Projects

Interested in working with the Center for Modular Manufacturing of Structural Tissues (CM2oST)? Take a look at our Service Projects (SPs) and Collaborative Projects (CPs), or contact us to start a new project. 

Collaborative Projects should present substantial technical challenges in the field of tissue manufacturing that make the work in the CPs difficult to solve with current approaches. 

Service Projects exploit the more mature capabilities of the Center and do not drive the development of new technologies or devices of the Center. 

Both Collaborative and Service Projects are expected to be externally funded prior to beginning work .

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Existing Service Projects

Locations of Service Project institutions. Red pins: new or continuing projects. Numbers correspond to table on left. Yellow pins: CCMEEC completed projects
Start a New Service Project
  • PI & Institution: Robby Bowles, The University of Utah, Salt Lake City, UT
  • Title: Identification of new target that will drive osteogenesis
  • Funding Source: U. of Utah Start-up Funds and NIH
  • PI & Institution:Tomas Kean, Biionix Cluster, College of Medicine, U. of Central Florida, Orlando, FL
  • Title: Use and validation of chondrocyte cell reporters for cartilage tissue engineering leading to improved in vitro culture and drug discovery
  • Funding Source: Biionix startup funds
  • PI & Institution: Anand R. Kumar, University Hospitals Cleveland, OH
  • Title: Muscle Derived Stem Cells for Healing Volumetric Muscle Loss
  • Funding Source: PSF/MTF Biologics Allograft Tissue Research
  • PI & Institution: Aijun Wang, UC Davis School of Medicine, Davis, CA
  • Title: Manufacturing GMP grade placental MSCs for clinical applications
  • Funding Source: NIH
  • PI & Institution: Alexander Revzin, Mayo Clinic, Rochester, MN
  • Title:Bioreactor process standardization during pancreatic islet differentiation culture
  • Funding Source: NIH
  • Philadelphia, PA  
  • Actuator interface for compression shear-stimuli bioreactor    
  • Children’s Hospital of Philadelphia (CHOP) startup Funds
  • PI & Institution: Jeffrey Millman, Ph.D., Washington University School of Medicine, St. Louis, MO
  • Title: Determining the mechanism of IFIH1 disease-associated variants on beta-cell and immune responses in Type 1 diabetes
  • Funding Source: NIH R01DK127497
  • PI & Institution: Emilio Barbera-Guillem, MD, Ph.D., Celartia® Ltd, Columbus, OH
  • Title: Oxygen monitoring in CAR-T cell therapy production system.
  • Funding Source: Celartia® corporate funds. NIH: 75N91021C00016-0-9999-1
  • PI & Institution:Fernando Albornoz, Inbiocriotec S.A. Valparaiso, Chile
  • Title: Preservation and transport of engineered tissues
  • Funding Source: Inbiocriotec corporate funds
  • PI & Institution: Lisa Larkin, Ph.D., University of Michigan, Ann Arbor, MI
  • Title:Engineering Skeletal Muscle Tissue in STEL Bioreactor on Tissue Foundry Line
  • Funding Source:DOD W911NF-17-3-003
  • PI & Institution: Agustin Martinez, Ph.D.,  Interdisciplinary Center of Neurosciences, Faculty of Science, Valparaiso University, Valparaiso, Chile
  • Co-PI: Caroline Weinstein, Ph.D., Faculty of Pharmacy, Valparaiso University.
  • Title: Development and optimization of a scaffold for the treatment of Venous ulcers
  • Funding Source: ID21I10153, Fondef, Chile
  • PI & Institution: Maneesh Dave, UC Davis
  • Title:Davis, Davis, CA Homing of mesenchymal cells to experimental mouse model of bowel diseases
  • Funding Source: NIH
  • PI & Institution: Aldo R. Boccaccini, Ph.D., University of Erlangen-Nuremberg, Institute of Biomaterials, Erlangen, Germany.
  • Title: Use and validation of sensor/reporters for bone tissue engineering using novel biomaterials and scaffold manufacturing processes.
  • Funding Source:Institute of Biomaterials internal funds

