Cosmetic Breast Augmentation with Autologous Ex Vivo-Expanded Adipose-Derived Mesenchymal Stem/Stromal Cell (Stemform®)-Enriched Fat Grafts: A Study of the First Twenty-Two Real-World Patients.

BACKGROUND: Fat grafting is commonly utilized in breast surgery, and since it was first described, clinicians and researchers have stridden towards improvement of graft retention. Current advancements include adding adipose-derived mesenchymal stem/stromal cells (MSC(AT)s), which have demonstrated promise for improved graft retention. OBJECTIVES: This study reports outcomes for the first twenty-two patients undergoing breast augmentation (Stemform BA) or artificial implant replacement (Stemform AIR) with MSC(AT)-enriched fat in a real-world setting. METHODS: Autologous MSC(AT)s were isolated and expanded ex vivo, then mixed with lipoaspirate and injected as enriched fat for Stemform BA and AIR. The breast volume was measured preoperatively and at 3 and 12 months postoperative using a 3D Infinity Dual-Lens Camera and LifeVizApp software. Additionally, independent plastic surgeons evaluated clinical images, and patient satisfaction was obtained at equal time points. RESULTS: Twenty-two patients were included. All completed 3 and 12 months clinical follow-up and 3 months volume measurements. Nineteen patients completed 12 months volume measurements. The median fat graft retention at 12 months was 95.7% (IQR = 82.44-103.12%) for Stemform BA patients and 113.0% (IQR = 94.8-131.2%) for Stemform AIR patients. The Stemform BA patients had a median breast enlargement of 172.0% (IQR = 156.7-241.0%). The implant replacement volume of Stemform AIR patients was 102% (IQR = 85.1-130.3%). The patient reported 92.8% and 100% would elect to repeat treatment if they had the opportunity for Stemform BA and Stemform AIR, respectively. CONCLUSION: Breast augmentation and breast implant replacement patients receiving ex vivo-expanded MSC(AT)-enriched fat grafts had high graft retention and patient satisfaction scores. The paper confirms the clinical efficacy of using ex vivo-expanded MSC(AT)s. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Enhanced Fat Graft Viability and Remodeling Using a Helium-based Radiofrequency Device to Prepare the Recipient Site.

BACKGROUND: Improvements to autologous fat grafting for soft tissue augmentation are needed to overcome the unpredictable volume retention. Approaches such as fat harvesting and processing, injection technique, preparation of the recipient site, and supplemental biologics are topics of ongoing research. Here, an energy-based device was investigated as a stimulatory tool for recipient site preparation for improving fat graft retention. OBJECTIVE: The objective was to measure the stimulatory responses in fat grafts after 4 weeks when using a helium-based radiofrequency device to pretreat the recipient tissue. METHODS: Using an autologous fat grafting mouse model, the inguinal fat pad was grafted in a small cranial pocket after either a saline injection alone (control) or a saline injection followed by pretreatment (treated). The fat pad was resected after 4 weeks, sectioned and stained with immunofluorescence markers to investigate tissue remodeling. RESULTS: Pretreatment resulted in higher viability of adipocytes, a higher concentration of viable ASCs in areas of adipose tissue regeneration, and localized macrophages in the areas of regeneration when compared to the control. There was no observable difference in vascularity or angiogenesis. The staining for ASCs was higher in the pretreated group in comparison with the control group (5.0% vs. 3.3%, p=0.36) when using a pixel classifier in QuPath in the viable adipose tissue regions. CONCLUSIONS: The use of a helium-based radiofrequency device as a pretreatment tool appears to increase the viability of the adipose tissue likely due to higher concentration of ASCs. The apparent increase in viable ASCs may be due to enhanced proliferation or paracrine recruitment of these cells in response to the helium-based radiofrequency treatment. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Bullet List of Important Points: Pretreatment of the fat graft recipient site increases the viability of the adipose tissue after 4 weeks in comparison with the control grafts. The increased viability is likely due to the observed increase in adipose-derived stem cells in the pretreated group. Pretreatment enhanced the adipose tissue remodeling as colocalization of adipose-derived stem cells and macrophages showed an active remodeling, whereas the control group exhibited more necrotic and fibrotic tissue.

