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View of the patient 8 years after burn injuries, after multiple surgical procedures, and before the first treatment with fat injection. Note the alar nose retraction remaining, skin texture, and color
Source publication
Despite civilization and progress, burns occur frequently in the world. Remarkable discoveries of wound healing mechanisms have been reported. On the other hand, long-term outcomes from burn injuries represent a barrier to improvement of patients' social, functional, and psychological condition. Lipofilling, described since the 1980s, currently is...
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Massive weight loss (MWL) brachioplasty is frequently requested for the improvement of the appearance and function of arms. Despite its diffusion, this procedure can be associated with significant complications. Liposuction-assisted brachioplasty (LAB) preserves the vascular, nervous, and lymphatic network and reduces the incidence of postoperative...
Citations
... In recent years autologous fat grafting has generated significant clinical interest for the treatment of hypertrophic scarring. Subcutaneous injections of adipose tissue have been shown to regenerate dermal tissue and improve skin function and appearance [6,7]. Adipose tissue is composed of adipocytes and a heterogeneous cell population called the stromal vascular fraction (SVF) [8], within which there is a stem cell-like population known as adipose-derived stromal cells (ADSC) [9]. ...
... Autologous fat grafting has been shown clinically to improve the appearance and patient perception of hypertrophic scars [6,7]. This novel treatment has great potential to improve the quality of life of patients living with scarring however further information is needed to understand the mechanism by which adipose tissue exerts these effects to utilize fat grafting to its full potential. ...
Background
Hypertrophic scarring results from myofibroblast differentiation and persistence during wound healing. Currently no effective treatment for hypertrophic scarring exists however, autologous fat grafting has been shown to improve scar elasticity, appearance, and function. The aim of this study was to understand how paracrine factors from adipose tissues and adipose-derived stromal cells (ADSC) affect fibroblast to myofibroblast differentiation.
Methods
The transforming growth factor-β1 (TGF-β1) induced model of myofibroblast differentiation was used to test the effect of conditioned media from adipose tissue, ADSC or lipid on the proportion of fibroblasts and myofibroblasts.
Results
Adipose tissue conditioned media inhibited the differentiation of fibroblasts to myofibroblasts but this inhibition was not observed following treatment with ADSC or lipid conditioned media. Hepatocyte growth factor (HGF) was readily detected in the conditioned medium from adipose tissue but not ADSC. Cells treated with HGF, or fortinib to block HGF, demonstrated that HGF was not responsible for the inhibition of myofibroblast differentiation. Conditioned media from adipose tissue was shown to reduce the proportion of myofibroblasts when added to fibroblasts previously treated with TGF-β1, however, conditioned media treatment was unable to significantly reduce the proportion of myofibroblasts in cell populations isolated from scar tissue.
Conclusions
Cultured ADSC or adipocytes have been the focus of most studies, however, this work highlights the importance of considering whole adipose tissue to further our understanding of fat grafting. This study supports the use of autologous fat grafts for scar treatment and highlights the need for further investigation to determine the mechanism.
... 35 Inspired by these results, Klinger et al. tried fat injection in severe burns. 36 They attained excellent clinical results, and histologic examination of the treated skin showed a tendency towards tissue regeneration with features of neo-collagen deposition, local hypervascularity, and dermal hyperplasia. Klinger et al. extended the application of autologous fat graft to scars and hard-to-heal wounds of widely differing etiologies and demonstrated its capability to induce architectural remodeling and tissue regeneration. ...
Fat grafting is a popular procedure that provides a physician with a range of aesthetic,
reconstructive, and regenerative clinical applications. It involves the harvest of fat tissue from one
region of the body and transfer to another. The indications and techniques of fat grafting have
undergone dramatic changes over time and. This review revisits the important milestones in the
historical evolution of fat grafting.
Key words
Fat graft; Autologous fat graft; Lipofilling; Lipoinjection; Graft harvest; Adipose derived stem cell;
Centrifuge; Regenerative medicine.
... Abouzaid's RCT further confirmed these findings and other improvements in major hospitalization-related clinical outcomes [9]. A small case series on three patients that was done by Klinger et al. [15] demonstrated mild asymmetry on MRI evaluation compared to healthy, unaffected area, suggesting the healing process after AFG on a scar is almost unnoticeable even on imaging. ...
... The dosage of the treatment is another concern, as not all studies provided information regarding the quantity of lipoaspirate extracted and injected or the dosage administered per unit per area. Previous studies suggested a dose of 1 ml per 3.5 cm 2 for aesthetic and functional improvement [15]. Aside from the dose, the number of sessions and the interval between sessions determine the outcomes, as the study suggested serial AFG for scar improvement [33]. ...
