BIOCHEMICAL AND CELLULAR RESPONSES TO BIOMATERIALS

全关节置换手术彻底改变了 终末期破坏性关节炎患者的治疗。 尽管生物材料和手术技术的进步 取得了良好的临床效果，长期随访研究 揭示了假体松动的惊人速度， 需要翻修手术 尽管有大量研究表明 与骨科植入物相关的组织反应， 关于特定的细胞和生物化学 决定组织学特征的事件， 结缔组织对这些材料的反应。 这个目标 本发明的建议是开发一种体外细胞培养模型， 骨和其他结缔组织细胞来研究 骨科植入物生物材料对 分化的细胞功能。 生化和分子 调节一般细胞活动的机制， 附着、增殖、细胞骨架组织和基质 生物合成将进行研究，并获得比较结果 在不同的细胞类型将有助于建立的特异性， 观察骨细胞。 此外，该模型还将 用于探索调节 骨和其他结缔组织细胞的表型表达 在植入材料上生长。 一种合适的体外模型， 研究参与相互作用的特定生物过程， 骨科生物材料和结缔组织细胞之间的关系 应该有助于开发改进的技术， 用于全关节置换的生物材料。

Procedures for total joint replacement have revolutionized the treatment of patients with end-stage destructive arthritis. Although improvements in biomaterials and surgical techniques have yielded excellent clinical results, long-term followup studies reveal an alarming rate of prosthetic loosening that ultimately requires revision surgery. Despite numerous studies describing the tissue reaction associated with orthopedic implants, very little is known regarding the specific cellular and biochemical events that determine the characteristics of the histologic and connective tissue response to these materials. The goal of this proposal is to develope an in vitro cell culture model employing bone and other connective tissue cells to study the effects of orthopaedic implant biomaterials on the expression of differentiated cell function. Biochemical and molecular mechanisms regulating general cellular activities such as attachment, proliferation, cytoskeletal organization and matrix biosynthesis will be investigated and comparative results obtained in different cell types will help establish the specificity of the observations made with bone cells. In addition this model will be used to explore experimental approaches for modulating the phenotypic expression of bone and other connective tissue cells grown on implant materials. A suitable in vitro model for studying the specific biologic processes involved in the interaction between orthopedic biomaterials and connective tissue cells should be useful in developing improved techniques and biomaterials for total joint replacement.