Hybrid Stromal Vascular Fraction (Hybrid-SVF): A New Paradigm in Mechanical Regenerative Cell Processing.

Enzymatic digestion of extracellular matrix (ECM) from lipoaspirate is the conventional form of harvesting stromal vascular fraction (SVF) called enzymatically digested SVF (E-SVF). Mechanical SVF (M-SVF) isolation has emerged as an alternative method, but it has also some limitations in terms of lower cell viability and diminished cell counts. To enhance the SVF qualitatively and quantitatively, we propose a novel concept called "hybrid-SVF," in which we combine M-SVF with the concentrated parts of adipose tissue after centrifugation, which is called stromal vascular matrix (SVM). Methods: Hybrid-SVF injection was applied as an adjunctive therapy to fat grafting in 88 patients and 11 samples were evaluated in the laboratory for cell count, viability and cell activity. Results: Experimental results determined that SVM part showed higher cellular activity. SVM and M-SVF showed higher cellular potency than E-SVF. Clinically, none of the patients required an additional session for fat grafting since there was no significant graft resorption. However, seven patients asked for further volume augmentation due to their individual preferences. No major complication was encountered. Conclusions: The usage of hybrid-SVF has a very high regenerative potential due to the ECM support and exceptionally high cell yield in addition to preserved cell potency. Although there are ongoing studies focusing on optimizing cell counts and further clinical applications, we believe that our preliminary results might create a paradigm shift in the area of regenerative fat grafting.

Systematic review: Advances of fat tissue engineering as bioactive scaffold, bioactive material, and source for adipose-derived mesenchymal stem cells in wound and scar treatment.

Fat tissue (FT) has been used for many years in regenerative surgery as a bioactive material through the lipofilling/fat graft (F-GRF)-nano-fat technique, as a bioactive scaffold when it was enriched with adipose-derived mesenchymal stem cells (AD-MSCs) contained in the stromal vascular fraction (SVF), and as a direct source of AD-MSCs used in wound healing (WH) and scar treatment (ST). This systematic review aims to describe the advances in FT engineering applied to regenerative surgery (from bench to clinic), through the use of AD-MSCs, SVF contained in F-GRF in WH and ST. The work has been performed by assessing in the selected studies autologous graft of AD-MSCs, SVF, and F-GRF compared to any control for ST and WH. The protocol was developed following the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov , Scopus database, and Cochrane databases has been performed to identify papers on AD-MSCs, SVF, and F-GRF use in WH and ST in which FT was used as bioactive material-scaffold and source of AD-MSCs. Of the 714 articles initially identified, 453 articles focusing on regenerative strategies in WH and ST were selected and, consequently, only 84 articles that apparently related to AD-MSC, SVF, and F-GRF were analyzed. Of these, 61 articles identified as pre-clinical, experimental, and in vitro, and 5 articles identified as a comment and systematic review were excluded. Only 18 original articles which strictly and exclusively focused on autologous AD-MSCs, SVF, and F-GRF in ST and WH were analyzed. The included studies had to match predetermined criteria according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach. The identified studies described microscopic and clinical outcomes in patients treated with AD-MSCs, SVF, and F-GRF. Collected data confirmed the safety and efficacy of FT both as bioactive material-scaffold and source of AD-MSCs in WH and ST without major side effects.

Research progress on Mesenchymal Stem Cells (MSCs), Adipose-Derived Mesenchymal Stem Cells (AD-MSCs), Drugs, and Vaccines in Inhibiting COVID-19 Disease.

