三维钛板假体表面原位生成MOFs涂层及其药物缓释机理研究

It is very active to study bone introduced activity on titanium plates by preparing coating layer in osseous tissue field, and the coating layer can load and release slowly BMP-2. Selecting proper carrier is very important to the effect of slow release. At the present time, many type of materials have been studied as carrier on BMP-2. However, no ideal carrier was founded. Utilizing characteristics of metal-organic framework compounds (MOFs) with high surface area, largepore volume, adjustable uniform pores, multiform pore structure and biocompatibility, we put forward a method of enhancing bone induced activity by MOFs coating on three-dimensional titanium plate. It is the main aim that high drug amount and slow release of BMP-2 are obtained simultaneously, and we will adopte experiment and molecular dynamics simulation method. The influence rule of pore property on charge number and pharmacokinetics will be explored systematically, and the growth mechanism of MOFs crystals searched on titanium plate. A new method is provided to solve the defect of present drug carrier that low load dosis is caused by the thin coating and poor slow release result by the short transmission path. Furthermore, theory and experiment basis could be supplied for application of MOFs in tissue engineering.

在钛基种植体表面制备能够有效负载及缓释骨形态发生蛋白-2（BMP-2）的载体涂层，提高钛材表面骨诱导活性是组织工程领域的研究热点之一，其中选择合适的载体材料对于BMP-2的缓释效果至关重要.目前已有多种有机、无机及复合材料被应用于BMP-2载体的研究,但尚未发现理想的载体.本项目利用金属有机骨架材料（MOFs）的特有优势，如具有超大比表面积和巨大孔体积、孔道尺寸可调、孔道结构多样化及部分材料具有生物相容性等，提出在三维钛板假体表面制备MOFs涂层担载BMP-2来提高其骨诱导能力的方法，以同时实现BMP-2的高担载量及缓控释为目标，采用实验及分子动力学模拟方法，系统研究MOFs孔道物理化学性质对载药量及释药动力学的影响规律，探索MOFs晶体在钛表面的生长机制，为解决目前由于载药涂层较薄造成载药量低、药物传输路径短造成缓释效果不理想的缺陷提供新方法，为MOFs应用于组织工程提供理论与实验依据。

通过涂层处理使金属基种植体表面具有优异的成骨活性是骨组织工程领域的研究热点之一。本项目利用金属有机骨架材料（MOFs）的特有优势，如具有超大比表面积和巨大孔体积、孔道尺寸可调、孔道结构多样化、孔壁内易简单修饰官能团化及部分材料具有生物相容性等，将MOF应用于金属基种植体表面改性。利用“双金属源”原位生长法在金属基底上制备了具有优良耐蚀性及亲水性能的Mg-MOF-74/MgF2复合涂层，并在Mg-MOF-74中负载了庆大霉素抗菌剂，证明了它的良好抗菌性；通过层层自组装方法在金属基底上制备了具有电负性的bio-MOF-1涂层，通过模拟体液浸泡法证实bio-MOF-1涂层具有优异的成骨活性；带有bio-MOF-1涂层材料浸提液与L929小鼠成纤维细胞共培养，采用MTT方法测试细胞活度，结果表明bio-MOF-1涂层材料具有良好的生物相容性；在制备MOFs涂层过程中，通过调节反应物浓度、温度及反应时间等实验参数得到了晶粒细小且连续致密的涂层，探索了MOFs晶体在金属基底表面的生长机制。此研究为MOFs应用于骨组织工程提供理论与实验依据。