A Novel Biomimetic Calcium Phosphate Coating for Metallic Orthopedic Implants

描述（由申请人提供）：本I期项目建议评估一种新方法，以诱导仿生磷酸钙（CaP）沉积在化学稳定且共价连接的生物分子单层上，在许多生物过程中以及金属植入物表面诱导羟基磷灰石（HA）成核。由于包被的生物分子仿生学地诱导了最佳的羟基磷灰石沉积，这反过来又有利于成骨细胞从其祖细胞HEPM细胞分化和生长。由于仿生分子涂层将通过稳定的化学键合机制与金属结合，从而提高金属-组织界面的键合强度。因此，建议在钛表面共价固定可聚合的连接功能。另一方面，一个可聚合的单体生物分子将被合成，表征，并将交联共价的连接器功能在钛表面。经过修饰的表面在与模拟体液接触后，将测试HA沉积和形成的HA的粘附强度。通过测定成骨细胞计数和碱性磷酸酶特异性活性，研究了用共价结合的生物分子包覆的实验钛种植体样品对成骨细胞分化、代谢和生长的影响。从这项研究中获得的数据将有助于开发最佳HA沉积的替代涂层，进而对骨再生的进一步研究具有价值。简而言之，与目前可用的等离子喷涂ha涂层植入物相比，本研究提出的新型表面修饰将有助于骨科植入物理想涂层性能的发展，仿生形成的薄磷灰石层将具有优越的涂层-基质界面强度，更好的成骨细胞分化、代谢、生长和蛋白基质的形成，从而更好地实现骨整合。本研究旨在减少种植体失败，减少种植体成本、手术成本、创伤和时间对患者造成的损失。在美国，每年有超过50万个与骨相关的假体被放置。其中11%的人在平均10年的时间里以失败告终。据估计，每年因植入物失败而产生的医疗费用为150亿美元，除了给患者带来的巨大痛苦和痛苦之外，总成本（医疗费用加上生产力损失）估计为650亿美元。该项目具有仿生固定种植体-骨界面的潜力，因此，与目前可用的商业种植体相比，它具有更好的骨整合性。

DESCRIPTION (provided by applicant): This Phase I project proposes to evaluate a novel methodology to induce biomimetic calcium phosphate (CaP) deposition on a chemically stable and covalently linked monolayer of a biomolecule, that induces hydroxyapatite (HA) nucleation in many biological process as well as on metallic implant surfaces. Because the coated biomolecules biomimetically induce the optimal hydroxyapatite depostion, this will in turn favorably affect the differentiation and growth of osteoblasts from their progenitors, the HEPM cells. Since the biomimetic molecular coating will be bound to metal by a stable chemical bonding mechanism, the bonding strength at metal-tissue interface will be enhanced. Thus, it is proposed to covalently immobilize a polymerizable linker functionality on Ti surface. On the other hand, a polymerizable monomer biomolecule will be synthesized, characterized and will be crosslinked covalently to the linker functionality on Ti surface. The modified surface will be tested for HA deposition and for adhesion strength of the HA formed, after they are incubated in contact with simulated body fluid. The experimental titanium implant samples, coated with the covalently bonded biomolecule will also be evaluated for their effects on osteoblast differentiation, metabolism and growth, as measured by osteoblast cell counts and the alkaline phosphatase specific activity. The data obtained from this study will contribute to the development of an alternative coating for optimum HA deposition and in turn will be valuable for further research on bone regeneration. In short, the novel surface modification in this proposal will contribute to the development of ideal coating properties for orthopedic implants with biomimetically formed thin apatite layer that will have superior coating-substrate interfacial strength, better osteoblast differentiation, metabolism, growth, and the formation of proteinaceous matrix, and in turn a better osseointegration, as compared to the currently available plasma sprayed HA-coated implants. This research is directed to reduce implant failures, which are costly to patients in implant cost, surgery cost, trauma and time. More than 500,000 bone related prostheses are placed annually in the US. A total of 11% of these, end up in failure in an average time of 10 years. Estimated annual medical care costs for implant failures is $15 billion, and total costs (medical care plus lost productivity) are estimated at $65 billion, besides the immense pain and suffering to the patients. This project has a potential for a biomimetic fixation of implant-bone interface, and therefore, its better osseointegration compared to the currently available commercial implants.