In patients, the anterior cruciate ligament (ACL) is a frequently injured knee structure and its reconstructions after surgery can fail in up to 27% of cases. Losing ACL function can dramatically alter joint kinematics, causing adverse loading on secondary ligamentous restraints in the short to intermediate term and cartilage damage, degenerative joint disease and osteoarthritis in the longer term. Investigators are now beginning to accurately characterize 3-D kinematics in the normal knee. However, critically important 3-D tissue forces that control these kinematics remain impossible to directly measure in patients and can only be inferred by recording ligament surface strains. Ligament forces can conceivably be determined in animal models, but only if: a) joint motions and tissue force transducer outputs are simultaneously recorded in vivo for activities of daily living (ADLs);and b) these instrumented limbs are then calibrated during simulations of these in vivo motions in the laboratory. In this grant, we propose to do just this: to measure in vivo knee motions for multiple ADLs in the normal and injured adult sheep knee and then use robotics to simulate these ADLs in the laboratory in order to determine the 3-D ACL force. These results will provide, in a large and relevant preclinical model, the ability to set design criteria and evaluation benchmarks for both existing and novel ACL treatment strategies such as tissue engineered repairs. To address these needs and build on our preliminary data, we now propose studies in the sheep model to examine activity-related changes in vertical ground reaction forces (VGRFs), knee motions, and total knee and ACL forces before and after controlled medial collateral ligament (MCL) injury and/or medial meniscectomy (MM). Our current studies are designed to answer five important research questions: 1) How does altering gait surface inclination in the normal sheep knee affect these response measures (VGRFs, knee motions, and knee and ACL forces)? How does 2) MCL injury or 3) medial meniscectomy affect these measures? 4) How does combining MCL injury and medial meniscectomy affect these measures? 5) How does combining these two injuries alter these response measures compared to those for both individual injuries? Aim 1: Examine how, compared to level and uphill surfaces, walking a sheep on a downhill gait surface alters normal knee VGRFs, 3-D knee motions, ACL force, and total knee force.
Aim 2 : Determine how MCL injury or medial meniscectomy influences all response measures for three gait surface inclinations and one speed at 12 weeks post surgery.
Aim 3 : Determine how combined MCL injury and medial meniscectomy influence our set of response measures for identical gait surface inclinations at 12 weeks post surgery. Contrast these results with those of the individual injuries.

Public Health Relevance

Measuring ligament forces and motions for different ADLs in a large animal model will permit us to study existing and novel treatment strategies for ACL reconstruction. This proposed research serves as the platform for subsequent investigation into ACL injury and reconstruction so we can develop more rational reconstruction strategies for common orthopaedic injuries.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Skeletal Biology Structure and Regeneration Study Section (SBSR)
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Panagis, James S
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University of Cincinnati
Engineering (All Types)
Schools of Engineering
United States
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Bates, Nathaniel A; Nesbitt, Rebecca J; Shearn, Jason T et al. (2018) The influence of internal and external tibial rotation offsets on knee joint and ligament biomechanics during simulated athletic tasks. Clin Biomech (Bristol, Avon) 52:109-116
Nesbitt, Rebecca J; Bates, Nathaniel A; Rao, Marepalli B et al. (2018) Effects of Population Variability on Knee Loading During Simulated Human Gait. Ann Biomed Eng 46:284-297
Bates, Nathaniel A; McPherson, April L; Nesbitt, Rebecca J et al. (2017) Robotic simulation of identical athletic-task kinematics on cadaveric limbs exhibits a lack of differences in knee mechanics between contralateral pairs. J Biomech 53:36-44
Bates, Nathaniel A; Nesbitt, Rebecca J; Shearn, Jason T et al. (2017) Knee Abduction Affects Greater Magnitude of Change in ACL and MCL Strains Than Matched Internal Tibial Rotation In Vitro. Clin Orthop Relat Res 475:2385-2396
Bates, Nathaniel A; Nesbitt, Rebecca J; Shearn, Jason T et al. (2016) Sex-based differences in knee ligament biomechanics during robotically simulated athletic tasks. J Biomech 49:1429-1436
Bates, Nathaniel A; Nesbitt, Rebecca J; Shearn, Jason T et al. (2016) Posterior Tibial Slope Angle Correlates With Peak Sagittal and Frontal Plane Knee Joint Loading During Robotic Simulations of Athletic Tasks. Am J Sports Med 44:1762-70
Ford, Kevin R; Schmitt, Laura C; Hewett, Timothy E et al. (2016) Identification of preferred landing leg in athletes previously injured and uninjured: A brief report. Clin Biomech (Bristol, Avon) 31:113-6
Nesbitt, Rebecca J; Bates, Nathaniel A; Karkhanis, Teja D et al. (2016) Impacts of Robotic Compliance and Bone Bending on Simulated in vivo Knee Kinematics. Am J Biomed Eng 6:12-18
Boguszewski, Daniel V; Wagner, Christopher T; Butler, David L et al. (2015) Effect of ACL graft material on anterior knee force during simulated in vivo ovine motion applied to the porcine knee: An in vitro examination of force during 2000 cycles. J Orthop Res 33:1789-95
Bates, Nathaniel A; Nesbitt, Rebecca J; Shearn, Jason T et al. (2015) A Novel Methodology for the Simulation of Athletic Tasks on Cadaveric Knee Joints with Respect to In Vivo Kinematics. Ann Biomed Eng 43:2456-66

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