Division of Cardiovascular Diseases Strategic Plan

Goals in Enabling Technologies and Methodologies for Cardiovascular Disease

1.5. Improve tissue engineering technologies for cardiovascular regenerative medicine

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Much progress has been made in the tissue engineering/regenerative medicine field, especially in the development of first generation products, and the understanding of cell-cell and cell-matrix interactions. However, significant knowledge gaps remain in our ability to control cell phenotype and direct tissue formation, which is the ultimate goal for both tissue engineering and regenerative medicine. This goal harnesses advances in stem cell and developmental biology, as well as nonviral delivery systems, to permanently restore function to compromised tissues while avoiding host rejection, tumorigenesis or other adverse events. The use of functionalized tissue engineered constructs for in vitro assays will also play a role in drug development and toxicity screening.

Strategies to Accomplish this Goal May Entail:

Basic Research:

  • Identify suitable cell sources, biomaterials, and cell-instructive strategies for specific application targets.
    • Identify optimal cells for differentiation into cardiac tissues, reproducible methods for differentiating into well-characterized cell products, reliable scale-up procedures.
    • Improve methods to control biomatrix composition, architecture, porosity, surface chemistry, degradation, strength, shape, and compliance for biomaterials.
    • Develop cell-instructive approaches to limit or reverse changes in phenotypic function to improve treatment of heart failure.
  • Establish new models and approaches to integrate extracellular matrix architecture, biomaterials, cellular pathways, physical, chemical, and electrical parameters for the design of biological substitutes.
  • Integrate technologies into improved functional structures.  An example may be improved small-diameter grafts for vascular surgery.
  • Establish computational modeling systems to guide the engineering of reproducible CV tissue constructs.

Translational Research:

  • Develop functional in vitro models of human disease for testing therapies and toxicities.
  • Engineer tissues from autologous cells to avoid rejection.
  • Foster the development of assays, bioreactors, and automation methods.
    • Improve cell culture protocols, together with reliable sources of stored cells for use in tissue engineering CV applications, to speed applications’ development.
    • Develop bioreactor devices to support self-assembly of multiple cell types into complex heart tissues.
  • Develop noninvasive real-time imaging for assessment of cell/tissue/organ fate and function for use in humans.
  • Assess durability of tissue-engineered constructs in clinically relevant models.
  • Promote multidisciplinary partnerships and collaborations between academic investigators and industry/biotechnology to test the safety and efficacy of tissue-engineered products for CV applications in clinically relevant disease models.
  • Employ human tissue-based drug screening to predict CV drug action more accurately.

Clinical Research:

  • Develop clinically effective strategies to induce immune tolerance of engineered tissues.
  • Perform clinical trials to assess safety of tissue-engineered products for regenerative and reparative medicine and to determine the durability of products.

Contributing Sources:

September 2008

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