The goal of the proposed research is to develop a tissue-engineered osteochondral construct that will result in functional resurfacing of the entire articular surface of the patella in dogs. Our long-term objective is to develop a clinically applicable biologic arthroplasty approach for treating articular cartilage loss due to injury or osteoarthritis in humans. The natural response of articular cartilage to insult and injury is variable and, at best, unsatisfactory. Current surgical approaches for addressing this unsatisfactory response involve synthetic arthroplasty, autogenous or allogeneic grafts, and tissue stimulation techniques. Unfortunately, current treatment options are limited by prosthetic wear, loosening, and infection, availability, poor integration, and poor anatomic size and shape matching. These limitations results in dysfunction, disability, morbidity, and financial and emotional costs to patients, the health-care industry, government agencies, and tax-payers. A potential means for overcoming these issues is to develop tissue-engineered osteochondral constructs matched to patients that will resurface the entire articular surface(s) affected. Initial work through our group's collaborative partnership suggests that functional osteochondral constructs can be created using advanced imaging, established chondrocyte culture techniques, and in vitro tissue engineering methodology. Further, these constructs can be created using allogeneic chondrocytes and be successfully implanted into articular cartilage defects in the knees of dogs, resulting in tissue viability and integration. Based on these data, we hypothesized that tissue-engineered osteochondral constructs can be created that will allow for functional resurfacing of the entire articular surface of the patella in dogs as assessed by lameness scoring, clinical imaging, biochemical, biomechanical, and histologic outcome measures. In testing this hypothesis, our specific aims are to: 1) Optimize in vitro culture of canine osteochondral constructs using a well-defined culture medium and growth factor supplementation for in vivo cartilage resurfacing of the patella, and 2) Assess in vivo implantation of engineered patellar osteochondral constructs implanted into knees of adult dogs. Completion of these aims will provide the basis for pursuing our stated long-term objective, which will have the potential for providing a clinical tool for repair of large articular cartilage defects in patients thereby delaying, or even eliminating, the need for artificial joint arthoplasty. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AR053530-01
Application #
7074879
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wang, Fei
Project Start
2006-03-01
Project End
2008-02-28
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
1
Fiscal Year
2006
Total Cost
$173,567
Indirect Cost
Name
University of Missouri-Columbia
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
153890272
City
Columbia
State
MO
Country
United States
Zip Code
65211
Ng, Kenneth W; O'Conor, Christopher J; Kugler, Lindsay E et al. (2011) Transient supplementation of anabolic growth factors rapidly stimulates matrix synthesis in engineered cartilage. Ann Biomed Eng 39:2491-500
Bian, Liming; Fong, Jason V; Lima, Eric G et al. (2010) Dynamic mechanical loading enhances functional properties of tissue-engineered cartilage using mature canine chondrocytes. Tissue Eng Part A 16:1781-90
Bian, Liming; Stoker, Aaron M; Marberry, Kevin M et al. (2010) Effects of dexamethasone on the functional properties of cartilage explants during long-term culture. Am J Sports Med 38:78-85
Lima, Eric G; Tan, Andrea R; Tai, Timon et al. (2008) Physiologic deformational loading does not counteract the catabolic effects of interleukin-1 in long-term culture of chondrocyte-seeded agarose constructs. J Biomech 41:3253-9
Lima, Eric G; Tan, Andrea R; Tai, Timon et al. (2008) Differences in interleukin-1 response between engineered and native cartilage. Tissue Eng Part A 14:1721-30
Lima, Eric G; Grace Chao, Pen-Hsiu; Ateshian, Gerard A et al. (2008) The effect of devitalized trabecular bone on the formation of osteochondral tissue-engineered constructs. Biomaterials 29:4292-9
Bian, L; Lima, E G; Angione, S L et al. (2008) Mechanical and biochemical characterization of cartilage explants in serum-free culture. J Biomech 41:1153-9