The objective of this investigation is to evaluate the progression of osteoarthritis (OA) following anterior cruciate ligament (ACL) reconstruction using an experimental model. Rupture of the ACL is a common debilitating injury that leads to post-traumatic OA. Surgical reconstruction of the ACL is necessary in many patients to restore joint function, and to stop the progression of OA that follows an ACL injury. Since the ACL is the primary restraint of anterior translation of the tibia relative to the femur, a properly implanted ACL graft should theoretically restore normal kinematics, and hence the distribution and magnitude of the tibiofemoral contact stresses, preventing the progression of OA. Furthermore, intra-operative parameters, such as the initial tension applied to the graft at the time of fixation (""""""""initial graft tension"""""""") may also affect the integrity of articular cartilage following surgery since it is a parameter that directly affects knee kinematics and the tibiofemoral contact stress. However, there is clinical evidence to suggest that ACL reconstruction may not stop OA progression. The benefits of ACL reconstruction and the effect of initial graft tension on OA progression have not been established. Five experimental groups will be compared in this study: 1) Goats with intact ACLs (control group); 2) Goats with a reconstructed ACL implanted under a low initial graft tension; 3) Goats with a reconstructed ACL implanted under a high initial graft tension; 4) Goats with a section ACL that is left untreated; and 5) Goats with intact-ACLs who undergo a sham surgical procedure in one leg. After the initial intervention, the animals will undergo a 26-week healing period, after which the mechanical properties (and histology) of the articular cartilage, and knee kinematics (A-P laxity) will be evaluated. The primary aim of the study is to compare the aggregate moduli (a material property) of articular cartilage obtained from the tibiofemoral joints to establish the relationship between ACL reconstruction and the progression of OA following 26 weeks of graft healing, and to determine how initial graft tension affects this relationship. The secondary aim is to measure temporal changes in A-P knee laxity following ACL surgery to establish the relationship between the material properties of the articular cartilage and knee kinematics in the ACL reconstructed knee. After completion of this work, the model could be used to investigate the effects of other parameters of ACL reconstruction surgery (such as the meniscal and subchondral bone status, graft position, and post-operative rehabilitation), and to evaluate potential mechanisms of OA progression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR049199-03
Application #
6931565
Study Section
Special Emphasis Panel (ZRG1-GRM (04))
Program Officer
Panagis, James S
Project Start
2003-09-01
Project End
2008-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
3
Fiscal Year
2005
Total Cost
$389,566
Indirect Cost
Name
Rhode Island Hospital
Department
Type
DUNS #
075710996
City
Providence
State
RI
Country
United States
Zip Code
02903
Waller, Kimberly A; Zhang, Ling X; Elsaid, Khaled A et al. (2013) Role of lubricin and boundary lubrication in the prevention of chondrocyte apoptosis. Proc Natl Acad Sci U S A 110:5852-7
Murray, Martha Meaney; Fleming, Braden C (2013) Biology of anterior cruciate ligament injury and repair: Kappa delta ann doner vaughn award paper 2013. J Orthop Res 31:1501-6
Proffen, Benedikt L; McElfresh, Megan; Fleming, Braden C et al. (2012) A comparative anatomical study of the human knee and six animal species. Knee 19:493-9
Waller, Kimberly A; Zhang, Ling X; Fleming, Braden C et al. (2012) Preventing friction-induced chondrocyte apoptosis: comparison of human synovial fluid and hylan G-F 20. J Rheumatol 39:1473-80
Mastrangelo, Ashley N; Vavken, Patrick; Fleming, Braden C et al. (2011) Reduced platelet concentration does not harm PRP effectiveness for ACL repair in a porcine in vivo model. J Orthop Res 29:1002-7
Fleming, Braden C; Vajapeyam, Sridhar; Connolly, Susan A et al. (2011) The use of magnetic resonance imaging to predict ACL graft structural properties. J Biomech 44:2843-6
Teeple, Erin; Elsaid, Khaled A; Jay, Gregory D et al. (2011) Effects of supplemental intra-articular lubricin and hyaluronic acid on the progression of posttraumatic arthritis in the anterior cruciate ligament-deficient rat knee. Am J Sports Med 39:164-72
Wei, Lei; Fleming, Braden C; Sun, Xiaojuan et al. (2010) Comparison of differential biomarkers of osteoarthritis with and without posttraumatic injury in the Hartley guinea pig model. J Orthop Res 28:900-6
Fleming, Braden C; Magarian, Elise M; Harrison, Sophia L et al. (2010) Collagen scaffold supplementation does not improve the functional properties of the repaired anterior cruciate ligament. J Orthop Res 28:703-9
Murray, Martha M; Magarian, Elise; Zurakowski, David et al. (2010) Bone-to-bone fixation enhances functional healing of the porcine anterior cruciate ligament using a collagen-platelet composite. Arthroscopy 26:S49-57

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