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Background: Autologous fat grafting is commonly used for soft-tissue repair (approximately 90,000 cases per year in the United States), but outcomes are limited by volume loss (20% to 80%) over time. Human allograft adipose matrix (AAM) stimulates de novo adipogenesis in vivo, but retention requires optimization. The extracellular matrix derived from superficial fascia, interstitial within the adipose layer, is typically removed during AAM processing. Thus, fascia, which contains numerous important proteins, might cooperate with AAM to stimulate de novo adipogenesis, improving long-term retention compared to AAM alone., Methods: Human AAM and fascia matrix proteins (back and upper leg regions) were identified by mass spectrometry and annotated by gene ontology. A three-dimensional in vitro angiogenesis assay was performed. Finally, AAM and/or fascia (1 mL) was implanted into 6- to 8-week-old male Fischer rats. After 8 weeks, the authors assessed graft retention by gas pycnometry and angiogenesis (CD31) and adipocyte counts (hematoxylin and eosin) histologically., Results: Gene ontology annotation revealed an angiogenic enrichment pattern unique to the fascia, including lactadherin, collagen alpha-3(V) chain, and tenascin-C. In vitro, AAM stimulated 1.0 ± 0.17 angiogenic sprouts per bead. The addition of fascia matrix increased sprouting by 88% (2.0 ± 0.12; P < 0.001). A similar angiogenic response (CD31) was observed in vivo. Graft retention volume was 25% (0.25 ± 0.13) for AAM, significantly increasing to 60% (0.60 ± 0.14) for AAM/fascia ( P < 0.05). De novo adipogenesis was 12% (12.4 ± 7.4) for AAM, significantly increasing to 51% (51.2 ± 8.0) for AAM/fascia ( P < 0.001) by means of adipocyte quantification., Conclusions: Combining fascia matrix with AAM improves angiogenesis and adipogenesis compared to AAM alone in rats. These preliminary in vitro and pilot animal studies should be further validated before definitive clinical adoption., Clinical Relevance Statement: When producing an off-the-shelf adipose inducing product by adding a connective tissue fascial component (that is normally discarded) to the mix of adipose matrix, vasculogenesis is increased and, thus, adipogenesis and graft survival is improved. This is a significant advance in this line of product., Competing Interests: Disclosure : Dr. Widgerow is chief scientific officer of Galderma and receives royalties on technology from Skin Medica; he has no conflict of interest in this study. Dr. Banyard is a paid consultant for Recros Medica, Inc.; he has no conflict of interest in this study. Dr. Chnari is an employee of MTF Biologics and participated in the study design, protocol development, manuscript review, and write-up of the allograft adipose matrix preparation methods. She did not impact the analysis or interpretation of the study results. The remaining authors have no financial interest to declare in relation to the content of this study ., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Introduction: Extracellular vesicles (EVs) are cell-secreted packages that deliver cargo to target cells to effect functional and phenotypic changes. They are secreted by many different cell types, including adipose-derived stem cells (ADSCs), which are a promising field of study in regenerative medicine. Our aim was to perform a systematic review of the literature to summarize the scientific work that has been conducted on ADSC EVs to date., Methods: The Pubmed database was queried with keywords (and variations of) "adipose derived stem cell," "stromal vascular fraction," and "extracellular vesicles." We excluded review papers, then manually screened articles based on title and abstract. Full-text articles were assessed for eligibility to include in final review., Results: While an extensive body of research exists on EVs, a much smaller proportion of that is original research on ADSC EVs. Of 44 manuscripts that met our database search criteria, 21 articles were selected for our systematic review., Conclusion: ADSC EVs were found to exert effects on angiogenesis, cell survival and apoptosis, inflammation, tissue regeneration, and reduction of disease pathology. Further studies examine characteristics of ADSC EVs. Future work should aim to further detail the safety profiles of ADSC EVs given their potential for cell-based therapies. The body of research studies characterizing ADSC EVs continues to expand, and much work remains to be done before human pilot studies can be considered. To our knowledge, we offer the first systematic review summarizing the research on ADSC EVs and their determined roles to date., (Copyright © 2019. Published by Elsevier Ltd.)

Level of Evidence: 4.

Treatment of hypertrophic scars and other fibrotic skin conditions with autologous fat injections shows promising clinical results; however, the underlying mechanisms of its antifibrotic action have not been comprehensively studied. Adipose-derived stem cells, or stromal cell-derived factors, inherent components of the transplanted fat tissue, seem to be responsible for its therapeutic effects on difficult scars. The mechanisms by which this therapeutic effect takes place are diverse and are mostly mediated by paracrine signaling, which switches on various antifibrotic molecular pathways, modulates the activity of the central profibrotic transforming growth factor β/Smad pathway, and normalizes functioning of fibroblasts and keratinocytes in the recipient site. Direct cell-to-cell communications and differentiation of cell types may also play a positive role in scar treatment, even though they have not been extensively studied in this context. A more thorough understanding of the fat tissue antifibrotic mechanisms of action will turn this treatment from an anecdotal remedy to a more controlled, timely administered technology.

