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一种具有抗感染活性的还原聚多巴胺纳米颗粒偶联可喷涂聚乙二醇水凝胶粘合剂,用于快速伤口封闭。

A reduced polydopamine nanoparticle-coupled sprayable PEG hydrogel adhesive with anti-infection activity for rapid wound sealing.

作者信息

Sun Junjie, Tan Haoqi, Liu Huan, Jin Dawei, Yin Meng, Lin Haodong, Qu Xue, Liu Changsheng

机构信息

Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of material science and engineering, East China University of Science and Technology, Shanghai 200237, China.

Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China.

出版信息

Biomater Sci. 2020 Dec 15;8(24):6946-6956. doi: 10.1039/d0bm01213k.

Abstract

There is a growing demand to develop sprayable hydrogel adhesives with rapid-forming and antibacterial abilities to instantly seal open wounds and combat pathogen infection. Herein, we propose to design a polydopamine nanoparticle (PDA NP) coupled PEG hydrogel that can quickly solidify via an amidation reaction after spraying as well as tightly binding PDA NPs to deliver reactive oxygen species (ROS) and induce a photothermal effect for bactericidal activity, and provide a hydrophilic surface for antifouling activity. The molecular structure of the 4-arm-PEG-NHS precursor was regulated to increase its reactivity with 4-arm-PEG-NH2, which thus shortened the gelation time of the PEG adhesive to 1 s to allow a fast solidification after being sprayed. The PEG-NHS precursor also provided covalent binding with tissue and PDA NPs. The reduced PDA NPs have redox activity to convey electrons to oxygen to generate ROS (H2O2), thus endowing the hydrogel with ROS dependent antibacterial ability. Moreover, NIR irradiation can accelerate the ROS release because of the photothermal effect of PDA NPs. In vitro tests demonstrated that H2O2 and the NIR-photothermal effect synergistically induced a fast bacterial killing, and an in vivo anti-infection test also proved the effectiveness of PEG-PDA. The sprayable PEG-PDA hydrogel adhesive, with rapid-forming performance and a dual bactericidal mechanism, may be promising for sealing large-scale and acute wound sites or invisible bleeding sites, and protect them from pathogen infection.

摘要

开发具有快速成型和抗菌能力的可喷涂水凝胶粘合剂以立即封闭开放性伤口并对抗病原体感染的需求日益增长。在此,我们提出设计一种聚多巴胺纳米颗粒(PDA NP)偶联的PEG水凝胶,其在喷涂后可通过酰胺化反应快速固化,同时紧密结合PDA NPs以产生活性氧(ROS)并诱导光热效应以实现杀菌活性,并提供亲水性表面以实现防污活性。对四臂PEG-NHS前体的分子结构进行调控,以提高其与四臂PEG-NH2的反应性,从而将PEG粘合剂的凝胶化时间缩短至1 s,使其在喷涂后能够快速固化。PEG-NHS前体还与组织和PDA NPs提供共价结合。还原的PDA NPs具有氧化还原活性,可将电子传递给氧气以产生活性氧(H2O2),从而赋予水凝胶ROS依赖性抗菌能力。此外,由于PDA NPs的光热效应,近红外(NIR)照射可加速ROS释放。体外试验表明,H2O2和NIR光热效应协同诱导快速杀菌,体内抗感染试验也证明了PEG-PDA的有效性。这种具有快速成型性能和双重杀菌机制的可喷涂PEG-PDA水凝胶粘合剂,有望用于封闭大面积急性伤口部位或隐形出血部位,并保护它们免受病原体感染。

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