CWRU Center for Multimodal Evaluation of Engineered Cartilage

CWRU 工程软骨多模式评估中心

• 批准号: 9895783
• 负责人: Arnold Irwin Caplan
• 金额: $ 118.85万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9895783
• 关键词: 3-Dimensional; Address; Affect; Assessment tool; Base Composition; Basic Science; Biochemical; Biological; Biomechanics; Biomedical Technology; Bioreactors; Cartilage; Cell Differentiation process; Cells; Chondrogenesis; Clinical; Complement; Data; Databases; Development; Engineering; Ensure; Environment; Evaluation; Extracellular Matrix; Failure; Goals; Grant; Growth; Hour; Implant; Institution; Maintenance; Mechanics; Metabolic; Methods; MicroRNAs; Minor; Monitor; Motivation; National Institute of Biomedical Imaging and Bioengineering; Performance; Problem Sets; Process; Production; Property; Prosthesis; Protocols documentation; Published Comment; Research; Research Personnel; Resources; Safety; Scientist; Services; Structure; System; Technology; Testing; Time; Tissue Differentiation; Tissue Engineering; Tissues; Training; Universities; Veterinarians; Work; base; cartilage degradation; clinical practice; clinical translation; disability; exhaustion; experience; experimental study; image guided; imaging modality; imaging system; implantation; improved; multimodality; patient population; premature; public health relevance; success; technology development; technology research and development; tissue resource; tool

 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.

 描述（由适用提供）：该nibib P41生物医学技术资源中心（BTRC）提案的目的是建立一个在Case Western Reserve University（CWRU）的工程软骨多模式评估中心。工程组织接近进入临床实践，并有可能取代各种假肢。在工程组织中使用细胞会在该过程中引入很大的可变性，从而导致组织工程（TE）构建体的不可预测质量。这是一个严重而有限的问题，因为这些结构必须最终替代植入目标组织的所有基本功能。失败可能在许多模式下发生，并且多个次要缺陷会产生累积影响。所有可用信息都表明，如果te构造在任何一种模式下失败，那么它尚未达到植入性。这使我们包括了可靠，经过验证且理想的非破坏性 /非侵入性工具，用于连续监测和评估整个TE过程及其最终产品，对于确保产生可植入软骨的生产至关重要。监视和评估不能仅关注TE过程的一个方面；相反，我们必须同时解决该过程的生物学，生化和生物力学方面。类似的问题，因此也会影响我们从事软骨TE的全球同事网络。因此，有必要建立技术和协议，以进行多模式的软骨评估。拟议的中心将通过成为开发，测试，验证和传播评估软骨TE流程和产品的新方法的平台，以及用于协作和服务交互的广泛访问资源。我们的团队纳入了CWRU多个部门的生物学和工程专业知识，并在软骨TE上合作了数十年。我们积累了与软骨评估相关的经验，专业知识和技术，这些经验是在其他地方无法使用的。提出了四个技术研发（TR＆D）项目，其中将：1）开发成像方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主要组成部分； 2）开发非侵入性方法来分析基于修饰细胞作为问题的细胞分化，以及基于组织生长过程中基于基质重塑的ECM组成的工具； 3）开发技术来评估软骨发生过程的内源性和外源性生化环境； 4）开发用于成像引导的多尺度，多模式机械评估的方法。每个TR＆D都会：i）在良好的系统中开发和验证技术； ii）将技术应用于我们合作者的TE构造； iii）使用“常规”方法在测试后进行详尽的分析； iv）接受有关软骨性能的信息的跨学科数据库。这项工作将有助于制定新的TE策略；尽管专注于软骨，但多模式评估的概念对于所有类型的组织构建体都是基础的，我们将开发的技术具有多功能性和对其他组织类型的扩展性。