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Arcani R, Velier M, Sabatier F, Simoncini S, Abellan-Lopez M, Granel B, Benyamine A, Gomes de Pinho Q, Dani V, Gentile P, Magalon G, Menkes S, Sampson S, Verpaele A, Vonk L, Magalon J, Daumas A. Nanofat Use in Regenerative Medicine: A Systematic Literature Review and Consensus Recommendations from Expert Opinions. Facial Plast Surg Aesthet Med 2025. [PMID: 40250993 DOI: 10.1089/fpsam.2024.0385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/20/2025] Open
Abstract
Objective: To report in vitro, preclinical, and clinical effectiveness of nanofat in adults undergoing reconstructive or functional surgery and to produce a series of consensus statements about nanofat definition by experts. Methods: We conducted a systematic review using PubMed and Web of Science database, retaining studies about nanofat alone. To produce consensus recommendations about nanofat, we invited experts to answer a survey about manufacturing, biological characteristics, and nomenclature of nanofat. Results: A review of 39 articles showed that nanofat seems to have strong regenerative potential. There were 16 studies about the clinical effectiveness of the nanofat in wound healing, aesthetic surgery, and functional disabilities. However, majority of applications lack robust clinical evidence, mainly due to the design of the clinical studies. The experts suggested that nanofat refers to lipoaspirate that benefits from a washing step, followed by emulsification (20-30 passes) with a connector size between 1.2 and 1.6 mm, and a final filtration step (pore size around 300-500 µm). Conclusion: Nanofat seems to have strong regenerative potentials but with a lack of robust clinical evidences. Our experts have suggested the first consensus about a definition of the nanofat that can be used by the academic societies in the coming years.
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Affiliation(s)
- Robin Arcani
- Internal Medicine and Therapeutics Department, CHU La Timone, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
| | - Mélanie Velier
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC, Marseille, France
| | - Florence Sabatier
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC, Marseille, France
| | - Stéphanie Simoncini
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
| | - Maxime Abellan-Lopez
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
- Plastic Surgery Department, Hôpital de la Conception, AP-HM, Marseille, France
| | - Brigitte Granel
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
- Internal Medicine Department, Hôpital Nord AP-HM, Marseille, France
| | - Audrey Benyamine
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
- Internal Medicine Department, Hôpital Nord AP-HM, Marseille, France
| | - Quentin Gomes de Pinho
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
- Internal Medicine Department, Hôpital Nord AP-HM, Marseille, France
| | | | - Pietro Gentile
- Department of Surgical Science, Medical School, "Tor Vergata" University, Rome, Italy
| | | | | | - Steve Sampson
- The Orthohealing Center, Los Angeles, California, USA
| | - Alexis Verpaele
- Tonnard and Verpaele Plastic Surgery Associates, Ghent, Belgium
| | - Lucienne Vonk
- Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands & Xintela AB, Lund, Sweden
| | - Jérémy Magalon
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
- Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC, Marseille, France
| | - Aurélie Daumas
- Internal Medicine and Therapeutics Department, CHU La Timone, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France
- Center for Cardiovascular and Nutrition Research (C2VN), INRA 1260, INSERM UMR_S 1263, Aix-Marseille University, Marseille, France
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Grünherz L, Kollarik S, Sanchez-Macedo N, McLuckie M, Lindenblatt N. Lipidomic Analysis of Microfat and Nanofat Reveals Different Lipid Mediator Compositions. Plast Reconstr Surg 2024; 154:895e-905e. [PMID: 39480647 PMCID: PMC11512614 DOI: 10.1097/prs.0000000000011335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 01/30/2024] [Indexed: 10/28/2024]
Abstract
BACKGROUND Microfat and nanofat are commonly used in various surgical procedures, from skin rejuvenation to scar correction, to contribute to tissue regeneration. Microfat contains mainly adipocytes and is well suited for tissue augmentation, and nanofat is rich in lipids, adipose-derived stem cells, microvascular fragments, and growth factors, making it attractive for aesthetic use. The authors have previously demonstrated that the mechanical processing of microfat into nanofat significantly changes its proteomic profile. Considering that mechanical fractionation leads to adipocyte disruption and lipid release, they aimed to analyze their lipidomic profiles for their regenerative properties. METHODS Microfat and nanofat samples were isolated from 14 healthy patients. Lipidomic profiling was performed by liquid chromatography tandem mass spectrometry. The resulting data were compared against the Human Metabolome and LIPID MAPS Structure Database. MetaboAnalyst was used to analyze metabolic pathways and lipids of interest. RESULTS From 2388 mass-to-charge ratio features, metabolic pathway enrichment analysis of microfat and nanofat samples revealed 109 pathways that were significantly enriched. Microfat samples revealed higher-intensity levels of sphingosines, different eicosanoids, and fat-soluble vitamins. Increased levels of coumaric acids and prostacyclin were found in nanofat. CONCLUSIONS This is the first study to analyze the lipidomic profiles of microfat and nanofat, providing evidence that mechanical emulsification of microfat into nanofat leads to changes in their lipid profiles. From 109 biological pathways, antiinflammatory, antifibrotic, and antimelanogenic lipid mediators were particularly enriched in nanofat samples when compared with microfat. Although further studies are necessary for a deeper understanding of the composition of these specific lipid mediators in nanofat samples, the authors propose that they might contribute to its regenerative effects on tissue. CLINICAL RELEVANCE STATEMENT Profiling the unique lipid mediators in nanofat and microfat enhances our understanding of their different therapeutic effects and allows us to link these specific mediators to antiinflammatory, pro-regenerative, or healing properties. Ultimately, this insight can advance personalized therapeutic strategies, where a specific type of fat is selected based on its optimal therapeutic effect.
