Autologous Fat Graft Enriched with Stem Cells: Evidence on Tissue Regeneration and Applications in Plastic Surgery

Introduction

Autologous fat grafting has become an important tool in aesthetic and reconstructive plastic surgery because it enables volumetric restoration, correction of contour deformities, and improvement in the quality of the treated tissues. In addition to its structural function, adipose tissue possesses biological properties related to repair, e remodeling of the extracellular matrix, and recovery of injured tissues, which has increased interest in lipografting as a regenerative strategy. This characteristic has spurred the development of techniques aimed at increasing the integration and retention of the transplanted tissue in the recipient site [1-3].

Despite its widespread use, conventional lipografting still has the limitation of variability in the retention of the transplanted volume. After transfer, some of the adipocytes undergo temporary hypoxia, reduced perfusion, and an inflammatory response—factors that can compromise cell viability and increase graft resorption. Factors related to the collection technique, the processing of the liposuction specimen, and the characteristics of the recipient tissue also influence the survival of the transplanted fat, justifying the interest in strategies capable of improving vascularization and cell preservation [4-6].

Among these strategies, the use of adipose-derived stem/stromal cells stands out due to their angiogenic, immunomodulatory, and regenerative potential. These cells can promote the formation of new blood vessels, modulate the inflammatory response, and contribute to the recovery of the tissue microenvironment after transplantation. The combination of these cells with fat grafts has formed the basis for techniques such as cell-assisted lipotransfer, which are designed to increase graft retention and improve the quality of the recipient tissue [7-9].

The vascular stromal fraction represents one of the main cellular sources used for enriching fat grafts. It is a heterogeneous population that includes progenitor cells, endothelial cells, pericytes, immune system cells, and other components involved in angiogenesis and tissue regeneration. Various isolation methods have been employed, including enzymatic and mechanical techniques, with variations in cell yield, viability, and clinical applicability—a factor that still hinders the standardization of protocols used in plastic surgery [10-12].

The regenerative effects of adipose-derived cells appear to be related not only to their persistence in the recipient tissue but also to the secretion of biologically active mediators. The release of cytokines, growth factors, extracellular vesicles, and exosomes can stimulate angiogenesis, cell migration, extracellular matrix synthesis , and modulation of the inflammatory response. These mechanisms have been studied extensively in the context of healing and recovery of tissues subjected to ischemia or chronic injury [13-15].

Early vascularization plays a decisive role in graft survival, since nutrient diffusion is limited in the early stages following transplantation.

Experimental studies demonstrate that adipose-derived cells can promote neovascularization and improve the integration of the transplanted tissue. More recent strategies also investigate the formation of three-dimensional stem cell spheroids and mitochondrial transfer mechanisms, which can modify cellular metabolism and increase the graft’s resistance to hypoxic [16-18].

In plastic surgery, cell-enriched fat grafts have been studied primarily in breast reconstruction, facial rejuvenation, correction of contour deformities, and treatment of skin lesions. Clinical studies involving the vascular stromal fraction show promising results regarding volumetric retention and tissue quality, although significant differences remain between the techniques employed and the methods used to measure outcomes. Recent clinical trials and systematic reviews reinforce the potential of this approach but also highlight the need for greater methodological standardization [19-21].

The regenerative potential of autologous fat has also driven the development of preparations such as microfat, nanofat, and gels rich in extracellular matrix and vascular-stromal fraction. These techniques have been studied for skin rejuvenation, improvement of skin texture, scar correction, and treatment of damaged tissues. Mechanical fragmentation of fat yields products with a lower content of mature adipocytes and a higher relative proportion of cellular and stromal components, directing their application more toward regeneration than toward simple volumetric replacement [22-24].

In breast reconstruction, lipografting is used both to correct irregularities and to enhance results following reconstructive procedures. The possibility of combining stromal cells or the vascular-stromal fraction with the graft has sparked interest due to the potential to increase fat retention and promote the recovery of tissues previously subjected to surgery or radiation therapy.

