CWRU Center for Multimodal Evaluation of Engineered Cartilage

 描述(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)建立工程软骨多模式评估中心(CWRU)。工程化组织即将进入临床实践，并有可能取代各种假体设备。细胞在工程化组织中的使用引入了相当大的可变性，导致组织工程(TE)构建的质量不可预测。这是一个严重而有限的问题，因为这些结构最终必须在植入时取代其目标组织的所有基本功能。故障可能在许多模式下发生，多个次要缺陷可能会产生累积效应。所有可用的信息表明，如果TE构建在任何一种模式下失败，那么它还没有达到可植入性。这使得我们得出结论，用于持续监测和评估整个TE过程及其最终产品的可靠、有效且理想的非破坏性/非侵入性工具对于确保可植入软骨的生产是必不可少的。监测和评估不能只侧重于TE进程的一个方面；相反，我们必须同时处理该进程的生物、生化和生物力学方面的问题。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，有必要建立用于TE软骨多模式评估的技术和方案。拟建的中心将成为一个开发、测试、验证和传播评估软骨TE过程和产品的新方法的平台，以及一个可广泛访问的协作和服务互动资源，从而满足这一需求。我们的团队融合了CWRU几个部门的生物和工程专业知识，并在软骨TE方面合作了数十年。我们积累了与软骨评估相关的经验、专业知识和技术，这是其他地方没有的。拟议的四个技术研发项目将：1)开发纵向跟踪软骨组织分化状态的成像方式--开发基于miRNA的成像系统是其中的主要组成部分；2)开发基于修饰细胞作为探针的非侵入性方法分析细胞分化，并开发基于组织生长过程中的基质重塑预测ECM组成的工具；3)开发评估软骨形成过程的内源和外源生化环境的技术；以及4)开发成像引导的多尺度、多模式的TE软骨力学评估方法。每个研发人员将：i)在特征良好的系统中开发和验证技术；ii)将技术应用于我们的合作者的TE结构；iii)使用“传统”方法在测试后对这些结构进行详尽的分析；以及iv)建立关于TE软骨性能的跨学科信息数据库。这项工作将有助于开发新的TE策略；尽管重点放在软骨上，但多模式评估的概念对所有类型的组织结构都是基本的，我们将开发的技术具有多功能性，并可扩展到其他类型的组织。

 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.