... Describe any sensitivity analyses conducted to assess the robustness of the synthesized results NA Reporting bias assessment 14 Describe any methods used to assess the risk of bias due to missing results in a synthesis (arising from reporting biases) NA Certainty assessment 15 Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome NA ...
A BSTRACT
Objectives
The objective of this study was to analyze all available research on the application of autologous fat grafting (AFG) and adipose-derived stem cells (ADSC) to present evidence-based recommendations, particularly in the clinical treatment of acute burns and burn-related scars.
Materials and Methods
We conducted a systematic search of PubMed, COCHRANE, and EMBASE, as well as a manual search of previous reviews’ reference lists up. The risk of bias (RoB) was assessed using RoB 2.0 and ROBINS-I, where appropriate.
Results
Six eligible studies were selected (2 randomized clinical trials [RCT], 1 retrospective cohort, and 3 experimental studies) with subjects ranging from 3 to 100. Only one study evaluated the use of AFG for acute burns. Improvements in wound healing, vascularization, scar characteristics, and tissue architecture were generally observed in some studies, supported by molecular markers, while one study reported nonsignificant results. Subjective patient satisfaction was reported to have improved. Functional outcomes improvement in the treated regions was minimal. However, study heterogeneity arose mainly from treatment protocols. Cautious results interpretation due to potential bias, especially in selection and confounding domains, and limited clinical trials are important to note. More studies are needed to evaluate.
Conclusion
AFG and ADSC hold potential as valuable treatment options for burn-related scars, supported by a body of evidence, but further well-designed RCT are needed. The efficacy of acute burn settings is yet to be further evaluated since evidence is limited.
... All patients presented improvements in facial movements, skin texture, softness, thickness, and elasticity. The clinical results were supported by histological analysis, showing new collagen deposition, local hypervascularity, and dermal hyperplasia [49]. Similarly, another group reported clinical improvement in a series of patients with reductions in scar retraction, thickness of scar, and improvement in elasticity, and the clinical results were further confirmed by histological analysis showing neo-angiogenesis, collagen deposition, and dermal hyperplasia [50]. ...
Skin scarring and fibrosis affect millions of people worldwide, representing a serious clinical problem causing physical and psychological challenges for patients. Stem cell therapy and regenerative surgery represent a new area of treatment focused on promoting the body’s natural ability to repair damaged tissue. Adipose-derived stem cells (ASCs) represent an optimal choice for practical regenerative medicine due to their abundance, autologous tissue origin, non-immunogenicity, and ease of access with minimal morbidity for patients. This review of the literature explores the current body of evidence around the use of ASCs-based regenerative strategies for the treatment of scarring and skin fibrosis, exploring the different surgical approaches and their application in multiple fibrotic skin conditions. Human, animal, and in vitro studies demonstrate that ASCs present potentialities in modifying scar tissue and fibrosis by suppressing extracellular matrix (ECM) synthesis and promoting the degradation of their constituents. Through softening skin fibrosis, function and overall quality of life may be considerably enhanced in different patient cohorts presenting with scar-related symptoms. The use of stem cell therapies for skin scar repair and regeneration represents a paradigm shift, offering potential alternative therapeutic avenues for fibrosis, a condition that currently lacks a cure.
... The multipotency of these adipose cells has also been shown in in-vivo studies to increase scar softness using fat. The main postulated theory is via stem connective tissue regeneration, thus releasing nerve pressure [18][19][20]. ...
Fat grafting has been described as a potential treatment for post-mastectomy pain syndrome (PMPS) following oncological breast surgery. The study's aim was to compare and contrast the current literature using a systematic review and meta-analysis to quantify the evidence.
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Databases, including MEDLINE, Google Scholar, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Central Register of Controlled Trials (CENTRAL), were searched. Data synthesis was conducted using Review Manager 5.4 (Cochrane Collaboration, London, UK), with 95% confidence intervals. All randomised controlled trials (RCT) and observational studies comparing lipofilling for PMPS were included. A total of six studies met the inclusion criteria with five articles being used in data analysis for the mean percentage reduction in visual analogue scale (VAS) score. The primary outcome measure was the mean percentage reduction in the VAS pain score. Secondary outcomes included the Neuropathic Pain Symptom Inventory (NPSI) and the quality of life assessments post treatment.
Overall, a total of 266 patients received fat transfer for PMPS, and 164 were in the control group. The mean percentage reduction in VAS score was 19.8 (10.82, 28.82; p < 0.0001). Secondary outcomes, including health-related quality of life, showed good outcomes post fat transfer. This involved breast softness, cosmesis, and psychosocial well-being.
The results from this meta-analysis suggest that autologous fat grafting is an efficacious treatment for reducing pain caused by PMPS. The authors suggest more high-quality trials are needed to enhance the current evidence base.
