AMIC combines microfracture treatment with the coverage of dedicated reabsorbable bilayer matrix developed with the aim to obtain an easy and effective one-step treatment and firstly indicated for knee cartilage disorders of small to medium sized, inferior to 2 cm². These indications have been extended to larger surfaces [17, 18, 20] and to other joints of the lower limb, as reported in the device label. The majority of patients gained in the literature good improvement until the first year after surgery and showed further improvement during the second year postoperation [17, 18, 20, 22, 23]. MRI scan, particularly in MOCART-weighted sequences, confirmed the clinical data, showing good defect filling in the majority of patients. In particular the beneficial effects of this procedure become more evident between the first and the second postoperative year. The original MOCART score system is generally used in longitudinal fashion to evaluate the repair tissue, remaining scores moderate and stable over time. In many studies [17, 22, 24–26] MRI findings of the repair tissue provided no signs of deterioration during a period of 24 months. Examining the results of the same procedure shifted in the ankle the quality of MOCART score after MRI evaluation, after a mean follow-up of 39.5 ± 18.4 months, appeared to be significantly correlated with the clinical outcome concerning postoperative pain and functional outcome in terms of the AOFAS score [25]. On other side, studies [9, 27] have confirmed the repair tissue formed after ACI is more hyaline-like and therefore of higher quality and durability compared to the regenerate formed following bone marrow stimulation techniques as provided by microfractures alone. However, the association between hyaline-like structural repair and clinical outcome remains controversial [23, 27]. In one comparative randomized trial, comparing ACI and microfracture procedures has been supposedly similar to clinical and radiographic results at 2 and 5 years after surgery: in particular correlations between histological findings and clinical outcome were not found [28]. To compare AMIC results with medium-term results of other cartilage regeneration techniques is difficult because the analysis samples published with this procedure are small and because of the different evaluation and scoring systems often utilized. Moreover, it is not evaluated in the right way how the number of previous surgeries and BMI can influence outcome before and after cartilage repair, and they are not always considered bias in all the present statistics [17, 20, 23, 24, 29]. Furthermore, no randomized controlled studies have been published comparing AMIC with other cartilage repair procedures. However, these studies confirm the effectiveness and the safety of Chondro-Gide matrix procedure which demonstrates that the good results observed at 1 year after surgery are maintained at 2 years, with some concerns about sutured techniques. Pain reduction and improvement of symptoms and hence function could be achieved up to 2 years postoperation [15]. The status of the studies where patients are evaluated 2 years after cartilage repair is considered an important indicator for the future outcome [26, 28]. In some studies [16, 24], the hypothesis that perforation of the subchondral bone plate gives a starter to mesenchymal stem cell pool activity and rises locally their number has been verified, producing the release of further marrow elements as with lineage cell progenitors, stromal cells, growth factors, and cytokines, that together can activate a cascade of elements sufficient to produce new repair tissue [11, 30]. On the other side, it is demonstrated in in vitro studies that the life of bone marrow MSCs seeded and adhered into Chondro-Gide matrix is superior to adipose tissue-derived MSCs, but they all remain incorporated after 28 days only in a low percentage (2%): working better if inducted to chondrogenic differentiation, bone marrow mesenchymal stem cells demonstrated the greatest increase in total number and deposition on cartilaginous tissue [31].