Mesenchymal Stem Cells (MSCs), and Adipose-Derived Mesenchymal Stem Cells (AD-MSCs) have been used for many years in regenerative medicine for clinical and surgical applications. Additionally, recent studies reported improved respiratory activity after intravenous administration of MSCs into patients affected by coronavirus disease 2019 (COVID-19) caused by the Coronavirus 2 (SARS-CoV-2) suggesting their role as anti-viral therapy. Severe COVID-19 patients usually progress to acute respiratory distress syndrome, sepsis, metabolic acidosis that is difficult to correct, coagulation dysfunction, multiple organ failure, and even death in a short period after onset. Currently, there is still a lack of clinically effective drugs for such patients. The high secretory activity, the immune-modulatory effect, and the homing ability make MSCs and in particular AD-MSCs both a potential tool for the anti-viral drug-delivery in the virus microenvironment and potential cellular therapy. AD-MSCs as the most important exponent of MSCs are expected to reduce the risk of complications and death of patients due to their strong anti-inflammatory and immune-modulatory capabilities, which can improve microenvironment, promote neovascularization and enhance tissue repair capabilities. In this literature review, the role of regenerative strategies through MSCs, AD-MSCs, and adipocyte-secreted exosomal microRNAs (A-SE-miRs) as a potential antiviral therapy was reported, comparing the results found with current research progress on drugs and vaccines in COVID-19 disease.

Regenerative application of stromal vascular fraction cells enhanced fat graft maintenance: clinical assessment in face rejuvenation.

OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of the use of FG-SVFs in face rejuvenation for esthetic improvement. METHODS: 33 female patients affected by face's soft-tissue defects with loss of volume, study group (SG), were treated with FG-SVFs, comparing results with a control group (CG) (n = 30) treated with fat graft not enhanced (FG). Clinical evaluation, a photographic assessment, magnetic resonance imaging (MRI), and ultrasound (US) were performed. Post-operative follow-up was performed at 1, 3, 7, 12, 24, 48, weeks, and then annually. RESULTS: SG patients showed 61% maintenance of the contour restoring and of volume after 3 years compared with the CG treated with FG, who showed 31% maintenance. 60.7% (n = 20) of SG patients, presented an increase of 6.6 mm in the soft tissue volume after 36 months, which was reported in only 33,3% (n = 10) of the CG. Volumetric persistence in the SG was higher than that in the CG (p <. 0001 vs. CG). MRI and US moreover confirmed the absence of important side effects, as fat necrosis, and cytosteatonecrotic areas. CONCLUSIONS: The use of FG-SVFs was safe and effective in this series of a case treated.

Systematic Review: Allogenic Use of Stromal Vascular Fraction (SVF) and Decellularized Extracellular Matrices (ECM) as Advanced Therapy Medicinal Products (ATMP) in Tissue Regeneration.

Stromal vascular fraction (SVF) containing adipose stem cells (ASCs) has been used for many years in regenerative plastic surgery for autologous applications, without any focus on their potential allogenic role. Allogenic SVF transplants could be based on the possibility to use decellularized extracellular matrix (ECM) as a scaffold from a donor then re-cellularized by ASCs of the recipient, in order to develop the advanced therapy medicinal products (ATMP) in fully personalized clinical approaches. A systematic review of this field has been realized in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. Multistep research of the PubMed, Embase, MEDLINE, Pre-MEDLINE, PsycINFO, CINAHL, Clinicaltrials.gov, Scopus database, and Cochrane databases has been conducted to identify articles and investigations on human allogenic ASCs transplant for clinical use. Of the 341 articles identified, 313 were initially assessed for eligibility on the basis of the abstract. Of these, only 29 met all the predetermined criteria for inclusion according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach, and 19 have been included in quantitative synthesis (meta-analysis). Ninety-one percent of the studies previously screened (284 papers) were focused on the in vitro results and pre-clinical experiments. The allogenic use regarded the treatment of perianal fistulas, diabetic foot ulcers, knee osteoarthritis, acute respiratory distress syndrome, refractory rheumatoid arthritis, pediatrics disease, fecal incontinence, ischemic heart disease, autoimmune encephalomyelitis, lateral epicondylitis, and soft tissue defects. The information analyzed suggested the safety and efficacy of allogenic ASCs and ECM transplants without major side effects.