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Affiliation(s)
- Lisanne Grünherz
- From the Department of Plastic Surgery and Hand Surgery, University Hospital Zurich
| | - Sedef Kollarik
- From the Department of Plastic Surgery and Hand Surgery, University Hospital Zurich
| | - Nadia Sanchez-Macedo
- From the Department of Plastic Surgery and Hand Surgery, University Hospital Zurich
| | - Michelle McLuckie
- From the Department of Plastic Surgery and Hand Surgery, University Hospital Zurich
| | - Nicole Lindenblatt
- From the Department of Plastic Surgery and Hand Surgery, University Hospital Zurich
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Chen Z, Gao J, Li L. New challenges in scar therapy: the novel scar therapy strategies based on nanotechnology. Nanomedicine (Lond) 2024; 19:2413-2432. [PMID: 39325688 PMCID: PMC11492664 DOI: 10.1080/17435889.2024.2401768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 09/04/2024] [Indexed: 09/28/2024] Open
Abstract
The pathological mechanism of pathological scar is highly complex, encompassing the abnormalities of diverse cytokines, signaling pathways and regulatory factors. To discover more preferable scar treatment options, a variety of distinct approaches have been utilized clinically. Nevertheless, these treatments possess certain side effects and are inclined to relapse. Presently, pathological scar treatment remains a clinical conundrum, and there is an urgent demand for treatment methods that are safe, less traumatic and have lower recurrence rates. New drug delivery systems, novel therapeutic drugs and therapy strategies can enable drugs to permeate the skin effectively, decrease side effects, enhance drug efficacy and even achieve pain-free self-administration. Currently, novel nanotechnologies such as nanomicroneedles, photodynamics mediated by novel photosensitizers, bioelectrical stimulation and 3D printed dressings have been developed for the effective treatment of pathological scars. Additionally, innovative nanoscale fillers, including nano-fat and engineered exosomes, can serve as novel therapeutic agents for the efficient treatment of pathological scars. The intervention of nanomaterials can enhance drug absorption, stabilize and safeguard the active ingredients of drugs, delay or control drug release and enhance bioavailability. This article reviews these new treatment strategies for scar to explore novel approaches for efficient and safe for keloid treatment.
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Affiliation(s)
- Zhuoyang Chen
- The second clinical college, China Medical University, Shenyang, PR China
| | - Jia Gao
- Department of Dermatology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, PR China
| | - Lili Li
- Department of Dermatology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, PR China
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Tran VVT, Jin X, Hong KY, Chang H. Effects of Nanofat in Plastic and Reconstructive Surgery: A Systematic Review. Plast Reconstr Surg 2024; 154:451e-464e. [PMID: 37400953 DOI: 10.1097/prs.0000000000010905] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/05/2023]
Abstract
BACKGROUND Since nanofat was first introduced by Tonnard in 2013, numerous studies have reported positive findings with its use; however, concerns exist regarding its effects and mechanisms, and the various methods used to generate nanofat also remain unclear. The authors conducted a systematic review to evaluate the efficacy of nanofat grafting alone in plastic and reconstructive surgery. METHODS The MEDLINE, Embase, Cochrane Central, Web of Science, and Scopus databases were searched for studies related to the use of nanofat grafting alone in plastic and reconstructive surgery. Outcomes of interest were all clinical results in humans or animals. RESULTS Twelve studies were included. No meta-analysis was conducted due to the clinical heterogeneity of the studies. In general, included studies had a low level of evidence. Six studies ( n = 253 patients) showed significant improvements in scar characteristics based on Patient and Observer Scar Assessment Scale, FACE-Q scale, physician assessment, patient satisfaction, and Vancouver Scar Scale scores. Four studies described the benefits of nanofat in skin rejuvenation (wrinkles, fine rhytides, pigmentation, and discoloration) through photographs, questionnaires, and indentation indices. Histologic evaluation illustrated overall increases in skin thickness, collagen, and elastic fibers. Three experimental studies showed the beneficial effects of nanofat on fat grafting, diabetic wound healing, and hair growth, with compelling histological evidence. No severe complication was reported. CONCLUSIONS Nanofat grafting shows potential benefits in scar and antiaging treatments, with conclusive histological evidence. Clinical studies of fat grafting, wound healing, and hair growth should be conducted, based on the results of this systematic review. Nanofat grafting could be a practical and safe procedure.
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Affiliation(s)
- Vinh Vuong The Tran
- From the Hi-Tech Center, Vinmec Healthcare System
- Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine
| | - Xian Jin
- Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine
| | - Ki Yong Hong
- Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine
| | - Hak Chang
- Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine
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Ramaut L, Moonen L, Geeroms M, Leemans G, Peters E, Forsyth R, Gutermuth J, Hamdi M. Improvement in Early Scar Maturation by Nanofat Infiltration: Histological and Spectrophotometric Preliminary Results From a Split Scar-Controlled, Randomized, Double-Blinded Clinical Trial. Aesthet Surg J Open Forum 2024; 6:ojae072. [PMID: 39360238 PMCID: PMC11446608 DOI: 10.1093/asjof/ojae072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/04/2024] Open
Abstract
Background The regenerative properties of stromal vascular fraction (SVF) in wound healing and scar formation are a subject of increasing clinical interest. Objectives Although preclinical studies have confirmed the angiogenetic, proliferative, and antifibrotic properties of SVF, there is limited clinical evidence from randomized controlled clinical trials. Methods Twelve patients who underwent abdominoplasty were included in this clinical study. Nanofat was mechanically obtained intraoperatively and infiltrated intradermally in the sutured surgical wound, randomly assigned to either the left or the right side. The abdominal scar was evaluated with the Patient and Observer Scar Assessment Scale, whereas erythema and pigmentation were measured with a reflectance spectrophotometry device (Mexameter, Courage + Khazaka electronic GmbH, Köln,Germany). Histological analysis and electron scan microscopy of tissue biopsies were performed at 8 months. Results The treated side of the scar showed significantly less erythema at 3- and 6-month follow-ups, but this difference reduced after 12 months. Patients reported better scar scores at the 6-month follow-up with a significantly better color at the treated side. Observers reported better overall scar scores at the treated side at 3-, 6-, and 12-month follow-ups, with better vascularization, pigmentation, and thickness. There was no statistically significant difference in terms of histological analysis between the 2 groups. There was no difference in the occurrence of adverse events between both sides. Conclusions Infiltration of nanofat exhibited promising results in surgical scar maturation characterized by less erythema and better texture. More clinical trials with a larger sample size are warranted to better elucidate the possible benefits of SVF on surgical scar formation. Level of Evidence 5
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Rong X, Tang J, Yang J, Wang K, Dang J, Yu Z, Zhang Z, Yi C. Immediate SVF-Gel Injection Reduced Incision Scar Formation: A Prospective, Double-Blind, Randomized, Self-control Trial. Aesthetic Plast Surg 2024; 48:3147-3153. [PMID: 38831065 DOI: 10.1007/s00266-024-04126-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 05/02/2024] [Indexed: 06/05/2024]
Abstract
BACKGROUND Skin incision scars are cosmetically displeasing; the effects of current treatments are limited, and new methods to reduce scar formation need to be found. OBJECTIVE We sought to determine whether immediate postoperative injection of stromal vascular fraction gel (SVF-gel) could reduce scar formation at skin incision sites. METHODS A prospective, randomized, double-blind, self-controlled trial was conducted in patients who underwent breast reduction. SVF-gel was intradermally injected into the surgical incision on one randomly selected side, with the other side receiving saline as a control. At the 6-month follow-up, the incision scars were evaluated using the Vancouver scar scale (VSS) and visual analog scale (VAS). Antera 3D camera was used for objective evaluation. RESULTS The VSS score and VAS score were significantly different between the SVF-gel-treated side (3.80 ± 1.37, 3.37±1.25) and the control side (5.25 ± 1.18, 4.94 ± 1.28). Moreover, the SVF-gel-treated side showed statistically significant improvements in scar appearance, based on evidences from Antera 3D camera. LIMITATIONS This was a single-center, single-race, and single-gender study. Furthermore, the results were available only for the 6-month interim follow-up period. CONCLUSION Postoperative immediate SVF-gel injection in surgical incisions can reduce scar formation, and exert a preventive effect on scars. LEVEL OF EVIDENCE I Evidence obtained from at least one properly designed randomized controlled trial. 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 .
