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用于治疗3D全层皮肤模型感染伤口的靶向抗菌内溶素:XZ.700的疗效

Targeted Antibacterial Endolysin to Treat Infected Wounds on 3D Full-Thickness Skin Model: XZ.700 Efficacy.

作者信息

Meloni Marisa, de Rooij Bob, Janssen Ferdinand W, Rescigno Francesca, Lombardi Bernadette

机构信息

VitroScreen s.r.l., In Vitro Innovation Center, Via Mosè Bianchi 103, 20149 Milan, MI, Italy.

Micreos Pharmaceuticals, Neuhofstrasse 12, CH-6430 Baar, ZG, Switzerland.

出版信息

Pharmaceutics. 2024 Dec 1;16(12):1539. doi: 10.3390/pharmaceutics16121539.

DOI:10.3390/pharmaceutics16121539
PMID:39771518
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11728803/
Abstract

Skin wound healing is a physiological process orchestrated by epithelial and mesenchymal cells able to restore tissue continuity by re-organizing themselves and the ECM. This research study aimed to develop an optimized in vitro experimental model of full-thickness skin, to address molecular and morphological modifications occurring in the re-epithelization and wound healing process. Wound healing starting events were investigated within an experimental window of 8 days at the molecular level by gene expression and immunofluorescence of key epidermal and dermal biomarkers. To mirror the behavior of infected wounds, the established wound healing model was then colonized with , and the efficacy of a novel antibacterial agent, XZ.700, was investigated. Viable counts (CFU/tissue), IF, and ultrastructural analysis (SEM) were performed to evaluate colonization inside and around the wound bed in an experimental window of 3 h of colonization and 24 h of treatment. Endolysin showed an efficacy in counteracting bacterial growth and invasion within the wound bed, reducing the load compared to its placebo, thanks to its selective antimicrobial activity interfering with biofilm formation. The preclinical in vitro infected wound model on FT-kin showed interesting applications to assess the repair efficacy of dermo-pharmaceutical and cosmetic formulations.

摘要

皮肤伤口愈合是一个由上皮细胞和间充质细胞精心编排的生理过程,这些细胞能够通过自我重组以及细胞外基质(ECM)来恢复组织的连续性。本研究旨在建立一种优化的全层皮肤体外实验模型,以研究在再上皮化和伤口愈合过程中发生的分子和形态学变化。通过关键表皮和真皮生物标志物的基因表达和免疫荧光,在8天的实验窗口期内从分子水平研究伤口愈合的起始事件。为了模拟感染伤口的行为,随后在建立的伤口愈合模型中接种细菌,并研究一种新型抗菌剂XZ.700的疗效。在接种3小时和治疗24小时的实验窗口期内,通过活菌计数(CFU/组织)、免疫荧光(IF)和超微结构分析(SEM)来评估伤口床内部和周围的细菌定植情况。溶菌酶显示出在抵抗伤口床内细菌生长和侵袭方面的疗效,与其安慰剂相比,由于其选择性抗菌活性干扰生物膜形成,从而降低了细菌载量。FT-kin上的临床前体外感染伤口模型在评估皮肤药物和化妆品配方的修复疗效方面显示出有趣的应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996a/11728803/92ae69e247a3/pharmaceutics-16-01539-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996a/11728803/6cd9fdb6ed4a/pharmaceutics-16-01539-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996a/11728803/64c32eb3155e/pharmaceutics-16-01539-g008.jpg
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