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ARRA Investments in Regenerative Medicine in Musculoskeletal and Skin Diseases


Public Health Burden
Regenerative medicine is a field of study focused on stimulating the natural healing processes of the body or regenerating tissues in vitro for subsequent implantation.  Muscle, tendon, bone, and skin are promising targets for therapy.  Most recently, approaches have focused on the potential of stem cells and biomolecules, as well as new bioengineering technologies developed by multi-disciplinary teams.

Molecular and Cellular Approaches to Regenerative Medicine
A better understanding of molecular and cellular processes, as well as the biological, chemical, and mechanical conditions that affect cell behavior, will allow scientists to guide and enhance tissue repair.  Approaches have focused on particular cells that can renew themselves, as well as differentiate into more specialized cells.  Examples of ARRA-funded research include:
  • Evaluating the role of two proteins thought to influence skin regeneration, wound repair, and hair follicle activity1
  • Testing the role of tension and compression in guiding human stem cell differentiation, for the purpose of producing engineered fibrocartilage tissue2
  • Characterizing the relative regenerative capacity of stem cells from fetal and adult tissue, and assessing the effectiveness of different strategies for their delivery for bone regeneration3
  • Testing the structural and biomechanical properties of tissue repaired with concentrated amounts of adult stem cells delivered to injured cartilage in a large animal model.4
  • Identifying specific biomaterial surface characteristics and biophysical signals that cause stem cells to become bone cells5
  • Identifying molecules that facilitate the production of therapeutic cell types from stem cells that reside in human skin.6
  • Defining the cellular, molecular, and mechano-regulatory processes involved in the postnatal development of cartilage.7
Biomaterial and Scaffold Development
In addition to basic research focused on the molecules and cells involved in the healing process, the creation of biomaterials and scaffolds that support the structural and functional development and maintenance of regenerated or repaired tissues is also important.  Examples of ARRA-funded research on the development of new regenerative medicine technologies include:
  • Mass-producing an implantable micropump prototype to determine if it can effectively deliver regulator molecules to muscle stem cells on a long-term basis, which is necessary for proper tissue regeneration8
  • Developing a strategy for harvesting cells that could heal serious bone fractures more effectively and less expensively9
  • Using specific muscle cells, which are seeded onto scaffolds, to build functional muscle tissue.10
  • Examining a cell-signaling pathway thought to influence how grafts are integrated into damaged bone in order to improve the healing of complex fractures.11
  • Developing and validating the efficacy of a dermal barrier to maintain the normal mechanical properties, and to confer a stable, infection-free skin attachment in needle-based bone implants.12
  • Producing a multi-polymer scaffold that can maintain structural integrity and direct appropriate tissue architecture, while promoting tissue formation throughout the regeneration period.13
  • Engineering a meniscus that cushions the knee joint and more closely mimics native tissue.14
Building Multi-disciplinary Research Teams
The pursuit of regenerative medicine benefits greatly from a diverse team with expertise in a wide range of fields.  ARRA-funded grants have been awarded to build on existing collaborations and better leverage these unique research environments.  Examples include:
  • Creating a new center that will focus on understanding the contributions of stem cells to the normal and abnormal growth of skin.15
  • Expanding a research team to better support translational research in tissue engineering in the musculoskeletal sciences16
  • Adding to a research core to develop novel imaging methodologies that will be used to understand musculoskeletal degeneration, pathologies, and regeneration17
  • Enhancing the bioengineering expertise within a research consortium which focuses on joint function, and particularly, healing at the interface between tendon, ligament, and bone18



  1. 2R01AR054982-11A2 -- A Study of Biological Function of Basonuclin -- Cotsarelis, George (PA)
  2. 1R01AR054939-01A1 -- Modulation of MSC Differentiation for Fibrocartilage Tissue Engineering -- Levenston, Marc E (CA)
  3. 1R01AR056694-01A1 -- Engineered Delivery of Adult Versus Fetal Stem Cells for Bone Regeneration -- Guldberg, Robert E (GA)
  4. 1RC2AR058929-01 -- Multicenter Cartilage Repair Preclinical Trial in Horses -- Chu, Constance R (PA)
  5. 3R01AR054937-01A2S1 -- Biophysical signals, biomaterial surface characteristics and hMSC differentiation -- Donahue, Henry J (PA)
  6. 1RC1AR058738-01 -- Delineating factors to control differentiation of skin derived precursor cells -- Schultz, Peter G (CA)
  7. 3R01AR053353-04S1 -- Inducing Skeletal Repair by Mechanical Stimulation -- Morgan, Elise F (MA)
  8. 1RC1AR059365-01 -- Remote-control mouse-implantable micropumps for establishment of regenerative cap -- Blau, Helen M; Santiago, Juan Gabriel (CA)
  9. 1RC1AR058776-01 -- Novel, Rapidly Translatable Technologies for Healing Long Bone Segmental Defects -- Evans, Christopher H (MA)
  10. 1R01AR057325-01 -- Development of Bioengineered Skeletal Muscle for Functional Replacement in vivo -- Christ, George Joseph (NC)
  11. 1RC1AR058435-01 -- Hedgehog pathway in periosteum-mediated repair and regeneration -- Zhang, Xinping (NY)
  12. 1RC1AR058356-01 -- Mobile Porous Subdermal Barrier to Maintain the Skin Seal of Percutaneous Devices-- Bloebaum, Roy Drake (UT)
  13. 3R01AR056624-01A1S1 -- Dynamic Fibrous Scaffolds for Engineering Dense Connective Tissues -- Burdick, Jason A; Mauck, Robert Leon (PA)
  14. 2R01AR047839-06 -- Toward tissue engineering of the knee meniscus -- Athanasiou, Kyriacos A (CA)
  15. 1P30AR058886-01 -- Biomedical Research Core Center on Skin Stem Cells -- Bickers, David Rinsey (NY)
  16. 1P30AR058879-01 -- Tissue Engineering and Therapeutic Advances in Musculoskeletal Medicine -- Puzas, J Edward (NY)
  17. 1P30AR058899-01 -- A Multi-Disciplinary Multi-Development Core on Musculoskeletal Imaging -- Majumdar, Sharmila (CA)
  18. 1P30AR058920-01 -- Faculty Recruitment to Musculoskeletal Research Consortium -- Goldstein, Steven A (MI)


 
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