Over 100,000 people rupture the anterior cruciate ligament (ACL) of the knee each year. The current best treatment, replacement of the ligament with a graft of tendon, does not replace the complex architecture and biomechanics of the original ligament, and as many as 50% of patients will have signs of arthritis at only 7 years after surgery. Because of the clinical importance of this injury and the lack of an optimal treatment method, I have become increasingly interested in developing new approaches to ACL injuries, and have spent the last five years working to combine a career conducting basic investigations in ligament healing with clinical practice as an orthopaedic surgeon. During that time, I have published seven first-author peer reviewed publications, served as the principal investigator on three grants, won three national awards for ligament research, spoken at national conferences and served as a reviewer and book section editor.
The specific aims of this career award are to gain independence in several specific cellular and molecular assays, scaffold manufacture, the use of in vivo animal models and statistical analysis through coursework, seminar attendance and training in well-established laboratories. The acquisition of these skills will enhance my ability to serve as an independent scientist by lessening my current dependence on collaborators in these areas. This research proposal focuses on developing a new method of treatment for ACL rupture: enhanced primary repair. This technique makes use of a provisional scaffold to supplement a primary ligament repair and encourage healing in the gap between the ends of the ruptured ACL. This procedure could potentially restore the architecture and biomechanics of the knee, while maintaining the proprioceptive function of the ACL, thus potentially decreasing the risk of post-operative instability and osteoarthritis. The first specific aim is to define the cell and tissue events in the ACL after injury and the changes in these events after placement of a bioadhesive scaffold in the ACL defect. In the second aim, in vitro assays will be conducted to define the composition of a provisional scaffold which best stimulates ACL cells to mimic the MCL healing process. In the third aim, the optimized scaffolds will be tested in an in vivo canine ACL non-union model. Information gained in each of these aims will serve to improve our understanding of mechanisms of ligament healing.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02AR049346-04
Application #
7214219
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Wang, Fei
Project Start
2004-04-01
Project End
2009-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
4
Fiscal Year
2007
Total Cost
$100,683
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
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
Mastrangelo, Ashley N; Magarian, Elise M; Palmer, Matthew P et al. (2010) The effect of skeletal maturity on the regenerative function of intrinsic ACL cells. J Orthop Res 28:644-51
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
Abreu, Eduardo L; Palmer, Matthew P; Murray, Martha M (2010) Collagen density significantly affects the functional properties of an engineered provisional scaffold. J Biomed Mater Res A 93:150-7
Pearse 2nd, Richard V; Esshaki, Diana; Tabin, Clifford J et al. (2009) Genome-wide expression analysis of intra- and extraarticular connective tissue. J Orthop Res 27:427-34
Murray, Martha M (2009) Current status and potential of primary ACL repair. Clin Sports Med 28:51-61
Palmer, M P; Abreu, E L; Mastrangelo, A et al. (2009) Injection temperature significantly affects in vitro and in vivo performance of collagen-platelet scaffolds. J Orthop Res 27:964-71
Jacobson, May; Fufa, Duretti; Abreu, Eduardo L et al. (2008) Platelets, but not erythrocytes, significantly affect cytokine release and scaffold contraction in a provisional scaffold model. Wound Repair Regen 16:370-8
Fufa, Duretti; Shealy, Blake; Jacobson, May et al. (2008) Activation of platelet-rich plasma using soluble type I collagen. J Oral Maxillofac Surg 66:684-90
Mesiha, Mena; Zurakowski, David; Soriano, Jamil et al. (2007) Pathologic characteristics of the torn human meniscus. Am J Sports Med 35:103-12

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