The human synovial joints are susceptible to osteoarthritis, rheumatoid arthritis, congenital anomalies, and trauma during war and peacetime, conditions that collectively affect many millions of individuals worldwide. The current clinical gold standards for surgical replacement of the articular condyle of synovial joints such as bone/cartilage grafts and artificial materials suffer from substantial deficiencies such as donor site defects, limited supply, immunorejection, and transmission of pathogens. In response to NIBIB's RFA (EB-03-010), the overall objective of the present proposal is to tissue-engineer human articular condyles of synovial joints using adult mesenchymal stem cells encapsulated in biocompatible polymers. Our long-term goal is to develop tissue-engineered human articular condyles of synovial joints by using patient's own adult stem cells with minimally invasive procedures, and make tissue-engineered condyles ready for operating room use. Our preliminary data demonstrate that human articular condyles were tissue-engineered de novo both in the dorsum of immunodeficient mice using rat stem cells, and in the dorsum of the rabbit using autologous rabbit stem cells, encapsulated in biocompatible polymers. The tissue-engineered articular condyles demonstrated structural characteristics similar to normal articular condyles. Since the adult stem cells were harvested with minimally invasive procedures from the same rabbits for which articular condyles were engineered, the present tissue-engineering approaches present a potential for direct translation into clinical applications. The overall goal of the present proposal is to optimize key parameters of the tissue-engineering process, and to functionalize the tissue-engineered articular condyles. The anticipated findings may have implications in the ultimate ex vivo fabrication of tissue-engineered articular condyles using cell-based regenerative approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB002332-05
Application #
7105015
Study Section
Special Emphasis Panel (ZRG1-SSS-M (57))
Program Officer
Kelley, Christine A
Project Start
2003-09-19
Project End
2008-07-31
Budget Start
2006-08-01
Budget End
2008-07-31
Support Year
5
Fiscal Year
2006
Total Cost
$334,085
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Dentistry
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
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Lee, Chang H; Cook, James L; Mendelson, Avital et al. (2010) Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study. Lancet 376:440-8
Lee, Chang H; Marion, Nicholas W; Hollister, Scott et al. (2009) Tissue formation and vascularization in anatomically shaped human joint condyle ectopically in vivo. Tissue Eng Part A 15:3923-30
Moioli, Eduardo K; Clark, Paul A; Chen, Mo et al. (2008) Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues. PLoS One 3:e3922
Mao, Jeremy J (2008) Stem cells and the future of dental care. N Y State Dent J 74:20-4
Clark, Paul A; Moioli, Eduardo K; Sumner, D Rick et al. (2008) Porous implants as drug delivery vehicles to augment host tissue integration. FASEB J 22:1684-93
Lewis, Naama T; Hussain, Mohammad A; Mao, Jeremy J (2008) Investigation of nano-mechanical properties of annulus fibrosus using atomic force microscopy. Micron 39:1008-19
(2008) Porous structures boost integration of host tissue with titanium implants. J Am Dent Assoc 139:402
Troken, A; Marion, N; Hollister, S et al. (2007) Tissue engineering of the synovial joint: the role of cell density. Proc Inst Mech Eng H 221:429-40

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