Tissue Engineering TMJ Articular Fibrocartilage

组织工程 TMJ 关节纤维软骨

• 批准号: 7799284
• 负责人: ANTHONY RATCLIFFE
• 金额: $ 32.28万
• 依托单位: SYNTHASOME, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7799284
• 关键词: Address; Biochemical; Biomechanics; Bioreactors; Cartilage; Cell Count; Cell-Matrix Junction; Cells; Clinical; Collagen; Degenerative polyarthritis; Deposition; Development; Extracellular Matrix; FGF2 gene; Family suidae; Fibrocartilages; General Population; Generations; Goals; Growth; Human; Hyaline Cartilage; Individual; Interdisciplinary Study; Joint repair; Joints; Knowledge; Lead; Mandible; Mechanics; Mesenchymal Stem Cells; Methodology; Methods; Outcome; Pathology; Perforation; Phenotype; Polymers; Population; Proliferating; Property; Proteoglycan; Provider; Research Personnel; Source; Supporting Cell; System; Temporomandibular Joint; Temporomandibular Joint Disorders; Testing; Time; Tissue Engineering; Tissues; Translational Research; Work; articular cartilage; cartilage cell; cartilage repair; density; implantation; in vivo; multidisciplinary; programs; repaired; scaffold

DESCRIPTION (provided by applicant): Successful treatment of temporomandibular joint (TMJ) disorders is a major unmet clinical need. The objective is to generate functional tissue engineered TMJ articular cartilage for the treatment of TMJ disorders. There are several major technical hurdles that still must be overcome for the development of clinically useful tissue engineered cartilage, including the generation of functional mechanical properties, and availability of an appropriate cell source. Recent studies indicate we have the components necessary to develop a TMJ cartilage with the potential to be used for implantation and TMJ repair. Our objective is to utilize these advances (cell source, bioreactor growth systems, scaffolds) to generate TMJ articular cartilage appropriate for implantation and repair of the TMJ. The overall hypothesis for this project is that proliferated cells, polymer scaffolds with functional tensile properties and bioreactor growth conditions, can be combined to form tissue engineered constructs with functional properties similar to native TMJ articular cartilage. To test this hypothesis and to achieve the stated goal,we have 3 Specific Aims. Specific Aim 1: Characterize the TMJ mandibular articular cartilage and identify a scaffold that can provide functional tensile properties similar to TMJ articular cartilage, and support cell attachment. Specific Aim 2. Determine the ability of TMJ articular cartilage cells and hMSCs to proliferate, and to maintain or modulate their differentiation to a fibrocartilage phenotype appropriate for synthesis of TMJ articular cartilage. Specific Aim 3: Identify and optimize bioreactor growth conditions for cell-seeded scaffolds to generate constructs similar to native TMJ articular cartilage. The successful outcome of this multidisciplinary and interdisciplinary study has several important critical outcomes to the development of a successful TMJ cartilage repair methodology. Critically, these studies will lead to translational research, where these tissue engineered constructs will be assessed in vivo for their ability to successfully repair TMJ articular cartilage

描述（由申请人提供）：颞下颌关节（TMJ）疾病的成功治疗是一个主要的未满足的临床需求。目标是产生功能性组织工程颞下颌关节软骨，用于治疗颞下颌关节疾病。开发临床上有用的组织工程软骨仍然必须克服几个主要的技术障碍，包括功能机械特性的产生以及适当细胞来源的可用性。最近的研究表明，我们拥有开发颞下颌关节软骨所需的组件，并且有可能用于植入和颞下颌关节修复。我们的目标是利用这些进步（细胞来源、生物反应器生长系统、支架）来生成适合颞下颌关节植入和修复的颞下颌关节软骨。该项目的总体假设是，增殖细胞、具有功能拉伸特性的聚合物支架和生物反应器生长条件可以组合形成具有与天然 TMJ 关节软骨相似的功能特性的组织工程构建体。为了检验这一假设并实现既定目标，我们有 3 个具体目标。具体目标 1：表征 TMJ 下颌关节软骨，并确定一种支架，该支架可以提供类似于 TMJ 关节软骨的功能拉伸特性，并支持细胞附着。具体目标 2. 确定 TMJ 关节软骨细胞和 hMSC 增殖的能力，以及维持或调节其分化为适合 TMJ 关节软骨合成的纤维软骨表型的能力。具体目标 3：确定并优化细胞接种支架的生物反应器生长条件，以生成类似于天然 TMJ 关节软骨的结构。这项多学科和跨学科研究的成功成果对于开发成功的颞下颌关节软骨修复方法具有几个重要的关键成果。至关重要的是，这些研究将导致转化研究，这些组织工程构建体将在体内评估其成功修复颞下颌关节软骨的能力