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Affiliation(s)
- Xiangke Rong
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
- Department of Plastic Surgery, No. 987 Hospital, Joint Logistics Support Force of PLA, No. 45 Dongfeng Road, Baoji, 721045, China
| | - Jiezhang Tang
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jizhong Yang
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Kai Wang
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Juanli Dang
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Zhou Yu
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Zhaoxiang Zhang
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Chenggang Yi
- Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
- Department of Plastic Surgery, The Second Affiliated Hospital, Medical School, Zhejiang University, 88 Jie Fang Road, Hangzhou, 310009, China.
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Qiu K, Gan W, Chen X. Efficacy of stromal vascular fraction in the treatment of scars: A systematic review and meta-analysis. Skin Res Technol 2024; 30:e13881. [PMID: 39086176 PMCID: PMC11291860 DOI: 10.1111/srt.13881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 07/05/2024] [Indexed: 08/02/2024]
Abstract
OBJECTIVE Our aim was to assess the effectiveness of stromal vascular fraction (SVF) in treating scars using the latest meta-analysis. METHODS We used PubMed, Embase, Cochrane, and Web of Science to search the studies used to evaluate the efficacy of SVF in scar treatment. At least one of the following outcome measures were reported: vascularity, pigmentation, thickness, relief, pliability, surface area, pain, itching and color. RESULTS A total of four eligible articles comprising 145 patients (64 SVF patients and 81 non-SVF patients) were included. The findings of this meta-analysis indicated that SVF had significant therapeutic effects in terms of vascularity (SMD/MD, 95% CI: -1.12, -0.02; p = 0.04), itching (SMD/MD, 95% CI: -0.61, -0.13; p = 0.002), POSAS (SMD/MD, 95% CI: -5.93, -1.47; p = 0.001), and thickness (SMD/MD, 95% CI: -1.04, -0.35; p < 0.001). In terms of OSAS (SMD/MD, 95% CI: -9.14, 0.59; p = 0.09), pigmentation (SMD/MD, 95% CI: -1.02, 0.06; p = 0.08), relief (SMD/MD, 95% CI: -1.14, 0.16; p = 0.14), surface area (SMD/MD, 95% CI: -0.91, 0.26; p = 0.27), PSAS (SMD/MD, 95% CI: -7.20, 0.49; p = 0.09), pain (SMD/MD, 95% CI: -0.87, 0.07; p = 0.10), pliability (SMD/MD, 95% CI: -0.57, 0.01; p = 0.06), and color (SMD/MD, 95% CI: -1.78, 0.48; p = 0.26), there were no significant statistical differences. CONCLUSION In view of the heterogeneity and potential selective bias, further large-scale, prospective, and multicenter clinical trials are needed to confirm the efficacy and reliability of SVF in the treatment of scars.
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Affiliation(s)
- Kaizhen Qiu
- Guangdong Medical UniversityZhanjiangGuangdongChina
| | - Wenjun Gan
- Guangdong Medical UniversityZhanjiangGuangdongChina
| | - Xiaodong Chen
- Guangdong Medical UniversityZhanjiangGuangdongChina
- Department of Burn SurgeryThe First People's Hospital of FoshanFoshanGuangdongChina
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Zocchi ML, Prantl L, Oliinyk D, Knoedler L, Siegmund A, Ahmad N, Duscher D, Larcher L, Raposio E, Pagani A. Potential benefits of adipose–derived SVF and MSCs to regenerate damaged tissues from alloplastic synthetic materials. EUROPEAN JOURNAL OF PLASTIC SURGERY 2024; 47:48. [DOI: 10.1007/s00238-024-02196-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 04/08/2024] [Indexed: 01/06/2025]
Abstract
AbstractRecent advancements in Plastic Surgery and Regenerative MedicineQuery have revolutionized tissue repair, remodeling, and regeneration. A promising approach involves Mesenchymal Stem cells and from the adipose–derived Stromal Vascular Fraction, aimed at improving tissue healing post the use of synthetic materials. This integration shows potential in mitigating adverse effects of synthetic materials like dermal fillers, offering new clinical interventions for tissue repair and regeneration. This article explores the benefits, complications, and applications of these technologies in Plastic Surgery and Cosmetic Medicine, focusing on their mechanisms of action and future perspectives. Level of evidence: Not ratable
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Mbiine R, Wayengera M, Kiwanuka N, Munabi I, Muwonge H, Nakanwagi C, Joloba M, Galukande M. Autologous adipose-derived stromal vascular fraction (SVF) in scar treatment among patients with keloids and hypertrophic scars: a systematic review and meta-analysis of current practices and outcomes. AMERICAN JOURNAL OF STEM CELLS 2023; 12:98-111. [PMID: 38213639 PMCID: PMC10776342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Accepted: 12/12/2023] [Indexed: 01/13/2024]
Abstract
BACKGROUND Keloids and hypertrophic scars are some of the most common skin conditions globally, associated with poor treatment response and high recurrence rates. Autologous adipose-derived stromal vascular fraction (SVF) is increasingly recognized as an emerging therapy albeit limited literature on its outcome in scar treatment. This review aimed to describe the current practices and outcomes of adipose-derived stromal Vascular Fraction in scar treatment. METHODS This systematic review assessed articles describing the use of SVF in scar treatment published between 2000 and 2023. Article searches of Medline/PubMed, Cochrane Library, and Embase databases using Mesh terms and the Boolean operators ("AND", "OR") by two independent researchers were done whilst following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Clinical studies assessing SVF in scar treatment with a primary outcome measure being an improvement in scar characteristics including the thickness, scar assessment scores were included. RESULTS Among the 1425 studies identified in the search, 20 studies met the inclusion criteria with a total of 493 patients included. Eight of these were clinical trials with the rest being observational studies. Follow-up ranged from 3 months to 24 months. In all studies, there was an improvement in scar characteristics following single-dose treatment with SVF or its equivalent. All studies reported SVF to be safe. CONCLUSION The review found that autologous adipose-derived SVF is a clinically effective therapy for keloids and scar treatment.
