Designing injectable dermal matrix hydrogel combined with silver nanoparticles for methicillin-resistant Staphylococcus aureus infected wounds healing

IF 13.4 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY
Sunfang Chen, Jun Yao, Shicheng Huo, Chennan Xu, Ruting Yang, Danhua Tao, Bin Fang, Gaoxiang Ma, Zaihua Zhu, Ye Zhang, JingJing Guo
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Abstract

Hydrogel-based delivery systems have now emerged as a pivotal platform for addressing chronic tissue defects, leveraging their innate capacity to suppress pathogenic infections and facilitate expedited tissue regeneration. In this work, an injectable hydrogel dressing, termed AgNPs-dermal matrix hydrogel (Ag@ADMH), has been designed to expedite the healing process of wounds afflicted with methicillin-resistant Staphylococcus aureus (MRSA), featuring sustained antibacterial efficacy. The synthesis of the hydrogel dressing entailed a self-assembly process of collagen fibers within an acellular dermal matrix to construct a three-dimensional scaffold, encapsulated with plant polyphenol-functionalized silver nanoparticles (AgNPs). The Ag@ADMH demonstrated exceptional biocompatibility, and enables a sustained release of AgNPs, ensuring prolonged antimicrobial activity. Moreover, the in vitro RT-qPCR analysis revealed that compared with ADMH, Ag@ADMH diminish the expression of iNOS while augmenting CD206 expression, thereby mitigating the inflammatory response and fostering wound healing. Especially, the Ag@ADMH facilitated a reduction in M1 macrophage polarization, as evidenced by a significant decrement in the M1 polarization trend and an enhanced M2/M1 ratio in dermal matrix hydrogels laden with AgNPs, corroborated by confocal microscopy and flow cytometry analyses of macrophage phenotypes. The in vivo assessments indicated that Ag@ADMH minimized fibrous capsule formation. In a full-thickness skin defect model of MRSA infection, the formulation significantly attenuated the inflammatory response by reducing MPO and CD68 expression levels, concurrently promoting collagen synthesis and CD34 expression, pivotal for vasculogenesis, thereby accelerating the resolution of MRSA-infected wounds. These attributes underscore the injectable extracellular matrix hydrogel as a formidable strategy for the remediation and regeneration of infected wounds.

Graphical Abstract

设计结合银纳米粒子的可注射真皮基质水凝胶,用于耐甲氧西林金黄色葡萄球菌感染伤口的愈合
基于水凝胶的给药系统利用其抑制病原体感染和促进组织快速再生的天生能力,现已成为解决慢性组织缺损问题的关键平台。在这项研究中,我们设计了一种名为 AgNPs-真皮基质水凝胶(Ag@ADMH)的可注射水凝胶敷料,用于加快耐甲氧西林金黄色葡萄球菌(MRSA)伤口的愈合过程,并具有持续抗菌功效。水凝胶敷料的合成需要在无细胞真皮基质中通过胶原纤维的自组装过程来构建一个三维支架,支架上封装有植物多酚功能化银纳米粒子(AgNPs)。Ag@ADMH表现出优异的生物相容性,并实现了AgNPs的持续释放,确保了抗菌活性的延长。此外,体外 RT-qPCR 分析表明,与 ADMH 相比,Ag@ADMH 可减少 iNOS 的表达,同时增加 CD206 的表达,从而减轻炎症反应,促进伤口愈合。特别是,Ag@ADMH 有助于减少巨噬细胞的 M1 极化,这体现在掺有 AgNPs 的真皮基质水凝胶中巨噬细胞的 M1 极化趋势显著下降,M2/M1 比率增强,巨噬细胞表型的共聚焦显微镜和流式细胞仪分析也证实了这一点。体内评估表明,Ag@ADMH 可最大限度地减少纤维囊的形成。在 MRSA 感染的全厚皮肤缺损模型中,该制剂通过降低 MPO 和 CD68 表达水平显著减轻了炎症反应,同时促进了胶原蛋白合成和 CD34 表达(对血管生成至关重要),从而加速了 MRSA 感染伤口的愈合。这些特性突出表明,可注射细胞外基质水凝胶是修复和再生受感染伤口的有力策略。
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来源期刊
Nano Convergence
Nano Convergence Engineering-General Engineering
CiteScore
15.90
自引率
2.60%
发文量
50
审稿时长
13 weeks
期刊介绍: Nano Convergence is an internationally recognized, peer-reviewed, and interdisciplinary journal designed to foster effective communication among scientists spanning diverse research areas closely aligned with nanoscience and nanotechnology. Dedicated to encouraging the convergence of technologies across the nano- to microscopic scale, the journal aims to unveil novel scientific domains and cultivate fresh research prospects. Operating on a single-blind peer-review system, Nano Convergence ensures transparency in the review process, with reviewers cognizant of authors' names and affiliations while maintaining anonymity in the feedback provided to authors.
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