Articular cartilage is the remarkably durable tissue that covers the articulating bone surfaces in our joints and permits pain-free movement by greatly reducing friction between bones and distributing stress. Unfortunately, when cartilage is damaged due to injury or disease, it has a limited capacity to heal and can lead to premature arthritis. Arthritis is a major health issue that is predicted to increase as our population ages. As such, there is considerable interest in the development of techniques to repair or reconstruct damaged articular cartilage. The implications of a successful method for cartilage repair would be great in terms of the number of patients affected and their quality of life. Importantly, in this era of escalating health care costs, successful cartilage repair would decrease the long-term costs of health care related to joint replacement and multiple revisions thereof. Our long-term objective is to develop a tissue engineering approach for cartilage repair using periosteum. Periosteal grafts have the potential to contribute to each of the three requirements for tissue engineering (scaffold, cells, growth factors), and have been used successfully in biological resurfacing for the repair of damaged articular cartilage. The principle obstacle to overcome for the use of periosteal tissue grafts for tissue engineering is the declining chondrogenic potential of periosteum with increasing age of the patient. We hypothesize that subperiosteal injection of specific growth factors can be used as a pretreatlnent to """"""""activate"""""""" periosteum for articular cartilage tissue engineering. In essence, the engineered tissue will be prepared in vivo for transplantation. In this proposal, we plan to examine the potential for subperiosteal injection of known chondrogenic growth factors to enhance (1) the number of chondrogenic precursor cells in periosteum in vivo (Aim 1), (2) the in vitro chondrogenic potential of periosteum (Aim 2) and (3) the potential of periosteum to repair articular cartilage defects (Aim 3). Beyond articular cartilage repair, these studies have the potential to impact the use of periosteum for other applications such as tissue engineering of bone. In addition, by eliminating the need for cell culture expansion facilities and expertise, the cost of this approach should be considerably less thereby making cartilage repair more globally accessible.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR052115-01
Application #
6862154
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Panagis, James S
Project Start
2004-09-30
Project End
2009-06-30
Budget Start
2004-09-30
Budget End
2005-06-30
Support Year
1
Fiscal Year
2004
Total Cost
$335,563
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
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Tarng, Yih-Wen; Casper, Michelle E; Fitzsimmons, James S et al. (2010) Directional fluid flow enhances in vitro periosteal tissue growth and chondrogenesis on poly-epsilon-caprolactone scaffolds. J Biomed Mater Res A 95:156-63
Schagemann, Jan C; Kurz, Haymo; Casper, Michelle E et al. (2010) The effect of scaffold composition on the early structural characteristics of chondrocytes and expression of adhesion molecules. Biomaterials 31:2798-805
Gonzalez, Carlos; Auw Yang, Kiem G; Schwab, Joseph H et al. (2010) Transforming growth factor-beta1 modulates insulin-like growth factor binding protein-4 expression and proteolysis in cultured periosteal explants. Growth Horm IGF Res 20:81-6
Olivos-Meza, A; Fitzsimmons, J S; Casper, M E et al. (2010) Pretreatment of periosteum with TGF-beta1 in situ enhances the quality of osteochondral tissue regenerated from transplanted periosteal grafts in adult rabbits. Osteoarthritis Cartilage 18:1183-91
Schagemann, J C; Chung, H W; Mrosek, E H et al. (2010) Poly-epsilon-caprolactone/gel hybrid scaffolds for cartilage tissue engineering. J Biomed Mater Res A 93:454-63
Reinholz, G G; Fitzsimmons, J S; Casper, M E et al. (2009) Rejuvenation of periosteal chondrogenesis using local growth factor injection. Osteoarthritis Cartilage 17:723-34