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Grant of the Month | August 2012

    Grant of the Month Grant of the Month | August 2012

    Grant of the Month | August 2012

    By: The McGowan Institute For Regenerative Medicine | Category: Grant of the Month, Grant of the Month 2012 | August 1, 2012

    PI Rocky S. Tuan

    Title 3-D Osteochondral Micro-tissue to Model Pathogenesis of Osteoarthritis

    Description Osteoarthritis (OA), the most prevalent form of arthritis, affects up to 15% of the adult population and is principally characterized by degeneration of the articular cartilage component of the joint, often with accompanying subchondral bone lesions. Understanding the mechanisms underlying the pathogenesis of OA is important for the rational development of disease modifying OA drugs (DMOADs). While most studies on OA have focused on the investigation of either the cartilage or the bone components of the articular joint, the osteochondral complex represents a more physiologically relevant target as the disease ultimately is a disorder of osteochondral integrity and function. In this application, we propose to construct an in vitro 3-dimensional microsystem that models the structure and biology of the osteochondral complex of the articular joint. Osteogenic and chondrogenic tissue components will be produced using adult human mesenchymal stem cells (MSCs) derived from bone marrow and adipose seeded within biomaterial scaffolds photostereolithographically fabricated with defined internal architecture. A 3D-printed, perfusion-ready container platform with dimensions to fit into a 96-well culture plate format is designed to house and maintain the osteochondral microsystem that has the following features: (1) an anatomic cartilage/bone biphasic structure with a functional interface; (2) all tissue components derived from a single adult mesenchymal stem cell source to eliminate possible age/tissue type incompatibility; (3) individual compartments to constitute separate microenvironment for the “synovial” and “osseous” components; (4) cell-seeded envelopes to represent “synovium” and “endothelium”; (5) accessible individual compartments that may be controlled and regulated via the introduction of bioactive agents or candidate effector cells, and tissue/medium sampling and compositional assays; (6) compatibility with the application of mechanical load and perturbation; and (7) imaging capability to allow for non-invasive functional monitoring. The robustness and physiological relevance of the osteochondral microsystem will be tested on the basis of: (1) structural integrity and potential connectivity of the separate “synovial” and “osseous” compartments; (2) maintenance of distinct cartilage and bone phenotypes and the development of a histologically distinct osteochondral junction or tidemark; (3) applicability and tissue responsiveness to mechanical loading; and (4) imaging and analytical capabilities. The consequences of mechanical injury, exposure to inflammatory cytokines, and compromised bone quality on degenerative changes in the cartilage component will be examined in the osteochondral microsystem as a first step towards its eventual application as an improved and high-throughput invitro model for prediction of efficacy, safety, bioavailability, and toxicology outcomes for candidate DMOADs. This grant is held in the Department of Orthopaedic Surgery, University of Pittsburgh.
    Source National Institutes of Health – National Center for Advancing Translational Sciences

    Term 7/24/12 – 6/30/14

    Amount $720,766 total costs for 2 years (includes $224,034 of indirect costs for 2 years)

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    A program of the University of Pittsburgh and the University of Pittsburgh Medical Center
    • Home
    • Our People
      • Faculty/Staff Bios (A-C)
      • Faculty/Staff Bios (D-I)
      • Faculty/Staff Bios (J-N)
      • Faculty/Staff Bios (O-S)
      • Faculty/Staff Bios (T-Z)
      • Core Faculty Publications
      • Administrative Resources
    • Our Innovations
      • Impact
      • Patent Matrix
      • Featured Innovations
        • Innovation Insights
        • Coulter Programs
        • Expert Exposés
        • Spinout Spotlight
      • Partnerships & Collaborations
        • Industry
        • Academia
        • Within Pitt
      • Contact
    • About Us
      • Welcome
      • Video
      • Statistics
      • Mission Statement
      • What Is Regenerative Medicine?
      • Contact Us
      • Clinical Site
    • Our Research
      • Focus Areas
        • Tissue Engineering and Biomaterials
        • Cellular Therapies
        • Medical Devices and Artificial Organs
        • Clinical Translation
      • Matrix
      • Centers
      • Laboratories
      • Clinical Trials
      • Initiatives
    • Media
      • Current News
      • News Archive
      • Video
      • Podcasts
      • Newsletter
      • Grant of the Month
      • Publication of the Month
      • Media Contact
      • Video Links
    • Professional Development
      • Seminar Series
      • Special Events
      • Student Interest Groups
      • CATER
      • Post-Doctoral Opportunities
      • Career Opportunities
      • Wiegand Summer Internship
      • Admissions
      • Summer School
      • 2019 Scientific Retreat
      • Human Performance Optimization Symposium
    Regenerative Medicine at the McGowan Institute