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颞下颌关节（TMJ）植入物与周围组织之间的界面。据估计，美国有超过1000万人患有颞下颌关节相关疾病症状，临床上需要具有骨整合倾向的颞下颌关节植入物设计。我们建议使用纳米结构功能梯度陶瓷涂层的关节面和纳米结构羟基磷灰石涂层的固定螺钉的颞下颌关节植入物。这四个具体目标是：（1）开发纳米技术工具和方法，用于沉积从涂层/植入物界面具有逐渐结构转变的陶瓷涂层（金属粘合）至植入物外表面（纳米级光滑陶瓷）（2）在固定螺钉上开发纳米结构羟基磷灰石涂层，以承受植入物插入过程中的剪切应力和TMJ植入物骨整合的表面功能化（3）在体外研究中比较间充质细胞（MSC）在纳米结构涂层上的粘附和成骨细胞分化。测试这些涂层从血液中吸附促粘附蛋白的能力，并确定通过应用合成的促粘附肽（RGD）功能化表面是否增强MSC粘附和分化，相对于吸附血清蛋白的未涂层材料，以及（4）体内研究，以表征短期（初始有机和细胞反应）和长期（软组织和骨整合）反应的控制和建议的生物材料，具有和不具有功能化的表面，具体到整体生物整合和生物相容性概况。 一个由物理学家、生物医学工程师、细胞生物学家、生物材料和牙科医生组成的多学科研究小组已经组装起来，以解决TMJ骨整合问题。主要重点是改善TMJ种植体的固定、耐磨性和骨整合，以获得长期成功，并降低多次手术或翻修手术的需求。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各种其他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.