Nanotechnology in Osseointegration of TMJ Implants

描述(由申请人提供)：我们建议使用纳米技术方法来控制TMJ植入物和周围组织之间的界面。据估计，在美国有超过1000万人患有TMJ相关障碍症状，临床上需要TMJ种植体设计显示出骨整合的倾向。我们建议在关节表面使用纳米结构功能梯度金属陶瓷涂层，在TMJ植入物中使用纳米结构羟基磷灰石固定螺丝。四个具体目标是：(1)开发纳米技术工具和方法，以沉积金属陶瓷涂层，其结构从涂层/种植体界面(金属粘结)逐渐过渡到种植体外表面(纳米级光滑陶瓷)；(2)开发固定螺丝上的纳米结构羟基磷灰石涂层，以承受种植体插入过程中的剪应力，并使表面功能化，以实现TMJ种植体的骨整合；(3)体外研究，比较间充质细胞(MSC)在纳米结构涂层上的黏附和成骨分化。测试这些涂层从血液中吸附促黏附蛋白的能力，并确定通过应用合成的促黏附多肽(RGD)对表面进行功能化处理是否相对于带有吸附的血清蛋白的未涂层材料增强了MSC的黏附和分化，以及(4)体内研究，以表征对照材料和建议生物材料具有或不具有针对整体生物整合和生物相容性特征的功能化表面的短期(初始有机和细胞反应)和长期(软组织和骨整合)反应。 一个由物理学家、生物医学工程师、细胞生物学家、生物材料和牙科外科医生组成的多学科研究小组已经成立，以解决TMJ的骨整合问题。主要的焦点是改善TMJ种植体的固定、耐磨性和骨整合，以获得长期的成功，并降低对多次或翻修手术的需求。通过我们的体外和体内研究验证的新型纳米结构功能梯度表面结构将对目前临床使用的其他各种金属对金属和金属对聚乙烯植入物产生更广泛的影响。

DESCRIPTION (provided by applicant): We propose the use of nanotechnology approaches for controlling interfaces between Temporomandibular Joint (TMJ) implants and the surrounding tissues. It is estimated that more than 10 million people suffer from the TMJ-related disorder symptoms in the Unites States with a clinical need for TMJ implant designs that will show propensity for osseointegration. We propose the use of nanostructured functionally graded metalloceramic coatings for articulating surfaces and nanostructured hydroxyapatitecoated fixation screws for the TMJ implants. The four specific aims are: (1) development of nanotechnology tools and methods for deposition of metalloceramic coatings having a gradual structural transition from the coating/implant interface (metallic bonding) to the outer implant surface (nanometer-level smooth ceramic) (2) development of nanostructured hydroxyapatite coatings on fixation screws to withstand the shear stresses during insertion of the implants and surface functionalization for osseointegration of the TMJ implant (3) In vitro investigations to compare the adhesion and osteoblastic differentiation of mesenchymal cells (MSC's) on the nanostructured coatings. Test the ability of these coatings to adsorb pro-adhesive proteins from blood, and determine whether functionalizing the surface via application of a synthetic pro-adhesive peptide (RGD) enhances MSC adhesion and differentiation, relative to uncoated materials with adsorbed serum proteins and (4) In vivo investigations to characterize the short term (initial organic and cellular responses) and long term (soft tissue and bone integration) responses of control and proposed biomaterials with and without functionalized surfaces specific to overall biointegration and biocompatibility profiles. A multidisciplinary research team consisting of physicists, a biomedical engineer, a cell biologist, and a biomaterials and dental surgeon has been assembled to address TMJ osseointegration. The primary focus is to improve the fixation, wear resistance and osseointegration for long-term success of TMJ implants and lower the need for multiple or revision surgeries. The novel nanostructured functionally graded surface architectures validated by our in vitro and in vivo studies will have a broader impact on a variety of other metal-on-metal and metal-on-polyethylene implants currently in clinical use.