Safety and Efficacy of Matrix-Associated Autologous Chondrocyte Implantation With Spheroids for Patellofemoral or Tibiofemoral Defects: A 5-Year Follow-up of a Phase 2, Dose-Confirmation Trial

Arnd Hoburg, Philipp Niemeyer, Volker Laute, Wolfgang Zinser, Thilo John, Christoph Becher, Kaywan Izadpanah, Peter Diehl, Thomas Kolombe, Jakob Fay, Rainer Siebold, Stefan Fickert, Arnd Hoburg, Philipp Niemeyer, Volker Laute, Wolfgang Zinser, Thilo John, Christoph Becher, Kaywan Izadpanah, Peter Diehl, Thomas Kolombe, Jakob Fay, Rainer Siebold, Stefan Fickert

Abstract

Background: Matrix-associated autologous chondrocyte implantation (ACI) is a well-established treatment for cartilage defects. High-level evidence at midterm follow-up is limited, especially for ACI using spheroids (spherical aggregates of ex vivo expanded human autologous chondrocytes and self-synthesized extracellular matrix).

Purpose: To assess the safety and efficacy of 3-dimensional matrix-associated ACI using spheroids to treat medium to large cartilage defects on different locations in the knee joint (patella, trochlea, and femoral condyle) at 5-year follow-up.

Study design: Cohort study; Level of evidence, 2.

Methods: A total of 75 patients aged 18 to 50 years with medium to large (4-10 cm2), isolated, single cartilage defects, International Cartilage Repair Society grade 3 or 4, were randomized on a single-blind basis to treatment with ACI at 1 of 3 dose levels: 3 to 7, 10 to 30, or 40 to 70 spheroids/cm2 of defect size. Outcomes were assessed via changes from baseline Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee score, and modified Lysholm assessments at 1- and 5-year follow-up. Structural repair was evaluated using MOCART (magnetic resonance observation of cartilage repair tissue) score. Treatment-related adverse events were assessed up to 5 years for all patients. The overall KOOS at 12 months was assessed for superiority versus baseline in a 1-sample, 2-sided t test.

Results: A total of 73 patients were treated: 24 in the low-dose group, 25 in the medium-dose group, and 24 in the high-dose group. The overall KOOS improved from 57.0 ± 15.2 at baseline to 73.4 ± 17.3 at 1-year follow-up (P < .0001) and 76.9 ± 19.3 at 5-year follow-up (P < .0001), independent of the applied dose. The different defect locations (patella, trochlea, and weightbearing part of the femoral condyles; P = .2216) and defect sizes (P = .8706) showed comparable clinical improvement. No differences between the various doses were observed. The overall treatment failure rate until 5 years was 4%. Most treatment-related adverse events occurred within the first 12 months after implantation, with the most frequent adverse reactions being joint effusion (n = 71), arthralgia (n = 14), and joint swelling (n = 9).

Conclusion: ACI using spheroids was safe and effective for defect sizes up to 10 cm2 and showed maintenance of efficacy up to 5 years for all 3 doses that were investigated.

Registration: NCT01225575 (ClinicalTrials.gov identifier); 2009-016816-20 (EudraCT number).

Keywords: ACI; cartilage; knee; patellofemoral; prospective randomized trial; spheroids; tibiofemoral.

Conflict of interest statement

One or more of the authors has declared the following potential conflict of interest or source of funding: The present study was funded by CO.DON. A.H. has received consulting fees from CO.DON. P.N. has received consulting fees from CO.DON and education support from Aesculap, Arthrex, Geistlich, Moximed, Stryker, and Medi. W.Z. has received consulting fees from CO.DON. S.F. has received consulting fees from Arthrex and Bauerfeind. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

© The Author(s) 2022.

Figures

Figure 1.
Figure 1.
Percentage of patients affected by joint effusion after implantation of Spherox.

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