钛表面的纳米管阵列装载雄激素-RGD对钛种植体成骨效应协同作用机制的研究

Recent fundamental research on dental implantation were fucoused on implant surface modification for rapid and improved osseointegration. Based on our research on the osseointegration of TiO2 nanotubes and novel medicine (Androgen-RGD) that stimulate osteogenesis and suppress osteoclast function as well, the hypothesis is assumed that the TiO2 nanotubes could be treated as controlled drug delivery carrier which the medicine could be loaded into and gradully released to further improve the implant osseointegration of TiO2 nanotube implant. To prove the combination effect of TiO2 nanotube and medicine on osseointegration, rate of medicine relased from TiO2 nanotubes, BMSCs culture observation, in vivo observation on tibia-implant model will be done at set time points. The measurement of the expression of osteogenesis related genes and proteins, detection of AR and TGF-β/BMP/Activin signal pathway will be studied to answer the questions of whether TiO2 nanotubes loaded medicine could influence the implant osseointegration, and detect the mechanism of cellular and molecular biology. The mechanism studies on rapid osseointegration improvemed by TiO2 nanotube implant loaded medicine might indicate a new way for implant surface modification.

通过表面改性技术促进钛种植体早期成骨、加速骨整合的进程是当今种植领域的研究方向之一。我们前期研究表明钛表面的TiO2纳米管结构可促进种植体早期骨整合。新型药物17β-(RGD-苯丙氨酰氨基)-11α-羟基雄甾-1,4-二烯-3-酮，可刺激成骨细胞的黏附与分化，同时抑制破骨细胞的迁移与黏附，而且在溶液中呈光滑的纳米球形。据此假设，将该药物直接装载入TiO2纳米管内，装载药物纳米管形成的缓释作用，进一步加强TiO2纳米管的促进早期成骨的作用。本研究拟通过药物释放试验、BMSCs培养、建立兔胫骨-种植体模型，检测装载/缓释该药物的TiO2纳米管种植体在体内外试验中对骨形成相关基因、蛋白表达及对AR、TGF-β/BMP/Activin信号通路的影响，观察其对种植体骨整合的影响，分析探讨其细胞和分子生物学机制，为钛种植体表面改性技术提供新思路和理论基础。

通过表面改性技术促进钛种植体早期成骨、加速骨整合的进程是当今种植领域的研究方向之一。我们前期研究表明钛表面的TiO2纳米管结构可促进种植体早期骨整合。TiO2纳米管本身可作为装载、缓释药物的装置，装载纳米级促成骨和抗菌药物，装载药物纳米管形成的缓释作用，进一步加强TiO2纳米管的促进早期成骨及抗菌的作用。通过药物释放试验、BMSCs培养、建立兔胫骨-种植体模型及抗菌实验，检测装载/缓释药物的TiO2纳米管种植体在体内外试验中对骨形成相关基因、蛋白表达及种植体周围炎易感菌抗菌作用的影响，观察其对种植体骨整合的影响，分析探讨其细胞和分子生物学机制，TiO2纳米管结构作为有效的药物装载释放装置，可有效装载促进成骨的小分子多肽（BMP2 knuckle peptide）、纳米药物（Androgen-RGD）及纳米级金属氧化物抗菌剂(ZnO)、有机抗菌肽(GL13K antimicrobial peptide)，协同纳米管结构的促进成骨作用，有效促进钛种植体早期成骨及预防种植早期感染。该研究为钛种植体表面改性技术提供新思路和理论基础。