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Grant of the Month | December 2020

    Home Grant of the Month Grant of the Month | December 2020

    Grant of the Month | December 2020

    By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2020 | Comments are Closed | 18 December, 2020 | 0

    PIs: David Vorp

    Title: Preclinical Optimization and Design for Manufacturability of Immunoregulatory Tissue-Engineered Vascular Graft

    Description: Despite the emergence of a few companies in recent years based on the clinical translation of small diameter tissue-engineered vascular grafts (TEVGs), the gold standard for arterial bypass in the clinic continues to be autologous vein or artery grafts. Our group has developed, with previous NIH funding, TEVGs based on the documented pro-regenerative immunoregulatory potency of mesenchymal stem/stromal cells (MSCs) and tubular, biodegradable scaffolds. MSCs are immunoregulatory in that they both recruit host neutrophils and macrophages via secreted factors and modulate the recruited cells to a tolerant and pro-regenerative phenotype. We have also demonstrated that MSCs can stimulate the production of new functional vascular extracellular matrix both in-vitro and in-vivo and that MSCs play an acute antithrombogenic role in our TEVGs. Our published work has rigorously tested the ability of human-derived MSCs to induce remodeling of TEVG constructs when implanted as rat aortic interposition grafts. In very recent unpublished work (embargoed pending IP protection), we have also successfully tested in the same rat model cell-free TEVG strategies based on immunoregulatory factors secreted by MSCs. These have included the use of cytokine- and MSC secreted factor-loaded microspheres and MSC-derived extracellular vesicles (EVs) loaded into TEVG scaffolds. We define our TEVG strategies in terms of feasible combinations of “payload” (MSCs, cytokine-loaded microspheres, MSC secreted factor-loaded microspheres, and MSC-derived EVs) loaded into three different types of scaffolds (poly(ester urethane)urea (PEUU), lyophilized silk fibroin (LyoGel), and bilayered porous silk). We have also begun to scale-up the fabrication processes of these TEVG configurations in anticipation of eventual large animal testing and have demonstrated success with a sheep implant pilot study in anticipation of this proposal submission. Our proposed milestone-driven project is ideal for this two-phase Catalyze grant mechanism and successful completion will lead to significant progress toward the clinical translation of our TEVG technology. The R61 phase has two objectives with milestones that will allow us to fully evaluate, in our well-established and relatively high-throughput rat model, all feasible TEVG configurations. The primary outcome of the R61 Phase will be to identify the best combination(s) of immunoregulatory payload and scaffold for a TEVG construct that can most optimally remodel in-vivo into a native-like artery. The R33 phase has five objectives with milestones that will first demonstrate successful fabrication of scaled-up versions of the TEVG configurations that meet the milestones of the R61 phase, and then perform large animal testing of the best (up to four) configuration(s). The outcome of this phase will be to identify the optimal TEVG configuration to move forward toward clinical testing and commercialization, and also to address design for manufacturability and development of regulatory and business plans and connections.

    Source: National Heart, Lung, and Blood Institute

    Term: August 15, 2020 – July 31, 2022

    Amount: $367,238 (one year)

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    • Home
    • Our People
      • Faculty/Staff Bios
      • Core Faculty Publications
      • Administrative Resources
    • Our Technologies
    • About Us
      • Welcome
      • Video
      • Mission Statement
      • What Is Regenerative Medicine?
      • Executive Committee
      • 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
      • 2021 Scientific Retreat
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