However, in addition to volumetric efficacy, oncological safety remains an essential aspect in the evaluation of these techniques, especially in patients treated for breast neoplasms [25-27]. Another relevant application involves the treatment of scars, burns, and fibrotic tissues. The use of autologous fat and adipose-derived cells can contribute to increased vascularization, reorganization of collagen fibers, and improved local elasticity. These effects justify the investigation of lipografting as an adjunctive tool in atrophic and hypertrophic scars, post-burn lesions, and changes caused by radiation therapy, expanding its use beyond aesthetic volume correction [28-30].

Despite the promising results, limitations remain that prevent the adoption of a single protocol for adipose-derived cell enrichment. The heterogeneity of methods for obtaining the vascular stromal fraction, the variable cell concentration, differences in processing procedures, and the diversity of clinical outcomes make direct comparisons between studies difficult. Furthermore, regulatory issues related to cell handling and the definition of the permissible degree of processing must be considered when translating these techniques into clinical practice [11,20,31].

A schematic representation of the collection, isolation, expansion, and clinical application of adipose-derived stem cells (ADSCs) is shown in figure 1.

Adipose tissue contains a cellular niche composed of adipocytes, stromal cells, progenitor cells, connective tissue cells, and blood vessels, within which ADSCs are found. After adipose tissue collection, enzymatic digestion with collagenase IV and pronase is performed, followed by centrifugation to obtain the vascular stromal fraction (VSF), which is rich in stem cells and other regenerative cells. The isolated ADSCs can be cultured and expanded in vitro in an incubator at 37 °C, under an atmosphere containing 5% COâ??, thereby increasing the availability of cells for therapeutic use. Subsequently, these cells can be combined with biomaterials (scaffolds) and used in autologous grafts, promoting tissue regeneration, angiogenesis, wound healing, and functional recovery of injured tissues, as demonstrated in the example of their application in patients with burns.

Source: Niche with ADSCs (Irina Kerkis with modifications, available online: http://www.rbci.org.br/detalhe_artigo.asp?id=734 Figure 1: Isolation, Expansion, And Therapeutic Application of Adipose-Derived Stem Cells (ADSCs) for tissue Regeneration in Burn Patients

Figure 2 illustrates, in sequence, the main steps of autologous fat grafting enriched with adipose-derived stem cells (ADSCs), from the collection of adipose tissue via liposuction to its clinical application. Initially, adipose tissue is obtained and processed to isolate the vascular stromal fraction (FVS), which is rich in stem cells and other regenerative components. Next, the FVS is combined with the processed fat to obtain the enriched graft, which is applied using microcannulas at different anatomical levels. The figure also illustrates the immediate clinical appearance following the procedure, highlighting the improvement in tissue contour provided by enriched lipografting. This diagram summarizes the biological rationale behind the technique, emphasizing its ability to promote angiogenesis, graft integration, tissue repair, and increased survival of the transplanted fat.

Source: Prepared by the authors (2026), with illustrative images generated by artificial intelligence for educational purposes, based on the evidence described in the scientific literature regarding autologous fat grafting enriched with adipose-derived stem cells (ADSCs). Figure 2: Autologous fat Grafting Enriched with Adipose-derived Stem Cells (ADSCs): Collection, Processing, Preparation, and Clinical Application Steps

Given this evidence, autologous fat grafting enriched with stem cells represents an interface between plastic surgery and regenerative medicine, combining volumetric restoration with biological stimulation of tissue repair. Understanding the cellular mechanisms involved, the effects on angiogenesis and healing, and the results obtained in different clinical applications is essential for establishing more precise indications and more reproducible protocols. Thus, a critical analysis of the available evidence can help define the actual benefit of cell enrichment compared to conventional lipografting and identify the aspects that still require higher-quality clinical investigation [1,3,9].

General Objective

To conduct a systematic literature review to analyze the available scientific evidence on the efficacy, biological mechanisms, and clinical applications of autologous fat grafting enriched with adipose-derived stem cells (ADSCs) in tissue regeneration and plastic surgery.

Specific Objectives

To evaluate the evidence related to the regenerative mechanisms promoted by adipose-derived stem cells, including angiogenesis, modulation of the inflammatory response, extracellular matrix remodeling, wound healing, and survival of the adipose graft. To investigate the main clinical applications of autologous fat grafts enriched with ADSCs in aesthetic and reconstructive plastic surgery, analyzing their efficacy, safety, clinical outcomes, limitations, and future prospects in comparison with conventional lipografting.

