The use of autologous fat grafting and related AD-MSCs have become popular surgical procedures during the past 10 years, in the treatment of STDs, CSW, scars, and chronic ulcers [27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51].

As in every surgical procedure, the success of fat grafting is dependent upon many factors: the techniques and instruments used to harvest the fat tissue, the fat tissue processing, the volumes of fat implantation, the recipient sites to be implanted, the levels of placement, and even the individual patient. Because of this variability and perhaps because of other factors that are not yet understood, the results of fat grafting with some techniques, in some patients, and in some areas, can be unpredictable. A standard procedure has not been adopted by all practitioners. There is no agreement as to the best way of processing the fat to ensure the maximal take and viability of the graft [27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51]. Successful, three-dimensional sculpting requires meticulous planning and optimizing the harvesting, storage, and transplantation of adipose tissue. There is an unpredictable degree of resorption of the transplanted fat and repeated treatment sessions are usually needed in order to achieve the final result. The average tissue loss because of reabsorption after injection in the buttock varies between 24% and 84% [27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51]. The concept of refining techniques for liposuction and fat injection, according to individual anatomical zones, is essential to the evolution of the procedure [27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51].

Recently, an increasing number of papers have been reported on the use of fat grafting enhanced with stromal vascular fraction cells (SVFs), including breast reconstruction [28,29,30,32,33,35], scars [37,38,39,40,44], ulcers [31,41,47,49], and breast augmentation [51].

AD-MSCs may be identified in the mixed cell population, referred to as SVFs [37,38,39,40,47,49,51]. SVFs containing AD-MSCs might increase fat graft maintenance by improving vascularity and via the secretion of GFs that increase fat survival with the final aim of improving STV.

Several investigators have published articles using fat grafting enhanced with SVFs and AD-MSCs, called by different commercial names, with favorable results employing different procedures of cell isolation [28,29,30,32,33,35,37,38,39,40,41,47,49,51]. Additionally, several studies have been published on the use of centrifuged fat grafting enriched with PRP in Regenerative Plastic Surgery (RPS) [31,32,33,37,38,40,44,45] as RS, compared with traditional procedures [46].

Full-thickness skin defects caused by severe trauma, extensive burns, diabetes, and other reasons are common clinical disorders; their healing is a dynamic and multi-stage process that includes inflammation, angiogenesis, matrix deposition, and cell recruitment [63,64]. Additionally, there are multiple kinds of cells involved, including keratinocytes, endothelial cells, fibroblasts, inflammatory cells, and so forth. [65]. Generally speaking, the conventional treatment is to debride the wound and then perform skin grafting or skin flap transplantation after the wound granulation tissue grows well [2]. Compared with skin flap transplantation, skin grafts have the distinctive advantages of less damage to the donor site and easy operation [4]. However, due to the lack of a sufficient dermal matrix, skin grafts are easily hindered by uncontrollable scar hyperplasia, lower mechanical resistance, and so forth in the later phase [66]. The development and application of skin tissue engineering may improve skin graft treatment to a certain extent. PRP has been reported to be a stocking source for various GFs (e.g., PDGF, IGF-1, VEGF, FGF-2, etc.), which stimulate neo-angiogenetic vascularization and various activities of fibroblasts [62]. VEGF is accepted as the principal stimulatory factor of angiogenesis. PDGF, capable of enlarging blood vessels and forming mature vessels, is a powerful chemoattractant for fibroblasts and smooth muscle cells. Nevertheless, the application of PRP is currently limited by the short half-life period and the burst release (causing low concentration of GFs in situ) [12]. It is necessary to find solutions to improve the clinical application of PRP.

Artificial dermis is a commercially available bi-layer scaffold (including the silicone layer and the collagen-based layer) that has been widely applied in various full-thickness skin defects. The porous structure and suitable pore size of the lower layer (that is, the collagen sponge scaffold (CSS), termed as a dermal regenerate template (DRT)) promote cell adhesion and diffusion, and the connection of pores plays a key role in nutrient transportation and vascularization, significantly reducing contracture and scar formation [67]. Currently, a two-step surgical procedure is the universal criteria in the application of artificial dermis. Briefly, wounds are implanted with bi-layer artificial dermis, following thorough wound debridement in the first stage, and after two to three weeks of the DRT’s vascularization, skin grafts are performed to cover the wound bed in the second stage [68,69]. Undoubtedly, the need for two surgical procedures is not only indeed frustrating and inconvenient, but also increases the hospital stay and the risk of infection [70]. Therefore, one-step transplantation (i.e., DRT implantation and skin transplantation are performed in one surgical procedure) implies an attractive clinical prospect. However, the current DRT of artificial dermis commercially available by means of the one-step strategy will counter-intentionally form a barrier between the wound bed and the grafted skin, leading to graft failure [71].

Previous studies have suggested that PRP has positive effects on the implantation of artificial dermis. Formigli et al. [10] reported that artificial dermis combined with PRP demonstrated an improved overall restoration of tissue functions. On the other hand, Harrison et al. [72] explored the use of collagen as a platelet activator in PRP, proving the sustained release effect for growth factors from PRP with collagen. The main challenge of this strategy was understanding how to promote the cells’ adhesion, and proliferation, and vascularization into the scaffolds in the short-term after surgery, thus achieving sustained and efficient tissue regeneration with enough vascularization to enable the skin grafts with desired survival.

In conclusion, this systematic review showed the efficacy of PRP, AD-MSCs, and biomaterials in the therapy of CSW, STDs, and skin defects. Given the current treatments differing in methodology and treatment technique, further studies are needed to define standardized protocols, and large-scale randomized trials still need to be conducted to confirm their efficacy. For these reasons, the authors invite all the audience to improve the level of publications in this field by focusing prevalently on EBM Level 1 studies.