Composite Face Lifting: The Combination of Stromal Enriched Lipograft With Face Minilift and Upper and Lower Blepharoplasty: A Review of 210 Cases.

BACKGROUND: Face rejuvenation is increasingly challenging because patients request minimally invasive surgery; rapid surgical course and recovery; and fast, tangible, and long-term results. Rejuvenation of face often requires surgery to multiple areas, that is, the lateral face, the midface, the neck, and periorbital areas, in addition to the emerging procedures of face volumizing and biostimulation through fat injection. At our institution, a systematic approach comprising all of these procedures has been developed, with consistent results. OBJECTIVE: The aim of this study was to describe the combination of blepharoplasty, minilift, and Stromal Enriched Lipograft (SEL) for thorough rejuvenation of face and neck regions. METHODS: A prospective study was performed to evaluate outcomes and patient satisfaction with composite face lifting, comprising upper and lower blepharoplasties, minilift, and SEL in 210 patients between 2009 and 2018. Overall improvement after the procedure was rated on a scale of 1 to 5, where 1 is "poor," 2 is "fair," 3 is "good," 4 is "very good," and 5 is "excellent." The evaluation was expressed at 6 months postoperatively by the patient. RESULTS: The amount of SEL transplanted varied from 22 to 56 mL per side (mean, 41). There were no cases of liponecrosis, infection of the grafted area, or pulmonary embolism. More than 85% of patients expressed a very good to excellent evaluation of the result obtained. No one expressed a degree of satisfaction less than good. CONCLUSIONS: Composite face lifting seems as a safe and effective combined procedure for the rejuvenation of face. Face harmony not only depends on redraping tissues toward a more natural, tense, and young conformation, but also on restoring volumes and improving the quality of the redraped tissues. More research is necessary, but the preliminary encouraging impression is that the composite face lifting is capable of addressing all issues, the necessity of correcting laxity, filling volumes, and improving the quality of cutaneous tissues.

Adipose Stem Cells (ASCs) and Stromal Vascular Fraction (SVF) as a Potential Therapy in Combating (COVID-19)-Disease.

A recent and interesting study reported improved respiratory activity after intravenous administration of mesenchymal stem cells (MSCs) into patients affected by coronavirus disease 2019 (COVID-19). These outcomes displayed that intravenous infiltration of MSCs is a safe and efficacy treatment for COVID-19 pneumonia, a severe acute respiratory illness caused by the coronavirus 2 (SARS-CoV-2). Only 7 patients were treated, but with extraordinary results, opening a new strategy in COVID-19 therapy. Currently, no specific therapies against SARS-CoV-2 are available. The MSCs therapy outcomes reported, are striking, as these cells inhibit the over-activation of the immune system, promoting endogenous repair, by improving the lung microenvironment after the SARS-CoV-2 infection. The MSCs could represent an effective, autologous and safe therapy, and therefore, sharing these published results, here is reported the potential use possibilities in COVID-19 of the most common MSCs represented by Adipose Stem Cells (ASCs).

Silicone Implant Versus Silicone Implant Assisted by Stromal Enriched Lipograft Breast Augmentation: A Prospective Comparative Study.

