Zhang Wei, Xia Sizhan, Weng Tingting, Yang Min, Shao Jiaming, Zhang Manjia, Wang Jialiang, Xu Pengqing, Wei Jintao, Jin Ronghua, Yu Meirong, Zhang Zhongtao, Han Chunmao, Wang Xingang
Department of Burns and Wound Care Center, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, 310000, China.
The Key Laboratory of the Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Hangzhou 310000, China.
Mater Today Bio. 2022 Aug 13;16:100395. doi: 10.1016/j.mtbio.2022.100395. eCollection 2022 Dec.
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, 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.
糖尿病足溃疡是典型的难愈合伤口，是一个严重的临床问题。晚期糖基化终产物（AGEs）在损伤部位营造了一个长期的促炎微环境，可能是这些溃疡难愈合的原因。巨噬细胞极化为M2表型有助于从促炎微环境向抗炎微环境转变，这已被证明是加速糖尿病伤口愈合的有效方法。在此，我们开发了模拟细胞外基质结构的同轴水凝胶膜，其具有抗炎和抗菌功能，用于糖尿病伤口修复。这些纤维膜维持湿润的微环境以支持细胞增殖。巨噬细胞在纤维膜表面呈细长形生长。纤维膜有效抑制了巨噬细胞AGE诱导的M1极化，并诱导巨噬细胞向M2表型极化。还研究了纤维膜在糖尿病条件下对巨噬细胞与修复细胞之间相互作用的影响。此外，全层糖尿病伤口模型的结果证实了同轴水凝胶膜加速伤口愈合的潜力。本研究结果表明，所开发的具有生物活性的抗炎抗菌伤口敷料可影响AGE诱导的巨噬细胞活化以及巨噬细胞与成纤维细胞之间的相互作用，用于治疗糖尿病伤口。