Existing Collaborative Projects

Locations of Collaborative Project institutions. Blue pins: new or continuing projects. Numbers correspond to table below. Green pins: CCMEEC completed projects
Start a New Collaborative Project
  • Investigator & Institution: Kevin Healy, Ph.D., University of California – Berkeley, Berkeley, CA
  • Title: Non-destructive assessment of cryopreserved microtissues post-thaw.
  • Funding Source: NSF
  • Investigator & Institution: John Moore, B.A., Scientific Bioprocessing, Inc., Pittsburgh, PA
  • Title: Real-time nutrient and metabolite monitoring during cell and tissue culture for quality engineering of tissue-engineered medical products
  • Funding Source: Scientific Bioprocessing, Inc. corporate funds
  • Investigator & Institution: Alexander Revzin, Ph.D., Mayo Clinic, Rochester, MN
  • Title: Bioreactor culture of hPSC spheroids for pancreatic β cells
  • Funding Source:Kieckhefer Foundation
  • Investigator & Institution: George Christ, Ph.D., University of Virginia, Charlottesville, VA
  • Title: Evaluation of novel, non-invasive CQAs for biomanufacturing of TEMPs in a modular, closed-loop bioreactor system
  • Funding Source: NIH, DOD
  • Investigator & Institution: Peter Alexander, Ph.D., Hang Lin, Ph.D., University of Pittsburgh, Pittsburgh, PA
  • Title: Bioreactor control of tissue-chip models for synovial joint pathologies
  • Funding Source: NIH
  • Investigator & Institution:Aaron Haubner, Celartia, Inc., Columbus, OH
  • Title: Developing novel strategies for shipping and storing Tissue-Engineered constructs at room temperature
  • Funding Source: Corporate funds
  • Investigator & Institution: Elizabeth Lipke, Ph.D., Auburn University, Auburn AL
  • Title:RECODE: Directing and Controlling Cardiac Differentiation Through Cellular and Microenvironmental Manipulation and Application of Machine-Learning
  • Funding Source: NSF
  • Investigator & Institution:Julia Oxford, Boise State University, Boise, ID
  • Title: Optimization of the MSC-responsive chondrogenic phenotype towards articular chondrocytes
  • Funding Source: NIH
  • Investigator & Institution: Dimitrios Kouroupis, Ph.D., University of Miami, FL
  • Title: Mesenchymal Stem Cell Functionalization in 3D Manufacturing Settings for Clinical Applications
  • Funding Source: Department start-up funds
  • Investigator & Institution: Sam Senyo, Ph.D., Case Western Reserve University, Cleveland, OH
  • Title: Cardiomyocyte differentiation by combinatorial paracrine signaling
  • Funding Source: Startup and NIH
  • Investigator & Institution: Riccardo Gottardi, Ph.D., Children Hospitals of Philadelphia, PA
  • Title: Bioinstructive reactors for mechanical conditioning of tissues
  • Funding Source: Startup funds
  • Investigator & Institution:Tomás Egaña, SYMBIO2 Inc. and Pontificia Universidad Católica de Chile, Santiago, Chile
  • Title: Transplant organ preservation
  • Funding Source:SYMBIO2 Inc. Corporate funds
  • Investigator & Institution: Eben Alsberg, Ph.D., University of Illinois, Chicago, IL
  • Title: Opposing RNAi molecule gradient constructs to repair osteochondral defects
  • Funding Source: Startup funds
  • Investigator & Institution: Aldo Leal-Egana, Ph.D., University of Heidelberg, Germany
  • Title: Bone osteotropism: Influence of confinement and mechanical properties of the seeds in the selection of the soil
  • Funding Source: LE-3418/4-1
  • Investigator & Institution: Aldo Boccacini, Ph.D., University of Erlangen-Nuremberg, Institute of Biomaterials, Erlangen, Germany
  • Title:Bioactive Glass-derived scaffolds for bone tissue engineering.
  • Funding Source:Institute of Biomaterials internal funds
  • Investigator & Institution:Carolyn Schutt Ibsen, Ph.D., Oregon Health & Science University, Portland, Oregon
  • Title: Energy-responsive biomaterial platforms for regenerative medicine
  • Funding Source: Department Start-Up funds
  • Investigator & Institution: Yolanda Fortenberry, Case Western Reserve University, Cleveland, OH
  • Title: Developing tissue-specific aptamers
  • Funding Source:Department of Biology startup funds
  • Investigator & Institution: Rhima Coleman, Ph.D., University of Michigan, Ann Arbor, MI
  • Title: Identification of –omics signatures related to the chondrogenic potential of hMSC
  • Funding Source: NIH/NSF

