With increasing activity and participation in organized sports within the pediatric and adolescent populations, injuries to the anterior cruciate ligament (ACL) of the knee joint are rising dramatically, with similar incidence levels as adults. The choic of non-surgical (conservative) or surgical treatment of both partial and complete ACL tears remains a subject of debate. However, reconstruction of a completely torn ACL is becoming increasingly popular to treat these injuries in children of all ages in order to restore knee stabiity and permit the return to sports while limiting secondary injuries to other structures, such as the medial meniscus. Unlike the adult scenario, the knee joint continues to evolve in these patients until skeletal maturity. During childhood growth, limited evidence suggests the orientation of the ACL changes considerably in addition to increased intrinsic maturation. Yet, little biomechanical data exists to support the use of surgical or non-surgical treatment or the use of one reconstruction technique over another. In fact, there is little knowledge about the joint-level function of the ACL during childhood and adolescence and whether age-dependent changes exist. Such information would be critical to guide age-specific treatment strategies for pediatric or adolescent patients with ACL injuries and significant growth remaining. The goal of this proposal is to utilize a surrogate animal model to study the age-dependent function of the ACL and its bundles in the growing joint as well as the impact of partial or complete ACL injury. The overall hypotheses of this proposal are that the porcine ACL undergoes similar postnatal changes as the human ACL, and that these changes, along with other changes in knee joint geometry and increasing tissue maturity during postnatal growth result in age-dependent 1) ACL function, 2) load distribution within the distinct anteromedial (AM) and posterolateral (PL) bundles of the ACL, and 3) impact of an ACL injury on the remaining soft tissues (e.g. medial meniscus, MCL, etc.) of the knee joint. To test these hypotheses, we will utilize a multi-disciplinary approach to rigorously assess ACL structure and function.
The first Aim of this proposal will assess changes in ACL geometry during growth in the porcine model using magnetic resonance imaging and spatial digitizing technologies and compare these changes to human data.
The second Aim will evaluate the age-dependent contribution of the entire ACL as well as its AM and PL bundles to joint function in the porcine model using a state-of-the-art robotic testing system to study the complex function of the ACL in multiple degrees-of-freedom (DOF).
The third Aim will determine the changes in loading of the remaining soft tissues (e.g. medial meniscus, MCL, etc.) in the porcine model with the loss of partial or complete ACL function with respect to age using the robotic testing system. Upon the successful completion of these aims, the knowledge obtained can be extended to guide surgical and/or non-operative treatment or inform exercise programs for injury prevention as well as to serve as design criteria for developing new replacement techniques.

Public Health Relevance

With increasing activity and participation in organized sports within the pediatric and adolescent populations, injuries to the anterior cruciate ligament (ACL) of the knee joint are rising dramatically, and the best age- dependent treatment algorithm is still unclear and hotly debated. The goal of this proposal is to develop and validate a surrogate animal model to study ACL function in the growing knee joint, and use the model to evaluate the age-dependent function of the ACL and its bundles as well as the impact of ACL injury. Such information will be critical to guide age-specific treatment strategies for pediatric or adolescent patients with ACL injuries and significant remaining growth, and the knowledge obtained can be extended to guide surgical and/or non-operative treatment as well as exercise training programs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Research Grants (R03)
Project #
5R03AR068112-02
Application #
9027798
Study Section
Special Emphasis Panel (ZAR1)
Program Officer
Washabaugh, Charles H
Project Start
2015-04-01
Project End
2018-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
North Carolina State University Raleigh
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
042092122
City
Raleigh
State
NC
Country
United States
Zip Code
27695
Cone, Stephanie G; Warren, Paul B; Fisher, Matthew B (2017) Rise of the Pigs: Utilization of the Porcine Model to Study Musculoskeletal Biomechanics and Tissue Engineering During Skeletal Growth. Tissue Eng Part C Methods 23:763-780
Cone, Stephanie G; Simpson, Sean G; Piedrahita, Jorge A et al. (2017) Orientation changes in the cruciate ligaments of the knee during skeletal growth: A porcine model. J Orthop Res 35:2725-2732