Collagen-membrane-covered matrix-associated chondrocyte implantation improves safety over periosteum-covered MACI for large knee cartilage defects: A real-world data analysis in the registry study

Purpose: This registry study aimed to evaluate the safety and effectiveness of collagen membrane-covered matrix-associated autologous chondrocyte implantation (cMACI) versus periosteum-covered MACI (pMACI) for large knee cartilage defects (Outerbridge III–IV, ≥4 cm²) in the femorotibial and/or patellofemoral joints with a minimum 2-year follow-up. Methods: The safety analysis included 662 knees from 645 patients (mean age: 41.6 ± 14.0 years) with trauma (586 knees, 88.5%) or osteochondritis dissecans (76 knees, 11.5%). Mean final defect size after debridement was 6.6 ± 3.6 cm² (range: 4.0–38 cm²), with ≥4 cm² in 101 knees (15.3%) receiving cMACI and 561 (84.7%) receiving pMACI. Adverse events (AEs) were assessed through physical examination, magnetic resonance imaging (MRI) and arthroscopy. AEs rates were compared between cMACI and pMACI. The effectiveness was assessed using the Lysholm Knee Score (LKS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) at 6, 12 and 24 months postoperatively. A mixed-effects model for repeated measures was used for comparative analysis. Results: Analyses showed no significant differences in patient characteristics between groups, except for age (older in the cMACI group), sex (predominantly female), disease aetiology (predominantly trauma) and meniscectomy prevalence (lower). cMACI showed reduced rates of graft hypertrophy (1.0% vs. 10.7%, p = 0.0176), delamination (5.9% vs. 14.1%, p = 0.0350), ossification (0% vs. 2.3%, not applicable), contracture (1.0% vs. 8.7%, p = 0.0302) and treatment failure (3% vs. 9%, p = 0.0037). The per-protocol set assessing effectiveness included 509 knees (cMACI/pMACI: 70/439), with no significant differences in patient characteristics between groups. The results demonstrated similar postoperative improvements in LKS and KOOS in both groups. Conclusion: cMACI showed superior safety compared with pMACI for large cartilage defects, with similarly improved outcomes in approximately 75% of patients. These findings suggest that the collagen membrane may address periosteum-related AEs and treatment failures in MACI. Level of Evidence: Level II.