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.
  • MSC-derived human collagen protein
  • Flow cytometry
  • Cell sorting
  • Aptamer development and validation
  • Troponin T-eGFP genetically-encoded reporter (under validation)
  • TGF-B1 Aptamer-CRISPRCas12 sensor (under validation)
  • Non-viral stable integration of reporter genes (tdTomato)
  • Flow cytometry
  • Confocal microscopy
  • 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
  • Adhesive oxygen optodes
  • Oxygen measurement system
  • Oxygen uptake rate sensor.
  • Modular bioreactor for tissue culture. The bioreactor is capable of culturing small 1 cm3 to 10 cm3 structural tissues. It has been optimized for mixing and oxygen sensor integration.
  • Gel Permeation Chromatography
    • Molecular weight determination
    • MW-based separation of carbohydrates, proteins, peptides, etc.
  • Extractables/Leachables (GC-MS/MS and GC-FID) per ISO 10993
  • 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
  • Actuator for flexion. A pneumatic actuator can flex tissues in a custom-bioreactor (see below) in a controlled fashion. A USB hardware/software allows for control of parameters (frequency, duration, ) of actuation.
  • Actuator for simultaneous compression/shear.
  • Bioreactor for flexion. A continuous flow bioreactor that allows for simultaneous flexing of five tissue samples.
  • Cloud-based data collection, storage and transformation
  • Unsupervised, supervised and deep machine learning
  • Exploratory data analysis
  • Descriptive and inferential statistics
  • Mechanical Testing for tissue and biomaterial characterization
  • Additional analytical capabilities
    • Gene expression profiling
    • ELISA and qPCR
  • Proteome (LC-MS/MS)
    • Protein identification
    • Untargeted proteomics
    • Molecular weight determination
    • Qualitative protein profiling
    • Identification of post-translational modifications
  • Metabolome (LC-MS/MS)
    • Untargeted metabolomics
    • Targeted metabolomics
    • Metabolite assay development
  • Lipidome (LC-MS/MS and GC-MS/MS)
    • Untargeted lipidomics
    • Targeted lipidomics
  • Development of cell type-specific chemically-defined culture media
  • Scalable expansion of autologous and allogeneic pluripotent stem cells, multi-potent stem cells and numerous primary cell types in closed, automated cell culture platforms
  • Application of scalable bioprocess equipment for cell and tissue handling
  • Closed, automated seeding of synthetic and naturally-derived scaffolds
  • Product-specific custom engineered systems for tissue and organ culture
    • In-process and final product perseveration strategies under a variety of temperature regimes
  • General regulatory strategy based upon potential regulatory identity (ies) of the product
    • Development and refinement of specific Target Product Profiles to guide product development toward an IND/IDE for clinical trials for a specific clinical indication.
    • Development of a “regulatory conducive” strategy for product develop for products that may need regulatory approval but may be used in a regulated environment, such as on-line sensors for a regenerative medicine product.
  • Preparation of and support for FDA meetings and submissions
    • Preparation of INTERACT, preIND, Qsub, meeting packages and full meeting support.
    • Preparation and electronic submission of 510(k)’s, IND’s, IDE’s, Master Files,
    • Preparation and submission of jurisdictional and special program applications to FDA.

Through its BioFab Startup Lab, ARMI works with startups of all kinds to provide a range of services from strategy, mentorship, physical and technical support from the robust and growing ARMI ecosystem in Manchester and nationwide.

Interested in initiating a new service or collaborative project?
Contact us

Campus Locations:

Millis Science Center
Room 118
2080 Adelbert Road
Cleveland, OH 44106-7120

ARMI | BioFabUSA
Technology Center- The Millyard
400 N Commercial St,
Manchester, NH 03101

Mailing Addresses:

10900 Euclid Ave.
Cleveland, OH 44106

400 Commercial Street
Manchester, NH 03101

Contact:

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The Advanced Regenerative Manufacturing Institute (ARMI) is a member-based, nonprofit organization whose mission is to advance the bioeconomy of the United States. The institute’s work will positively impact not only manufacturing but also healthcare and education and workforce development in the country.

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