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多功能含铜介孔玻璃纳米粒子作为慢性伤口的抗菌和促血管生成剂

Multifunctional Copper-Containing Mesoporous Glass Nanoparticles as Antibacterial and Proangiogenic Agents for Chronic Wounds.

作者信息

Paterson Thomas E, Bari Alessandra, Bullock Anthony J, Turner Robert, Montalbano Giorgia, Fiorilli Sonia, Vitale-Brovarone Chiara, MacNeil Sheila, Shepherd Joanna

机构信息

School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom.

Department of Applied Science and Technology, Politecnico di Torino, Turin, Italy.

出版信息

Front Bioeng Biotechnol. 2020 Mar 31;8:246. doi: 10.3389/fbioe.2020.00246. eCollection 2020.

DOI:10.3389/fbioe.2020.00246
PMID:32296691
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7136418/
Abstract

The physiological wound healing process involves a cascade of events which could be affected by several factors resulting in chronic, non-healing wounds. The latter represent a great burden especially when bacterial biofilms are formed. The rise in antibiotic resistance amongst infectious microorganisms leads to the need of novel approaches to treat this clinical issue. In this context, the use of advanced biomaterials, which can enhance the physiological expression and secretion of the growth factors involved in the wound healing process, is gaining increasing attention as a robust and appealing alternative approach. Among them, mesoporous glasses are of particular interest due to their excellent textural properties and to the possibility of incorporating and releasing specific therapeutic species, such as metallic ions. One of the most attractive therapeutic ions is copper thanks to its proangiogenic and antibacterial effects. In this contribution, copper containing mesoporous glass nanoparticles were proposed as a multifunctional device to treat chronic wounds. The developed nanoparticles evidenced a very high specific surface area (740 m/g), uniform pores of 4 nm and an almost total release of the therapeutic ion within 72 h of soaking. The produced nanoparticles were biocompatible and, when tested against Gram positive and Gram negative bacterial species, demonstrated antibacterial activity against both planktonic and biofilm bacteria in 2D cell monolayers, and in a 3D human model of infected skin. Their proangiogenic effect was tested with both the aortic ring and the chick chorioallantoic membrane assays and an increase in endothelial cell outgrowth at a concentration range between 30 and 300 ng/mL was shown. Overall, in this study biocompatible, multifunctional Cu-containing mesoporous glass nanoparticles were successfully produced and demonstrated to exert both antibacterial and proangiogenic effects.

摘要

生理性伤口愈合过程涉及一系列事件,这些事件可能会受到多种因素的影响,从而导致慢性、不愈合伤口。后者带来了巨大负担,尤其是在形成细菌生物膜时。感染性微生物中抗生素耐药性的增加导致需要新的方法来治疗这一临床问题。在这种背景下,使用先进的生物材料作为一种强大且有吸引力的替代方法正日益受到关注,这种生物材料可以增强伤口愈合过程中涉及的生长因子的生理性表达和分泌。其中,介孔玻璃因其优异的结构性能以及掺入和释放特定治疗性物质(如金属离子)的可能性而特别受关注。最具吸引力的治疗性离子之一是铜,这得益于其促血管生成和抗菌作用。在本论文中,含铜介孔玻璃纳米颗粒被提议作为一种治疗慢性伤口的多功能器件。所制备的纳米颗粒具有非常高的比表面积(740 m/g)、4 nm的均匀孔径,并且在浸泡72小时内治疗性离子几乎完全释放。所制备的纳米颗粒具有生物相容性,在针对革兰氏阳性和革兰氏阴性细菌进行测试时,在二维细胞单层以及三维感染皮肤人体模型中均显示出对浮游细菌和生物膜细菌的抗菌活性。通过主动脉环和鸡胚绒毛尿囊膜试验对其促血管生成作用进行了测试,结果表明在30至300 ng/mL的浓度范围内内皮细胞生长增加。总体而言,在本研究中成功制备了具有生物相容性的多功能含铜介孔玻璃纳米颗粒,并证明其具有抗菌和促血管生成作用。

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