Administrative Supplement to CWRU Center for Multimodal Evaluation of Engineered Cartilage

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)能够 在临床上或商业上取得了成功，因为一个重大的技术差距，被称为“死亡之谷”，已经 阻碍了它们可扩展、一致和具有成本效益的生产。这项提案是关于过渡性资金的待定方案 目前“工程软骨多模式评估案例中心”的竞争性更新。的确有 在多个应用程序中对临时工的需求日益增长。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、演示和部署新的 能够按设计制造各种结构组织的质量的技术，从而架起 前面提到的死亡之谷。该中心的目标是让临时工采用我们的技术 整个社区。因此，该中心将更名为“结构模块化制造中心” 纸巾“(CM2OST)，并将应用在头5年中开发的知识和技术来制造- 面向ING的挑战。该中心将由CWRU和高级再生人联盟组成- 制造研究所(ARMI)，并将专注于实现可扩展、模块化、自动化、封闭式 (SMAC)制造业。这项行政补充建议的具体目的是完成一个子集 在A0提交的技术研究和开发(tr&d)部分提出的任务中， 具体地说，Aim 1将追求研发-1的目标，为动态生成遗传编码的细胞传感器 感知细胞表型和功能，并开发用于动态非侵入性监测的分子传感器- 使用CRISPR-CAS13为基础的报告程序对细胞表型和功能进行检测。目标2将继续进行适配的研发-2 将氧和乳酸光导入支架以测量局部代谢物水平和细胞摄氧量 费率。目标3将执行研发任务，开发具有反馈控制集成传感器的生物反应器。 Trol，并将把它们与Tablet Foundry进行物理集成，这是ARMI的自动临时装配原型 排队。目标4将演示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。所要求的资金将使我们能够保持该中心作为国家 协作资源，作为开发、测试、验证和传播新技术的平台- 用于临时工制造的名称、方法和协议。

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.