Regarding the previous studies, fat grafting, adipose-derived mesenchymal stem cells (AD-MSCs) and SVFs have played a role in improving the hair regrowth [26,27,28], wound healing [9, 10, 22] and tissue regeneration [29, 30] when used alone or in combining with hyaluronic acid, biomaterials, platelet-rich plasma [10, 31, 32], and also, AD-MSCs have been used in inhibiting COVID-19 recently [33, 34].
In previous researches, the therapeutic function of SFV in improving skin fibrosis and scar-related complications has been identified [21, 25, 35]. This study has paid much attention to investigate the effect of SFV on acne scar in terms of case–control. Our findings showed that finally, epidermal thickness, dermal thickness and complete thickness during one month in the control and intervention groups have improved significantly. But in both groups, no significant difference was observed during the one-month period with three-month period. In addition, in an intergroup comparison, there was a significant difference between dermal thickness and complete thickness in the first month between the case and control groups. The findings of this research were consistent with similar studies [25, 35].
In 2018, Shan et al. evaluated the effect of injecting adipose stem cells (ASCs) from SVF cell solution into the treatment of acne vulgaris scars. Their findings showed that the infiltration of inflammatory cells in weeks 2 and 4 was significantly decreased after injection and also re-epithelialization improved in the SVF injection group. In addition, the levels of inflammatory factors such as TNF-α and IL-1α and the protein levels of MMP-2 and K16 were decreased. They stated that there is a significant treatment for acne vulgaris scars, since that conditioned media plays a key role in the treatment. This subject can be used as a therapeutic method to regenerate and treat the scars . However, in the present study, sonographic variables such as dermis, epidermis and total density lost their difference with baseline state after 3 months. This lack of significance, of course, can be related to the low number of samples that ultrasound was performed three months later and the sample size was limited in this regard.
In another co-study by Gentile et al., three different nanofat procedures, including supercharged, evo and centrifuged, were compared with the classical nanofat method. In this study, it was found that the supercharged-modified nanofat method generates the best results in terms of clinical results and SVF performance. This study showed the effectiveness of SVF well in wound healing . In the present study, the apparent variables of the wound such as its volume, area and depth on the SVF-treated side improved significantly during one month, but such an improvement did not occur on the face control side. This significant difference over time can be observed within the groups as well as between the groups in Fig. 1 and Table 2.
In a study by Zhou et al., in a co-study, the effect of conditioned environments of fat-derived stem cells with fractional carbon dioxide laser was investigated for acne atrophy wounds and skin rejuvenation. Nine patients were treated in the skin rejuvenation group and thirteen patients were treated in the acne scar group, and all of peoples underwent three FxCR sessions. This study showed that ADSC-CM with FxCR is a good combination therapy for the treatment of acne atrophic scars and skin rejuvenation . Of course, in some studies, any significant difference was observed in relation to aesthetic results and patients’ satisfaction in SVF injection, but fat accumulation and reabsorption were improved in the SVF-treated groups and beneficial results were observed in this regard [37, 38]. In a similar study, Zhou et al. observed that sebaceous and sweat glands, which are usually absent or sparse at the site of a scar, were found in patients 6 months after SVF nanofat injection. They showed that topical application of SVF-containing medium to skin tissue improves fiber alignment .
In addition, a study by Tenna et al. about the comparison of the use of autologous fat grafting with PRP with or without fractional CO2 laser in the treatment of acne scars showed that the improvement of subcutaneous tissue thickness in group A was 0.668 cm and 0.63 cm in group B. All patients in both groups had therapeutic benefits that were confirmed by postoperative FACE-Q module, but no significant difference was observed between the two groups. Finally, this study stated that nanofat subcutaneous injection and PRP seem to be effective in improving atrophic scars, alone or in combination with fractional CO2 laser . In the present study, sonographic findings (epidermal, dermal and complete thicknesses) were improved significantly in the case group than its predecessors and the apparent findings related to visual face including volume, area and depth were significantly different.
Of course, in the control group and in comparison with the baseline, ultrasound findings were significantly different, but the findings of visual face (apparent) despite improving had not statistically significant difference. In addition, in the comparison of the end of the first and third months between the two groups there was no significant difference between the findings. Our findings show that after one month, the apparent variables in the case group had a significant difference from the control group, which shows the significant effect of SVF on the apparent criteria. Also, SVF along with nanofat improves all apparent and sonographic effects of nanofat and makes the effect more and faster, but this effect is more evident in apparent variables compared to sonographic indices.
In general, the findings of our study showed that in terms of scar, sonographic and apparent variables of patients in the SVF group revealed better results than patients in the non-SVF group. In this regard, studies by Lee et al. have shown that in most cases, patients in the SVF group indicated better results than patients in the non-SVF group in scar tissue repair. They reported that subsets of these scales reflected favorable results in terms of height and flexibility. However, there was no significant change in the arteries .
The therapeutic performance of SVF injection on skin pores, blemishes, skin clarity, skin melanin content and skin elasticity has also been observed. The results showed that a high percentage of patients reported a good satisfaction after treatment . A systematic review of 665 patients also showed the beneficial effects of SVF-related interventions in the treatment of scarring. Some studies show that SVF injection interventions can be moderately effective in scar healing and are not inferior to PRP or fractional CO2 laser . Past studies have shown that acne can lead to create a variety of prominent and erythematosus scars and influence patients' lives, so it is important to identify new therapeutic strategies [44,45,46]. Goodarzi et al. stated in their studies that although many therapeutic methods have been used to manage hypertrophic scars, despite the variety of medical interventions, in many cases the therapeutic effectiveness is low and its treatment is still a clinical challenge that requires long-term interventions [47,48,49,50]. On the other hand, other findings have shown that paying attention to scar therapeutic options and data collecting about therapeutic methods can help to better choose the therapeutic method [51,52,53].
The present study showed that the case and control groups in the baseline had not statistically significant difference in terms of apparent and sonographic criteria. Also, at the end of the first month, in the control group, sonographic criteria improved significantly despite the apparent criteria and in the case group, the apparent and sonographic indices had significantly improved. At the end of the third month, only sonographic criteria were examined which in the case and control groups, both dermal and complete thicknesses were significantly better than the baseline, but epidermal thickness was significantly better than the baseline only in the case group. There was no difference between the first and third month in terms of changes in the case and control groups in for sonographic criteria. As a result, SVF enhances and accelerates the positive effects of nanofat treatment, and its positive effect on improving the appearance of scar is more significant than its positive effect on sonographic indices that could be a good complement for nanofat, especially in promoting the effectiveness of scar appearance.
The present study is one of the few clinical trials which evaluates the effect of SVF on acne scar treatment, and compared to them, a longer follow-up period was considered. In this study, the opposite side of the face was also selected as a control, which eliminates the genetic and basic parameters of patients regarding skin repair abilities as confounding variables. However, in this study, no difference was observed between the position of SVF and its effectiveness according to the pilot and low number of patients and re-examination based on the location of scars and the position of SVF product can be effective in optimizing treatment.