Microfragmented Adipose Tissue Versus Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: Response

We thank Anna Boada-Pladellorens and coauthors for their letter to the editor and the interest shown in our work. This study8 offered significant suggestions on the potential of microfragmented adipose tissue (MF-AT) for the treatment of knee osteoarthritis (OA), considering the inclusion of a large number of patients, the high-level design, the imaging assessment, and the follow-up of 2 years. The major concern of the authors of the letter was on the conclusions of our work. In particular, the authors affirmed that MF-AT should not be considered the first-line biologic treatment for knee OA, while the stromal vascular fraction (SVF) should be considered instead. We agree with the first statement, and this is actually the message of our findings reported in this study. In fact, although the biological rationale for using MF-AT holds promise and its use is increasing in clinical practice, the clinical evidence on this orthobiologic product is still limited, and we could not demonstrate a clear superiority versus a single platelet-rich plasma (PRP) injection, with comparable results in all clinical scores and in terms of failures, adverse events, radiographic and magnetic resonance evaluations, and minimal clinically important difference achievement in the overall population. For this reason, we underlined in the Discussion section that MF-AT, considering its relative invasiveness, should be considered a second-line treatment for patients not responding to other injectable solutions. On the other hand, as a secondary outcome, MF-AT was associated with better clinical results in patients with moderate to severe OA compared with PRP treatment. Thus, MF-AT seems preferable compared with PRP in patients with a high degree of knee OA, in which PRP already showed a lower potential,5,6 although further studies are needed to confirm the potential of MF-AT in challenging knees with more severe OA, as reported in the Discussion section. Regarding the second statement, it is important to keep a critical approach also for SVF, for which the clinical evidence is still limited. Accordingly, we cannot support the statement of Boada-Pladellorens et al to consider this product as first line among the orthobiologic products for the treatment of knee OA. The same authors in a recent systematic review of the literature1 found just 9 clinical studies investigating SVF injections for knee OA treatment, of which there were only 2 randomized controlled trials (SVF vs placebo and hyaluronic acid, respectively) with a very small number of patients (39 and 16 patients, respectively).3,4 These underpowered studies do not allow us to draw any meaningful conclusion on the real potential of this type of adipose-derived product. The authors also showed that the available clinical studies on SVF are characterized by a low level of evidence and a high risk of bias, with only 1 study with an overall low risk of bias, 1 study with some concerns, and all the remnant studies having a high risk. Moreover, although data on the direct comparison between MF-AT and SVF in the clinical setting are still lacking, a recent preclinical study demonstrated that a single intra-articular MF-AT injection provided better histological results compared with enzymatic SVF in terms of synovitis reduction and articular cartilage status in a rabbit OA model.2 Therefore, considering the limited available evidence on both MF-AT and SVF and the lack of direct comparative clinical studies, currently it is not possible to claim the superiority of one product over the other. Finally, regarding the concerns on the statement about the higher secretory activity of MF-AT product compared with SVF, it is supported by an in vitro study showing that MF-AT is able to release many more growth factors and cytokines involved in tissue repair and regeneration compared with SVF.7 Nevertheless, future studies should further analyze the differences between these 2 adipose tissue–derived products, in both the preclinical research and the clinical settings, in order to identify the best orthobiologic injective approach for the treatment of patients with knee OA.