Philipp Niemeyer1, Volker Laute2, Thilo John3, Christoph Becher4, Peter Diehl5, Thomas Kolombe6, Jakob Fay7, Rainer Siebold8, Milan Niks9, Stefan Fickert10, Wolfgang Zinser11. 1. Department of Orthopedic Surgery and Traumatology, Freiburg University Hospital, Freiburg, Germany philipp.niemeyer@uniklinik-freiburg.de. 2. Joint and Spine Centre Berlin, Berlin, Germany. 3. Clinic for Traumatology and Orthopedic Surgery, DRK Hospital Berlin Westend, Berlin, Germany. 4. Department of Orthopedic Surgery, Medical University Annastift Hannover, Hannover, Germany. 5. Department of Orthopedic Surgery, University of Rostock, Rostock, Germany. 6. Traumatology and Reconstructive Surgery, DRK Hospital Luckenwalde, Luckenwalde, Germany. 7. Department of Traumatology and Arthroscopic Surgery, Lubinus Clinicum Kiel, Kiel, Germany. 8. Center for Hip, Knee and Foot Surgery, ATOS Clinic Heidelberg, Heidelberg, Germany. 9. Department of Orthopedic Surgery and Traumatology, Mannheim University Hospital, Mannheim, Germany. 10. Sporthopaedicum Straubing, Straubing, Germany. 11. Department of Orthopedic Surgery and Traumatology, St Vinzenz-Hospital Dinslaken, Dinslaken, Germany.
Abstract
BACKGROUND: Although autologous chondrocyte implantation (ACI) has been established as a standard treatment for large full-thickness cartilage defects, the effect of different doses of autologous chondrocyte products on structural outcomes has never been examined. HYPOTHESIS: In ACI, the dose level may have an influence on medium-term magnetic resonance morphological findings after treatment. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 75 patients who underwent ACI using a pure, autologous, third-generation matrix-associated ACI product were divided into 3 groups representing different doses: 3 to 7 spheroids/cm(2), 10 to 30 spheroids/cm(2), and 40 to 70 spheroids/cm(2). Magnetic resonance imaging was performed at 1.5, 3, 6, and 12 months after ACI and was evaluated by the magnetic resonance observation of cartilage repair tissue (MOCART) score and the Knee injury and Osteoarthritis Outcome Score (KOOS). RESULTS:MOCART scores showed improvements after 3 months, with slight dose dependence, and further improvement after 12 months, although without significant dose dependence. The mean MOCART scores after 3 months (0 = worst, 100 = best) were 59.8, 64.5, and 64.7 for the low-, medium-, and high-dose groups, respectively, and 62.9 for all patients; at 12 months, these were 74.1, 74.5, and 68.8 for the respective dose groups and 72.4 for all patients. Several MOCART items (surface of repair tissue, structure of repair tissue, signal intensity of repair tissue, subchondral bone, and synovitis) showed a more rapid response with the medium and high doses than with the low dose, suggesting a potential dose relationship. No significant correlation between the MOCART (overall and subscores) with clinical outcomes as assessed by the overall KOOS was detected at 3- and 12-month assessments. CONCLUSION: This study reveals a trend toward earlier recovery after treatment with higher spheroid doses in terms of better defect filling for full-thickness cartilage defects of the knee, while outcomes after 12 months were similar in all dose groups. However, a correlation with clinical outcomes or the failure rate at 1 year after ACI was not found. A longer follow-up will be required for more definite conclusions on the clinical relevance of ACI cell density to be drawn. REGISTRATION: NCT01225575 (ClinicalTrials.gov identifier); 2009-016816-20 (EudraCT number).
RCT Entities:
BACKGROUND: Although autologous chondrocyte implantation (ACI) has been established as a standard treatment for large full-thickness cartilage defects, the effect of different doses of autologous chondrocyte products on structural outcomes has never been examined. HYPOTHESIS: In ACI, the dose level may have an influence on medium-term magnetic resonance morphological findings after treatment. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 75 patients who underwent ACI using a pure, autologous, third-generation matrix-associated ACI product were divided into 3 groups representing different doses: 3 to 7 spheroids/cm(2), 10 to 30 spheroids/cm(2), and 40 to 70 spheroids/cm(2). Magnetic resonance imaging was performed at 1.5, 3, 6, and 12 months after ACI and was evaluated by the magnetic resonance observation of cartilage repair tissue (MOCART) score and the Knee injury and Osteoarthritis Outcome Score (KOOS). RESULTS: MOCART scores showed improvements after 3 months, with slight dose dependence, and further improvement after 12 months, although without significant dose dependence. The mean MOCART scores after 3 months (0 = worst, 100 = best) were 59.8, 64.5, and 64.7 for the low-, medium-, and high-dose groups, respectively, and 62.9 for all patients; at 12 months, these were 74.1, 74.5, and 68.8 for the respective dose groups and 72.4 for all patients. Several MOCART items (surface of repair tissue, structure of repair tissue, signal intensity of repair tissue, subchondral bone, and synovitis) showed a more rapid response with the medium and high doses than with the low dose, suggesting a potential dose relationship. No significant correlation between the MOCART (overall and subscores) with clinical outcomes as assessed by the overall KOOS was detected at 3- and 12-month assessments. CONCLUSION: This study reveals a trend toward earlier recovery after treatment with higher spheroid doses in terms of better defect filling for full-thickness cartilage defects of the knee, while outcomes after 12 months were similar in all dose groups. However, a correlation with clinical outcomes or the failure rate at 1 year after ACI was not found. A longer follow-up will be required for more definite conclusions on the clinical relevance of ACI cell density to be drawn. REGISTRATION: NCT01225575 (ClinicalTrials.gov identifier); 2009-016816-20 (EudraCT number).
Authors: Philipp Niemeyer; Volker Laute; Wolfgang Zinser; Thilo John; Christoph Becher; Peter Diehl; Thomas Kolombe; Jakob Fay; Rainer Siebold; Stefan Fickert Journal: Knee Surg Sports Traumatol Arthrosc Date: 2020-01-02 Impact factor: 4.342
Authors: Arnd Hoburg; Philipp Niemeyer; Volker Laute; Wolfgang Zinser; Christoph Becher; Thomas Kolombe; Jakob Fay; Stefan Pietsch; Tomasz Kuźma; Wojciech Widuchowski; Stefan Fickert Journal: Cartilage Date: 2020-01-01 Impact factor: 3.117