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Affiliation(s)
- Ronald Mbiine
- Department of Surgery, College of Health Sciences, Makerere UniversityKampala, Uganda
| | - Misaki Wayengera
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere UniversityKampala, Uganda
| | - Noah Kiwanuka
- School of Public Health, College of Health Sciences, Makerere UniversityKampala, Uganda
| | - Ian Munabi
- Department of Human Anatomy, School of Biomedical Sciences, College of Health Sciences, Makerere UniversityKampala, Uganda
| | - Haruna Muwonge
- Department of Physiology, College of Health Sciences, Makerere UniversityKampala, Uganda
| | | | - Moses Joloba
- School of Biomedical Sciences, College of Health Sciences, Makerere UniversityKampala, Uganda
| | - Moses Galukande
- Department of Surgery, College of Health Sciences, Makerere UniversityKampala, Uganda
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Schipper JAM, van Laarhoven CJHCM, Schepers RH, Tuin AJ, Harmsen MC, Spijkervet FKL, Jansma J, van Dongen JA. Mechanical Fractionation of Adipose Tissue-A Scoping Review of Procedures to Obtain Stromal Vascular Fraction. Bioengineering (Basel) 2023; 10:1175. [PMID: 37892905 PMCID: PMC10604552 DOI: 10.3390/bioengineering10101175] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 09/26/2023] [Accepted: 09/28/2023] [Indexed: 10/29/2023] Open
Abstract
Clinical indications for adipose tissue therapy are expanding towards a regenerative-based approach. Adipose-derived stromal vascular fraction consists of extracellular matrix and all nonadipocyte cells such as connective tissue cells including fibroblasts, adipose-derived stromal cells (ASCs) and vascular cells. Tissue stromal vascular fraction (tSVF) is obtained by mechanical fractionation, forcing adipose tissue through a device with one or more small hole(s) or cutting blades between syringes. The aim of this scoping review was to assess the efficacy of mechanical fractionation procedures to obtain tSVF. In addition, we provide an overview of the clinical, that is, therapeutic, efficacy of tSVF isolated by mechanical fraction on skin rejuvenation, wound healing and osteoarthritis. Procedures to obtain tissue stromal vascular fraction using mechanical fractionation and their associated validation data were included for comparison. For clinical outcome comparison, both animal and human studies that reported results after tSVF injection were included. We categorized mechanical fractionation procedures into filtration (n = 4), centrifugation (n = 8), both filtration and centrifugation (n = 3) and other methods (n = 3). In total, 1465 patients and 410 animals were described in the included clinical studies. tSVF seems to have a more positive clinical outcome in diseases with a high proinflammatory character such as osteoarthritis or (disturbed) wound healing, in comparison with skin rejuvenation of aging skin. Isolation of tSVF is obtained by disruption of adipocytes and therefore volume is reduced. Procedures consisting of centrifugation prior to mechanical fractionation seem to be most effective in volume reduction and thus isolation of tSVF. tSVF injection seems to be especially beneficial in clinical applications such as osteoarthritis or wound healing. Clinical application of tSVF appeared to be independent of the preparation procedure, which indicates that current methods are highly versatile.
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Affiliation(s)
- Jan Aart M. Schipper
- Department of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands
| | | | - Rutger H. Schepers
- Department of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands
| | - A. Jorien Tuin
- Department of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands
| | - Marco C. Harmsen
- Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, 9712 Groningen, The Netherlands
| | - Fred K. L. Spijkervet
- Department of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands
| | - Johan Jansma
- Department of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands
| | - Joris A. van Dongen
- Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, 9712 Groningen, The Netherlands
- Department of Plastic, Reconstructive and Hand Surgery, University Medical Center Utrecht, Utrecht University, 3584 Utrecht, The Netherlands
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La Padula S, Ponzo M, Lombardi M, Iazzetta V, Errico C, Polverino G, Russo F, D'Andrea L, Hersant B, Meningaud JP, Salzano G, Pensato R. Nanofat in Plastic Reconstructive, Regenerative, and Aesthetic Surgery: A Review of Advancements in Face-Focused Applications. J Clin Med 2023; 12:4351. [PMID: 37445386 DOI: 10.3390/jcm12134351] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 06/19/2023] [Accepted: 06/25/2023] [Indexed: 07/15/2023] Open
Abstract
Nanofat is a relatively novel technique in fat grafting that has gained significant interest in the fields of regenerative medicine, aesthetic and translational research. It involves the extraction of autologous fat from a patient, which is then transformed into "nanofat", consisting of small fat particles with a diameter of less than 0.1 mm and containing high concentrations of stem cells and growth factors. This article focuses on the use of nanofat in facial rejuvenation and its potential for lipomodelling. Fat tissue is a "stem cell depot" and nanofat contains many stem cells that can differentiate into various cell types. The Lipogem technology, developed in 2013, enables the isolation of nanofat with an intact perivascular structure, utilizing the high concentration of mesenchymal stromal cells near the pericytes of the adipose vascular system. Nowadays nanofat is used primarily for cosmetic purposes particularly in rejuvenating and improving the appearance of the skin, especially the face. Indeed, it has wide applicability; it can be used to treat fine lines, wrinkles, acne scars, sun-damaged skin, scar repair, and as an alopecia treatment. However, further studies are needed to assess the long-term efficacy and safety of this technique. In conclusion, nanofat is a safe and minimally invasive option for tissue regeneration with considerable therapeutic potential. This study reviews the application and effects of nanofat in regenerative medicine and facial cosmetic surgery.
