Engineering cartilage: an approach to joint repair

工程软骨：一种修复关节的方法

• 批准号: 6871451
• 负责人: JEAN F WELTER
• 金额: $ 33.66万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-05 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6871451
• 关键词: SCID mouse; articular cartilage; bioengineering /biomedical engineering; biological transport; bioreactors; cartilage development; cartilage transplantation; cell differentiation; cell line; clinical research; goats; human genetic material tag; musculoskeletal regeneration; stem cell transplantation; technology /technique development; tissue engineering

DESCRIPTION (provided by applicant): Articular cartilage degeneration in osteoarthritis is a major cause of disability affecting more than 43 million lives in the US. Damaged cartilage does not heal. Cartilage tissue engineering based on mesenchymal stem cell (MSC) technology offers the promise of manufacturable autologous tissue replacements of arbitrary size and shape, using cells from a bone marrow biopsy. This Bioengineering Research Grant proposal is driven by the need for cartilage tissue engineering to make the transition to a reproducible clinical therapy. To accomplish this, the processes involved must be thoroughly understood, and standardized protocols must be established. The global hypothesis underlying this proposal is that by exposing the cell scaffold constructs in a controlled, in vitro environment to conditions that favor chondrogenic differentiation, these constructs will develop the specific properties required for survival after implantation in the joint. Two major problems must be solved before tissue engineering can become a routine treatment for cartilage defects: transport of nutrients and waste products to and from the cells within the construct, and mechanical conditioning of the constructs to allow function in situ. We propose five Specific Aims, which address specific issues related to mass transport and mechanical conditioning, and their impact on construct functionality in vivo. These are: Specific Aim 1: To assess the mass transfer problem in cartilage tissue engineering. This will lead to better understanding of mass transfer within the constructs and will serve to evaluate the counter-measures proposed to improve mass transfer. Specific Aim 2: To develop a cartilage bioreactor monitoring and process control system. We will implement this technology to identify and characterize process control parameters in cartilage tissue engineering systems. Specific Aim 3: To develop countermeasures to specific mass transport limitations. In this Specific Aim, we will examine strategies to improve mass transfer in the constructs. Specific Aim 4: To implement and assess mechanical stimulation of the composites, using a system in which controlled, physiologically relevant loads can be applied, and identifying loading parameters that improve the mechanical properties of the construct. Specific Aim 5: To evaluate the composite constructs in vivo, as survival and integration of the manufactured construct in the joint defines the success of the tissue engineering process. The practical value of the proposed research is in the new insights it will provide into the technical issues surrounding cartilage tissue engineering and cartilage repair, and into the complex biology of the joint. If successful, these studies will provide novel principles and guidelines for the successful management of articular cartilage injuries.

描述（由申请人提供）： 骨关节炎的关节软骨变性是影响美国超过4300万人生命的主要原因。软骨损坏无法治愈。基于间充质干细胞（MSC）技术的软骨组织工程提供了使用骨髓活检中的细胞，可以承诺自体组织替换任意尺寸和形状。这项生物工程研究补助金提案是由软骨组织工程需要过渡到可重复的临床疗法的必要性驱动的。为此，必须彻底理解所涉及的过程，并且必须建立标准化的协议。该提案的基础全球假设是，通过将受控的，体外环境中的细胞支架构建体暴露于有利于软骨分化的条件下，这些构建体将发展关节植入后生存所需的特定特性。在组织工程成为软骨缺陷的常规处理之前，必须解决两个主要问题：养分和废物产物传输到构造中的细胞，以及构造的机械条件以原位功能。我们提出了五个特定目标，这些目标解决了与大规模运输和机械条件有关的特定问题及其对体内构建功能的影响。这些是：特定目的1：评估软骨组织工程中的传质问题。这将使人们更好地了解结构内的传质，并将有助于评估提议改善传质的反措施。特定目的2：开发软骨生物反应器监测和过程控制系统。我们将实施这项技术，以识别和表征软骨组织工程系统中的过程控制参数。特定目的3：开发对特定的质量运输限制的对策。在这个具体目标中，我们将研究改善结构中传质的策略。特定目的4：使用可以使用受控的，生理相关的负载的系统来实施和评估复合材料的机械刺激，并识别改善构建体机械性能的加载参数。特定目的5：在体内评估复合构建体，因为关节中制造构建体的生存和整合定义了组织工程过程的成功。拟议研究的实际价值在于它将在软骨组织工程和软骨修复的技术问题上提供的新见解，以及关节的复杂生物学。如果成功，这些研究将为成功管理关节软骨伤害的新原则和准则。