多孔钛孔壁铜-银双因子生物活性涂层构筑及其光热响应协同抗菌机制

Porous design of titanium implants will lead to not only enhanced osteointegration but also minimized stress shielding effects. However, the success of their clinic application is being challenged due to lack of angiogenic and antibacterial functions. Modification of porous titanium (PT) surfaces with coatings is considered as an effective solution, while it is rather difficult to coat PT with homogeneous, robust coatings which exhibit controlled delivery of angiogenic and antibacterial agents. Taking advantages of near infrared (NIR) photothermal properties of rice-like silver nanoparticles, in this study, core-shell structured and copper-silver dual-doped mesoporous silica nanoparticles namely Ag@MSN@Cu are synthesized. With the help of a homemade anti-gravity perfusion EPD setup, Ag@MSN@Cu nanoparticles are homogeneously deposited on the entire surface of PT. The adhesion strength of the deposited coating and the sustained release of copper ion for stimulating angiogenesis are further optimized by post-thermal treatment. Then poly(N-isopropylacrylamide-co-acrylic acid) copolymer is synthesized and grafted on the mesoporous channels of MSN. Due to NIR-induced photothermal silver release as well as temperature-responsive “switching effect” of the release channels, the NIR-triggered release of silver ions in an accurate manner could be achieved. This project will establish new methods to modify PT with Ag@MSN@Cu coating, and also elucidate the kinetics of NIR-responsive silver release and copper-silver synergistic antibacterial mechanism. It is expected the output of this project will be beneficial for the biofunctionalization of other porous biomaterials for bone tissue engineering.

钛种植体多孔化能有效促进骨整合并缓解应力屏蔽效应，但仍存在血管化不足和感染问题。涂层改性是提高多孔钛生物活性的有效途径，如何在多孔钛孔壁构筑均匀、附着力强且能可控释放血管化-抗菌因子的涂层，是多孔钛生物功能化研究的难点。本项目利用米粒状纳米银特殊的近红外光热效应，首先合成核-壳结构的纳米银-铜双因子掺杂介孔氧化硅纳米粒(Ag@MSN@Cu)，并提出反重力灌注式电泳沉积的思路，将纳米粒均匀沉积于多孔钛孔壁；在优化涂层附着力以及铜元素缓释促血管化的基础上，合成N-异丙基丙烯酰胺/丙烯酸温敏共聚物修饰MSN介孔孔道，利用近红外光对银离子热激发逸出及其释放通道的“开关”效应，实现银离子的光热响应精准释放，以及铜-银双因子协同抗菌效应。本项目的研究，将建立多孔钛孔壁生物活性涂层新方法，阐明银离子近红外光热响应释放机制以及铜-银双因子协同抗菌机制，也有望为其它多孔骨修复材料的生物功能化研究提供新思路。

钛植入体术后细菌感染依然是造成植入失效的重要原因。通过对多孔钛材料表面进行载药涂层修饰使其具有抗菌作用，同时利用体外光热信号来调节抗菌药物的按需释放，降低药物使用剂量，提高植入材料的生物相容性，对于开发功能化骨植入材料具有重要的研究意义。.本研究探索了棒状纳米银制备方法，探索了纳米银为核、介孔二氧化硅为壳的核壳结构的制备方法，探索了温敏材料的制备方法，构建了具有光热响应性可控释放药物的介孔二氧化硅纳米涂层材料，实现银离子和所装载药物的光热响应控制释放，研究了银离子和所装载药物协同抗菌效应，研究了材料在多孔钛表面的沉积情况。.结果表明，制备得到了一种近红外光热响应型药物释放的纳米材料AgNR@MSN @NIPAAm-co-NMA。该材料具有良好的光热转换性能，浓度为0.25 mg/mL时，在1.5 W/cm2的808 nm激光功率下，照射10 min，材料悬浊液温度能够达到42.7 ℃，该复合材料的LCST为40.8 ℃。.实验发现，在42 ℃下，14 天内的累积药物释放率约为79.3 %，而在37 ℃时仅为 14.5 %，银离子也具有同样的光热控释放行为。可见，材料具有明显光触发释放药物和银离子的特性。 .实验表明，该材料在体外具有显著的抗菌能力，对金黄色葡萄球菌的杀菌效率比大肠杆菌高。细胞毒性试验显示，该材料具有较好的细胞相容性，可满足作为骨植入体表面改性涂层材料的基本生物性能要求。.本项目通过探索棒状纳米银、金种子法纳米银的制备方法，优化了制备条件，构建了光热响应载药涂层，明确了光热响应药物释放和抗菌机制，涂层材料具有非常好的应用前景，具有潜在的临床应用价值。