A Novel Biomimetic Calcium Phosphate Coating for Metallic Orthopedic Implants

描述（由申请人提供）：该I期项目拟评价一种新方法，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，从而在许多生物过程以及金属植入物表面上诱导羟基磷灰石（HA）成核。由于包被的生物分子生物仿生诱导最佳的羟基磷灰石沉积，这将反过来有利地影响成骨细胞从其祖细胞HEPM细胞的分化和生长。由于仿生分子涂层与金属之间通过稳定的化学键合机制结合，从而提高了金属-组织界面的结合强度。因此，提出了在Ti表面上共价连接可聚合连接基官能团。另一方面，可聚合单体生物分子将被合成、表征并将共价交联到Ti表面上的连接基官能团。在与模拟体液接触孵育后，将测试改性表面的HA沉积和形成的HA的粘附强度。还将评价涂覆有共价键合生物分子的实验钛植入物样品对成骨细胞分化、代谢和生长的影响，如通过成骨细胞计数和碱性磷酸酶比活性所测量的。从这项研究中获得的数据将有助于开发一种替代涂层的最佳HA沉积，反过来将是有价值的骨再生的进一步研究。简而言之，与目前可用的等离子喷涂HA涂层植入物相比，本提案中的新型表面改性将有助于开发具有生物仿生形成的薄磷灰石层的骨科植入物的理想涂层特性，该薄磷灰石层将具有上级涂层-基底界面强度、更好的成骨细胞分化、代谢、生长和蛋白质基质的形成，进而具有更好的骨整合。本研究旨在减少植入失败，这是昂贵的植入成本，手术成本，创伤和时间的患者。在美国，每年有超过500，000例骨相关假体植入。其中11%的项目平均在10年内以失败告终。估计每年用于植入失败的医疗护理成本为150亿美元，总成本（医疗护理加上生产力损失）估计为650亿美元，此外还有患者的巨大疼痛和痛苦。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，其具有更好的骨结合。

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.