Anterior Cruciate Ligament Injuries
Conditions
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.
Interventions
All patients will undergo a standardized single-bundle technique with a hamstring or bone-patellar tendon-bone autograft.
Sponsors
Study design
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
* \- 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| colony-forming units (CFU) | 12 months after operation | The CFU assay is a common means of analyzing MSC concentration in bodily fluids |
| Cartilage morphology | 12 months after operation | Quantitative MRI of cartilage morphology |
| 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; |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lysholm Knee Scale | 12 months after operation | knee evaluation are commonly used to document a patient's functional outcomes |
| International Knee Documentation Committee (IKDC) subjective Scale | 12 months after operation | knee evaluation are commonly used to document a patient's functional outcomes |
| Tegner Activity Scale | 12 months after operation | knee evaluation are commonly used to document a patient's activity level |
Countries
China