A dual-functional implant with an enzyme-responsive effect for bacterial infection therapy and tissue regeneration
A dual-functional implant with an enzyme-responsive effect for bacterial infection therapy and tissue regeneration
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具有酶响应作用的双功能植入物，用于细菌感染治疗和组织再生
DOI：
10.1039/c9bm01924c
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发表时间：
2020-04-07
影响因子：
6.6
通讯作者：
Cai, Kaiyong
中科院分区：
文献类型：
--
作者：
Ding, Yao;Hao, Yansha;Cai, Kaiyong
生物材料相关的细菌感染是种植体失败的主要原因之一。这种植入物感染的治疗通常需要同时消除细菌和加速植入物周围的组织再生。为了解决这个问题，理想的植入材料应同时具有细菌感染治疗和组织再生的双重功能。本文中，制造酶响应纳米平台以治疗植入物相关的细菌感染并加速体内组织再生。首先，通过一锅法将银纳米颗粒预包封在介孔二氧化硅纳米颗粒（MSNs）中。然后，利用层层组装技术将聚谷氨酸（PG）和聚烯丙基胺盐酸盐（PAH）组装到MSN-Ag上，形成LBL@MSN-Ag纳米粒子。此外，LBL@MSN-Ag纳米颗粒沉积在聚多巴胺改性的Ti基底的表面上。PG是由酰胺键组成的均相聚酰胺，其可被金黄色葡萄球菌分泌的谷氨酰内切酶降解。电感耦合等离子体光谱（ICP）结果证明LBL@MSN-Ag颗粒显示出Ag离子的显著酶响应性释放。体外抗菌实验结果表明，LBL@MSN-Ag纳米涂层修饰的钛基体具有良好的抗菌效果。在体内动物实验中，在细菌感染的股骨缺损大鼠模型中，改性钛植入物有效地治疗了细菌感染。更重要的是，显微CT、苏木精-伊红染色和Masson三色染色结果表明，改良钛植入物在植入4周后显著促进了新骨组织的形成。本系统为开发具有治疗细菌感染和促进组织再生功能的下一代植入物铺平了道路。
Biomaterial-associated bacterial infection is one of the major causes of implant failure. The treatment of such an implant infection typically requires the elimination of bacteria and acceleration of tissue regeneration around implants simultaneously. To address this issue, an ideal implanted material should have the dual functions of bacterial infection therapy and tissue regeneration at the same time. Herein, an enzyme-responsive nanoplatform was fabricated in order to treat implant-associated bacterial infection and accelerate tissue regeneration in vivo. Firstly, Ag nanoparticles were pre-encapsulated in mesoporous silica nanoparticles (MSNs) by a one-pot method. Then, poly-l-glutamic acid (PG) and polyallylamine hydrochloride (PAH) were assembled by the layer-by-layer (LBL) assembly technique on MSN-Ag to form LBL@MSN-Ag nanoparticles. Furthermore, the LBL@MSN-Ag nanoparticles were deposited on the surface of polydopamine-modified Ti substrates. PG is a homogeneous polyamide composed of an amide linkage, which can be degraded by glutamyl endonuclease secreted by Staphylococcus aureus. Inductively coupled plasma spectroscopy (ICP) results proved that the LBL@MSN-Ag particles show a significant enzyme responsive release of Ag ions. Furthermore, results of antibacterial experiments in vitro showed that the Ti substrates modified with an LBL@MSN-Ag nanocoating presented an excellent antibacterial effect. As for an animal experiment in vivo, in a bacterium infected femur-defect rat model, the modified Ti implants effectively treated bacterial infection. More importantly, the results of micro-CT, haematoxylin-eosin staining and Masson's trichrome staining demonstrated that the modified Ti implants significantly promoted the formation of new bone tissue after implantation for 4 weeks. The present system paves the way for developing the next generation of implants with the functions of treating bacterial infection and promoting tissue regeneration.