BMP-2 Releasing Implant Surface for Bone Regeneration

描述(申请人提供)：这项拟议的研究将评估一种短链、可生物降解的间隔物作为钛(钛)种植体表面骨再生蛋白输送机制的有效性。我们的总体假设是，BMP-2与种植体表面的共价结合，使其在伤口处得到控制释放，将直接影响早期骨诱导。本研究的目的是：1)通过含有6-12个原子链的连接物在钛表面偶联BMP-2，这些连接物与几种可生物降解的聚合物如聚乳酸、聚乙醇酸、聚羟基丁酸酯具有相同的单体官能度，从而使连接物既能保持生物脱胶的特性，又不会因降解不完全而继承残基积累的副作用。2)研究该连接体作为BMP-2在细胞条件培养液中输送系统的效率；3)研究与BMP-2共价结合的植入材料对骨细胞体外早期成熟的影响。在这项建议中，Aim-1将通过测量钛表面蛋白质的释放速率来评估上述连接物作为骨再生蛋白输送机制的相对效率。我们将首先用氨基末端的化学实体对钛表面进行修饰，然后通过具有生物可降解功能的短链连接物将其偶联到BMP-2的氨基末端。然后将蛋白结合的钛表面浸入细胞条件培养液中。还将使用氚标记的连接物进行放射性版本的表面修饰，并将方便地测量蛋白质随时间的释放。目的2确定骨形态发生蛋白-2修饰的撞击表面在多大程度上影响体外培养的成骨细胞的增殖、分化和代谢。所产生的数据将为信息油提供一种新型涂层，作为BMP-2的输送机制，以及对该新型涂层对骨细胞成熟的影响。此外，产生的信息将有助于开发理想的仿生和生物相容的植入材料，从而减少长期的植入失败。

DESCRIPTION (provided by applicant): The proposed study will evaluate the efficacy of a short chain, biodegradable spacer as a delivery mechanism for a bone regenerative protein on titanium (Ti) implant surface. Our overall hypothesis is that the covalent binding of BMP-2 on a implant surface for its controlled release on wound site will directly affect early bone induction. The objectives of this study are 1) to couple BMP-2 on Ti surface by the linkers consisting of 6-12 atom chains having the same monomeric functionalities as that of a few biodegradable polymers, such as poly-lactic acid, poly-glycolic acid, poly-hydroxy butyrate, so that the linker may retain the property of biodegardation, yet does not inherit the side effect of residue accumulation as a result of incomplete degradation. 2) to investigate the efficiency of the said linker as a delivery system for BMP-2 in the cell conditioned culture medium, and 3) to correlate the effect of implants material covalently bound with BMP-2 with early maturation of bone cells in-vitro. In this proposal, aim-1 will evaluate the relative efficiency of the aforesaid linkers as a delivery mechanism for the bone regenerative protein by measuring the release rate of protein from the Ti surface. We will first modify the Ti surface by an amino terminating chemical entity, which will then be coupled with to the amino terminus of BMP-2 through a short chain linker having biodegradable functionality. The protein bound Ti surface will then be immersed in a cell conditioned culture medium. A radioactive version of the surface modification will also be made, using tritium labeled linker and the release of the protein over time will be measured conveniently. Aim 2 will determine the extent to which the BMP-2 modified imptant surface effects osteobtast proliferation, differentiation, and metabolism in vitro. Data generated will provide information oil a novel coating useful as a delivery mechanism for BMP-2 and the effect on the novel coating on eady maturation of bone cells. Additionally, the information generated will contribute to development of an ideal biomimetic and biocompatible implant material, thereby reducing long-term implant failures.