Injuries to intra-articular tissues, including the anterior cruciate ligament (ACL), menisci, cartilage and tendon, are of great clinical importance. Over 1 million patients each year sustain these injuries and the high rate of failure of repair of these injuries (as high as 90%) leads to loss of tissue and joint integrity and high rates of premature arthritis. Our preliminary work has demonstrated that a collagen-platelet hydrogel can stimulate healing in the wound site of a complete ACL transection. In the work outlined in this proposal, we wish to further understand the mechanisms behind the ability of platelets to stimulate wound healing in the joint in vivo. In our first aim, we propose to study the influence of platelet concentration on the cellular and vascular repopulation of the ACL wound site using in vitro and in vivo assays.
The second aim focuses on defining the effects of differences in wound site biology with the return of strength to the ligament as a functional outcome measure. As a secondary outcome, correlations between the biomechanical properties and findings on magnetic resonance imaging (volume measures and signal to noise ratios) will also be sought to enable us to begin to identify non-invasive measure for functional healing of this important intra-articular ligament.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR052772-04
Application #
7877951
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Tyree, Bernadette
Project Start
2007-09-07
Project End
2011-12-30
Budget Start
2010-07-01
Budget End
2011-12-30
Support Year
4
Fiscal Year
2010
Total Cost
$352,522
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Kiapour, Ata M; Fleming, Braden C; Murray, Martha M (2015) Biomechanical Outcomes of Bridge-enhanced Anterior Cruciate Ligament Repair Are Influenced by Sex in a Preclinical Model. Clin Orthop Relat Res 473:2599-608
Yoshida, Ryu; Cheng, Mingyu; Murray, Martha M (2014) Increasing platelet concentration in platelet-rich plasma inhibits anterior cruciate ligament cell function in three-dimensional culture. J Orthop Res 32:291-5
Yoshida, Ryu; Murray, Martha M (2013) Peripheral blood mononuclear cells enhance the anabolic effects of platelet-rich plasma on anterior cruciate ligament fibroblasts. J Orthop Res 31:29-34
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
Vavken, Patrick; Proffen, Benedikt; Peterson, Chris et al. (2013) Effects of suture choice on biomechanics and physeal status after bioenhanced anterior cruciate ligament repair in skeletally immature patients: a large-animal study. Arthroscopy 29:122-32
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
Vavken, Patrick; Fleming, Braden C; Mastrangelo, Ashley N et al. (2012) Biomechanical outcomes after bioenhanced anterior cruciate ligament repair and anterior cruciate ligament reconstruction are equal in a porcine model. Arthroscopy 28:672-80
Yoshida, Ryu; Vavken, Patrick; Murray, Martha M (2012) Decellularization of bovine anterior cruciate ligament tissues minimizes immunogenic reactions to alpha-gal epitopes by human peripheral blood mononuclear cells. Knee 19:672-5
Vavken, Patrick; Murray, Martha M (2011) The potential for primary repair of the ACL. Sports Med Arthrosc Rev 19:44-9
Harrison, Sophia; Vavken, Patrick; Kevy, Sherwin et al. (2011) Platelet activation by collagen provides sustained release of anabolic cytokines. Am J Sports Med 39:729-34

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