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.
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.
Study Type
OBSERVATIONAL
Enrollment
76
All patients will undergo a standardized single-bundle technique with a hamstring or bone-patellar tendon-bone autograft.
Peking university third hospital
Beijing, Beijing Municipality, China
RECRUITINGObjectives 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.
Time frame: 3 months, 6 months, 12 months
COMP
Cartilage Biomarker Analysis;
Time frame: 12 months after operation
Interleukin-1
Chemokines and Pro-Inflammatory Cytokines in Synovial Fluid;
Time frame: 12 months after operation
MMP-1
Soft Tissue Protease and Protease Inhibitor Analysis in Synovial Fluid
Time frame: 12 months after operation
colony-forming units (CFU)
The CFU assay is a common means of analyzing MSC concentration in bodily fluids
Time frame: 12 months after operation
Cartilage morphology
Quantitative MRI of cartilage morphology
Time frame: 12 months after operation
Magnetic resonance imaging
Quantitative MRI of Cartilage Composition
Time frame: 12 months after operation
Tegner Activity Scale
knee evaluation are commonly used to document a patient's activity level
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Time frame: 12 months after operation
Lysholm Knee Scale
knee evaluation are commonly used to document a patient's functional outcomes
Time frame: 12 months after operation
International Knee Documentation Committee (IKDC) subjective Scale
knee evaluation are commonly used to document a patient's functional outcomes
Time frame: 12 months after operation