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Sustained superiority in KOOS subscores after matrix-associated chondrocyte implantation using spheroids compared to microfracture

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Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

Abstract

Purpose

To evaluate the safety and efficacy of matrix-associated autologous chondrocyte implantation (ACI) using spheroids in comparison to arthroscopic microfracture for the treatment of symptomatic cartilage defects of the knee.

Methods

In a prospective multicenter-controlled trial, patients aged between 18 and 50 years, with single symptomatic focal cartilage defects between 1 and 4 cm2 (mean 2.6 ± 0.8, median 2.75, range 1.44–5.00) in the knee were randomized to treatment with ACI with spheroids (n = 52) or microfracture (n = 50). Primary clinical outcome was assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Analyses were performed in a defined hierarchical manner where outcomes of ACI were first compared to baseline values followed by a comparison to the microfracture group with repeated-measures ANCOVA with a non-inferiority approach. Subgroup analyses were performed to investigate the influence of age and defect size on the overall KOOS. Secondary clinical outcomes were the magnetic resonance observation of cartilage repair tissue (MOCART), modified Lysholm score and International Knee Documentation Committee (IKDC) examination form. Safety data focused on adverse events. Here the 5 years results are presented at which there were 33 observed cases in the ACI group and 30 in the microfracture group.

Results

The overall KOOS and its five subscores were significantly improved compared to baseline for both the ACI and microfracture group. Non-inferiority of ACI to microfracture was confirmed for the overall KOOS and the subscores, while for the subscores activities of daily living, quality of life and sports and recreation of the threshold for superiority was passed. In the ACI group, a notably more rapid initial improvement of the KOOS was found at three months for the older age group compared to the younger age group and the microfracture group. No other differences were found based on age or defect size. In addition, clinical improvement was found for the MOCART, modified Lysholm and IKDC examination form both the ACI and microfracture group. No safety concern related to either treatment was observed.

Conclusion

This study confirms the safety and efficacy of matrix-associated ACI with spheroids at a mid to long-term follow-up. Non-inferiority of ACI to microfracture was confirmed for the overall KOOS and all subscores, while superiority was reached for the subscores activities of daily living, quality of life and sports and recreation in the ACI group. This underlines the importance of ACI for the young and active patients.

Level of evidence.

I.

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Funding

The study was funded by CO.DON AG.

Author information

Authors and Affiliations

  1. Med Center 360 degree Berlin, Kieler Straße 1, 12163, Berlin, Germany

    Arnd Hoburg & Volker Laute

  2. Department of Orthopedic Surgery and Traumatology, University Hospital, Freiburg, Germany

    Philipp Niemeyer

  3. OCM Clinic, Munich, Germany

    Philipp Niemeyer

  4. Department of Orthopedic Surgery and Traumatology, St. Vinzenz-Hospital, Dinslaken, Germany

    Wolfgang Zinser

  5. Department of Orthopedic Surgery, Medical University Annastift, Hannover, Germany

    Christoph Becher

  6. Traumatology and Reconstructive Surgery, DRK Hospital, Luckenwalde, Germany

    Thomas Kolombe

  7. Department of Traumatology and Arthroscopic Surgery, Lubinus Clinicum, Kiel, Germany

    Jakob Fay

  8. Department of Orthopedic Surgery and Traumatology, Rudolf Elle Hospital, Eisenberg, Germany

    Stefan Pietsch

  9. Department of Orthopedic Surgery and Traumatology, Center of Sports Medicine, Orthopedic Clinic, Warsaw, Poland

    Tomasz Kuźma

  10. Hospital of Orthopedics and Trauma Surgery, Piekary Slaskie, Poland

    Wojciech Widuchowski

  11. Sporthopaedicum Straubing, Straubing, Germany

    Stefan Fickert

  12. Department of Orthopedic Surgery and Traumatology, Medical Faculty Mannheim, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany

    Stefan Fickert

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  1. Arnd Hoburg
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  2. Philipp Niemeyer
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  3. Volker Laute
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  9. Tomasz Kuźma
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  10. Wojciech Widuchowski
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  11. Stefan Fickert
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Contributions

All authors were clinical study investigators. All authors reviewed the manuscript and gave substantial input for improvements.

Corresponding author

Correspondence to Arnd Hoburg.

Ethics declarations

Conflict of interest

A.H. received royalties for medical consultancy for CO.DON AG. W.Z. has been paid honorary by CO.DON AG for consultant activities. S.F. has received consultant fees from Arthrex and Bauerfeind. P.N. has received grants for educational purposes, including CO.DON AG. Each author has been rewarded with an investigator fee as outlined in the initial clinical trial authorization documents and accepted by the corresponding ethic committees. No further sponsorship was granted.

Ethical approval

The trial was approved by the ethics committees responsible for the respective centers and by the local regulatory authorities. The main ethics committee was Mannheim, Germany (2009-070F-MA).

Informed consent

Written informed consent was obtained from all participants before the study.

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Hoburg, A., Niemeyer, P., Laute, V. et al. Sustained superiority in KOOS subscores after matrix-associated chondrocyte implantation using spheroids compared to microfracture. Knee Surg Sports Traumatol Arthrosc 31, 2482–2493 (2023). https://doi.org/10.1007/s00167-022-07194-x

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