BMP-2 Releasing Implant Surface for Bone Regeneration

BMP-2 释放植入物表面以促进骨再生

• 批准号: 6582613
• 负责人: Rajiv Kumar Satsangi
• 金额: $ 13.65万
• 依托单位: RANN RESEARCH CORPORATION
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2004-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6582613
• 关键词: biodegradable product; biomaterial compatibility; biomaterial development /preparation; biomimetics; bone morphogenetic proteins; bone regeneration; cell differentiation; cell proliferation; drug delivery systems; implant; medical implant science; osteoblasts; osteogenesis; surface coating; tissue /cell culture; titanium

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.

描述（由申请方提供）：拟定研究将评价短链生物可降解垫片作为钛（Ti）植入物表面骨再生蛋白的输送机制的有效性。我们的总体假设是BMP-2在植入物表面上的共价结合用于其在伤口部位的受控释放将直接影响早期骨诱导。本研究的目的是：1）通过与聚乳酸、聚乙醇酸、聚羟基丁酸酯等几种可生物降解聚合物具有相同单体官能团的6-12个原子链组成的连接体，将BMP-2偶联到钛表面，使连接体保持生物降解性，而不会继承由于不完全降解而导致的残留物积累的副作用。2)研究所述接头作为BMP-2在细胞条件培养基中的递送系统的效率，和3）将与BMP-2共价结合的植入物材料的作用与体外骨细胞的早期成熟相关联。在该提议中，aim-1将通过测量蛋白质从Ti表面的释放速率来评估上述接头作为骨再生蛋白的递送机制的相对效率。我们将首先通过氨基封端化学实体修饰Ti表面，然后通过具有生物可降解功能的短链接头将其偶联到BMP-2的氨基末端。然后将蛋白质结合的Ti表面浸入细胞条件培养基中。还将使用氚标记的连接体进行放射性形式的表面改性，并且将方便地测量蛋白质随时间的释放。目的2：研究BMP-2修饰的表面对成骨细胞增殖、分化和代谢的影响。所产生的数据将提供关于可用作BMP-2的递送机制的新型涂层的信息以及新型涂层对骨细胞的快速成熟的影响。此外，所产生的信息将有助于开发理想的仿生和生物相容性植入材料，从而减少长期植入失败。