Antibacterial coaxial hydro-membranes accelerate diabetic wound healing by tuning surface immunomodulatory functions
Wei Zhang, Sizhan Xia, Tingting Weng, Min Yang, Jiaming Shao, Manjia Zhang, Jialiang Wang, Pengqing Xu, Jintao Wei, Ronghua Jin, Meirong Yu, Zhongtao Zhang, Chunmao Han, Xingang Wang
Abstract
Diabetic foot ulcers, typical non-healing wounds, represent a severe clinical problem. Advanced glycation end-products (AGEs), which create a prolonged pro-inflammatory micro-environment in defective sites, can be responsible for refractoriness of these ulcers. Macrophages are polarized to the M2 phenotype to facilitate the transition from a pro-inflammatory microenvironment to an anti-inflammatory microenvironment, which has been demonstrated to be an effective way to accelerate diabetic wound closure. Herein, we developed coaxial hydro-membranes mimicking the extracellular matrix structure that are capable of anti-inflammatory and antibacterial functions for diabetic wound repair. These fibrous membranes maintain a moist microenvironment to support cell proliferation. Macrophages grow in an elongated shape on the surface of the fibrous membranes. The fibrous membranes effectively impaired macrophage AGE-induced M1 polarization and induced macrophage polarization towards the M2 phenotype. The effects of the fibrous membranes on the interactions between macrophages and repair cells under a diabetic condition were also investigated. Furthermore, in vivo results from a full-thickness diabetic wound model confirmed the potential of the coaxial hydro-membranes to accelerate wound healing. This study's results indicate that the developed bioactive anti-inflammatory and antibacterial wound dressing can affect AGE-induced macrophage activation and crosstalk between macrophages and fibroblasts for treating diabetic wounds.