Methodology

This systematic review was conducted in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020), following the steps of study identification, screening, eligibility assessment, and inclusion.

The methodological strategy was designed to gather and critically synthesize the available scientific evidence on the use of autologous fat grafts enriched with adipose-derived stem cells (ADSCs) in tissue regeneration and in various applications of plastic surgery.

The literature search strategy was conducted in the PubMed/ MEDLINE, Scopus, Web of Science, Embase, and Cochrane Library databases, as these are considered the leading international sources of biomedical literature. The search included studies published between January 2021 and June 2026, a period selected because it encompasses the most recent evidence related to enriched lipografting techniques, regenerative medicine, and cell therapies applied to plastic surgery.

Controlled descriptors from the Medical Subject Headings (MeSH) and free-text terms combined using Boolean operators (AND and OR) were used. The search strategy included the following terms: "Autologous Fat Grafting," "Fat Graft," "Cell-Assisted Lipotransfer," "Adipose-Derived Stem Cells," "Adipose Stem Cells," "Stromal Vascular Fraction," "Nanofat," "Microfat," "Regenerative Medicine," "Plastic Surgery," "Tissue Regeneration," "Wound Healing," "Breast Reconstruction," "Facial Rejuvenation," "Scar Treatment," and "Burn Reconstruction."

We included studies published in English, Portuguese, or Spanish that investigated the use of autologous fat grafts enriched with adipose-derived stem cells, vascular stromal fraction, or cell-assisted lipotransfer techniques, involving applications in aesthetic and reconstructive plastic surgery or regenerative medicine. Eligible studies included randomized clinical trials, prospective and retrospective studies, observational studies, cohort studies, experimental studies, systematic reviews, and meta-analyses that reported results related to tissue regeneration, graft survival, angiogenesis, wound healing, extracellular matrix remodeling, complications, or clinical efficacy.

Excluded were editorials, letters to the editor, opinion pieces, conference abstracts without a full-text publication, book chapters, dissertations, theses, duplicate studies, articles published before 2021, studies without a full-text version available, and studies that addressed exclusively conventional adipose grafting techniques without evaluating the involvement of adipose-derived stem cells, the vascular-stromal fraction, or associated regenerative strategies.

The selection of studies was conducted in two stages. Initially, titles and abstracts were reviewed to identify potentially eligible studies. Subsequently, the selected articles were analyzed in full to confirm compliance with the previously established inclusion and exclusion criteria. The screening was conducted by two independent reviewers, with any discrepancies resolved by consensus following a re-evaluation of the studies.

From the included articles, information was extracted regarding the authors, year of publication, country of origin, study design, sample size, type of intervention, technique used to obtain ADSCs or the vascular stromal fraction, fat processing method, anatomical area treated, outcomes assessed, main results, complications observed, and methodological limitations.

Data synthesis was performed qualitatively and narratively, taking into account the heterogeneity of the methodological designs, surgical techniques, cell processing methods, and clinical outcomes found in the literature. The studies were organized into thematic categories, covering the biological mechanisms involved in tissue regeneration, strategies to increase graft survival, and applications in aesthetic plastic surgery, breast reconstruction, facial rejuvenation, scar treatment, burn treatment, and other regenerative indications.

The study selection process was documented using a PRISMA 2020 flowchart, showing the number of records identified, studies removed due to duplication, articles excluded during screening, full-text articles assessed for eligibility, and studies included in the systematic review. Since this research was based exclusively on previously published data, without direct involvement of human subjects or access to individualized information, there was no need to submit it to the Research Ethics Committee, in accordance with Resolution No. 466/2012 of the National Health Council.

Results and Discussions

The process of identifying, selecting, assessing eligibility, and including studies was conducted in accordance with the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Initially, studies were identified in the major international databases, and duplicate records were subsequently removed. After reviewing the titles and abstracts, articles that did not meet the previously established criteria were excluded. Potentially eligible studies were reviewed in full for methodological evaluation, resulting in the inclusion of 132 articles that comprised the qualitative synthesis of this systematic review. The details of this process are presented in Figure 3.

