Research Project
10468459
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.
