TISSUE ENGINEERED CARTILAGE

组织工程软骨

• 批准号: 2470362
• 负责人: MICHAEL J YAREMCHUK
• 金额: $ 7.06万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-15 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2470362
• 关键词: age difference; alginates; aprotinin; athymic mouse; bioengineering /biomedical engineering; cartilage; cartilage development; cell cycle; cell transplantation; chondrocytes; extracellular matrix; fibrin; immunocytochemistry; polymers; swine; tissue /cell culture; transplantation immunology

DESCRIPTION (from the application): Cartilaginous defects, both in articulating joints as well as other structural tissues like ears and tracheal C-rings, present challenging reconstructive problems to surgeons trying to restore normal structure and function to patients. Several tissue engineering techniques have been developed for growing chondrocytes on or in synthetic or naturally occurring biodegradable polymers in vitro and in vivo in nude mice. These polymers, in the form of hydrogels or porous, branching networks, can serve as a scaffold upon which chondrocytes can produce extracellular matrix resulting in new tissue. This technology allows the transplantation of cell-polymer constructs as a unit with successful engraftment for new cartilage formation. Although our laboratory has generated cartilage in several preliminary studies using different biodegradable matrices in vitro and in vivo in nude mice, we have encountered unexpected obstacles when attempting to employ similar techniques in an immune-competent animal model (rabbit). The objective of this study is to examine the feasibility of employing the techniques for creating tissue engineered cartilage in a model (swine) that more closely parallels the human condition. Experiments have been designed to address the following specific aims: Aim 1: To investigate (A) the rates at which hydrogel spheres of calcium alginate and fibrin-based substrates decay after being implanted subcutaneously in an immune-competent animal model (swine) and (B) to establish the degree to which polymers of calcium alginate and fibrin-based substrates promote cartilage formation in an immune-competent animal model (swine). Aim 2: To determine if autologous chondrocytes will provoke an immune response when their cell membranes are exposed to the immune system by stripping them of their encasing matrix. Aim 3: To investigate (A) whether the number of cell divisions (replicative age) a chondrocyte has undergone in culture influences its rate of matrix production and (B) to investigate what effect chondrocyte donor age has on the rate of matrix production.

描述（来自应用程序）： 软骨缺陷，无论是在阐明关节和其他方面 耳朵和气管C形圆环等结构组织，目前具有挑战性 试图恢复正常结构和的外科医生的重建问题 对患者的功能。 几种组织工程技术已经 开发用于在合成或天然发生的或自然发生的软骨细胞的开发 裸鼠的体外和体内可生物降解聚合物。 这些聚合物， 以水凝胶或多孔的分支网络的形式可以用作 软骨细胞可以在其上产生细胞外基质的脚手架 在新组织中。 该技术允许移植细胞聚合物 构造作为一个成功植入新软骨的单位 形成。 尽管我们的实验室已经产生了多个软骨 初步研究使用不同的可生物降解矩阵在体外和 裸鼠的体内，我们在尝试时遇到了意想不到的障碍 在免疫能力动物模型（兔子）中采用类似的技术。 这项研究的目的是检查采用 在模型（猪）中创建组织工程软骨的技术 更紧密地与人类状况平行。 已经设计了实验 解决以下特定目标：目标1：调查（a） 藻酸钙和基于纤维蛋白的水凝胶球的速率 底物在免疫能力植入的植入后腐烂 动物模型（猪）和（b）建立了哪种程度 藻酸钙和基于纤维蛋白的底物促进软骨形成 免疫能力动物模型（猪）。 目标2：确定是否 自体软骨细胞会在其细胞时引起免疫反应 膜通过剥离它们的免疫系统暴露于免疫系统 包裹矩阵。 目标3：调查（a）是否有单元格的数量 划分（复制年龄）软骨细胞在培养中经历了 影响其基质生产速率和（b）研究什么影响 软骨细胞供体的年龄对基质产生速率具有。