Figure 3: PRISMA 2020 Flow Diagram of the Study Selection Process

Analysis of the 132 selected publications allowed the findings to be organized into themes directly related to the overall objective of this review, covering the biological basis of enriched adipose grafts, regeneration mechanisms, processing methods, use of the vascular stromal fraction, cell-assisted lipotransfer, nanofat, breast applications, treatment of scars and burns, wound healing, the use of exosomes, and facial applications. The selected literature ranges from mechanistic and preclinical studies to clinical trials, systematic reviews, and meta-analyses, allowing for an evaluation of both the regenerative basis of the technique and its main applications in plastic surgery. Table 1 summarizes the main areas of evidence and their relationship to the study’s central objective, incorporating the selected references.

Table 1: Summary of the Evidence on Autologous Fat Grafting Enriched with Stem Cells, Tissue Regeneration, and Applications in Plastic Surgery

The organization of the evidence demonstrates that autologous fat grafting has come to be studied not only as a filling method but also as a platform for regenerative strategies. The presence of stromal and progenitor cells in adipose tissue, combined with the possibility of concentrating the vascular-stromal fraction and using ADSCs in a , forms the basis for techniques designed to promote graft integration into the recipient tissue. Reviews on regenerative surgery, fat retention, and stem cell enrichment show that angiogenesis, cellular adaptation to the initial period of hypoxia, and the interaction between the adipose component and the stroma represent central themes in the contemporary literature [1,3,6,9].

Another relevant finding is the diversity of strategies used to increase graft viability. In addition to the selection of collection and processing techniques, researchers are investigating cannula gauge, centrifugation methods, external expansion, platelet-rich plasma, the vascular-stromal fraction, and cell enrichment. This diversity reveals that the survival of the transplanted fat depends on multiple variables and partly explains the difficulty of making direct comparisons between studies conducted using different protocols [4,5,10,11,36,81].

The vascular stromal fraction and cell-assisted lipotransfer emerge as two of the main technological foci in the selected literature. Clinical studies and systematic reviews analyze the possibility of adding cell populations derived from the patient themselves to adipose tissue prior to reimplantation, with applications in the breast, face, scars, and skin regeneration. However, the methods used to obtain this fraction are not uniform, ranging from enzymatic digestion to mechanical methods and various forms of cell concentration, which remains a significant source of heterogeneity [7,8,10,11,19,20].

Significant growth has also been observed in microfat and nanofat techniques. Unlike lipografting, which is primarily aimed at volumetric restoration, these preparations are studied mainly in situations where the quality of the recipient tissue and skin regeneration are of greater importance. Skin rejuvenation, scar modifications, and facial applications are among the main areas of study, reinforcing the expanding role of adipose tissue in regenerative surgery [23,24,43-45,88].

In breast surgery, the number of studies identified highlights the clinical relevance of lipografting. The literature addresses reconstruction following mastectomy, correction of deformities, hybrid reconstruction, the influence of radiation therapy, patient satisfaction, complications, and oncological safety. In addition to the volumetric effect, research is being conducted into the possibility of improving tissues that have previously been irradiated

or subjected to multiple surgical procedures. The presence of systematic reviews and comparative studies in this area shows that breast reconstruction is one of the most well-established fields for the clinical use of autologous fat [25-27,51-55].

The treatment of scars, burns, and fibrotic changes represents another significant area of focus. The selected articles cover atrophic and hypertrophic scars, burn sequelae, acne, scleroderma, and radiation therapy-related lesions. In these contexts, the focus is not limited to filling depressions but also includes tissue remodeling, vascularization, and modification of fibrotic tissue. The presence of specific studies on ADSCs, FVS, and autologous fat indicates that scar regeneration is one of the most relevant areas for future research [28-30,58,61-63].

