Cell membrane-camouflaged nanoparticles activate fibroblast-myofibroblast transition to promote skin wound healing.

IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Qi Jia, Yijuan Ding, Ziwen Su, Heying Chen, Jialing Ye, Dafeng Xie, Yubo Wu, Haiyan He, Yanlin Peng, Yilu Ni
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Abstract

The fibroblast-myofibroblast transition marked by extracellular matrix (ECM) secretion and contraction of actomyosin-based stress fibers, plays central roles in the wound healing process. This work aims to utilize the cell membrane-based nanoplatform to improve the outcomes of dysregulated wound healing. The cell membranes of myofibroblasts isolated from mouse skin are used as the camouflage for gold nanoparticles loaded with IL-4 cytokine. The membrane-modified nanoparticles show effective in situ clearance of bacterial infection, and act as the activator in IL-4Rα signaling pathway to induce pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype. Thus, the poor bacteria-clearance and non-stop inflammation in refractory wounds are improved and accelerated. Furthermore, the nanoplatform releases myofibroblast membranes to propel primitive fibroblasts toward the fibroblast-myofibroblast transition in an epigenetic manner. Matrix-production, vascularization, and epithelial regeneration are then initiated, leading to the satisfactory wound closure. Our study devises a new strategy for activating fibroblasts into myofibroblasts under prolonged and continuous exposure to the fibrotic environment, and develops a promising biomimetic nanoplatform for effective treatment of dysregulated chronic wound healing.

细胞膜伪装纳米颗粒激活成纤维细胞-肌成纤维细胞转化,促进皮肤伤口愈合。
以细胞外基质(ECM)的分泌和肌动球蛋白为基础的应激纤维的收缩为标志的成纤维细胞-肌成纤维细胞转变在伤口愈合过程中起着核心作用。这项工作旨在利用基于细胞膜的纳米平台来改善失调伤口愈合的结果。从小鼠皮肤中分离出肌成纤维细胞的细胞膜,并用IL-4辅助细胞因子作为伪装包封金纳米颗粒。膜伪装纳米颗粒显示出对细菌感染的原位清除效果,并作为IL-4Rα信号通路的激活剂,诱导促炎M1亚型巨噬细胞向抗炎m2表型转变。从而改善和加速难治性伤口的细菌清除率差和持续炎症。接下来,纳米平台释放肌成纤维细胞膜,进一步推动原始成纤维细胞以表观遗传方式经历成纤维细胞-肌成纤维细胞的转变。然后开始基质生成、血管形成和上皮再生,导致令人满意的伤口愈合。我们的研究设计了一种新的策略,通过表观遗传修饰使成纤维细胞在长时间持续暴露于纤维化环境下转变为肌成纤维细胞,并开发了一种有前途的仿生纳米平台,用于有效治疗慢性伤口愈合失调。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biofabrication
Biofabrication ENGINEERING, BIOMEDICAL-MATERIALS SCIENCE, BIOMATERIALS
CiteScore
17.40
自引率
3.30%
发文量
118
审稿时长
2 months
期刊介绍: Biofabrication is dedicated to advancing cutting-edge research on the utilization of cells, proteins, biological materials, and biomaterials as fundamental components for the construction of biological systems and/or therapeutic products. Additionally, it proudly serves as the official journal of the International Society for Biofabrication (ISBF).
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