Polymeric Matrices with Defined Cell Adhesion

具有明确细胞粘附力的聚合物基质

• 批准号: 6871354
• 负责人: David J Mooney
• 金额: $ 36.9万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6871354
• 关键词: alginates; biological signal transduction; biomaterial development /preparation; biotechnology; bone regeneration; cell adhesion; cell differentiation; cell line; crosslink; gel; gene expression; human tissue; integrins; laboratory rat; ligands; nanomedicine; osteoblasts; osteogenesis; phenotype; physical property; polymers; stem cell transplantation; stem cells; tissue /cell culture; tissue engineering; tissue support frame

DESCRIPTION (provided by applicant): Diseases and trauma involving the loss of bony tissue are the most common clinical dental problems, and we propose to develop new polymeric materials for bone tissue engineering. We hypothesize that controlling the nanoscale organization of adhesive ligands presented to transplanted cells from the polymer, as well as the susceptibility of these ligands to cell-mediated rearrangement, will regulate the gene expression of the cells. Alginate will be used as a model matrix system to address the hypothesis guiding this proposal. Cells exhibit little to no adhesion or interaction with alginate, and thus alginate provides an ideal "blank slate" on which one can confer specific cellular interaction properties in a controlled manner. Alginate also, in contrast to most model systems, is a practical biomaterial for in vivo application of this work. We specifically aim to: (1) Control the nanoscale presentation of RGD-containing peptides to a model pre-osteoblast cell line and human mesenchymal stem cells, and determine how this regulates focal adhesion formation and cell phenotype, (2) determine if the stiffness of the ligand presenting gels regulates the cells ability to rearrange the adhesion ligands, and (3) determine if these variables allow one to regulate new bone formation in vivo. The time-frame required for the gel, before it degrades, to present this information in order to regulate the cell response and bone formation will also be determined. Successful completion of these aims will have significant impact in both basic and applied sciences, and may eventually lead to improved therapies for regenerating bone defects. Establishing the mechanism by which nanoscale ligand organization and matrix mechanical properties regulate cell phenotype will provide an important new variable for design of biomaterials in tissue engineering and regeneration. The biomaterials developed in this proposal may be directly useful in therapies utilizing precursor cells to regenerate bony tissues in a variety of clinical settings.

描述（由申请人提供）： 骨组织缺损的疾病和创伤是临床上最常见的牙科问题，我们建议开发新的骨组织工程聚合物材料。我们假设，控制从聚合物向移植细胞呈递的粘附配体的纳米级组织，以及这些配体对细胞介导的重排的易感性，将调节细胞的基因表达。藻酸盐将被用作模型矩阵系统，以解决指导本提案的假设。细胞几乎不与藻酸盐粘附或相互作用，因此藻酸盐提供了一种理想的“白板”，人们可以以受控的方式赋予其特定的细胞相互作用性质。与大多数模型系统相反，藻酸盐也是本研究体内应用的实用生物材料。我们的具体目标是：（1）控制含RGD的肽对模型前成骨细胞系和人间充质干细胞的纳米级呈递，并确定这如何调节粘着斑形成和细胞表型，（2）确定配体呈递凝胶的硬度是否调节细胞重排粘着配体的能力，和（3）确定这些变量是否允许在体内调节新骨形成。还将确定凝胶在降解之前呈现该信息以调节细胞反应和骨形成所需的时间范围。这些目标的成功实现将对基础科学和应用科学产生重大影响，并可能最终导致骨缺损再生疗法的改进。阐明纳米配体的组织结构和基质力学性质对细胞表型的调控机制，将为组织工程和再生生物材料的设计提供新的重要变量。在该提议中开发的生物材料可能直接用于在各种临床环境中利用前体细胞再生骨组织的治疗。