钛种植体表面pH响应智能性释药体系的构建及其抗感染性能研究

Titanium implant is an important method for the rehabilitation in patients with organ defects. But implant-related infection is still a high risk factor for patients' health and main cuase for implant failure. Because of its advantages over systemic drug dulivery strategies, local drug delivery has shown as a promising strategy. However, in the previous studies, the local antibacterial drug delivery systems failed to regulat the release kinetics according to the micro-environment around the implant, which will have a negative effect in therapeutic efficacy of antibiotics. In our study, the discrepancy of pH between the normal tissues and inflammatory tissues will be used to design a novel pH-sensitive drug delivery system. The titania nanotube arrays on the surface of implants will be fribcated by anodic oxidation technique and then the poly (L,- glutamic acid) (PLGA) be grafted at the gate of nanotubes. Conformational transition of PLGA will be induced by the change of pH, which will regulate the release kinetics of antibiotics. Taking advantages of this feature, we will establish a pH-dependent release system with the function of "on-off". To investigate the controlled release properties and regulation mechanism of this new system, study model of drug release, drug release kinetics testing, antibacterial experiment, cell experiment and animal experiment will be conducted. The system reported here will be a promising therapy strategy for implant related infection. The system may also provides a new thinking for local drug delivery of implants.

钛基种植体已经成功地广泛应用于组织器官缺损缺失，但感染仍是种植体失败的重要原因。钛种植体表面缓释抗菌药物的方法因其诸多优点成为解决感染问题的研究热点。然而目前的钛种植体表面释药系统难以对种植体局部组织炎症做出相应反应，缺乏对药物释放的智能调控，不能有效抗感染。本课题设计了对pH响应的TiO2纳米管释药系统，利用炎症组织与正常组织的pH值差异，实现药物智能释放。首先在钛种植体表面制备TiO2纳米管阵列，作为药物装载缓释装置，然后在TiO2纳米管口接枝聚L-谷氨酸（PLGA），利用PLGA的二级结构具有随pH值改变发生可逆性改变的特性，制备具有"开关"功能的药物控释系统；通过建立纳米管薄膜研究模型、药物释放动力学测试、抗菌实验、细胞试验和动物实验等手段探讨药物控释机制并验证其抗感染性能。本课题将为治疗种植体周围感染提供更有效的途径，同时为种植体局部药物控释提供新思路。

钛基种植体已经成功地广泛应用于组织器官缺损缺失，但感染仍是种植体失败的重要原因。钛种植体表面缓释抗菌药物的方法因其诸多优点成为解决感染问题的研究热点。然而目前的钛种植体表面释药系统不能对种植体局部组织炎症做出相应反应，缺乏对药物释放的智能调控，不能有效抗感染。本课题设计的对pH响应的TiO2纳米管释药系统，利用炎症组织与正常组织的pH值差异，实现药物智能释放。首先在钛种植体表面制备TiO2纳米管阵列，作为药物装载缓释装置，然后在钛纳米管口接枝具有pH相应性能的分子链并装载纳米银作为抗菌剂，制备具有pH响应功能的药物控释系统；并通过药物释放动力学测试、抗菌实验、细胞试验和动物实验等手段探讨药物控释机制并验证其抗感染性能。其中纳米银在酸性条件中的释放速率能达到在中性条件中的3.77倍证实了其良好的pH响应控释性能。本课题为治疗种植体周围感染提供了更有效的途径，也为种植体局部药物控释提供了新思路。

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