... Due to its rich composition, it has regenerative potential beyond simple volume augmentation. (19)(20)(21)(22)(23)(24)(25)(26)(27)(28) Beneficial effects of fat grafting have been reported in wound healing (29,30), peripheral nerve regeneration (31), scarring (32,33), scleroderma (34,35), radiotherapy damage (36), ulcerations (37), rheumatoid arthritis (38), osteoarthritis (39), dermal atrophy (40), and fibrosis (41). ...
Global interest in fat grafting has increased year after year, and its applications have expanded from the field of plastic and reconstructive surgery to several other disciplines. Through ongoing research, our community has improved the outcome and widened the indications of fat grafting. However, we still struggle with some drawbacks such as fat necrosis and resorption, often leading to unpredictable or disappointing results.
This chapter provides the reader with an historical overview of fat grafting, discusses its main limitations, and identifies the vascular state of the fat graft as one of the key determinants in its success. Different cell-enrichment modalities are analyzed in this chapter, including their advantages, their limitations, and their properties on inducing vascularization in non-vascularized grafted adipose tissue. A novel cell-enrichment modality is described, which consists of Quality and Quantity (QQ)-cultured vascular stem cells. From a peripheral blood sample, mononuclear cells (MNC) can be isolated and QQ-cultured into a highly vasculogenic EPC- and M2-macrophage-containing cell solution for therapeutic vasculogenesis. Fat grafts enhanced with QQ-cultured MNC show promising results in a pre-clinical stage.
... The regenerative effect of lipofilling and the containing of mesenchymal stem cells (MSCs) for scar treatment were first demonstrated in detail by Rigotti et al. in radiodermatitis [8]. Subsequently, in 2008, Klinger et al. demonstrated the first successes of treating hypertrophic scars with adipogenic MSCs (ADSCs) [9]. Since then, numerous clinical studies in regenerative medicine followed on lipofilling and ADSCs in relation to the treatment of scars and wound healing disorders [5]. ...
Background
Post-surgical abdominal and inguinal scars are a frequent challenge in plastic surgery. There are limited non-invasive alternatives to address depressed and retracted scars. The associated retraction and fibrosis might cause lymphatic dysfunction with subsequent regional edema. The authors describe a combined surgical approach of liposuction, the use of dissecting cannulas, lipofilling, and Scarpa’s fascia suspension sutures in a prospective case series.
Methods
The proposed procedure was performed in 22 consecutive patients between November 2012 and May 2015. Complications were assessed according to the Clavien-Dindo scale. Postoperative psychosocial, edema reduction, and patient satisfaction outcomes were gathered and analyzed based on blinded questionaries (Rosenberg Self-Esteem scale and a Cosmetic Procedures Screening Questionnaire (COPS)).
Results
At 6 months, no major complications and 27.2% minor complications (Clavien-Dindo 1) were recorded. Four patients had superficial infections that settled with oral antibiotics and two patients developed a seroma. A significant improvement in self-esteem, aesthetic satisfaction, and social competence was found postoperatively in all patients. The novel technique reduced regional edema and scar-related self-consciousness. Patient satisfaction was rated very high, and all patients would recommend this surgery for abdominal or inguinal retracted scars.
Conclusions
This study shows that the proposed technique is a safe minimally invasive alternative for the treatment of abdominal and inguinal retracted scars. The relatively high rate of minor complications is mainly due to the strict definition of the scale used. The results showed an improvement of local edema and high patient satisfaction.
Level of evidence: Level IV, therapeutic
... Klinger et al reported significant improvement in all the parameters of the observer scale over 3 months. 5 Pallua et al reported significant improvement in pigmentation and pliability. Improvement was also noted in the remaining parameters but remained statistically nonsignificant. ...
... 8 Klinger et al show epithelial hyperplasia and neoangiogenesis in lipofilled scar tissue. 5 In their study, Brongo et al also reported histologic findings, which showed new collagen deposition, neoangiogenesis, and dermal hyperplasia in the context of new tissue, demonstrating tissue regeneration. 9 Lipofilling has efficacy in remodeling the scar, and the effect can be seen clinically as early as the initial 6 months. ...
Introduction Any injury involving the dermis will lead to scarring. Scar tissue can cause functional limitations, cosmetic impairments, pain, and itch. Adipose-derived stem cells have also been shown to play a role in scar modulation. This study evaluates changes in lipofilled scar over the period of time and compares it with non-lipofilled scar tissue.
Materials and Methods A prospective case–control study with intraindividual follow-up was performed on 30 adult patients with post-burn scars from November 2016 to May 2019. Clinical, histopathological, and immunohistochemical parameters were assessed among the case and control regions of the scar.
