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载抗生素的多功能水凝胶敷料用于感染伤口的愈合。

A multifunctional hydrogel dressing loaded with antibiotics for healing of infected wound.

机构信息

School of Medicine, Sun Yat-sen University, Shenzhen 518107, China; Department of Pharmacy, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang 621000, China.

School of Pharmaceutical Science (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, PR China.

出版信息

Int J Pharm. 2024 Dec 5;666:124770. doi: 10.1016/j.ijpharm.2024.124770. Epub 2024 Sep 29.

Abstract

Wound bacterial infections can significantly delay the healing process and even lead to fetal sepsis. There is a need for multifunctional dressings that possess antibacterial property, tissue adhesive property, self-healing capability, and biocompatibility to effectively treat bacteria-infected wound. In this study, we report a dual dynamically crosslinked hydrogel, OHA-PBA/PVA/Gen, which incorporates the antibiotic gentamicin (Gen) as a dynamic crosslinker. The hydrogel is formed through the formation of Schiff base bonds between phenylboronic acid-grafted oxidized hyaluronic acid (OHA-PBA) and Gen, as well as boronic acid ester bonds between OHA-PBA and polyvinyl alcohol (PVA). This unique composition imparts tissue adhesiveness, injectability and self-healing property to the hydrogel. The hydrogel also exhibits pH-responsive antibiotic release behavior due to the acid-responsive dissociation of Schiff base bonds. As a result, it demonstrates strong antibacterial activity against both Gram-positive bacteria S. aureus and Gram-negative bacteria E. coli through contact killing and diffusion killing mechanisms. Importantly, the OHA-PBA/PVA/Gen hydrogel avoids incorporation of toxic small molecular crosslinking agents, and all the components of the hydrogel are biocompatible, ensuring its biosafety. In a S. aureus-infected wound mouse model, this hydrogel effectively eradicated bacteria and promoted angiogenesis, leading to significantly accelerated wound healing. These results highlight the potential of the dual dynamically crosslinking hydrogel OHA-PBA/PVA/Gen as a multifunctional wound dressing for the treatment of bacteria-infected wound.

摘要

伤口细菌感染会显著延迟愈合过程,甚至导致胎儿败血症。因此,需要多功能敷料,这些敷料应具有抗菌性、组织黏附性、自修复能力和生物相容性,从而有效治疗细菌感染性伤口。在本研究中,我们报告了一种双重动态交联水凝胶 OHA-PBA/PVA/Gen,它将抗生素庆大霉素(Gen)作为动态交联剂。水凝胶通过苯硼酸接枝氧化透明质酸(OHA-PBA)与 Gen 之间形成席夫碱键,以及 OHA-PBA 与聚乙烯醇(PVA)之间形成硼酸酯键而形成。这种独特的组成赋予水凝胶组织黏附性、可注射性和自修复性。由于席夫碱键的酸响应解离,水凝胶还表现出 pH 响应性抗生素释放行为。因此,它通过接触杀伤和扩散杀伤机制对革兰氏阳性菌金黄色葡萄球菌和革兰氏阴性菌大肠杆菌表现出强烈的抗菌活性。重要的是,OHA-PBA/PVA/Gen 水凝胶避免了掺入有毒小分子交联剂,并且水凝胶的所有成分都是生物相容的,确保了其生物安全性。在金黄色葡萄球菌感染的伤口小鼠模型中,这种水凝胶有效地消除了细菌并促进了血管生成,从而显著加速了伤口愈合。这些结果突出了双重动态交联水凝胶 OHA-PBA/PVA/Gen 作为多功能伤口敷料治疗细菌感染性伤口的潜力。

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