Introduction

Introducation: Matrix-associated autologous chondrocyte implantation (ACI) and microfracture (MF) are well-established treatments for full-thickness cartilage defects of the knee. However, clinical studies of high-level evidence comparing matrix-associated ACI to MF are still limited. Additionally, since different products and principles of ACI vary significantly, there is a specific need for clinical evidence in terms of efficiency and safety for every individual approach. With regard to this, the present prospective randomized clinical trial was initiated to investigate confirm the non-inferiority and investigate the superiority of a pure autologous spheroid based ACI (SPHEROX ^TM) compared with microfracture by a statistical hierarchical approach for focal and isolated cartilage defects of the knee op to a defect size of 2 cm^2.

Content

Methods: Patients with focal cartilage defects of the knee between 1 and 4 cm² were randomized to be treated by ACI or microfracture. No concomitant procedures were included. Both procedures followed standard protocols. In short, at time of screening arthroscopy the availability of the patients for the present study was confirmed and the patient was randomizend in either the ACI group or the microfracture group. While microfracturing was performed immediately in this group, for the ACI group cell harvesting was performed during index arthroscopy followed by the expansion period of approximately 8 weeks. In the ACI group, the transplantation was performed as a second surgery in a mini-open approach. For the ACI 10–70 spheroids/cm² were administered. Rehabilitation was similar in both group. In short, partial weight bearing was recommended for a period of 8 weeks and limited range of motion was recommended in preference of the individual surgeon. CPM was used routinely. The primary outcome measure was the Knee Injury and Osteoarthritis Outcome Score (KOOS) at the time of surgery and 6,12, 24 and 36 months following index surgery. This report presents results for 24 and 36 months after treatment.

Results: Both ACI and microfracture led to a significant improvement treated over the three-year observation period. For the overall KOOS, the statistical hypothesis of non-inferiority (the intended primary goal of the study) was formally confirmed; additionally, for the three subscores “Quality of Life”, “Activities of daily living” and “Sport and Recreation”, superiority of the ACI over MF was shown at different timepoints during the follow-up period. Occurrence of adverse events were not different between both treatments (ACI 77%; MF 74%). Concerning patient's safety, 9 Serious adverse events were reported for ACI and 10 for MF. However, none of the SAE was considered treatment related in the ACI group, while in the MF group 5 were possible treatment related.

Conclusion: Patients treated with matrix-associated ACI with spheroid technology showed substantial improvement in various clinical outcomes after 36 months. The advantage of ACI compared with microfracture was underlined by the clear, formal demonstration of its statistical non-inferiority, approaching superiority, and by (descriptive) superiority in the KOOS subscores ‘Activities of daily living’ and ‘Sport/Recreation’. Age and defect size showed no significant effect on clinical outcome, indicating that the treatment of limited focal defects – i.e., smaller than currently recommended by national and international orthopedic societies – should be considered.