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Affiliation(s)
- Simone La Padula
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
- Department of Plastic, Reconstructive and Maxillo-Facial Surgery, Henri Mondor Hospital, University Paris, XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
| | - Martina Ponzo
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
| | - Mariagiovanna Lombardi
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
| | - Vincenzo Iazzetta
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
| | - Concetta Errico
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
| | - Gianmarco Polverino
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
| | - Francesca Russo
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
| | - Luca D'Andrea
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
| | - Barbara Hersant
- Department of Plastic, Reconstructive and Maxillo-Facial Surgery, Henri Mondor Hospital, University Paris, XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
| | - Jean Paul Meningaud
- Department of Plastic, Reconstructive and Maxillo-Facial Surgery, Henri Mondor Hospital, University Paris, XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
| | - Giovanni Salzano
- Maxillofacial Surgery Unit, Federico II University of Naples, 80131 Naples, Italy
| | - Rosita Pensato
- Department of Plastic and Reconstructive Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
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Quintero Sierra LA, Biswas R, Conti A, Busato A, Ossanna R, Zingaretti N, Parodi PC, Conti G, Riccio M, Sbarbati A, De Francesco F. Highly Pluripotent Adipose-Derived Stem Cell-Enriched Nanofat: A Novel Translational System in Stem Cell Therapy. Cell Transplant 2023; 32:9636897231175968. [PMID: 37243545 DOI: 10.1177/09636897231175968] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/29/2023] Open
Abstract
Fat graft is widely used in plastic and reconstructive surgery. The size of the injectable product, the unpredictable fat resorption rates, and subsequent adverse effects make it tricky to inject untreated fat into the dermal layer. Mechanical emulsification of fat tissue, which Tonnard introduced, solves these problems, and the product obtained was called nanofat. Nanofat is widely used in clinical and aesthetic settings to treat facial compartments, hypertrophic and atrophic scars, wrinkle attenuation, skin rejuvenation, and alopecia. Several studies demonstrate that the tissue regeneration effects of nanofat are attributable to its rich content of adipose-derived stem cells. This study aimed to characterize Hy-Tissue Nanofat product by investigating morphology, cellular yield, adipose-derived stem cell (ASC) proliferation rate and clonogenic capability, immunophenotyping, and differential potential. The percentage of SEEA3 and CD105 expression was also analyzed to establish the presence of multilineage-differentiating stress-enduring (MUSE) cell. Our results showed that the Hy-Tissue Nanofat kit could isolate 3.74 × 104 ± 1.31 × 104 proliferative nucleated cells for milliliter of the treated fat. Nanofat-derived ASC can grow in colonies and show high differentiation capacity into adipocytes, osteocytes, and chondrocytes. Moreover, immunophenotyping analysis revealed the expression of MUSE cell antigen, making this nanofat enriched of pluripotent stem cell, increasing its potential in regenerative medicine. The unique characteristics of MUSE cells give a simple, feasible strategy for treating a variety of diseases.
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Affiliation(s)
| | - Reetuparna Biswas
- Human Anatomy and Histology Section, Department of Neuroscience, Biomedicine, and Movement, University of Verona, Verona, Italy
| | - Anita Conti
- Human Anatomy and Histology Section, Department of Neuroscience, Biomedicine, and Movement, University of Verona, Verona, Italy
| | - Alice Busato
- Human Anatomy and Histology Section, Department of Neuroscience, Biomedicine, and Movement, University of Verona, Verona, Italy
- Safety Assessment Department, Aptuit (Verona) S.r.l., an Evotec Company, Verona, Italy
| | - Riccardo Ossanna
- Human Anatomy and Histology Section, Department of Neuroscience, Biomedicine, and Movement, University of Verona, Verona, Italy
| | - Nicola Zingaretti
- Department of Medical Area (DAME), Clinic of Plastic and Reconstructive Surgery, Academic Hospital of Udine, University of Udine, Udine, Italy
| | - Pier Camillo Parodi
- Department of Medical Area (DAME), Clinic of Plastic and Reconstructive Surgery, Academic Hospital of Udine, University of Udine, Udine, Italy
- Research and Training Center in Regenerative Surgery, Accademia del Lipofilling, Montelabbate, Italy
| | - Giamaica Conti
- Human Anatomy and Histology Section, Department of Neuroscience, Biomedicine, and Movement, University of Verona, Verona, Italy
| | - Michele Riccio
- Research and Training Center in Regenerative Surgery, Accademia del Lipofilling, Montelabbate, Italy
- Department of General and Specialties Surgery, SOD of Reconstructive Surgery and Hand Surgery, Azienda Ospedaliera Universitaria delle Marche, Ancona, Italy
| | - Andrea Sbarbati
- Human Anatomy and Histology Section, Department of Neuroscience, Biomedicine, and Movement, University of Verona, Verona, Italy
- Research and Training Center in Regenerative Surgery, Accademia del Lipofilling, Montelabbate, Italy
| | - Francesco De Francesco
- Department of General and Specialties Surgery, SOD of Reconstructive Surgery and Hand Surgery, Azienda Ospedaliera Universitaria delle Marche, Ancona, Italy
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Ding P, Lu E, Li G, Sun Y, Yang W, Zhao Z. Research Progress on Preparation, Mechanism, and Clinical Application of Nanofat. J Burn Care Res 2022; 43:1140-1144. [PMID: 35015870 PMCID: PMC9435497 DOI: 10.1093/jbcr/irab250] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Autologous adipose tissue is an ideal soft tissue filling material in theory, which has the advantages of easy access, comprehensive source, and high biocompatibility and is now widely used in clinical practice. Based on the above benefits of autologous fat, autologous fat grafting is an essential technique in plastic surgery. Conventional macrofat is used to improve structural changes after soft tissue damage or loss caused by various causes such as disease, trauma, or aging. Due to the large diameter of particles and to avoid serious complications such as fat embolism, blunt needles with larger diameters (2 mm) are required, making the macrofat grafting difficult to the deep dermis and subdermis. Nanofat grafting is a relatively new technology that has gained popularity in cosmetic surgery in recent years. Nanofat is produced by mechanical shuffling and filtration of microfat, which is harvested by liposuction. The harvesting and processing of nanofat are cost-effective as it does not require additional equipment or culture time. Unlike microfat, nanofat particles are too small to provide a notable volumizing effect. Studies have shown that nanofat contains abundant stromal vascular fraction cells and adipose-derived stem cells, which help reconstruct dermal support structures, such as collagen, and regenerate healthier, younger-looking skin. Moreover, the fluid consistency of nanofat allows application in tissue regeneration, such as scars, chronic wounds, and facial rejuvenation. This article reviews the current research progress on the preparation, mechanism, and clinical application of nanofat.
