One-Year Clinical and Radiological Results of a Prospective, Investigator-Initiated Trial Examining a Novel, Purely Autologous 3-Dimensional Autologous Chondrocyte Transplantation Product in the Knee

Abstract

Background:The 3-dimensional autologous chondrocyte transplantation (ACT3D) comprises isolation of chondrocytes from cartilage biopsies, cultivation to spheroids, and transplantation into the cartilage defect.Objectives:To evaluate the patients’ general health and functionality and to assess the defect repair after ACT3D with spheroids by MRI and MOCART scoring.Methods:Thirty-seven patients with isolated chondral lesions of the knee underwent ACT3D with spheroids through medial arthrotomy. Patient-administered scores were assessed at baseline (day before transplantation), at 6 weeks, and at 3, 6, and 12 months. MRI and MOCART scoring were performed at 3 and 12 months after ACT3D.Results:Patients were diagnosed with full-thickness patellofemoral (n = 16), femoral condylar (n = 18), or both defect types (n = 3), International Cartilage Repair Society (ICRS) grade 3 or 4, with defect sizes between 1.0 and 12.0 cm2. On average, 59.5 spheroids/cm2 in defect size were transplanted. An overall statistically significant improvement from baseline to 12 months was observed for all assessment scores (Lysholm, International Knee Documentation Committee [IKDC], SF-36, Tegner) combined with a significant reduction in the visual analog scale (VAS) for pain and an advanced defect filling. Subgroup analyses revealed a positive clinical outcome independent on defect size, defect locations, spheroid dosage, age, duration of symptoms, and severity of complaints at baseline. Seven patients experienced in total 8 adverse events, of which knee joint effusion and blocking were assessed as possibly or probably related to ACT3D.Conclusions:The patient-administered assessment scores along with the fast defect filling with ACT3D using spheroids demonstrated an increase in activity level and quality of life after a 1-year follow-up.

Cell-based tissue engineering strategies used in the clinical repair of articular cartilage

“…The spheroid outer layer was stated to contain a zone of proliferating and migratory cells that facilitate integration with other spheroids and adjacent native tissue (47, 48). The Chondrosphere ® product is available 5-10 weeks after the first surgery (49). …”

“…Generally, subchondral bleeding is avoided or the bleeding is stopped before implantation (49). Information on a planned Phase III clinical trial recommends a dose of 10-70 spheroids/cm 2 in the defect (50).…”

Emergence of Scaffold-Free Approaches for Tissue Engineering Musculoskeletal Cartilages

“…In a 1 year follow-up study, patients’ Lysholm, International Knee Documentation Committee (IKDC), SF-36, and Tegner scores significantly increased after treatment of full-thickness patellofemoral or femoral condylar defects with Chondrosphere. 23 Therefore, aggregate engineering represents a highly versatile tool with which to engineer musculoskeletal cartilages. Aggregate tissue engineering represents a versatile TE tool to form musculoskeletal neocartilage, both indirectly by forming aggregates to (re)differentiate cells and then dissociating them to form tissues by other methods and directly by using aggregates to fill defects or assembling them into larger tissue structures 6 (Figure 4).…”

Spheroidal Organoids Reproduce Characteristics of Longitudinal Depth Zones in Bovine Articular Cartilage

“…Conceptually similar to tissue development, a cell-based therapy arouses great interest in repairing degeneration in articular cartilage by implanting autologous chondrocytes or mesenchymal stem cells and by stimulating bone marrow bleeds. Even spheroids themselves have been used for improving cell transplantation [Anderer and Libera, 2002;Polacek et al, 2011;Fickert et al, 2012;Zscharmack et al, 2015;Lopa et al, 2015]. To our knowledge, although these therapies have been shown to fill the defects with some disorganized tissue, the regeneration of their longitudinal zone has not yet been seen in the repaired cartilage.…”