In this study, the efficacy of type I collagen-based MACT to mediate regenerative cartilage repair was demonstrated in a prospective clinical study with a 2-year follow-up. Positive clinical and morphologic outcomes were consistently evident across all 20 patients involved without any significant adverse events.
In the current study, the Knee injury and Osteoarthritis Outcome Score (KOOS) was used as the primary outcome. All five domains improved equally in all cases, and this improvement was sustained within the 2-year follow-up. The sports and recreation and quality were somewhat lower than for the other sections. This might be related to the fearful psychological factors after cartilage mechanical initial damage. Due to concerns regarding reinjury, patients felt hesitant to participate in the active exercise on a regular basis or other recommended moderate physical activity to facilitate rehabilitation after an operation, and this suggested that the doctor needed to supply the appropriate psychological counseling according to the psychological characteristics of patients to promote patients to recover to health earlier. However, this operation has achieved satisfactory results in patients in the second year after the operation. Our study showed good clinical efficacy with a large number of cartilage-like tissues filling the lesion, and this had also been evaluated in several studies. In a prospective clinical following 31 patients with MACI for 5 years, Ebert JR et al.  found good clinical outcomes, and all grafts were preserved on follow-up MRI except for two graft failure cases due to the complications. Moreover, Barié et al. aimed to establish whether MACI or the second-generation ACI provided superior long-term outcomes in terms of patient satisfaction, clinical assessment, and MRI evaluation by following up 16 patients for an average of 9.6 years in a randomized clinical trial, and this study suggested that MACI method was equally effective treatments for isolated full-thickness articular cartilage lesions. The current study was different from the above-mentioned studies in that it had a shorter follow-up time of 24 months, and that the entire procedure was performed using the mini-open parapatellar arthrotomy. In parallel, arthroscopic exploration of nascent tissue formation was speculated to be the immature cartilage tissue accounting for the regenerated cartilage presenting with generalized tissue fragility, and the regenerated cartilage and subchondral bone were not fully integrated. This was consistent with the results of the quantitative MRI T2-mapping according to the T2 values, which were still more than the surrounding cartilage. At the moment, we could only speculate that the postoperative recovery phase was more than 24 months.
Several reports involved another technique for MACI just as in the current study. Yoon et al., in a prospective study, enrolling ten patients undergoing arthroscopic gel-type autologous chondrocyte implantation (GACI), manifested that GACI produced satisfactory clinical, radiologic, and histologic evaluation, which confirmed sufficient regeneration of hyaline-like cartilage that correlated improved symptoms. Since the GACI was infused in liquid form, it was applied to the dependent position of the lesion regardless of its geometry, and the implant could then spread by itself over the lesion site. Perhaps it could be a considerably simpler technique than other arthroscopic MACI methods. However, it required meticulous bleeding control for clear visualization of the lesion during the application of chondrocytes by using a suction syringe and cotton bud. The amount of handling and manipulation of the implant to prepare it for an arthroscopic procedure might lead to additional chondrocyte cell apoptosis. The GACI was the lack of fixation causing the graft to fall off, and cell leakage and chondrocyte distribution were still an issue. On the contrary, because the implant in the current study was treated with a solid scaffold made of a kind of non-flowing gel, it was fixed in place with fibrin glue and no membrane cover, and MACT was performed as a mini- arthrotomy procedure for reimplantation. Furthermore, as the cases in this study, a small cadaveric study demonstrated that 16 times more viable cells remained on the membrane scaffold after implantation when the procedure was performed via a mini-open arthrotomy compared with arthroscopically.
MRI was widely performed to evaluate the quality of the repair cartilage while avoiding the potential sampling bias accompanying tissue biopsy, and its results confirmed the lesion filling with homogeneous tissue and a high integration ratio[21, 22]. The quantitative MRI was claimed to be currently the best tool to assess repair quality after implantation and before operation. However, the ability of quantitative T2 mapping was still in dispute, referring to providing a sufficiently detailed structural evaluation of regenerated cartilage considering the somewhat limited resolution of the currently available imaging technology. Our results for MRI T2 mapping could not detect the morphologic differences between the superficial and mid to deep zone of the repaired tissue, and that could be detected from the histologic elevation. Thus, although invasive, the histologic assessment was likely still the most reliable method for detailed structural quality evaluation of cartilage repair.
Histologic evaluation was performed on one of the twenty patients at 12 months after the transplantation. Evaluation of the distribution of type II collagen showed hyaline-like cartilage in one patient who underwent second-look arthroscopy with biopsy. Similarly, Enea et al. found hyaline cartilage, or a mixture of hyaline–fibrocartilage in 9 of 33 cases at a mean of 15 months after MACI. David et al.  revealed excellent histological results regarding the regeneration of hyaline articular cartilage in all patients. Although the current study included a smaller number of cases and follow-up time than these previous studies, its outcome was still comparable. Moreover, direct comparisons between the findings of the current study and these previous series may not be feasible, due to variations among studies in their patient demographics, follow-up duration, cell handling techniques, and histologic grading systems. Alternatively, one biopsy showed an intensive expression of collagen II in the superficial zone of the biopsy with a slight decrease of intensity in the basal and middle of the specimen. Nonetheless, the clinical outcomes of this study showed bigger improvements compared to those of preoperation. However, the current study was still inferior to the above research. The reason for this might be the higher baseline scores and shorter follow-up time of the current study, and it caused a relatively narrow improvement when it was compared to the previous literature.
This study had several limitations. First, the procedure of this study was not compared to other operative techniques. Although performing reimplant steps of the procedure under mini-open and using the non-flowing gel scaffold might theoretically provide several advantages, further studies were required to compare operative time, postoperative rehabilitation, and clinical and radiologic outcomes with arthroscopic autologous chondrocytes combined with type I collagen scaffold. Second, since the sample size calculation was not performed with a certain clinical outcome measurement tool, an important drawback of this study was the small sample size. Third, the follow-up time was also relatively short for some evaluations. Clinical outcomes were followed for up to 5 years, and it was confirmed that improved clinical scores were maintained for a long period. Lastly, histological evaluations were performed on just one patient at 12 months after implantation, and the number of histological evaluations was relatively small. Therefore, the current study was not able to assess implant integrity and any change in composition and distribution of type II collagen in the long-term, and it posed a significant challenge to get complete data to support our view.