Primary chondrocytes and bone marrow cells on a 3D co-polymer scaffold: 2-year results of a prospective, multicenter, single-arm clinical trial in patients with cartilage defects of the knee

Abstract

Introduction The potency of the combination of primary chondrocytes with multipotent cells to support cartilage tissue regeneration, without the need for cell culture, was first evidenced in 2001. INSTRUCT (CellCoTec B.V., Netherlands) is a patented technology that combines freshly isolated autologous chondrocytes and mono-nucleated cells from bone marrow with a porous scaffold in a single surgical procedure. Objectives The objective of the INSTRUCT study was to assess the safety and efficacy of a cell mixture of non-expanded chondrocytes and bone marrow cells seeded on a co-polymer scaffold for the treatment of symptomatic cartilage defects of the knee. Methods Forty patients were enrolled at 6 European sites in a prospective, open-label, single-arm clinical trial. Patients were to be aged 18–55 years, with a Modified Outerbridge grade III or IV focal cartilage defect on the femoral condyle. Mal-alignment, ligament laxity and osteoarthritis (KL grade III or IV) were exclusion criteria. Safety and efficacy endpoints (clinical improvement: KOOS, IKDC, Pain VAS and structural repair: MRIs and histology) were evaluated at baseline, 3, 6, 12, 18 and 24 months. A macroscopic evaluation of the repair tissue was performed during the second-look arthroscopy using the ICRS cartilage repair assessment score. Results A total of 40 patients were enrolled and treated. Ninety percent of patients (36/40) completed the 2-year follow-up. Patients were predominantly male patients (72%), the mean age was 35 years, the mean BMI was 26. Lesions were mostly Modified Outerbridge grade IV (70%) lesions of traumatic origin (60%) with a mean size of 2.1 cm 2 . The results showed a clinically and statistically significant ( P P P Conclusions The results from the INSTRUCT study show that the treatment of cartilage lesions with a combination of primary chondrocytes and bone marrow cells results in articular cartilage tissue repair associated with a sustained and significant clinical improvement and a safety profile in line with existing treatment options. This first clinical experience suggests that this single-surgery solution is a viable treatment option for patients with full-thickness cartilage defects of the knee.