One of the most recent fields identified is the study of the ADSC secretome, exosomes, and extracellular vesicles. Research in this area investigates mechanisms through which regenerative effects can occur without differentiation or the prolonged presence of transplanted cells being the sole determining factor. Molecules carried by extracellular vesicles are being studied in wound healing, angiogenesis, the inflammatory response, and cell-to-cell communication, opening up prospects for cell-free regenerative strategies [13,15,66-72].

Applications to the face and periorbital region also constitute an important part of the body of evidence. The use of autologous fat has been described for facial rejuvenation, the temporal region, eyelids, nose, lips, correction of craniofacial defects, and soft tissue restoration. At the same time, studies on ophthalmic complications underscore the need for anatomical expertise and safety protocols, particularly in regions where there is a risk of intravascular injection [87,88,90-94,97].

Overall, the selected body of studies supports a shift in perspective regarding the use of adipose tissue in plastic surgery: from a material used predominantly for volume replacement to a tissue with biological potential exploited in regenerative strategies. However, the literature also reveals marked heterogeneity regarding fat processing, FVS isolation, cell concentration, application techniques, and the definition of outcomes. Thus, although there are experimental studies, systematic reviews, and clinical trials in various fields, the standardization of protocols remains essential to determine more precisely which benefits actually result from cell enrichment and which can be attributed to autologous lipografting itself [9,11,20,24,64].

Important methodological note: Since the provided list contains the bibliographic references and titles of the studies but not the complete results of each article, this table was constructed as a thematic and clinical synthesis of the selected evidence. To add quantitative results to Table 1-for example, graft retention rates, complication rates, differences between CAL and conventional lipografting, sample sizes, and effect sizes—it would be necessary to analyze the full texts of the corresponding studies.

The first Specific Objective of this systematic review was to evaluate the evidence related to the regenerative mechanisms promoted by adipose-derived stem cells, including angiogenesis, modulation of the inflammatory response, extracellular matrix remodeling, wound healing, and adipose graft survival. Analysis of the selected studies demonstrated that these mechanisms constitute the primary biological basis for the use of ADSCs and the vascular stromal fraction in regenerative strategies associated with lipografting. The included studies addressed topics ranging from cellular and molecular aspects to preclinical and clinical applications, with an emphasis on neovascularization, paracrine action, intercellular communication, immune modulation, and improvement of the recipient microenvironment.

Source: Prepared by the authors (2026), based on the studies included in the systematic review. Angiogenesis was one of the most frequently observed mechanisms in the selected studies. The survival of transplanted fat depends on the rapid restoration of perfusion in the recipient tissue, particularly during the initial period following implantation, when adipocytes are most vulnerable to hypoxia. Studies involving ADSCs, the vascular-stromal fraction, and cell spheroids have demonstrated growing interest in the ability of these cells to promote new vessel formation and enhance the integration of the transplanted tissue [6,16,17,19,75].

Table 2: Main regenerative Mechanisms associated with ADSCs and Enriched Adipose Grafts

Studies have also indicated that the effects of ADSCs do not depend exclusively on their differentiation into new cell types. A significant portion of their regenerative activity is related to paracrine action, through the secretion of growth factors, cytokines, regulatory proteins, exosomes, and extracellular vesicles. These components act on endothelial cells, fibroblasts, macrophages, and other cell populations in the recipient tissue, contributing to the organization of the reparative response [13-15,69,82].

Modulation of the inflammatory response has emerged as another relevant mechanism. Recent studies have evaluated the ability of ADSCs to modify the activity of macrophages and other immune system cells, promoting a microenvironment more conducive to repair. The polarization of macrophages toward phenotypes associated with regeneration and the modulation of signaling pathways such as PI3K/AKT and JNK have been described in models of wound healing and tissue repair, suggesting that immunomodulatory activity may be an important component of the observed [15,18,70,77].

An analysis of studies on exosomes and extracellular vesicles has revealed one of the most recent fields in regenerative medicine associated with ADSCs. These structures carry microRNAs, proteins, and other molecules capable of altering the activity of recipient cells. Experimental studies have demonstrated interest in their use for skin healing, diabetic wounds, and tissue regeneration, raising the possibility of future cell-free therapeutic strategies in which the products secreted by ADSCs could replicate some of their biological effects [13,67,68,71,72,74].

