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聚阴离子水凝胶作为聚阳离子抗生素替代品的储库,提供长效抗菌活性。

Polyanionic Hydrogels as Reservoirs for Polycationic Antibiotic Substitutes Providing Prolonged Antibacterial Activity.

机构信息

Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121 Biomaterials and Bioengineering, 11 rue Humann, 67085 Strasbourg Cedex, France.

Faculté de Chirurgie Dentaire, Université de Strasbourg, 8 rue Sainte Elisabeth, 67000 Strasbourg, France.

出版信息

ACS Appl Mater Interfaces. 2020 Apr 29;12(17):19258-19267. doi: 10.1021/acsami.9b23140. Epub 2020 Apr 15.

DOI:10.1021/acsami.9b23140
PMID:32292035
Abstract

Implantation of biomedical devices is often followed by bacterial infections that may seriously affect implant functionalities and lead to their failure. In the context of bacterial resistance to antibiotics, which is a growing problem worldwide, new strategies that are able to overcome these problems are needed. In this work, we introduce a new formulation of hyaluronic acid (HA)-based antimicrobial material: HA hydrogels loaded with polyarginine (PAR), a polycationic antibiotic substitute. The loading is possible through electrostatic interactions between negatively charged HA and positively charged PAR. Such hydrogels absorb high quantities of PAR, which are then gradually released from the hydrogel. This original system provides a long-lasting antibacterial effect on an in vitro model of repetitive infection, thus demonstrating a strong potential to fight multiple rounds of infections that are resistant to antibiotic treatment. In addition, HA-PAR hydrogels could be deposited onto/into medical devices such as wound dressings and mesh prostheses used in clinical applications. Finally, we performed first in vivo tests of hydrogel-coated mesh materials to verify their biocompatibility in a rat model, which show no difference between control HA hydrogel and PAR-loaded hydrogel in terms of inflammation.

摘要

生物医学设备的植入后常伴随着细菌感染,这可能严重影响植入物的功能并导致其失效。在全球范围内抗生素耐药性日益严重的背景下,需要新的策略来克服这些问题。在这项工作中,我们引入了一种新型的基于透明质酸(HA)的抗菌材料:负载聚精氨酸(PAR)的 HA 水凝胶,PAR 是一种阳离子抗生素替代品。通过带负电荷的 HA 和带正电荷的 PAR 之间的静电相互作用可以实现负载。这种水凝胶可以吸收大量的 PAR,然后 PAR 会从水凝胶中逐渐释放出来。该原创系统在体外重复感染模型中提供了持久的抗菌效果,因此具有很强的潜力来对抗对抗生素治疗有耐药性的多轮感染。此外,HA-PAR 水凝胶可以沉积到/进入医疗设备上,如用于临床应用的伤口敷料和网片假体。最后,我们对水凝胶涂层网材进行了首次体内试验,以验证其在大鼠模型中的生物相容性,结果表明在炎症方面,载 PAR 水凝胶与对照 HA 水凝胶之间没有差异。

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