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（由申请人提供）：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。工程组织即将进入临床实践，并有可能取代各种假体装置。细胞在工程组织中的使用给过程带来了相当大的可变性，导致组织工程 (TE) 构建体的质量不可预测。这是一个严重且限制性的问题，因为这些构建体在植入时最终必须取代其目标组织的所有基本功能。故障可能以多种方式发生，多个小缺陷可能会产生累积效应。所有可用信息都表明，如果 TE 构造在任何一种模式下失败，则它尚未达到可植入性。这使我们得出结论，用于连续监测和评估整个 TE 流程及其最终产品的稳健、经过验证且理想的非破坏性/非侵入性工具对于确保植入式软骨的生产至关重要。监控和评估不能只关注 TE 流程的某一方面；相反，我们必须同时解决该过程的生物、生物化学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，需要建立 TE 软骨多模式评估的技术和协议。拟议的中心将成为开发、测试、验证和传播评估软骨 TE 流程和产品的新方法的平台，以及可广泛访问的协作和服务交互资源，从而满足这一需求。我们的团队融合了 CWRU 多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，这是其他类似领域所没有的。提出了四个技术研究与开发（TR&D）项目，这些项目将：1）开发成像模式来纵向跟踪软骨组织分化的状态——开发基于 miRNA 的成像系统是主要组成部分； 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，以及基于组织生长过程中基质重塑来预测ECM成分的工具； 3）开发评估软骨形成过程内源性和外源性生化环境的技术； 4) 开发成像引导的 TE 软骨多尺度、多模式力学评估方法。每个 TR&D 将： i) 在特征良好的系统中开发和验证技术； ii) 将我们合作者的技术应用于 TE 构造； iii) 使用“传统”方法在测试后详尽地分析这些结构； iv) 积累有关 TE 软骨性能的跨学科信息数据库。这项工作将有助于制定新的 TE 战略；尽管重点关注软骨，但多模式评估的概念对于所有类型的组织构建都是基础，并且我们将开发的技术具有通用性并可扩展到其他组织类型。