Administrative Supplement to CWRU Center for Multimodal Evaluation of Engineered Cartilage

CWRU 工程软骨多模式评估中心的行政补充

• 批准号: 10468459
• 负责人: Arnold Irwin Caplan
• 金额: $ 31.23万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10468459
• 关键词: Administrative Supplement; Adoption; Animal Testing; Appearance; Automation; Biological Products; Bioreactors; Cartilage; Cells; Cessation of life; Clinical; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Communities; Congenital Abnormality; Data Management Resources; Disease; Drug Screening; Engineering; Evaluation; Feedback; Funding; Generations; Goals; Institutes; Knowledge; Laboratories; Measures; Medical; Methods; Molecular; Oxygen; Patients; Pharmacologic Substance; Phenotype; Protocols documentation; Reporter; Resources; Structure; Technology; Testing; Time; Tissue Engineering; Tissues; Trauma; base; cost effective; design; multimodality; new technology; non-invasive monitor; personalized medicine; prevent; prototype; regenerative; research and development; scaffold; sensor; technology research and development; uptake

Despite significant advances over several decades, very few Tissue Engineered Medical Products (TEMPs) have been clinically or commercially successful, as a significant technology gap, known as the “Valley of Death”, has prevented their scalable, consistent and cost-effective manufacture. This proposal is for bridge funding pending the competing renewal of the current “Case Center for Multimodal Evaluation of Engineered Cartilage”. There is a growing need for TEMPs in multiple applications. We therefore believe that now is the time for a bold shift from our original focus on cartilage-centric evaluation technologies to developing, demonstrating, and deploying novel technologies to enable Quality-by-Design manufacturing of a variety of structural tissues, and to, thus, bridge the aforementioned Valley of Death. The goal of the Center is the adoption of our technologies by the TEMP community at large. Consequently, the Center, will be renamed “Center for Modular Manufacturing of Structural Tissues” (CM2OST), and will apply knowledge and technology developed during the first 5 years to manufactur- ing-oriented challenges. The Center will be a consortium between CWRU and the Advanced Regenerative Man- ufacturing Institute (ARMI), and will focus on technologies that enable scalable, modular, automated, closed (SMAC) manufacturing. The Specific Aims of this Administrative Supplement proposal are to complete a subset of the tasks proposed in the Technology Research and Development (TR&D) components of the A0 submission, specifically, Aim 1 will pursue the TR&D-1 goals to generation genetically encoded cell sensors for dynamic sensing of cellular phenotype and function, and to develop molecular sensors for dynamic non-invasive monitor- ing of cell phenotype and function using CRISPR-Cas13 based reporters. Aim 2 will pursue the TR&D-2 of adapt- ing oxygen and lactate optodes into scaffolds to measure local metabolite levels and cellular oxygen uptake rates. Aim 3 will pursue TR&D-3 task towards developing bioreactors with integrated sensors for feedback con- trol, and will physically integrate them with the Tissue Foundry, an ARMI prototype automated TEMP assembly line. Aim 4 will be to demonstrate integration of O2 and OUR sensors with the automation and data management system of the Tissue Foundry. The requested funding will allow us to keep the Center operational as a national resource for collaborations and as a platform for developing, testing, validating, and disseminating new technol- ogy, methods, and protocols for TEMP manufacturing.

尽管几十年来取得了重大进展，但很少有组织工程的医疗产品（TEMP）拥有 在临床或商业上成功，作为一个重要的技术差距，称为“死亡谷” 防止其可扩展，一致且具有成本效益的制造。该提议是用于桥梁资金未决的 当前“工程软骨多模式评估案例中心”的竞争续约。有 在多个应用程序中对温度的需求日益增长。因此，我们认为现在是时候大胆地转变了 我们最初关注以软骨为中心的评估技术，以开发，演示和部署新颖 技术能够逐个设计的质量制造各种结构组织，从而使桥梁 理性的死亡谷。该中心的目的是通过临时工采用我们的技术 整个社区。因此，该中心将被更名为“结构模块化中心” 组织”（CM2OST），并将在最初5年应用知识和技术应用于制造商 面向挑战。该中心将是CWRU和高级再生人造的联盟 ufacturing Institute（ARMI），并将专注于启用可扩展，模块化，自动化，封闭的技术 （SMAC）制造。该行政补充建议的具体目的是完成子集 A0提交的技术研发（TR＆D）组件中提出的任务 具体而言，AIM 1将追求TR＆D-1目标，以产生一般编码的细胞传感器以进行动态 传感细胞表型和功能，并为动态非侵入性监测器开发分子传感器 使用基于CRISPR-CAS13的记者使用细胞表型和功能。 AIM 2将追求适应的TR＆D-2- 将氧气和乳酸酸盐选择到支架中，以测量局部代谢物水平和细胞氧气摄取 费率。 AIM 3将追求TR＆D-3的任务，以开发具有集成传感器的生物反应器，以进行反馈。 trol，并将它们与组织铸造厂（Armi原型自动化温度组件）物理整合 线。 AIM 4将证明O2和我们的传感器与自动化和数据管理的集成 组织铸造系统。要求的资金将使我们能够将中心作为国家运作 合作的资源，作为开发，测试，验证和传播新技术的平台 临时制造的OGY，方法和协议。