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Affiliation(s)
- Pengbing Ding
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China
| | - Enhang Lu
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China
| | - Guan Li
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China
| | - Yidan Sun
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China
| | - Wenhui Yang
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China
| | - Zhenmin Zhao
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China
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Che D, Zhou Y, Wang J, Liu Y, Gao F, Lv T, Cui C, Xiao Z. Experimental study on the influence of different aperture connectors on nanofat. J Plast Reconstr Aesthet Surg 2022; 75:3595-3602. [PMID: 35672247 DOI: 10.1016/j.bjps.2022.04.055] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 03/12/2022] [Accepted: 04/12/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND Nanofat, as a derivative of adipose tissue, has gradually become a research hotspot in beauty and regenerative medicine. However, the nanofat preparation method has not yet been standardized; it remains unknown whether the aperture of the connector has any influence on the transplantation effect. METHODS Adipose tissue was mechanically emulsified into nanofat tissue through different connector apertures (1.0, 1.5, and 2.0 mm). Cell survival and apoptosis were measured using the volume of oil droplets, glucose transportation test, flow cytometry, cell counting kit-8 (CCK-8), wound healing assay, transwell migration assay, and fluorescence staining. The expression of adiponectin, GluT4, and PPAR-γ in nanofat-derived stem cells (NFSCs) was detected using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS The fineness of nanofat tissue texture decreased with an increase in the aperture connector. The amounts of glucose transferred in the three groups (1, 1.5, and 2 mm) were 4.7 ± 0.894, 6.1 ± 1.026, and 6.9 ± 0.868 mmol/L, respectively. Flow cytometric analysis showed that the proportion of NFSCs in the 2.0 mm group was the highest (91.267±1.210%). Cell proliferation and migration abilities were stronger in the 1.5 and 2.0 mm groups. The numbers of late apoptotic and dead cells in the 2.0 mm group were significantly fewer than those in the two other groups. Expression levels of lipid-related genes were as follows: adiponectin > GluT4 > PPAR-γ in each component. CONCLUSIONS As nanofat is emulsified, the use of larger aperture connectors (2.0 mm) appeared to decrease the degree of adipocyte lysis and increase the biological activity of adipose tissue.
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Affiliation(s)
- Dehui Che
- Department of Plastic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China
| | - Yongting Zhou
- Department of Plastic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China
| | - Jie Wang
- Department of Plastic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China
| | - Ying Liu
- Department of Plastic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China
| | - Feng Gao
- Department of Plastic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China
| | - Tianqi Lv
- Department of Plastic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China
| | - Chenyang Cui
- Department of Plastic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China
| | - Zhibo Xiao
- Department of Plastic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
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15
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Tripathy S, VinayKumar D, Mohsina S, Sharma R, Bhatia A. Histological analysis of the effect of nanofat grafting in scar rejuvenation. J Cutan Aesthet Surg 2022; 15:147-153. [PMID: 35965912 PMCID: PMC9364463 DOI: 10.4103/jcas.jcas_106_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Introduction: Aims: Materials and Methods: Results: Conclusion:
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Jeyaraman M, Muthu S, Sharma S, Ganta C, Ranjan R, Jha SK. Nanofat: A therapeutic paradigm in regenerative medicine. World J Stem Cells 2021; 13:1733-1746. [PMID: 34909120 PMCID: PMC8641019 DOI: 10.4252/wjsc.v13.i11.1733] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/15/2021] [Accepted: 10/27/2021] [Indexed: 02/06/2023] Open
Abstract
Adipose tissue is a compact and well-organized tissue containing a heterogeneous cellular population of progenitor cells, including mesenchymal stromal cells. Due to its availability and accessibility, adipose tissue is considered a "stem cell depot." Adipose tissue products possess anti-inflammatory, anti-fibrotic, anti-apoptotic, and immunomodulatory effects. Nanofat, being a compact bundle of stem cells with regenerative and tissue remodeling potential, has potential in translational and regenerative medicine. Considering the wide range of applicability of its reconstructive and regenerative potential, the applications of nanofat can be used in various disciplines. Nanofat behaves on the line of adipose tissue-derived mesenchymal stromal cells. At the site of injury, these stromal cells initiate a site-specific reparative response comprised of remodeling of the extracellular matrix, enhanced and sustained angiogenesis, and immune system modulation. These properties of stromal cells provide a platform for the usage of regenerative medicine principles in curbing various diseases. Details about nanofat, including various preparation methods, characterization, delivery methods, evidence on practical applications, and ethical concerns are included in this review. However, appropriate guidelines and preparation protocols for its optimal use in a wide range of clinical applications have yet to be standardized.
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Affiliation(s)
- Madhan Jeyaraman
- Department of Biotechnology, School of Engineering and Technology, Sharda University , Greater Noida 201306, Uttar Pradesh, India
| | - Sathish Muthu
- Department of Biotechnology, School of Engineering and Technology, Sharda University , Greater Noida 201306, Uttar Pradesh, India
| | - Shilpa Sharma
- Indian Stem Cell Study Group, Lucknow 226010, Uttar Pradesh, India
| | - Charan Ganta
- Indian Stem Cell Study Group, Lucknow 226010, Uttar Pradesh, India
| | - Rajni Ranjan
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida 201306, Uttar Pradesh, India
| | - Saurabh Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University , Greater Noida 201306, Uttar Pradesh, India
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Stachura A, Paskal W, Pawlik W, Mazurek MJ, Jaworowski J. The Use of Adipose-Derived Stem Cells (ADSCs) and Stromal Vascular Fraction (SVF) in Skin Scar Treatment-A Systematic Review of Clinical Studies. J Clin Med 2021; 10:3637. [PMID: 34441935 PMCID: PMC8396936 DOI: 10.3390/jcm10163637] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 08/11/2021] [Accepted: 08/13/2021] [Indexed: 12/15/2022] Open
Abstract
In recent years, lipofilling became a popular scar treatment method. Its beneficial outcomes have been partly attributed to the regenerative capacity of adipose-derived stem cells (ADSCs), suspended in an extracellular matrix-the stromal vascular fraction (SVF). The aim of this review was to verify if existing data support the clinical use of ADSC-related interventions in scar treatment. A systematic search of the literature was performed in July 2020 in five databases (Medline, Cochrane, Web of Science, Scopus and Embase). Articles written in English, except for reviews, letters and editorials, were identified and screened for eligibility. We looked for reports of any outcomes in scars treated with ADSCs or SVF. Data from selected articles were extracted and the quality of each study was assessed. Five hundred and fourteen studies were identified in the primary search, of which nineteen were eventually included in the systematic review. Extracted data pointed to beneficial microscopic, functional and aesthetic outcomes in a total of 665 patients. Six studies included comparative interventions-platelet-rich plasma or CO2 fractional laser. Collected data give low-to-average quality evidence for beneficial effects of ADSC-related interventions in scar treatment. Some studies suggest that these interventions are noninferior to PRP or fractional CO2 laser.