Background: Implant-assisted breast augmentation is among the most performed surgeries performed by plastic surgeons today. This prospective study evaluated the patient satisfaction and complication rates using high-profile round silicone implant alone (traditional breast augmentation) Group A versus the high-profile round silicone implant assisted with stromal enriched lipograft (composite breast augmentation) Group B. Methods: A total of 50 female patient candidates to undergo breast augmentation between January to September 2017 were randomly assigned to either group. The periareolar technique for breast augmentation and the subfascial plane were used in both groups for the insertion of the high-profile round silicone implants. The stromal enriched lipograft (SEL) was used in Group B for the preparation of the autologous fat grafting to the breast. The satisfaction of each patient with body appearance following breast augmentation was rated using an already published scale of 1-5. The rate of complications was analysed. Results: AS performed all the surgeries. In Group A, the age range was between 19 and 48 years (mean of 22.5 years). In Group B, the age range was between 20 and 47 years (mean of 24.1 years). The average BMI of Group A was 24 m/kg2 and 23 m/kg2 of Group B. Patient satisfaction meta-analysis for Group A and B at 12 months shows that patients in Group B expressed a satisfaction that is superior when compared to Group A patients. The ability to camouflage the implant could explain the higher satisfaction rates in Group B. The rate of complications appears similar in both groups. Conclusions: Composite breast augmentation using a combination of round high-profile implants and SEL in breast augmentation can achieve a higher patient satisfaction and aesthetic outcome as compared to the round high-profile breast augmentation alone. The technique is safe, simple and fast with low complication rates. Large multicentre, controlled, prospective studies need to be performed to further confirm the favourable results that were observed in this study.

Fluid Cartilage as New Autologous Biomaterial in the Treatment of Minor Nose Defects: Clinical and Microscopic Difference Amongst Diced, Crushed, and Fluid Cartilage.

Developing cartilage constructs with injectability, appropriate matrix composition, and persistent cartilaginous phenotype remains an enduring challenge in cartilage repair. Fourteen patients with minor contour deformity were treated with fluid cartilage filler gently injected as autologous fluid graft in deep planes of defect of the nose that were close to the bone or the cartilage. A computerized tomographic scan control was performed after 12 months. Pearson's Chi-square test was used to investigate differences in cartilage density between native and newly formed cartilages. The endpoints were the possibility of using fluid cartilage as filler with aesthetic and functional improvement and versatility. Patients were followed up for two years. The constructs of fluid cartilage graft that were injected in the deep plane resulted in a persistent cartilage tissue with appropriate morphology, adequate central nutritional perfusion without central necrosis or ossification, and further augmented nasal dorsum without obvious contraction and deformation. This report demonstrated that fluid cartilage grafts are useful for cartilage regeneration in patients with outcomes of rhinoplasty, internal nasal valve collapse, and minor congenital nose aesthetics deformity.

Revision Abdominoplasty with Truncal Liposculpting: A 10-Year Experience.

INTRODUCTION: Abdominoplasty is one of the most popular body-contouring procedures. Despite its popularity, classic abdominoplasty is still associated with a significant rate of complaints from patients such as: fullness of flanks and epigastric areas, lack of a posterior lumbar curve, hanging skin over the incision line, and visible scars over the flanks and beyond underwear or swimming suit coverage. This study reviews the authors' experience in redo abdominoplasty when the patient is not or partially satisfied with the primary procedure. PATIENTS AND METHODS: A total of 115 female and 32 male patients underwent revision abdominoplasty with truncal liposculpting between 2007 and 2016. The age distribution of patients ranged from 33 to 73 years, with a mean of 43.1 years. All the patients included in the study had undergone classic abdominoplasty in a different institution. Overall satisfaction with the body appearance after the combined procedure was rated on a scale of 1-5, where 1 is 'poor,' 2 is 'fair,' 3 is 'good,' 4 is 'very good,' and 5 is 'excellent.' The evaluation was made 12 months after the composite body-contouring procedure. RESULTS: Four hundred to 1500 ml of fat were obtained with liposuction (mean 840 ml). The amount of clean, adipose tissue transplanted to the buttocks varied from 95 to 425 (mean 286 ml) and to the lower limbs from 75 to 270 ml (mean 195 ml). The stromal-enriched lipograft technique was used in all the cases to enrich the fat transplantation. There was no hematoma, infection or deep vein thrombosis. Seventy-five percent reported that their appearance after composite body contouring was 'very good' to 'excellent' (30% 'excellent' and 45% 'very good') and 20% responded that their appearance was 'good.' Only 5% of patients thought their appearance was less than good ('fair'). The average follow-up time for this group of patients has been 6.3 years (range 1-10 years). CONCLUSION: Truncal liposculpting with modified abdominoplasty accomplishes very good aesthetic results in a single surgical procedure with a low rate of complications and high patient satisfaction in cases of revision abdominoplasties. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Human auricular tissue engineering in an immunocompetent animal model.

