Cartilage Injury and Remodeling After ACL Rupture and Reconstruction: Functional Imaging and Biomarkers

Brief Summary: The proposed study will establish novel relationships between intra-articular MSC recruitment, synovial inflammation, biomarkers of cartilage degeneration and joint inflammation, clinical patient factors, and downstream alterations in cartilage composition and morphology to provide novel insights into the pathoetiology of PTOA after ACL injury and reconstruction.

Detailed Description: In efforts to study the pathoetiology of post-traumatic osteoarthritis (PTOA), we propose a collaborative, prospective cohort study of 38 patients undergoing primary anterior cruciate ligament (ACL) reconstruction after ACL rupture. We will assess the longitudinal progression of patient-reported outcomes, knee laxity, MRI-based articular cartilage morphology and composition, and serum-borne biomarkers of cartilage degeneration up to 1 year of follow-up. Furthermore, stem cell mobilization, chemokine and pro-inflammatory cytokine concentrations, and inflammatory cell recruitment into synovial tissue will be measured from intraoperatively-collected samples. We will perform mixed multivariate linear regression modeling to elucidate potentially novel relationships between patient demographics, anatomy, biological factors, and downstream alterations in articular cartilage morphology and composition. We request $200,000 in funding over a two-year duration.

Recruitment & Eligibility

Inclusion Criteria

- Males and females, aged 18 - 30 years
Isolated, traumatic primary anterior cruciate ligament rupture requiring surgical reconstruction
Surgical reconstruction performed using a single-bundle technique utilizing an autograft
No history of ipsilateral traumatic knee injury or fracture
No evidence of PCL injury or more than grade 1 injury to the MCL or LCL

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
Patients with ACL Rupture	ACL reconstruction	All patients will undergo a standardized single-bundle technique with a hamstring or bone-patellar tendon-bone autograft.

Primary Outcome Measures

Name	Time	Method
Cartilage morphology	12 months after operation	Quantitative MRI of cartilage morphology
Magnetic resonance imaging	12 months after operation	Quantitative MRI of Cartilage Composition
MMP-1	12 months after operation	Soft Tissue Protease and Protease Inhibitor Analysis in Synovial Fluid
Objectives measure of knee stability	3 months, 6 months, 12 months	Knee stability (anterior-posterior laxity) will be measured utilizing the KT-2000 arthrometer, based on the side-to-side difference (SSD) observed between the injured and the healthy, contralateral knee. Subjects will be tested at 90 days, 180 days, and 1 year after surgery, with maximum manual force performed at 30 and 90 degrees of knee flexion.
COMP	12 months after operation	Cartilage Biomarker Analysis;
Interleukin-1	12 months after operation	Chemokines and Pro-Inflammatory Cytokines in Synovial Fluid;
colony-forming units (CFU)	12 months after operation	The CFU assay is a common means of analyzing MSC concentration in bodily fluids

Secondary Outcome Measures

Name	Time	Method
Tegner Activity Scale	12 months after operation	knee evaluation are commonly used to document a patient's activity level
International Knee Documentation Committee (IKDC) subjective Scale	12 months after operation	knee evaluation are commonly used to document a patient's functional outcomes
Lysholm Knee Scale	12 months after operation	knee evaluation are commonly used to document a patient's functional outcomes