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Affiliation(s)
- Albert Stachura
- Center for Preclinical Research, Department of Methodology, Medical University of Warsaw, 02-091 Warsaw, Poland;
- Timeless Plastic Surgery Clinic, 02-091 Warsaw, Poland; (M.J.M.); (J.J.)
- Doctoral School, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Wiktor Paskal
- Center for Preclinical Research, Department of Methodology, Medical University of Warsaw, 02-091 Warsaw, Poland;
- Timeless Plastic Surgery Clinic, 02-091 Warsaw, Poland; (M.J.M.); (J.J.)
| | - Weronika Pawlik
- Faculty of Medicine and Dentistry, Pomeranian Medical University, 70-204 Szczecin, Poland;
| | - Maciej J. Mazurek
- Timeless Plastic Surgery Clinic, 02-091 Warsaw, Poland; (M.J.M.); (J.J.)
- West Pomeranian Center for Severe Burns and Plastic Surgery, 72-300 Gryfice, Poland
- Plastic Surgery Department, Centre for Postgraduate Medical Education, 02-091 Warsaw, Poland
| | - Janusz Jaworowski
- Timeless Plastic Surgery Clinic, 02-091 Warsaw, Poland; (M.J.M.); (J.J.)
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Gentile P, Sterodimas A, Calabrese C, Garcovich S. 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. Stem Cell Res Ther 2021; 12:318. [PMID: 34078470 PMCID: PMC8173738 DOI: 10.1186/s13287-021-02397-4] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 05/18/2021] [Indexed: 02/07/2023] Open
Abstract
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.
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Affiliation(s)
- Pietro Gentile
- Department of Surgical Science, “Tor Vergata” University, Via Courmayeur, 102, 00133 Rome, Italy
- Academy of International Regenerative Medicine & Surgery Societies (AIRMESS), 1201 Geneva, Switzerland
| | - Aris Sterodimas
- Department of Plastic and Reconstructive Surgery, Metropolitan General Hospital, 18547 Athens, Greece
| | | | - Simone Garcovich
- Institute of Dermatology, F. Policlinico Gemelli IRCSS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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Pignatti M, Spinella A, Cocchiara E, Boscaini G, Lusetti IL, Citriniti G, Lumetti F, Setti G, Dominici M, Salvarani C, De Santis G, Giuggioli D. Invited Response on: Comments on "Autologous Fat Grafting for the Oral and Digital Complications of Systemic Sclerosis: Results of a Prospective Study". Aesthetic Plast Surg 2021; 45:1344-1345. [PMID: 33145615 DOI: 10.1007/s00266-020-02024-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 10/14/2020] [Indexed: 11/30/2022]
Affiliation(s)
- Marco Pignatti
- Plastic Surgery, Policlinico di Sant'Orsola, DIMES, University of Bologna, Bologna, Italy.
| | - Amelia Spinella
- Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, Modena, Italy
| | - Emanuele Cocchiara
- Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, Modena, Italy
| | - Giulia Boscaini
- Plastic Surgery, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, Modena, Italy
| | - Irene Laura Lusetti
- Plastic Surgery, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, Modena, Italy
| | - Giorgia Citriniti
- Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, Modena, Italy
| | - Federica Lumetti
- Rheumatology Unit, University of Modena and Reggio Emilia, Medical School, Azienda Ospedaliero-Universitaria, Policlinico di Modena, Modena, Italy
| | - Giacomo Setti
- Unit of Dentistry and Oral-Maxillofacial Surgery, University of Modena and Reggio Emilia, Modena, Italy
| | - Massimo Dominici
- Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, Modena, Italy
| | - Carlo Salvarani
- Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, Modena, Italy
| | - Giorgio De Santis
- Plastic Surgery, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, Modena, Italy
| | - Dilia Giuggioli
- Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, Modena, Italy
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Comments on: Autologous Fat Grafting for the Oral and Digital Complications of Systemic Sclerosis: Results of a Prospective Study. Aesthetic Plast Surg 2021; 45:1342-1343. [PMID: 33403420 DOI: 10.1007/s00266-020-02014-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 10/13/2020] [Indexed: 10/22/2022]
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Sesé B, Sanmartín JM, Ortega B, Llull R. Human Stromal Cell Aggregates Concentrate Adipose Tissue Constitutive Cell Population by In Vitro DNA Quantification Analysis. Plast Reconstr Surg 2020; 146:1285-1293. [PMID: 33234958 DOI: 10.1097/prs.0000000000007342] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Regenerative cell strategies rely on stromal cell implants to attain an observable clinical outcome. However, the effective cell dose to ensure a therapeutic response remains unknown. To achieve a higher cell dose, the authors hypothesized that reducing the volume occupied by mature adipocytes in lipoaspirate will concentrate the stromal vascular fraction present in the original tissue. METHODS Human standardized lipoaspirate (n = 6) was centrifuged (1200 g for 3 minutes) and the water phase was discarded. Mechanical disaggregation was achieved by shearing tissue through 2.4- and 1.2-mm Luer-to-Luer transfers. After a second centrifugation (800 g for 10 minutes), stromal cell aggregates were separated from the supernatant oil phase. Lipoaspirate percentage composition was determined by its constituent weights. Cell content was measured by total DNA quantification, and partial cell viability was determined by image cytometry. Tissue sections were evaluated histologically (hematoxylin and eosin and Masson trichrome stains). RESULTS Stromal cell aggregates reduced the standardized lipoaspirate mass to 28.6 ± 4.2 percent. Accordingly, the cell density increased by 222.6 ± 63.3 percent (from 9.9 ± 1.4 million cells/g to 31.3 ± 6.6 million cells/g; p < 0.05). Cell viability was unaffected in stromal cell aggregates (71.3 ± 2.5 percent) compared to standardized lipoaspirate (72.2 ± 2.3 percent), and histologic analysis revealed high-density areas enriched with stromal cells (622.9 ± 145.6 percent) and extracellular matrix (871.2 ± 80.3 percent). CONCLUSION Stromal cell aggregates represent a biological agent that triplicates the cell density versus unprocessed lipoaspirate, low on oil and water fluids, and enriched extracellular matrix components.
