Background:Autologous matrix-induced chondrogenesis (AMIC) is a single-stage alternative to autologous chondrocyte implantation for treatment of localized cartilage defects of the knee. To our knowledge, no randomized controlled trial exists comparing the 2 methods.Purpose:To evaluate any difference in the outcome of AMIC as compared with collagen-covered autologous chondrocyte implantation (ACI-C).Study Design:Randomized controlled trial; Level of evidence, 2.Methods:A prospective randomized controlled clinical trial was designed to assess any differences in the outcomes between ACI-C and AMIC for the treatment of ≥1 chondral or osteochondral defects of the distal femur and/or patella. The inclusion period was set to 3 years, and the aim was to include 80 patients (40 in each group). Patient inclusion was broad, with few exclusion criteria. The primary outcome was change in Knee injury and Osteoarthritis Outcome Score (KOOS) at 2 years as compared with baseline. The secondary outcomes were the number of failures in each group at 2 years and the change in KOOS subscale, Lysholm, and pain visual analog scale (VAS) scores at 2 years as compared with baseline. A 2-sample t test with a significance level of P < .05 was used to compare the change in score from baseline between groups.Results:A total of 41 patients over 3 years were included in the study: 21 in the ACI-C group and 20 in the AMIC group. All the patients had prior surgery to the index knee. At 2-year follow-up, the clinical scores for both groups improved significantly from baseline. No significant differences between groups were seen in the change from baseline for KOOS (AMIC, 18.1; ACI-C, 10.3), any of the KOOS subscales, the Lysholm score (AMIC, 19.7; ACI-C, 17.0), or the VAS pain score (AMIC, 30.6; ACI-C, 19.6). Two patients in the AMIC group had progressed to a total knee replacement by the 2-year follow-up as compared with none in the ACI-C group.Conclusion:At 2-year follow-up, no significant differences were found regarding outcomes between ACI-C and AMIC. Mid- and long-term results will be important.Registration:NCT01458782 ( ClinicalTrials.gov identifier).

BackgroundAutologous chondrocyte implantation (ACI) has been used over the last two decades to treat focal cartilage lesions aiming to delay or prevent the onset of osteoarthritis; however, some patients do not respond adequately to the procedure. A number of biomarkers that can forecast the clinical potency of the cells have been proposed, but evidence for the relationship between in vitro chondrogenic potential and clinical outcomes is missing. In this study, we explored if the ability of cells to make cartilage in vitro correlates with ACI clinical outcomes. Additionally, we evaluated previously proposed chondrogenic biomarkers and searched for new biomarkers in the chondrocyte proteome capable of predicting clinical success or failure after ACI.MethodsThe chondrogenic capacity of chondrocytes derived from 14 different donors was defined based on proteoglycans staining and visual histological grading of tissues generated using the pellet culture system. A Lysholm score of 65 two years post-ACI was used as a cut-off to categorise “success” and “failure” clinical groups. A set of predefined biomarkers were investigated in the chondrogenic and clinical outcomes groups using flow cytometry and qPCR. High-throughput proteomics of cell lysates was used to search for putative biomarkers to predict chondrogenesis and clinical outcomes.ResultsVisual histological grading of pellets categorised donors into “high” and “low” chondrogenic groups. Direct comparison between donor-matched in vitro chondrogenic potential and clinical outcomes revealed no significant associations. Comparative analyses of selected biomarkers revealed that expression of CD106 and TGF-β-receptor-3 was enhanced in the low chondrogenic group, while expression of integrin-α1 and integrin-β1 was significantly upregulated in the high chondrogenic group. Additionally, increased surface expression of CD166 was observed in the clinical success group, while the gene expression of cartilage oligomeric matrix protein was downregulated. High throughput proteomics revealed no differentially expressed proteins from success and failure clinical groups, whereas seven proteins including prolyl-4-hydroxylase 1 were differentially expressed when comparing chondrogenic groups.ConclusionIn our limited material, we found no correlation between in vitro cartilage-forming capacity and clinical outcomes, and argue on the limitations of using the chondrogenic potential of cells or markers for chondrogenesis as predictors of clinical outcomes.Electronic supplementary materialThe online version of this article (10.1186/s12891-018-2380-4) contains supplementary material, which is available to authorized users.