Biomaterials and Mesenchymal Stem/Stromal Cells in the Treatment of Knee Articular Surface Lesions

Sponsor

University Medical Centre Ljubljana (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT06078072

Collaborator

(none)

150

Enrollment

Location

Anticipated Duration (Months)

11.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this observational study is to evaluate the combined single-step approach with biomaterials and mesenchymal stem/stromal cells in the treatment of knee articular surface lesions. The clinical analysis of the treatment outcomes, regarding postoperative improvements and safety, is going to be accompanied with laboratory analysis of the intraoperatively applied cellular products.

The main hypothesis are: (1) such combined single-step procedure significantly improves patients' functioning and quality of life; (2) this therapeutic approach is safe; (3) cellular parameters of the applied filtered bone marrow aspirate (fBMA) impact treatment outcomes, among other potential predictors.

Researchers will compare subjective (questionnaire) and objective (clinical examination) status of patients before and after the operation, record any potential complications and perform regression analysis to assess the influence of potential predictors on postoperative improvements.

Condition or Disease	Intervention/Treatment	Phase
Knee Injuries Cartilage Injury Osteochondral Defect	Procedure: Biomaterials augmented with mesenchymal stem/stromal cells

Study Design

Study Type:

Observational

Anticipated Enrollment :

150 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

Biomaterials and Mesenchymal Stem/Stromal Cells in the Treatment of Knee Articular Surface Lesions

Actual Study Start Date :

Sep 1, 2022

Actual Primary Completion Date :

Aug 31, 2023

Anticipated Study Completion Date :

Oct 1, 2023

Outcome Measures

Primary Outcome Measures

Knee injury and Osteoarthritis Outcome Score (KOOS) subscale Pain postoperative improvement [At least 24 months after the operation]
Knee injury and Osteoarthritis Outcome Score (KOOS) assesses patients' pain (9 items), other symptoms (7 items), function in daily living (17 items), function in sport and recreation (5 items), and knee related quality of life (4 items). Scores range from 0 to 100 with a score 0 being the worst score and 100 indicating no impairment. KOOS subscale Pain postoperative improvement will be calculated as difference between preoperative and postoperative scores at the final follow up. Paired Student t test will be applied to compare preoperative and postoperative values of KOOS subscale Pain.

Secondary Outcome Measures

Knee injury and Osteoarthritis Outcome Score (KOOS) subscales postoperative improvements [At least 24 months after the operation]
Originally published in 1998, the Knee injury and Osteoarthritis Outcome Score (KOOS) assesses patient pain (9 items), other symptoms (7 items), function in daily living (17 items), function in sport and recreation (5 items), and knee related quality of life (4 items). Scores range from 0 to 100 with a score 0 being the worst score and 100 indicating no impairment. KOOS subscales postoperative improvements will be calculated as differences between preoperative and postoperative scores at the final follow up. As secondary outcome measures will be calculated all KOOS subscales improvements, beside KOOS subscale Pain, which is determined as the primary outcome measure. Paired Student t test will be applied to compare preoperative and postoperative values of all KOOS subscales.
Complications (SAE and GF) [Recording until the final follow up (minimum 24 months after the operation)]
Serious adverse events (SAE) are defined as any hospitalization or revision surgery (arthrofibrosis, synovitis, infection, hardware problem, pulmonary embolism, etc.), while graft failures (GF) as revision surgery to the lesion or confirmed indication for it. SAE will be further classified as related (arthrofibrosis, synovitis, graft hypertrophy/delamination, etc.) or unrelated (hardware removal, meniscus or ligament injuries, new cartilage lesions, pulmonary embolism, etc.) to the graft.
Cellular parameters of intraoperatively applied filtered Bone Marrow Aspirate (fBMA) [Finsihed in 14 days after the procedure]
Samples for cell counting (100 µl), fibroblast colony forming units (CFU-F) assay (1-2 ml) and flow cytometry (1-2 ml) will be taken before and after BMA processing with filter-based separation device. The total nucleated cell (TNC) count will be determined by counting white blood cells with hematology analyzer COULTER® Ac·T diff2™ (Beckman Coulter, Fullerton, CA, USA). MSCs content will be estimated with flow cytometry (FACSCalibur, BD Biosciences, San Jose, CA, USA) by determining CD271+ and CD45-cells, and concomitant assessment of their viability using 7-amino-actinomycin D (7-AAD) dye. Also, the CFU-F assay, which is a functional assay for measuring the frequency of MSCs with the colony forming abilities, will be performed. Briefly, cells will be seeded at least in duplicates into well culture plates and cultured in standard conditions: 37 °C, 5% CO2. After 14 days, colonies containing ≥ 50 fibroblastic cells will be manually counted under the stereomicroscope.
Tegner Activity Scale (TAS) postoperative improvement [At least 24 months after the operation]
Tegner Activity Scale (TAS) is a one-item score that graded activity based on work and sports activities on a 11-level scale from 0 to 10. Zero represents disability because of the knee problems and 10 represents national or international level soccer. TAS postoperative improvement will be calculated as difference between preoperative and postoperative scores at the final follow up. Paired Student t test will be applied to compare preoperative and postoperative values of TAS.
European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L) postoperative improvement [At least 24 months after the operation]
EQ-5D-3L descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression . Each dimension has 3 levels: no problems, some problems, and extreme problems. The respondent is asked to indicate his or her health state by ticking the box that marks the most appropriate level of problems in each dimension. A unique health state can be described according to the responses to the 5 questions. Health states defined in this way may be converted into a single summary index by applying a formula that attaches values to each of the levels in each dimension. States can be converted to a single value where 1 is equivalent to full health and 0 to a state equivalent to death. EQ-5D-3L postoperative improvement will be calculated as difference between preoperative and postoperative scores at the final follow up. Paired Student t test will be applied to compare preoperative and postoperative values of EQ-5D-3L .
EuroQol Visual Analogue Scale (EQ-VAS) postoperative improvement [At least 24 months after the operation]
EQ-VAS records the patient's self-rated health on a vertical visual analogue scale from 0 to 100, where 0 represents the worst health state imaginable and 100 represents the best health state imaginable. EQ-VAS postoperative improvement will be calculated as difference between preoperative and postoperative scores at the final follow up. Paired Student t test will be applied to compare preoperative and postoperative values of EQ-VAS5.
Potential predictors (patients' demographics, medical history, joint and lesions' characteristics, surgical and cellular parameters) of the clinical outcomes (KOOS subscales, EQ-5D-3L, EQ-VAS, TAS) [At the time of statistical analysis]
Regression models will be used to assess the influence of proposed predictors (patients' demographics, medical history, joint and lesions' characteristics, surgical and cellular parameters) on the postoperative improvements in clinical outcome measures (KOOS subscales, EQ-5D-3L, EQ-VAS, TAS). Statistical analysis will be performed with SPSS (version 25.0; IBM, Chicago, IL, USA).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Inclusion Criteria:

informed consent
patients treated with combined single-step procedure (scaffold and fBMA) for knee articular surface lesions, between January 2013 and December 2020
symptomatic knee articular surface lesions (International cartilage repair society (ICRS) grades 3-4, size ≥ 1.5 cm2) unresponsive to conservative treatment,
only mild concomitant osteoarthritis (Kellgren-Lawrence grades 1-2)

Exclusion Criteria:

patients that refuse to participate in the study
non responders to the invitation to answer PROMs at the follow-up
associated medical conditions (inflammatory, metabolic, neoplastic, etc.) that could directly handicap the musculoskeletal system or indirectly impact the quality of life