In the skeletally mature individual, hyaline articular cartilage does not heal effectively when injured and the natural progression of acquired articular cartilage defects is predictably poor, commonly culminating in joint arthrosis. Physician and patient demands are fueling interest in biological resurfacing and restoration as an alternative to prosthetic joint replacement in an active patient population with an increased life expectancy. Fresh osteochondral allografting currently remains the only treatment option that reliably restores anatomically appropriate, mature hyaline cartilage in weight bearing osteoarticular defects. This transplantation paradigm is associated with unique challenges mostly related to balancing the essential and seemingly conflicting considerations of graft safety with timely patient-donor matching. Maximizing the storage interval of allograft tissue has become a focal topic in tissue banking by extending cold storage times and optimizing storage media. Our recent studies determined that (1) serum-enhanced 4?C storage media is superior to both modified serum-free storage media and lactated ringer's solution for allograft storage, (2) chondrocyte viability of allografts declines rapidly after 14 days of 4?C storage in culture media, with (3) the superficial zone of the cartilage appearing preferentially affected, (4) and that these changes are induced in part by upregulation of apoptotic and matrix-related gene expression, and (5) that 37?C storage media maintains chondrocyte viability for up to 4 weeks. Also (6) impact insertion of osteochondral grafts induces chondrocyte death with a similar pattern of the superficial zone being preferentially affected. While results using traditional fresh allograft protocols have been consistently good even in long-term follow-up, the clinical consequences of prolonged cold storage of articular cartilage on chondrocyte health and overall graft quality remain largely unquantified. Likewise, while mechanisms of cartilage injury sustained during graft insertion have been postulated, their extent and clinical effect on graft performance have not been established in vivo. The objectives of this proposal are to investigate how storage parameters and insertion modality affect chondrocyte viability, and, consequently, the efficacy of osteochondral allografts in vivo by (1) testing innovative modifications to allograft storage method in vitro, and (2) to determine effects of storage and select allograft insertion techniques on graft performance and clinically relevant outcomes in vivo.

Public Health Relevance

The proposed research will foster understanding of the performance of osteochondral allograft transplants in the treatment of cartilage injury and disease. This may lead to improved clinical outcomes in affected individuals, as well as decreased disability associated with joint injuries and subsequent arthritis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR055637-03
Application #
7796728
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wang, Fei
Project Start
2008-07-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
3
Fiscal Year
2010
Total Cost
$336,501
Indirect Cost
Name
University of California San Diego
Department
Orthopedics
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Su, Alvin W; Chen, Yunchan; Wailes, Dustin H et al. (2017) Impact insertion of osteochondral grafts: Interference fit and central graft reduction affect biomechanics and cartilage damage. J Orthop Res :
Bugbee, William D; Pallante-Kichura, Andrea L; Görtz, Simon et al. (2016) Osteochondral allograft transplantation in cartilage repair: Graft storage paradigm, translational models, and clinical applications. J Orthop Res 34:31-8
Chang, Eric Y; Pallante-Kichura, Andrea L; Bae, Won C et al. (2014) Development of a Comprehensive Osteochondral Allograft MRI Scoring System (OCAMRISS) with Histopathologic, Micro-Computed Tomography, and Biomechanical Validation. Cartilage 5:16-27
Mologne, Timothy S; Cory, Esther; Hansen, Bradley C et al. (2014) Osteochondral allograft transplant to the medial femoral condyle using a medial or lateral femoral condyle allograft: is there a difference in graft sources? Am J Sports Med 42:2205-13
Grissom, Murray J; Temple-Wong, Michele M; Adams, Matthew S et al. (2014) Synovial Fluid Lubricant Properties are Transiently Deficient after Arthroscopic Articular Cartilage Defect Repair with Platelet-Enriched Fibrin Alone and with Mesenchymal Stem Cells. Orthop J Sports Med 2:
Pallante-Kichura, Andrea L; Chen, Albert C; Temple-Wong, Michele M et al. (2013) In vivo efficacy of fresh versus frozen osteochondral allografts in the goat at 6 months is associated with PRG4 secretion. J Orthop Res 31:880-6
Raub, C B; Hsu, S C; Chan, E F et al. (2013) Microstructural remodeling of articular cartilage following defect repair by osteochondral autograft transfer. Osteoarthritis Cartilage 21:860-8
Pallante-Kichura, Andrea L; Cory, Esther; Bugbee, William D et al. (2013) Bone cysts after osteochondral allograft repair of cartilage defects in goats suggest abnormal interaction between subchondral bone and overlying synovial joint tissues. Bone 57:259-68
Chan, Elaine F; Liu, I-Ling; Semler, Eric J et al. (2012) Association of 3-Dimensional Cartilage and Bone Structure with Articular Cartilage Properties in and Adjacent to Autologous Osteochondral Grafts after 6 and 12 months in a Goat Model. Cartilage 3:
Pallante, Andrea L; Görtz, Simon; Chen, Albert C et al. (2012) Treatment of articular cartilage defects in the goat with frozen versus fresh osteochondral allografts: effects on cartilage stiffness, zonal composition, and structure at six months. J Bone Joint Surg Am 94:1984-95

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