CWRU Center for Multimodal Evaluation of Engineered Cartilage

 描述（由申请人提供）：本NIBIB P41生物医学技术资源中心（BTRC）提案的目的是在凯斯西储大学（CWRU）建立一个工程软骨多模式评估中心。工程组织即将进入临床实践，并有可能取代各种假体装置。在工程化组织中使用细胞将相当大的可变性引入到该过程中，导致组织工程化（TE）构建体的不可预测的质量。这是一个严重的限制性问题，因为这些结构在植入时必须最终取代其靶组织的所有基本功能。故障可能发生在许多模式中，多个小缺陷可能会产生累积效应。所有可用信息表明，如果TE结构在任何一种模式下失效，则其尚未达到可植入性。这使我们得出结论，用于连续监测和评估整个TE过程及其最终产品的稳健、经验证且理想的非破坏性/非侵入性工具对于确保可植入软骨的生产至关重要。监测和评估不能只侧重于TE过程的一个方面;相反，我们必须同时处理该过程的生物、生物化学和生物力学方面。类似的问题和需求也影响着我们从事软骨TE的全球同事网络。因此，需要建立用于TE软骨的多模式评估的技术和方案。拟议的中心将通过成为开发，测试，验证和传播评估软骨TE过程和产品的新方法的平台，以及协作和服务互动的广泛访问资源，来满足这一需求。我们的团队结合了CWRU几个部门的生物和工程专业知识，并在软骨TE方面合作了几十年。我们积累了与软骨评估相关的经验，专业知识和技术，这是其他地方无法获得的。提出了四个技术研究和开发（TR&D）项目，将：1）开发成像模式以纵向跟踪软骨组织分化的状态-基于miRNA的成像系统的开发是一个主要组成部分; 2）开发基于修饰细胞作为探针的非侵入性方法来分析细胞分化，以及基于组织生长期间基质重塑预测ECM组成的工具; 3）开发技术以评估软骨形成过程的内源性和外源性生化环境;以及4）开发用于TE软骨的成像引导的多尺度、多模式机械评估的方法。每个TR&D将：i）在良好表征的系统中开发和验证技术; ii）将该技术应用于我们的合作者的TE构建体; iii）使用“常规”方法在测试后详尽地分析这些构建体;以及iv）积累关于TE软骨性能的信息的跨学科数据库。这项工作将有助于开发新的TE策略;尽管重点是软骨，但多模式评估的概念对于所有类型的组织构建都是至关重要的，我们将开发的技术是通用的，可扩展到其他组织类型。

 DESCRIPTION (provided by applicant): The aim of this NIBIB P41 Biomedical Technology Resource Center (BTRC) proposal is to establish a Center for Multimodal Evaluation of Engineered Cartilage at Case Western Reserve University (CWRU). Engineered tissues are close to entering clinical practice, and have the potential to replace a variety of prosthetic devices. The use of cells in engineered tissue introduces considerable variability into the process, resulting in unpredictable quality of tissue engineered (TE) constructs. This is a severe and limiting problem, as these constructs must ultimately replace all the essential functions of their target tissue when implanted. Failure can occur in many modes, and multiple minor deficiencies can have cumulative effects. All available information suggests that if a TE construct fails in any one mode, then it has not yet reached implantability. This has led us to conclude that robust, validated, and ideally non-destructive / non-invasive tools for continuous monitoring and assessment of the entire TE process, and of its end-product, are essential to ensure the production of implantable cartilage. Monitoring and assessment cannot focus on just one aspect of the TE process; rather, we must address the biological, biochemical and biomechanical aspects of the process in parallel. Similar problems, and thus needs, also affect our global network of colleagues engaged in cartilage TE. Hence, there is a need to establish technology and protocols for multimodal evaluation of TE cartilage. The proposed Center will fill that need by becoming a platform for developing, testing, validating, and disseminating new methods of evaluating cartilage TE processes and products, and a broadly accessible resource for Collaborative and Service interactions. Our team incorporates the biological and engineering expertise of several departments at CWRU, and has collaborated for decades on cartilage TE. We have accumulated experience, expertise, and technology related to cartilage evaluation that is not available elsewhere in a like concentration. Four Technology Research and Development (TR&D) projects are proposed, which will: 1) develop imaging modalities to longitudinally track the state of cartilage tissue differentiation - development of a miRNA-based imaging system is a major component; 2) develop non-invasive methods to analyze cell differentiation based on modified cells as probes, and tools to predict the ECM composition based on matrix remodeling during tissue growth; 3) develop technologies to evaluate the endogenous and exogenous biochemical environment of the chondrogenesis process; and 4) develop methods for imaging-guided multiscale, multimodal mechanical evaluation of TE cartilage. Each TR&D will: i) develop and validate technologies in well-characterized systems; ii) apply the technology to TE constructs from our collaborators; iii) exhaustively analyze these constructs post-test using "conventional" methods; and iv) accrue a cross- disciplinary database of information on the performance of TE cartilage. This work will assist in the development of new TE strategies; despite the focus on cartilage, the concept of multimodal evaluation is fundamental for all types of tissue constructs, and the technology we will develop is versatile and extensible to other tissue types.