BACKGROUND: Tissue engineering has the potential to provide ear-shaped cartilaginous constructs in the near future. Previous attempts to engineer human ear-shaped constructs mimicked human shape and characteristics but were done in immunocompromised animal models. OBJECTIVES: The authors design and evaluate a novel, 3-dimensional (3D) cell-copolymer construct resembling a human ear that was subsequently implanted in an immunocompetent rabbit model. MATERIALS: Mesenchymal progenitor cells that were obtained from perichondrium and chondrium of a rabbit auricular cartilaginous site were expanded in vitro to chondrocytes and seeded onto biodegradable alginate and silk polymer ear-shaped scaffolds. After implantation in the back of 6 immunocompetent rabbits for 8 weeks, cell/scaffold constructs were harvested and analyzed in terms of size, shape, and histology. RESULTS: Data from this study suggest that auricular mesenchymal progenitor cells derived from rabbit perichondrium and chondrium are suitable for development of tissue-engineered human ear models with retention over time of 3D construct architecture. Gross morphology revealed that the silk alginate scaffold diminished slightly the size dimensions but maintained shape and flexibility. Histological analysis showed formation of cartilage tissue along with type II collagen and proteoglycan extracellular matrix components of the silk alginate construct. CONCLUSIONS: This study demonstrates for the first time that it is possible to engineer an ear cartilage construct that resembles the human ear not only in shape but also in size and flexibility in a real test model. This study also confirms that the association of silk, alginate, and perichondrium and chondrium mesenchymal cells is a reliable method to produce an engineered auricular cartilage construct. Further long-term research needs to be done to confirm these observations.

Bilateral calf augmentation for aesthetic purposes.

BACKGROUND: The shape of the calf is determined by the development of the soleus and gastrocnemius muscles, the length and orientation of the crural bones, and the distribution of subcutaneous fat. Some people have a naturally thin or underdeveloped calf that remains small despite exercise. Calf augmentation is indicated for cosmetic reasons or for reconstruction of a shrunken lower leg resulting from injury, illness, or congenital disability. METHODS: A total of 53 consecutive patients (40 women and 13 men) had surgery for calf augmentation between January 2004 and January 2007. The patients ranged in age from 25 to 51 years (mean, 29.5 years). All the patients included in the study requested calf augmentation for aesthetic purposes. Asymmetric-base silicone elastomer smooth-surface implants were used. Overall satisfaction after silicone calf augmentation was rated on a scale of 1 (poor), 2 (fair), 3 (good), 4 (very good), and 5 (excellent). All the patients had surgery by the same team of surgeons (L.H.P., A.S., B.N.). The evaluation was made at follow-up office consultations after 1 year. The total mean follow-up time was 4.4 years. RESULTS: In this study, 53 bilateral calf augmentations were performed, for a total of 106 procedures. The 125-ml implant was used in 37 bilateral cases, the 70-ml implant in 10 cases; and the 175-ml implant in 6 cases. In three cases, unilateral seroma formation needed to be drained by a partial skin incision opening. There were no cases of infection or hematoma. Hypertrophic scar was observed in four patients bilaterally. One patient requested removal of the implants, and the procedure was performed on an outpatient basis. There were no cases of compartment syndrome or deep vein thrombosis, and no pulmonary embolisms occurred. There were no cases of rotation or displacement of the implant. At 12 months, 73% of the patients rated their appearance after calf augmentation as "very good" to "excellent," and 19% responded that their appearance was "good." Only 8% of the patients thought their appearance was less than good. At this writing, the average follow-up time for this group of patients has been 3.4 years. CONCLUSION: Calf augmentation by silicone-filled implants for cosmetic purposes appears to be effective, safe, and aesthetically pleasing, with minor side effects.