Fat grafting is commonly employed by plastic and reconstructive surgeons to address contour abnormalities and soft-tissue defects; however, because retention rates and thus volume filling effects are unpredictable, there is a search for new and innovative approaches. Initial studies on the use of human decellularized adipose tissue extracellular matrix (hDAM) show promise for its use not only in tissue engineering, but also in fat grafting. In this review, we examine and analyze the literature for the preparation, characterization, and use of hDAM and its derivatives in tissue engineering and plastic surgery applications. All studies reviewed involve physical, chemical, and/or biological treatment stages for the preparation of hDAM; however a distinction should be made between detergent and nondetergent-based processing, the latter of which appears to preserve the native integrity of the hDAM while most-efficiently achieving complete decellularization. Methods of hDAM characterization vary among groups and included simple and immunohistochemical staining, biochemical assays, 3-dimensional (3D) imaging, and mechano-stress testing, all of which are necessary to achieve a comprehensive description of this novel tissue. Finally, we examine the various preclinical models utilized to optimize hDAM performance, which primarily include the addition of adipose-derived stem cells or cross-linking agents. Overall, hDAM appears to be a promising adjunct in fat-grafting applications or even possibly as a stand-alone soft-tissue filler with off-the-shelf potential for commercial applications., (© 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

Adipose tissue is a rich source of cells with emerging promise for tissue engineering and regenerative medicine. The stromal vascular fraction (SVF), in particular, is an eclectic composite of cells with progenitor activity that includes preadipocytes, mesenchymal stem cells, pericytes, endothelial cells, and macrophages. SVF has enormous potential for therapeutic application and is being investigated for multiple clinical indications including lipotransfer, diabetes-related complications, nerve regeneration, burn wounds and numerous others. In Part 2 of our review, we explore the basic science behind the regenerative success of the SVF and discuss significant mechanisms that are at play. The existing literature suggests that angiogenesis, immunomodulation, differentiation, and extracellular matrix secretion are the main avenues through which regeneration and healing is achieved by the stromal vascular fraction., (Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

There has been much debate concerning the pathologic consequences of diabetes on the plantar fat pad and its subsequent association with the development of a foot ulcer. This review article documents two theories regarding pathophysiology in diabetic foot ulcer formation as they are related to the plantar fat pad and discusses current treatment options for this pathophysiological phenomenon. Traditionally, fat pad atrophy in diabetic patients was thought to result as an irregular arrangement of collagen fibrils within the septal walls as a result of glycation as well as diminishing adipocyte size due to thickened septal walls. Contrary to this traditional theory, a model depicting distal fat pad migration from under the metatarsal heads has been described in the diabetic patient. Such pad migration renders the metatarsal heads vulnerable to increased pressure, which, in turn, predisposes to foot ulceration. This migratory fat pad theory plays a significant role in approaches to the prevention of diabetic foot ulceration and subsequent amputation. Various methods of fat pad supplementation and claw toe management are impacted by the pathophysiological changes described and new avenues of therapy may be based on these changes., (© 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Although lipotransfer, or fat grafting, is a commonly used procedure in aesthetic and reconstructive surgery, there is still variability in graft survival and neoadipogenesis from one procedure to the next. A better understanding of the sequential molecular events occurring with grafting would allow us to strategize methods to improve the regenerative potency of the grafted tissue. These steps begin with an autophagic process, followed by the inclusion of stromal vascular fraction and matrix components. By tailoring and modifying each of these steps for a particular type of aesthetic or reconstructive procedure, strategic sequencing represents a dynamic approach to lipotransfer with the aim of maximizing adipocyte viability and growth. In the implementation of the strategic sequence, it remains important to consider the clinical viability of each step and its compliance with the US Food and Drug Administration regulations. This review highlights the basic science behind clinically translatable approaches to supplementing various fat grafting procedures.

Adipose-derived stem cells (ADSCs) are a subset of mesenchymal stem cells (MSCs) that possess many of the same regenerative properties as other MSCs. However, the ubiquitous presence of ADSCs and their ease of access in human tissue have led to a burgeoning field of research. The plastic surgeon is uniquely positioned to harness this technology because of the relative frequency in which they perform procedures such as liposuction and autologous fat grafting. This review examines the current landscape of ADSC isolation and identification, summarizes the current applications of ADSCs in the field of plastic surgery, discusses the risks associated with their use, current barriers to universal clinical translatability, and surveys the latest research which may help to overcome these obstacles., (© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

The development of autologous fat grafting to augment or reconstruct tissue defects has become an increasingly popular modality among plastic surgeons. Despite its popularity, a standardized fat grafting protocol has yet to be developed. Great variations exist with regard to almost all the technical features, yielding a reported fat graft survivability that ranges from 40% to 80%. Recent bench approaches have been proposed to improve the long-term viability of fat grafts: although promising results have been shown, empirical evidence has yet to prove the superiority of one particular method. Nevertheless, currently available literature still provides some evidence for optimal results in differing clinical scenarios, in the wait of validating and ultimate studies.The issues of enriched fat grafting techniques and variations in harvesting and delivery in the background of US regulatory constraints demand alterations and variations in techniques. These only complicate the process of validation of any single technique. However, recent studies have brought us closer to making informed decisions on technical choices in lipotransfer. These are elaborated on in this review.