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可重复的光动力疗法,通过触发成纤维细胞增殖和分化的信号通路,促进细菌伴随的伤口愈合。

Repeatable Photodynamic Therapy with Triggered Signaling Pathways of Fibroblast Cell Proliferation and Differentiation To Promote Bacteria-Accompanied Wound Healing.

机构信息

School of Materials Science & Engineering, Tianjin University , Tianjin 300072, China.

Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry of Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Key Laboratory of Polymer Materials, School of Materials Science & Engineering, Hubei University , Wuhan 430062, China.

出版信息

ACS Nano. 2018 Feb 27;12(2):1747-1759. doi: 10.1021/acsnano.7b08500. Epub 2018 Feb 2.

DOI:10.1021/acsnano.7b08500
PMID:29376340
Abstract

Despite the development of advanced antibacterial materials, bacterial infection is still a serious problem for wound healing because it usually induces severe complications and cannot be eradicated completely. Most current materials cannot simultaneously provide antibacterial activity, reusability, and biocompatibility as well as participate in stimulating cell behaviors to promote bacteria-accompanied wound healing. This work fabricated a hybrid hydrogel embedded with two-dimensional (2D) few-layer black phosphorus nanosheets (BPs) via simple electrostatic interaction. Within 10 min, 98.90% Escherichia coli and 99.51% Staphylococcus aureus can be killed rapidly by this hybrid, due to its powerful ability to produce singlet oxygen (O) under simulated visible light. In addition, this hydrogel also shows a high repeatability; that is, the antibacterial efficacy can still reach up to 95.6 and 94.58% against E. coli and S. aureus, respectively, even after challenging bacteria up to four times repeatedly. In vitro and in vivo results reveal that BPs in this hybrid hydrogel can promote the formation of the fibrinogen at the early stages during the tissue reconstruction process for accelerated incrustation. In addition, BPs can also trigger phosphoinositide 3-kinase (PI3K), phosphorylation of protein kinase B (Akt), and extracellular signal-regulated kinase (ERK1/2) signaling pathways for enhanced cellular proliferation and differentiation. Moreover, the hydrogel causes no appreciable abnormalities or damage to major organs (heart, liver, spleen, lung, and kidney) in rats during the wound healing process. Therefore, this BP-based hydrogel will have great potential as a safe multimodal therapeutic system for active wound healing and sterilization.

摘要

尽管已经开发出了先进的抗菌材料,但细菌感染仍然是伤口愈合的一个严重问题,因为它通常会引起严重的并发症,并且无法完全消除。目前大多数材料都不能同时提供抗菌活性、可重复使用性和生物相容性,并且不能参与刺激细胞行为来促进带菌伤口愈合。本工作通过简单的静电相互作用,制备了一种嵌入二维(2D)少层黑磷纳米片(BPs)的杂化水凝胶。在模拟可见光下,该杂化水凝胶由于其产生单线态氧(O)的强大能力,可在 10 分钟内迅速杀死 98.90%的大肠杆菌和 99.51%的金黄色葡萄球菌。此外,该水凝胶还表现出很高的可重复性;也就是说,即使在反复挑战细菌 4 次的情况下,对大肠杆菌和金黄色葡萄球菌的抗菌效率仍分别高达 95.6%和 94.58%。体外和体内结果表明,该杂化水凝胶中的 BPs 可以促进纤维蛋白原在组织重建过程中的早期形成,从而加速结痂。此外,BPs 还可以触发磷酸肌醇 3-激酶(PI3K)、蛋白激酶 B(Akt)和细胞外信号调节激酶(ERK1/2)信号通路,促进细胞增殖和分化。此外,在伤口愈合过程中,水凝胶不会对大鼠的主要器官(心脏、肝脏、脾脏、肺和肾脏)造成明显的异常或损伤。因此,这种基于 BP 的水凝胶有望成为一种安全的多模式治疗系统,用于主动伤口愈合和杀菌。

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