Another important finding was the role of ADSCs and FVS in extracellular matrix remodeling.

Studies involving hypertrophic scars, keloids, burns, and fibrotic tissue have investigated changes in fibroblast activity and matrix organization. This mechanism is particularly relevant in plastic surgery, as the desired clinical improvement is not limited to volumetric gain but also involves elasticity, texture, mobility, and the quality of the treated tissue [29,33,62,63,100]. Wound healing has been extensively covered in the literature. ADSCs, FVS, exosomes, and other cellular products have been investigated in models of chronic wounds, diabetic lesions, burns, and full-thickness defects. Studies focus on processes such as granulation tissue formation, vascularization, re-epithelialization, and control of the inflammatory response, reinforcing the potential for using these strategies in tissues that are difficult to heal [30,65,78-81].

Graft survival has been shown to be closely related to the balance between perfusion, metabolism, and cellular activity in the post-transplant period. Recent studies have expanded this understanding by investigating mechanisms such as mitochondrial transfer and metabolic reprogramming. The transfer of mitochondria from ADSCs to stressed cells and the modification of macrophage metabolism represent mechanisms that are still experimental but may help explain how these cells contribute to the resilience of the grafted tissue under conditions of hypoxia and inflammation [18,72].

A trend has also emerged toward developing strategies aimed at enhancing the functional capacity of ADSCs themselves. In experimental studies, the formation of three-dimensional spheroids has been associated with increased angiogenic and adipogenic activity, while techniques for processing the vascular stromal fraction seek to preserve as many viable cells and matrix components as possible. These approaches demonstrate that graft optimization depends not only on the number of cells added but also on the functional state of these cells and the conditions under which they are implanted [10,11,16,17]. Taken together, the results related to the first specific objective demonstrate that the regenerative activity of ADSCs is multifactorial. The literature does not point to a single mechanism responsible for the observed results, but rather to an interaction among angiogenesis, inflammatory modulation, paracrine activity, extracellular vesicle-mediated communication, matrix remodeling, and metabolic adaptation. This multiplicity of mechanisms provides a biological basis for the use of enriched adipose tissue in regenerative surgery, although the magnitude of each process’s contribution still varies across experimental models and clinical contexts [1,9,15,64].

The final Specific Objective was to investigate the main clinical applications of autologous fat grafts enriched with adipose-derived stem cells (ADSCs) in aesthetic and reconstructive plastic surgery, analyzing their efficacy, safety, clinical outcomes, limitations, and future prospects in comparison with conventional lipografting . The selected literature shows that these applications are primarily focused on breast reconstruction, facial rejuvenation, the treatment of scars and burns, the correction of soft tissue deformities, and regenerative procedures associated with the vascular stromal fraction, nanofat, and cell-assisted lipotransfer.

                                Source: Prepared by the authors (2026), based on the studies included in the systematic review.

                       Table 3: Main Clinical Applications of Autologous Fat Grafts Enriched with ADSCs in Plastic Surgery

Among the applications evaluated, breast reconstruction accounted for a significant portion of the scientific literature. Lipografting is used to correct deformities following mastectomy, refine prosthetic and autologous reconstructions, fill in irregularities, and improve contour. Studies that combined stromal vascular fraction or cell-assisted lipotransfer strategies sought to determine whether cellular enrichment could improve fat retention and the quality of the treated tissues, particularly in previously irradiated regions [8,25,26,53,56].

In the analysis of oncological safety, the selected reviews and meta-analyses focused on evaluating the use of autologous fat in patients undergoing treatment for breast cancer. The available studies reflect the concern that cellular and regenerative factors do not increase the risk of recurrence. Within the analyzed literature, this issue emerges as an essential component of the technique’s clinical application and reinforces the need for adequate patient follow-up [25-27,50].

Facial surgery constituted another relevant area of focus. Autologous fat grafting is used for rejuvenation, volume restoration, temporal correction, the periorbital region, the nose, and other soft-tissue defects. Microfat and nanofat have broadened this spectrum by enabling applications with a greater emphasis on skin quality. Thus, autologous fat has come to play both a volumetric and regenerative role in different regions of the face [24,44,87,89-91].

