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（TEMPs） 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“死亡谷”， 阻碍了它们的可扩展、一致和具有成本效益的制造。这项建议是桥梁资金待定 目前的“工程车辆多模式评估案例中心”的竞争性更新。有 在多种应用中对TEMP的需求日益增长。因此，我们认为，现在是大胆转变的时候， 我们最初专注于以软骨为中心的评估技术， 技术，使质量的设计制造的各种结构组织，并因此，桥梁 前面提到的死亡之谷。该中心的目标是通过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”。 组织”（CM 2 OST），并将应用知识和技术开发的第一个5年， 面向挑战。该中心将是CWRU和高级再生人之间的联盟- 制造研究所（ARMI），并将专注于技术，使可扩展的，模块化的，自动化的，封闭的， （SMAC）制造。本行政补充提案的具体目标是完成一个子集 在A0号文件的技术研究和开发部分中提出的任务中， 具体地说，目标1将致力于实现TR&D-1的目标，即产生遗传编码的细胞传感器，用于动态的 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-Cas 13的报告基因检测细胞表型和功能。目标2将追求TR&D-2的适应- 将氧气和乳酸盐光电二极管植入支架中以测量局部代谢物水平和细胞氧摄取 rates.目标3将继续执行TR&D-3任务，开发具有集成传感器的生物反应器，用于反馈控制。 trol，并将它们与TissueFoundry（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 组织铸造系统。所要求的资金将使我们能够保持该中心作为一个国家运作， 合作资源，并作为开发、测试、验证和传播新技术的平台， TEMP制造的逻辑、方法和方案。

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.