About CM2OST

The Center for Modular Manufacturing of Structural Tissues (CM2oST) is a joint effort of Case Western Reserve University (CWRU) and the Advanced Regenerative Manufacturing Institute’s BioFabUSA team to address the manufacturing challenges and promote new technologies to support manufacturing replacement human cells, tissues and organs in a scalable, consistent and cost-effective manner.

Despite significant advances over several decades, very few Tissue Engineered Medical Products (TEMPs) have been clinically or commercially successful. There is a growing need for TEMPs in multiple applications, but a significant technology gap, known as the “Valley of Death”, has prevented their scalable, consistent and cost-effective manufacture. We therefore believe that now is the time for a bold shift from the “Case Center for Multimodal Evaluation of Engineered Cartilage” with its focus on cartilage-centric evaluation technologies to instead develop, demonstrate, and deploy novel technologies to enable Quality-by-Design manufacturing of a variety of structural tissues, and to, thus, bridge the aforementioned Valley of Death.

Our objective is now to promote 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 center’s first five years to manufacturing-oriented challenges. 

  • Assist our Collaborative Projects and Service Projects by pushing the technologies developed by the Center's four Technology Research and Development Projects (TR&Ds) out to them.
  • Through our TR&Ds, develop a cohesive set of innovative technologies, methods, and protocols that enable structural tissue manufacturing,
  • Develop a new, state-of-the-art, training and dissemination program.

Focus & Capabilities

We emphasize the following areas: control of cell phenotype and function, smart scaffold development, bioinstructive bioreactors, and finally integration and automation, each embodied in one TR&D project. 

There are four principal research groups under the umbrella of the Center, each focusing on a Technology Research and Development (TR&D) project:

TR&D-1 covers dynamic control of cell phenotype 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 integrates sensors and biosensors into scaffolds to measure/monitor cellular attachment and function. 

TR&D-3 develops bio-instructive bioreactors with integrated actuators and sensors for feedback control, and will physically integrate them with the Tissue Foundry, an ARMI prototype automated TEMP assembly line. 

TR&D-4 integrates sensors and actuators with the automation and data management system of the Tissue Foundry, and will perform a manufacturing demonstration run.

Available Services

  • Magnetic Resonance Imaging
  • Computed Tomography
  • Single Photon Emission Computed Tomography
  • Positron Emission Tomography
  • Bioluminescence
  • Fluorescence
  • Cryofluorescence Imaging
  • X-ray and Scintigraphy
  • Clinical Imaging Systems for Research
  • Universal lentiviral vector luciferase reporter backbone for tracking expression of nearly any miRNA
    • Currently available:
      • Lv-miR-control vector (lacks a miRNA target sequence)
      • Lv-Luc-miR-145-5p
      • Lv-Luc-miR-27b-5p
      • Lv-Luc-miR-27b-3p
      • Lv-Luc-miR-21-3p (validation in process)
  • Next generation RNA-sequencing (RNA-seq)
  • Available Reporter Vectors (validated)
    • Human Aggrecan promoter reporter (Lentiviral vector, dTomato)
    • Human Aggrecan promoter reporter (Lentiviral vector, secreted Gaussia Luciferase)
    • Human COL10A1 promoter reporter (Lentiviral vector, secreted Gaussia Luciferase)
    • Human COL2A1 promoter reporter (Lentiviral vector, secreted Gaussia Luciferase)
    • Human Col2 promoter reporter (Plasmid, Firefly Luciferase)
    • Human Osteocalcin promoter reporter (Lentiviral vector, Firefly Luciferase)
    • Human Osteocalcin promoter reporter (Lentiviral vector, dTomato)
    • Human Runx2 promoter reporter (Lentiviral vector, secreted Gaussia Luciferase)
    • Human Sox9 promoter reporter (Lentiviral vector, Firefly Luciferase)
    • Human Sox9 promoter reporter (Lentiviral vector, secreted Gaussia Luciferase)
    • Human Sox9 promoter reporter short sequence (Plasmid, Firefly Luciferase)
    • Human Sox9 promoter reporter full sequence (Plasmid, Firefly Luciferase)
    • Mouse Sox9 promoter reporter full sequence (Plasmid, Firefly Luciferase)
    • Human Sox9 promoter reporter (Lentiviral vector, eGFP)
  • Available lentiviral vectors for cell tracking:pLV-Puromicin-dTomato-Luciferase
    • pLV-Puromicin-CyPet
    • pLV-Puromicin-YPet
    • pLV-Puromicin-Luciferase
    • pLV-Blasticidin-mCherry-Luciferase
    • pLV-Neomicin-dTomato
    • pLV-Puromicin-eGFP
    • pLV-Secreted Nano-Luciferase
    • pLV-Puromicin-eGFP-Luciferase
  • Generation of differentiation markers / promoter-specific viral vectors with traceable gene reporters.
  • Efficient viral transduction of primary cells and cell lines.
  • Large-scale generation of hybrid structures for in vitro chondrogenesis.
  • Bioluminescence Imaging (BLI) of created hybrid structures to assess cell differentiation in real time.
  • Structural analysis of engineered tissue sections (Immunohistochemistry) with a panel of Proteoglycan (PG)- and Glycosaminoglycan (GAG)-specific antibodies.
  • Immunological assessment of conditioned medium (ELISA) with the same panel of specific antibodies, as an indirect analysis of ECM remodeling.
  • Biochemical determination of the GAG composition of generated cartilage ECM.
  • Transport modeling and parameter estimation for glucose consumption in aggregate culture
  • Biomolecular rate cut-off determination for success/failure in aggregate culture.
  • Donor-specific assessment of metabolism of client-MSC aggregates (glucose, lactate)
  • Donor-specific assessment of metabolism of client-MSC aggregates under varying exogenous factors (to be specified by clients)
  • LC/QQQ Amino acid analysis of culture samples
  • Amino acid pathway flux balance analysis
  • Microbioreactor and splitter for feeding for use in MSC chondrogenesis
    • 16-well conical bottom perfusion microreactor (10 microliter wells)
    • 16-well flat-bottom perfusion microreactor (9 microliter wells)
    • 100-well conical bottom perfusion microreactor (10 microliter wells)
    • 4-way microsplitter
  • Quantitative evaluation of metabolism and mass transport in client-TE constructs
  • Fluid mixing analysis in bioreactors
  • USB-based actuator; hardware and software
  • Perfusion bioreactor for culture and mechanical stimulation (flexion) of tissues
  • Coefficient of friction measurements for native and engineered cartilage
  • High-frequency ultrasound interrogation (50 MHz) of native and engineered tissue to visualize small features
  • Surface and internal damage evaluation in tissue engineered and native cartilage using high frequency (30 MHz) ultrasound
  • Acoustic anisotropy of cartilage
  • Biphasic mechanical properties of native and engineered cartilage using indentation
  • Friction and potential damage of native and engineered cartilage under normal load and sliding shear
  • Depth dependent shear properties of tissues and tissue engineered constructs
  • Quasi-static and dynamic properties of tissues in compression or tension