Results Mean age of the study population was 30.6 years. The duration of the scar included in this study ranged from 1 to 28 years, with a mean duration of 5.91 years. There was a significant reduction in pain, itch, stiffness, and an increase in the pliability of the scar, and a substantial improvement in the modified Vancouver Scar Score in the lipofilled group. In histopathological analysis, the case group showed organized parallel collagen fibers, a significant reduction in melanocytes, improvement in vascularity, and a significantly increased amount of collagen fibers at the reticular dermis. Immunohistochemical analysis indicated new cell synthesis in the scar tissue and reduced melanocytes.
Conclusion The remodeling effect of adipocyte-derived stem cells is long-lasting, and there is a gradual improvement in most of the parameters. Lipofilling has regenerative capacity, which leads to the improved overall appearance of scar and improvement at the cellular level.
... Autologous fat grafting (AFG) is an inevitable revolutionizing technique employed for soft tissue augmentation following congenital, traumatic, and post-surgical loss [1][2][3][4][5][6][7][8][9]. These soft tissue deformities render patients psychologically impaired due to disfiguration of the body. ...
Autologous fat grafting (AFG) is the most prevailing tool for soft tissue regeneration in clinics, although efficiency is limited to unpredictable volume resorption due to poor vascularization and eventual necrosis. This study sought to improve the AFG efficiency using a hydrogel as a carrier for human fat graft (F) with and without platelet-rich plasma (PRP). PRP is clinically well known for the local release of several endogenous growth factors and has been in clinical use already. A human-fat-graft-encapsulated pectin–alginate hydrogel (FG) was developed and characterized. PRP was added to F to develop a human fat graft with PRP (FP). FP was admixed with a pectin–alginate hydrogel to develop FGP. FG and FGP showed the smooth injectable, elastic, and shear-thinning properties. FG and FGP groups showed enhanced cell viability and proliferation compared to the control F in vitro. We also investigated the in vivo angiogenesis and neo-adipogenesis ability of F, FG, FGP, and FP in nude mice after subcutaneous injection. After 2 and 4 weeks, an MRI of the mice was conducted, followed by graft explantation. The explanted grafts were also assessed histologically and with immunohistochemistry (IHC) studies. MRI and histology results revealed better vascularity of the FG and FGP system compared to fat graft alone. Further, the IHC studies, CD 31, and perilipin staining also revealed better vasculature and adipogenesis of FG and FGP systems. These results indicate the enhanced angiogenesis and adipogenesis of FG and FGP. Thus, developed pectin–alginate hydrogel-based fat graft systems FG and FGP replenish the native microenvironment by mediating angiogenesis and adipogenesis, thereby maximizing the clinical outcomes of autologous fat grafting.
... Adipose tissue has garnered special attention in wound healing and scar repair as a rich source of bioactive substances Guo et al., 2022). Scholars have found that fat grafting could significantly accelerate burn wound healing and improve scar quality (Klinger et al., 2008;Klinger et al., 2020). He et al. confirmed the inductive effect of cell-free adipose tissue extract prepared from human subcutaneous adipose tissue on wound healing in C57BL/6 mice . ...
Background: The regenerative capabilities of derivatives derived from the fat layer of lipoaspirate have been demonstrated. However, the large volume of lipoaspirate fluid has not attracted extensive attention in clinical applications. In this study, we aimed to isolate the factors and extracellular vesicles from human lipoaspirate fluid and evaluate their potential therapeutic efficacy.
Methods: Lipoaspirate fluid derived factors and extracellular vesicles (LF-FVs) were prepared from human lipoaspirate and characterized by nanoparticle tracking analysis, size-exclusion chromatography and adipokine antibody arrays. The therapeutic potential of LF-FVs was evaluated on fibroblasts in vitro and rat burn model in vivo. Wound healing process was recorded on days 2, 4, 8, 10, 12 and 16 post-treatment. The scar formation was analyzed by histology, immunofluorescent staining and scar-related gene expression at day 35 post-treatment.
Results: The results of nanoparticle tracking analysis and size-exclusion chromatography indicated that LF-FVs were enriched with proteins and extracellular vesicles. Specific adipokines (adiponectin and IGF-1) were detected in LF-FVs. In vitro, LF-FVs augmented the proliferation and migration of fibroblasts in a dose-dependent manner. In vivo, the results showed that LF-FVs significantly accelerated burn wound healing. Moreover, LF-FVs improved the quality of wound healing, including regenerating cutaneous appendages (hair follicles and sebaceous glands) and decreasing scar formation in the healed skin.
Conclusion: LF-FVs were successfully prepared from lipoaspirate liquid, which were cell-free and enriched with extracellular vesicles. Additionally, they were found to improve wound healing in a rat burn model, suggesting that LF-FVs could be potentially used for wound regeneration in clinical settings.