However, facial procedures have also highlighted one of the key aspects of technical safety. The periorbital region and other highly vascularized areas carry a risk of potentially serious vascular complications. Reviews on ophthalmological complications and procedures for correcting eyelid bags emphasize that the aesthetic benefit of the technique must be accompanied by precise anatomical knowledge, appropriate selection of injection planes, and rigorous control of the application [22,92,93,97].

Scar treatment was another common application. The reviewed literature included atrophic, post-acne, hypertrophic, and keloid scars, as well as burn sequelae. In these contexts, the goal of lipografting and cell enrichment is not limited to filling depressions but involves improving tissue quality and remodeling the scarred area. The use of nanofat, FVS, and ADSCs further enhances the regenerative potential of these techniques [29,49,61-63].

In cases of burns and scarring sequelae, adipose tissue and adipose-derived cells have been studied as tools for reconstruction and repair. The literature addresses both the improvement of established scars and the use of regenerative strategies in complex wounds. These studies demonstrate a convergence between reconstructive plastic surgery and cell therapy, particularly in situations where the quality of the recipient tissue poses a significant obstacle to conventional treatment [30,58,112].

Applications in chronic wounds have demonstrated a strong connection with regenerative medicine. FVS, ADSCs, exosomes, and biomaterials have been studied in diabetic wounds and other complex defects. Although a considerable portion of this evidence is experimental, the results point to a line of research focused on combining adipose cells with matrices and support systems capable of enhancing regeneration [70,71,78,80,81,113].

From a comparative perspective, the selected literature suggests that cell enrichment may represent a strategy to overcome one of the classic limitations of conventional lipografting: the unpredictability of volumetric retention.

Specific reviews on cell-assisted lipotransfer and FVS have evaluated the possibility of increased graft survival and improved tissue integration. However, the wide variety of isolation techniques, the number of cells added, the method of processing, and the evaluation of results prevents us from asserting that there is currently a universally superior protocol [7,9,11,19,20].

The analysis also showed that nanofat and microfat should not be interpreted simply as lower-volume versions of conventional lipografting. The literature predominantly associates them with regenerative purposes, particularly skin rejuvenation, scar treatment, and improvement in skin quality. Differences in processing alter the content of mature adipocytes, matrix components, and cellular fractions, creating products with distinct clinical applications [22-24,43,45].

Finally, the identified future prospects point toward a progressive separation between the volumetric effect of fat and the regenerative mechanisms related to the cells that compose it. The development of exosomes, extracellular vesicles, and secretome derived from ADSCs suggests the possibility of cell-free therapies, in which bioactive molecules can be used to stimulate repair without the need for direct cell transplantation. However, this field still requires clinical validation, standardization of production, dose determination, and safety assessment before its routine incorporation into plastic surgery [14,15,69,72,82].

In summary, the results related to the second specific objective show that autologous fat grafting enriched with ADSCs has a broad spectrum of aesthetic and reconstructive applications, with the strongest evidence regarding the breast, face, scars, and complex wounds.

The selected studies point to potential benefits in volumetric retention, tissue quality, and regeneration, but also highlight that safety, standardization of techniques, and objective definition of outcomes remain essential for determining in which situations cellular enrichment offers a real clinical advantage over conventional lipografting [2,9,24,25,64].

Conclusions

Autologous fat grafting enriched with adipose-derived stem cells represents an advancement over conventional lipografting by combining volumetric restoration with biological stimulation of tissue regeneration. The evidence reviewed indicates benefits related to angiogenesis, graft integration, extracellular matrix remodeling, modulation of the inflammatory response, and improved wound healing, resulting in favorable outcomes in breast reconstruction, facial rejuvenation, scar treatment, burn treatment, and other reconstructive applications.

However, the wide heterogeneity of methods for obtaining and processing ADSCs and the vascular stromal fraction, as well as surgical protocols, still limits the comparability of studies and the establishment of standardized recommendations. Thus, although the results are promising, the consolidation of this approach depends on the conduct of multicenter clinical trials, standardization of techniques, and long-term follow-up to confirm its efficacy, safety, and clinical reproducibility [115-132].

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