Rupture of the anterior cruciate ligament (ACL) of the knee is an increasingly common injury in adolescents. Current treatment is ACL reconstruction where the torn ligament is removed from the knee and a tendon graft is placed through the knee to replace it. While this procedure is good at restoring gross stability to the knee, as many as 78% of patients will develop premature osteoarthritis of the knee 14 years after surgery. For the estimated 38,000 high school students who sustain this injury each year, this is a significant risk for permanent disability. Thus, new solutions for this injury are required, especially for young patients. Recent work in our laboratory has demonstrated that the ACL can be induced to heal if suture repair is supplemented with a collagen-platelet rich plasma hydrogel placed in the wound site. Stimulating healing of the ACL has several important advantages over replacement of the torn ligament: there is no required harvest of tendons from elsewhere in the knee, the proprioceptive fibers of the ACL are preserved, and the complex anatomy of the ligament is more closely restored. We anticipate that preserving the dynamic proprioceptive function and complex anatomy of the ligament will decrease the risk of osteoarthritis. However, it is unknown if children and adolescents will also be able to successully heal the ACL with this technique. In the work outlined in this proposal, the effects of skeletal maturity on the functional healing process for this injury is examined in four specific aims.
In Specific Aim I, cell migration as a function of age is studied in a previously established in vitro model.
In Specific Aims 2, the rates of cell migration into an acellular scaffold in vivo will be measured.
In Specific Aim 3, the effect of age on the revascularization of an acellular scaffold in vivo will be evaluated using in vivo MRI as well as histomorphometry.
In Specific Aim 4, the effect of age on the restoration of biomechanical strength, stiffness and knee laxity after ACL repair will be examined. CLINICAL

Public Health Relevance

Tears of the anterior cruciate ligament of the knee affect over 100,000 patients each year and current treatments do not prevent premature osteoarthrititis. New treatments are being developed, where the ligament is stimulated to heal instead of being replaced, and this project will enable us to determine whether children and adolescents will be good candidates for this new approach. ? ? ?

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Musculoskeletal Tissue Engineering Study Section (MTE)
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Tyree, Bernadette
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Children's Hospital Boston
United States
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Kiapour, Ata M; Fleming, Braden C; Murray, Martha M (2017) Structural and Anatomic Restoration of the Anterior Cruciate Ligament Is Associated With Less Cartilage Damage 1 Year After Surgery: Healing Ligament Properties Affect Cartilage Damage. Orthop J Sports Med 5:2325967117723886
Perrone, Gabriel S; Proffen, Benedikt L; Kiapour, Ata M et al. (2017) Bench-to-bedside: Bridge-enhanced anterior cruciate ligament repair. J Orthop Res 35:2606-2612
Sieker, Jakob T; Ayturk, Ugur M; Proffen, Benedikt L et al. (2016) Immediate Administration of Intraarticular Triamcinolone Acetonide After Joint Injury Modulates Molecular Outcomes Associated With Early Synovitis. Arthritis Rheumatol 68:1637-47
Proffen, Benedikt L; Sieker, Jakob T; Murray, Martha M et al. (2016) Extracellular matrix-blood composite injection reduces post-traumatic osteoarthritis after anterior cruciate ligament injury in the rat. J Orthop Res 34:995-1003
Kelly, Brian A; Proffen, Benedikt L; Haslauer, Carla M et al. (2016) Platelets and plasma stimulate sheep rotator cuff tendon tenocytes when cultured in an extracellular matrix scaffold. J Orthop Res 34:623-9
Chin, K E; Karamchedu, N P; Patel, T K et al. (2016) Comparison of micro-CT post-processing methods for evaluating the trabecular bone volume fraction in a rat ACL-transection model. J Biomech 49:3559-3563
Proffen, Benedikt L; Vavken, Patrick; Haslauer, Carla M et al. (2015) Addition of autologous mesenchymal stem cells to whole blood for bioenhanced ACL repair has no benefit in the porcine model. Am J Sports Med 43:320-30
Kiapour, Ata M; Fleming, Braden C; Proffen, Benedikt L et al. (2015) Sex Influences the Biomechanical Outcomes of Anterior Cruciate Ligament Reconstruction in a Preclinical Large Animal Model. Am J Sports Med 43:1623-31
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
Bennike, Tue Bjerg; Barnaby, Omar; Steen, Hanno et al. (2015) Characterization of the porcine synovial fluid proteome and a comparison to the plasma proteome. Data Brief 5:241-7

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