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，但很少有组织工程医疗产品 (TEMP) 临床或商业上取得成功，因为存在被称为“死亡之谷”的重大技术差距 阻碍了其可扩展、一致且具有成本效益的制造。该提案适用于悬而未决的过桥资金 目前的“工程软骨多模式评估案例中心”的竞争更新。有 多种应用对 TEMP 的需求不断增长。因此，我们认为现在是大胆转变的时候了 我们最初专注于以软骨为中心的评估技术，以开发、演示和部署新颖的技术 技术能够实现各种结构组织的质量源于设计制造，从而弥合 前面提到的死亡谷。该中心的目标是 TEMP 采用我们的技术 整个社区。因此，该中心将更名为“结构模块化制造中心” Tissues”（CM2OST），并将应用前 5 年开发的知识和技术来制造 面向的挑战。该中心将是 CWRU 和先进再生人类研究所之间的联合体 ufacturing Institute (ARMI)，将专注于实现可扩展、模块化、自动化、封闭式的技术 （SMAC）制造。本行政补充提案的具体目标是完成一个子集 A0 提交的技术研究与开发 (TR&D) 部分提出的任务， 具体来说，目标 1 将追求 TR&D-1 的目标，即生成用于动态变化的基因编码细胞传感器。 传感细胞表型和功能，并开发用于动态非侵入性监测的分子传感器 使用基于 CRISPR-Cas13 的报告基因来分析细胞表型和功能。目标 2 将追求适应的 TR&D-2 将氧气和乳酸光极放入支架中以测量局部代谢物水平和细胞摄氧量 费率。目标 3 将继续开展 TR&D-3 任务，开发带有集成传感器的生物反应器，用于反馈控制 trol，并将它们与 Tissue Foundry（ARMI 原型自动化 TEMP 组件）进行物理集成 线。目标 4 将展示 O2 和 OUR 传感器与自动化和数据管理的集成 组织铸造厂系统。所请求的资金将使我们能够保持该中心作为国家中心的运作 合作资源以及作为开发、测试、验证和传播新技术的平台 TEMP 制造的技术、方法和协议。