility limits its biological function through cytosis. In this study, we designed F127 micelles to encapsulate berberine with the aim of improving its solubility and bioavailability. Meanwhile, in order to achieve effective drug delivery at the wound site, we designed an injectable ferrocene-cyclodextrin self-assembled oxidation-reactive supramolecular hydrogel drug delivery system. Cellular experiments have shown that the hydrogel can reduce intracellular ROS and AGE production, attenuate cellular damage, promote macrophage polarization toward inhibition of inflammation, and reduce the secretion of inflammatory factors. In an animal model of diabetic mice, this hydrogel dressing reduces the level of inflammation in diabetic wounds, optimizes collagen deposition in diabetic wounds, and ultimately achieves high-quality diabetic wound healing. The work offers a straightforward and effective solution to the challenge of administering hydrophobic anti-inflammatory agents in the context of diabetic wound therapy.

Keywords: Anti-inflammation; Berberine; Diabetic wound healing; Hydrogel; Micelle.