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具有酶触发抗菌性能并增强体内骨整合的钛植入物表面工程。

Surface engineering of titanium implants with enzyme-triggered antibacterial properties and enhanced osseointegration in vivo.

作者信息

Yuan Zhang, Huang Suzhou, Lan Shaoxiong, Xiong Haizhou, Tao Bailong, Ding Yao, Liu Yisi, Liu Peng, Cai Kaiyong

机构信息

Key Laboratory of Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.

出版信息

J Mater Chem B. 2018 Dec 28;6(48):8090-8104. doi: 10.1039/c8tb01918e. Epub 2018 Nov 21.

DOI:10.1039/c8tb01918e
PMID:32254929
Abstract

Preventing bacterial infection and improving the osseointegration of titanium (Ti) and its alloys are both highly crucial factors for their long-term successful implantation in clinical applications. However, the straightforward applications of antibacterial surfaces on Ti-based materials remain limited due to their side effects on cytocompatibility. Herein, catechol-functionalized multilayer films composed of dopamine-modified hyaluronic acid (HA-c) and 3,4-dihydroxyhydrocinnamic acid-modified chitosan (Chi-c) were developed on Ti substrates modified with TiO nanotube arrays loaded with an antibacterial drug. The treated Ti substrate showed strong hydrophilicity, with a water contact angle of about 20°, and obviously inhibited early-stage bacterial adhesion. Moreover, this system displayed an enzyme-responsive release of antibacterial drug triggered by the hyaluronidase degradation of HA-c, which exhibited effective antibacterial ability and eliminated side effects caused by burst release of antibiotics. Meanwhile, the modified Ti substrates significantly promoted initial osteoblast adhesion through up-regulating the expression of adhesion-related genes, including integrin αv and β3. More importantly, this prepared coating with bacterial self-responsiveness improved osseointegration and prevented bacterial infection of Ti implants in vivo. Overall, our developed catechol-functionalized and bacterial self-responsive coating on Ti substrate has great significance in clinical applications of orthopedic and dental implants.

摘要

预防细菌感染以及改善钛(Ti)及其合金的骨整合,对于它们在临床应用中的长期成功植入而言都是至关重要的因素。然而,抗菌表面在钛基金属材料上的直接应用由于其对细胞相容性的副作用而仍然有限。在此,在负载抗菌药物的TiO纳米管阵列修饰的钛基底上,制备了由多巴胺修饰的透明质酸(HA-c)和3,4-二羟基肉桂酸修饰的壳聚糖(Chi-c)组成的儿茶酚功能化多层膜。处理后的钛基底表现出很强的亲水性,水接触角约为20°,并且明显抑制了早期细菌黏附。此外,该体系表现出由HA-c的透明质酸酶降解触发的抗菌药物的酶响应释放,其展现出有效的抗菌能力并消除了抗生素突发释放所引起的副作用。同时,修饰后的钛基底通过上调包括整合素αv和β3在内的黏附相关基因的表达,显著促进了初始成骨细胞的黏附。更重要的是,这种制备的具有细菌自响应性的涂层在体内改善了钛植入物的骨整合并预防了细菌感染。总体而言,我们在钛基底上开发的儿茶酚功能化且具有细菌自响应性的涂层在骨科和牙科植入物的临床应用中具有重要意义。

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