gms | German Medical Science

Introduction: INSTRUCT (CellCoTec B.V., Netherlands) is a technology that combines freshly isolated autologous chondrocytes and mono-nucleated cells from bone marrow with a porous scaffold filling the defect and providing cartilage matching mechanical stability. Based on (pre-)clinical data it is anticipated that the scaffold is degraded within a 2 year timeframe while tissue is building up to contribute to mechanical stability, in parallel. 2-year results of a prospective, multicenter, single-arm clinical trial are presented.

Objectives: The objective of the INSTRUCT Clinical 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. Part of the secondary efficacy end points of the study was to study defect filling, rehabilitation, presence of scaffold and repair tissue.

Methods: 40 patients were enrolled at 6 European sites in a prospective, open-label, single-arm clinical trial. Patients were aged 18-55 years, with a Modified Outerbridge grade III or IV focal cartilage defect on the femoral condyle. Malalignment, ligament laxity and osteoarthritis (KL grade III or IV) were exclusion criteria. Lesion filling and repair tissue were examined though MRIs at baseline, 3, 6, 12, 18 and 24-month and biopsy histology at 6M, 12M or 24M. Rehabilitation protocol was conservatively based on current standards and progress was monitored.

Results: A total of 40 patients were enrolled and treated. 90 % of patients (36/40) completed the 2-year follow-up. Patients were predominantly male patients (72%), the mean age was 35 years, mean BMI was 26. Lesions were mostly Modified Outerbridge grade IV (70%) lesions of traumatic origin (60%) with a mean size of 2.1 cm². On average, lesion filling on MRIs was consistently greater than 95% at all time-points. In average, patients returned to full-weight bearing in 7 weeks and to full range of motion in 9 weeks. Hyaline cartilage was found in 65% of biopsies taken at 6, 12 or 24-month. During these second-look arthroscopies, the ICRS overall repair assessment was rated as normal (grade I) or nearly normal (grade II) in 83% of patients. Scaffold degradation was graded to be between 75%-100% for 2 patients, 50-75% for 6 patients and 25%-50% for the remaining patients.

Conclusions: These first clinical results from the INSTRUCT study show that the treatment of cartilage lesions with a combination of primary chondrocytes and bone marrow cells and a porous, degradable, biocompatible PEGT/PBT scaffold with mechanical properties matching human cartilage leads to early rehabilitation and continuous defect filling while the scaffold is degraded and repair tissue is building up in concert during the first 2 years.