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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Longitudinal Assessment of Cartilage Injury and Remodeling After Anterior Cruciate Ligament Rupture and Reconstruction: A Correlational Study of Functional Imaging and Biomarkers

Conditions
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Anterior Cruciate Ligament Injuries

Intervention / Treatment
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* Procedure: ACL reconstruction


Participation Criteria
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Eligibility Criteria
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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: - BMI < 18.5 or >35 kg/m2 Injury occurred longer than 4 weeks before enrollment Intra-articular steroid injection within 3 months of injury Chondral defects greater than 3 cm2 or Outerbridge grade II or higher lesions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy Volunteers<br>Volunteers were healthy people without ACL rupture | |
| Patients with ACL Rupture<br>All patients will undergo a standardized single-bundle technique with a hamstring or bone-patellar tendon-bone autograft. | Procedure: ACL reconstruction<br>* All patients will undergo a standardized single-bundle technique with a hamstring or bone-patellar tendon-bone autograft.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objectives measure of knee stability | 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. | 3 months, 6 months, 12 months | 
| COMP | Cartilage Biomarker Analysis; | 12 months after operation | 
| Interleukin-1 | Chemokines and Pro-Inflammatory Cytokines in Synovial Fluid; | 12 months after operation | 
| MMP-1 | Soft Tissue Protease and Protease Inhibitor Analysis in Synovial Fluid | 12 months after operation | 
| colony-forming units (CFU) | The CFU assay is a common means of analyzing MSC concentration in bodily fluids | 12 months after operation | 
| Cartilage morphology | Quantitative MRI of cartilage morphology | 12 months after operation | 
| Magnetic resonance imaging | Quantitative MRI of Cartilage Composition | 12 months after operation | 

Secondary Outcome Measures

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