Mechanical Stimulation of Cells in Photopolymerized Gels

光聚合凝胶中细胞的机械刺激

• 批准号: 7119671
• 负责人: Stephanie J Bryant
• 金额: $ 13.5万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-06 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7119671
• 关键词: animal tissue; biological signal transduction; biomechanics; biotechnology; calcium flux; cell adhesion molecules; cell cell interaction; cell proliferation; chondrocytes; collagen; crosslink; extracellular matrix; gel; gene expression; mechanical stress; mechanoreceptors; mucopolysaccharides; nitric oxide; peptides; polyethylene glycols; proteoglycan; temporomandibular joint syndrome; tissue engineering; tissue support frame

DESCRIPTION (provided by applicant): This career transition award will provide the candidate with the opportunity to investigate new areas of research: mechanotransduction and mechanical stimulation for regenerating condylar cartilage of the temporomandibular joint (TMJ). The environment in the Dept. of Chemical and Biological Eng. at the University of Colorado and the School of Dentistry at the Health Science Center will provide the candidate with fruitful collaborations, mentorship and a plethora of shared equipment. The long-term goals of the candidate are (i) to develop a successful research career in tissue engineering, (ii) to make a substantial advancement in developing tissue engineering strategies for treating patients with TMJ disorders, and (iii) to provide a positive learning environment for the next generation of researchers and tissue engineers. The overall objective of this proposal is to stimulate the regeneration of cartilage through mechanical conditioning of tissue engineering scaffolds for the replacement of condylar cartilage of the TMJ. The global hypothesis of this research is photopolymerized gels can be designed with high fidelity to provide insight into the mechanotransduction pathways of chondrocytes, and this knowledge can then be used to engineer gel environments that when subjected to mechanical conditioning will promote functional tissue development. Specifically, the aims of this research are to: Aim 1: Elucidate the chondrocyte's response (cell proliferation and ECM synthesis) to a range of loading conditions as a function of gel material properties and chemistries; Aim 2: Isolate and study the mechanotransduction pathways in chondrocytes that involve nitric oxide and intracellular calcium and their potential role in the cell's response to changes in cell deformation and streaming potentials and to the presence of cell-ECM interactions. Aim 3: Incorporate degradable crosslinks into the hydrogels and examine the macroscopic tissue composition and mechanical properties as a function of loading regimes and degradation profiles.

描述（由申请人提供）：该职业过渡奖将为候选人提供研究新研究领域的机会：用于再生颞下颌关节（TMJ）髁软骨的机械传导和机械刺激。化学与生物工程系的环境。科罗拉多大学和健康科学中心牙科学院将为候选人提供富有成效的合作、指导和大量共享设备。候选人的长期目标是（i）在组织工程领域发展成功的研究事业，（ii）在开发治疗颞下颌关节疾病患者的组织工程策略方面取得实质性进展，以及（iii）提供积极的帮助为下一代研究人员和组织工程师提供学习环境。 该提案的总体目标是通过组织工程支架的机械调节来刺激软骨再生，以替代颞下颌关节髁软骨。这项研究的总体假设是光聚合凝胶可以高保真度设计，以深入了解软骨细胞的机械转导途径，然后可以利用这些知识来设计凝胶环境，当受到机械调节时，该环境将促进功能组织的发育。具体来说，本研究的目的是： 目标 1：阐明软骨细胞对一系列负载条件的反应（细胞增殖和 ECM 合成）作为凝胶材料特性和化学成分的函数；目标 2：分离并研究软骨细胞中涉及一氧化氮和细胞内钙的机械转导途径，及其在细胞对细胞变形和流动电位变化以及细胞-ECM 相互作用的存在的反应中的潜在作用。目标 3：将可降解的交联结合到水凝胶中，并检查宏观组织成分和机械性能作为负载模式和降解曲线的函数。