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Principal Investigator: JEAN F WELTER
Organization: CASE WESTERN RESERVE UNIVERSITY
Fiscal Year: 2024
Award: $1,119,931
Funding agency: National Institute of Biomedical Imaging and Bioengineering
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 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 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 manufacturing-oriented challenges. The Center
will be a consortium between CWRU and the Advanced Regenerative Manufacturing Institute (ARMI), and will
focus on technologies that enable scalable, modular, automated, closed (SMAC) manufacturing. The Specific
Aims of the proposal are to 1) Assist our CPs and SPs by pushing the technologies developed at the Center
out to them. 2) Develop a cohesive set of innovative technologies, methods, and protocols that enable
structural tissue manufacturing through 4 TR&D projects, described below, and 3) Develop a new, state-of-the-
art, training and dissemination program. Strategically, we will break the overall R&D program into 4 TR&Ds
representing key components of the TEMP assembly-line model. TR&D-1 covers dynamic control of cell pheno-
type and function during the manufacturing process, and development of tissue-specific sensors for dynamic
non-invasive monitoring of cell phenotype and function. TR&D-2 will develop sensor-enabled scaffolds and novel
optode-based optical sensors to automate cell seeding and to monitor metabolites and provide feedback on local
and bulk medium conditions. TR&D-3 will develop bio-instructive bioreactors with integrated actuators and sen-
sors for feedback control, and will physically integrate them with the Tissue Foundry, an ARMI prototype auto-
mated TEMP assembly line. TR&D-4 will integrate sensors and actuators with the automation and data man-
agement system of the Tissue Foundry and will perform a manufacturing demonstration run. Demonstrating
technologies developed in the TR&Ds will provide insights into TEMP development, process development and
automation, and expose unanticipated technology gaps. Each TR&D represents a step in the TEMP assembly-
line model, thus, though the technologies are developed independently, each TR&D feeds into the next. TR&Ds,
Collaborative and Service Projects synergize, integrating and exploiting each other’s technologies as they come
online. CM2OST will be a national resource for collaborations and a platform for developing, testing, validating,
and disseminating new technology, methods, and protocols for TEMP manufacturing.
Terms: <Adoption><Animal Testing><Appearance><Automation><Basic Research><Basic Science><Biological><Biological Agent><Biological Products><Biomedical Engineering><Bioreactors><Biosensing Technics><Biosensing Techniques><Birth Defects><Body Tissues><Cartilage><Cartilaginous Tissue><Cell Body><Cell Culture Techniques><Cell Function><Cell Physiology><Cell Process><Cells><Cellular Function><Cellular Physiology><Cellular Process><Cessation of life><Characteristics><Clinical><Collaborations><Communities><Community Developments><Conditioned Culture Media><Conditioned Medium><Congenital Abnormality><Congenital Anatomical Abnormality><Congenital Defects><Congenital Deformity><Congenital Malformation><Data Management Resources><Data Management System><Death><Development><Development and Research><Disease><Disorder><Drug Screening><Education><Educational aspects><Engineering><Ensure><Evaluation><Evolution><Feedback><Feeds><Funding><Generalized Growth><Generations><Goals><Growth><Individual><Institute of Medicine><Institute of Medicine (U.S.)><Intervention><Intervention Strategies><Knowledge><Laboratories><Mechanical Stimulation><Medical><Methods><Modeling><Molecular><Monitor><NAS/IOM><Names><Pathway interactions><Patients><Pharmaceutical Agent><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Phenotype><Process><Property><Protocol><Protocols documentation><Publications><Quality Control><R & D><R&D><Regenerative Medicine><Reporter><Reproducibility><Research Resources><Resources><Running><Science><Scientific Publication><Services><Shapes><Site-Directed Mutagenesis><Site-Specific Mutagenesis><Spinal Column><Spine><Subcellular Process><Targeted DNA Modification><Targeted Modification><Technology><Testing><Time><Tissue Engineering><Tissue Growth><Tissue constructs><Tissues><Training><Trauma><Vertebral column><backbone><bio-engineered><bio-engineers><bioengineered tissue><bioengineering><biologic><biological engineering><biologics><biomedical imaging><biopharmaceutical><biosensing><biotherapeutic agent><bridge program><cell culture><cell cultures><conference><convention><cost effective><design><designing><developmental><engineered tissue><experience><fabrication><fabrication technology><flexibility><flexible><improved><innovate><innovation><innovative><innovative technologies><insight><interventional strategy><manufacture><manufacturing process><manufacturing systems><manufacturing technology><meeting><meetings><microbioreactor><multi-modality><multimodality><name><named><naming><new technology><non-invasive monitor><noninvasive monitor><novel><novel technologies><ontogeny><optical sensor><pathway><personalization of treatment><personalized medicine><personalized therapy><personalized treatment><pharmaceutical><prevent><preventing><product development><program dissemination><programs><project dissemination><prototype><regenerative><research and development><scaffold><scaffolding><sensor><success><summit><symposia><symposium><synergism><tool><user-friendly><web site><website>