Targeted Integration of Tissue Engineered Cartilage

组织工程软骨的靶向整合

• 批准号: 6726445
• 负责人: JENNIFER H ELISSEEFF
• 金额: $ 20.44万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-20 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6726445
• 关键词: athymic mouse; biomaterial compatibility; biomaterial evaluation; biomaterial interface interaction; biomechanics; biotechnology; cartilage; cell component structure /function; cell differentiation; chondrocytes; covalent bond; extracellular matrix; immunocytochemistry; interferometry; membrane reconstitution /synthesis; polymerization; scanning electron microscopy; tissue engineering; tissue support frame

DESCRIPTION (provided by applicant): The overall goal of this research project is to integrate tissue engineered cartilage with native tissue. Specifically, we will achieve this goal by creating covalent bonds between a photopolymerizing hydrogel and the cartilage extracellular matrix. Cartilage is an avascular tissue that acts as a cushion and lubricating surface for proper articulating joint function and provides smactural function in numerous other tissues. Cartilage has been the focus of significant tissue engineering research since it lacks the ability to self repair when it is lost due to trauma, disease, or congenital abnormalities. For example, we have investigated photopolymerizing hydrogel scaffolds that may be formed in situ for engineering cartilage using differentiated chondrocytes and bone marrow-derived mesenchyrnal stem cells. Unfortunately, numerous barriers remain for translating this research to a successful clinical application. Integration of tissue-engineered cartilage with the native host tissue remains one of the most significant challenges in translating this research. Lack of integration with the surrounding tissues allows micromotion of the implant to occur, often causing dislocation. Furthermore, the extracellular matrix of the transplanted tissue rarely forms a contiguous network with the host which prevents proper tissue maintenance and ultimately leads to implant failure. Unlike other tissue engineering strategies that focus on improving the scaffold or implantation technique, we have focused on modifying the native cartilage tissue in order to initiate polymerization and scaffold formation. We propose to solve this problem by designing a method to covalently attach a tissue engineering scaffold directly to the strong collagen fibers in native cartilage will improve tissue integration, preventing implant movement while providing a bridge for engineered and native cartilage extracellular matrix to integrate. Furthermore, the technique we have developed, tissue-initiated photopolymerization, allows in situ hydrogel formation to occur without an exogenous photoinitiator, improving biocompatibility. To achieve the goal of designing a novel system for hydrogel integration to cartilage and testing the hypothesis that it will improve matrix integration the following specific aims have been developed: Specific Aim 1. Development of an efficient and biocompatible method to directly bond a photopolymerizing hydrogel to cartilage tissue. Specifically, collagen fibers will be exposed on the cartilage surface and oxidized to generate a radical and initiate photopolymerization. Specific Aim 2. Test the hypothesis that covalent attachment of a cell-hydrogel construct to the cartilage surface will improve integration of cartilage engineered from chondrocytes and bone marrow-derived mesenchymal cells and host cartilage matrix both in vitro and in vivo. Tissue integration will be monitored by morphological, biochemical, and mechanical analysis.

描述（由申请人提供）：本研究项目的总体目标是将组织工程软骨与天然组织相结合。具体来说，我们将通过在光聚合水凝胶和软骨细胞外基质之间建立共价键来实现这一目标。软骨是一种无血管组织，作为缓冲和润滑表面，为正常的关节功能和提供许多其他组织的结构功能。由于软骨由于创伤、疾病或先天性异常而丢失，缺乏自我修复能力，因此一直是组织工程研究的重点。例如，我们已经研究了利用分化的软骨细胞和骨髓间充质干细胞在原位形成的光聚合水凝胶支架。不幸的是，将这项研究转化为成功的临床应用仍然存在许多障碍。组织工程软骨与原生宿主组织的整合仍然是翻译本研究中最重要的挑战之一。缺乏与周围组织的整合使得植入物发生微动，经常导致脱位。此外，移植组织的细胞外基质很少与宿主形成连续的网络，这阻碍了组织的正常维护，最终导致植入失败。与其他专注于改善支架或植入技术的组织工程策略不同，我们专注于修改天然软骨组织，以启动聚合和支架形成。我们建议通过设计一种将组织工程支架直接共价附着在天然软骨强胶原纤维上的方法来解决这一问题，这将改善组织整合，防止植入物移动，同时为工程软骨和天然软骨细胞外基质的整合提供桥梁。此外，我们开发的组织引发光聚合技术允许在没有外源光引发剂的情况下原位形成水凝胶，从而提高了生物相容性。为了实现设计一种水凝胶与软骨结合的新系统的目标，并测试它将改善基质结合的假设，我们制定了以下具体目标：一种有效的生物相容性方法的发展直接结合光聚合水凝胶软骨组织。具体来说，胶原纤维将暴露在软骨表面并被氧化以产生自由基并引发光聚合。具体目标2。在体外和体内验证细胞-水凝胶结构与软骨表面的共价附着将改善由软骨细胞、骨髓源间充质细胞和宿主软骨基质组成的软骨工程的整合。组织整合将通过形态学、生化和力学分析来监测。