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Affiliation(s)
- Borja Sesé
- From the Cancer Cell Biology Group, Institut d'Investigació Sanitària Illes Balears; Servei de Genètica, Hospital Universitari Son Espases; Institut Català d'Oncologia, Hospital Germans Trias i Pujol; Cell Pro Tech Spain; and the University of Florida College of Medicine
| | - Javier M Sanmartín
- From the Cancer Cell Biology Group, Institut d'Investigació Sanitària Illes Balears; Servei de Genètica, Hospital Universitari Son Espases; Institut Català d'Oncologia, Hospital Germans Trias i Pujol; Cell Pro Tech Spain; and the University of Florida College of Medicine
| | - Bernat Ortega
- From the Cancer Cell Biology Group, Institut d'Investigació Sanitària Illes Balears; Servei de Genètica, Hospital Universitari Son Espases; Institut Català d'Oncologia, Hospital Germans Trias i Pujol; Cell Pro Tech Spain; and the University of Florida College of Medicine
| | - Ramon Llull
- From the Cancer Cell Biology Group, Institut d'Investigació Sanitària Illes Balears; Servei de Genètica, Hospital Universitari Son Espases; Institut Català d'Oncologia, Hospital Germans Trias i Pujol; Cell Pro Tech Spain; and the University of Florida College of Medicine
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Ghiasloo M, Lobato RC, Díaz JM, Singh K, Verpaele A, Tonnard P. Expanding Clinical Indications of Mechanically Isolated Stromal Vascular Fraction: A Systematic Review. Aesthet Surg J 2020; 40:NP546-NP560. [PMID: 32358957 DOI: 10.1093/asj/sjaa111] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Mechanically isolated stromal vascular fraction (tSVF, tissue SVF) is a potent regenerative solution, increasingly used as a therapeutic modality for a variety of pathologies. With recent evidence conclusively favoring mechanical isolation over enzymatic alternatives, the therapeutic share and indications of tSVF are expected to grow even further. OBJECTIVES The aim of this study was to provide a systematic review of all studies reporting on the use of tSVF. METHODS A systematic search was undertaken of the Embase, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials databases. Outcome measures included clinical indications, such as recipient area, adverse events, clinical results recipient area, method of application, follow-up duration and evaluation methods. RESULTS Of the total of 4505 articles identified, 186 full-texts were screened. Thirty-four studies, reporting on 1443 patients were included. tSVF-based therapy was observed for 10 different pathologies, including aged skin (8 studies), scars (5), wounds (6), osteoarthritis (6), tendinopathy (2), temporomandibular joint disorders (1), androgenic alopecia (1), perianal fistula (3), migraine (1), and vocal fold scarring (1). Across all studies, tSVF-based therapy resulted in favorable clinical results. Overall, 50 (3.43%) minor and one (0.07%) major adverse events were observed, mainly related to the liposuction procedure. CONCLUSIONS tSVF offers a safe, easy and legal treatment modality for a range of indications. Future research is indicated to identify the optimal isolation protocol, dose and timing. In addition, basic research remains crucial to identify the mechanism of action of SVF within different pathologies. LEVEL OF EVIDENCE: 4
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Affiliation(s)
- Mohammad Ghiasloo
- Department of Plastic and Reconstructive Surgery, Ghent University Hospital, Ghent, Belgium
| | | | | | - Kashika Singh
- Department of General and Visceral Surgery, Evangelical Hospital Bethel, Bielefeld, Germany
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The Effect of Chyle Fat Injection on Human Hypertrophic Scars in an Animal Model: A New Strategy for the Treatment of Hypertrophic Scars. Ann Plast Surg 2020; 82:622-627. [PMID: 30633019 DOI: 10.1097/sap.0000000000001784] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND Chyle fat transplantation has shown positive effects on preexisting human hypertrophic scars (HSs) in a nude mouse HS graft model. METHODS Hypertrophic scar fragments were obtained from 5 surgically treated burn patients and implanted into the backs of nude mice in 3 groups: group A, control; group B, triamcinolone; and group C, chyle fat. The specimens were implanted after the corresponding intralesional injection in each group, and the mice were observed for 4 weeks. In total, 18 mice and 72 scar specimens were studied. After 4 weeks, the HSs were removed from the mice. Then, the scar weights, histology, and decorin staining were assessed to evaluate the therapeutic efficacy. RESULTS An obviously significant difference was observed in the HS weight reduction between groups A and C (P < 0.01), and a significant difference in the HS weight reduction was observed between groups A and B (P < 0.05). However, there was no significant difference between groups B and C. The treatment groups (groups B and C) showed strong decorin staining. Furthermore, the decorin staining was much stronger in group C than in group B (P < 0.05). Significant differences in extracellular matrix deposition were observed among the 3 groups, as determined by Masson trichrome staining. Both groups B and C showed significant therapeutic efficacy compared with group A, and group C exhibited a significant therapeutic effect compared with group B (P < 0.05). CONCLUSIONS This study indicates that chyle fat grafting is beneficial for treating HSs.
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Kamat P, Frueh FS, McLuckie M, Sanchez-Macedo N, Wolint P, Lindenblatt N, Plock JA, Calcagni M, Buschmann J. Adipose tissue and the vascularization of biomaterials: Stem cells, microvascular fragments and nanofat-a review. Cytotherapy 2020; 22:400-411. [PMID: 32507607 DOI: 10.1016/j.jcyt.2020.03.433] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Revised: 02/27/2020] [Accepted: 03/12/2020] [Indexed: 12/13/2022]
Abstract
Tissue defects in the human body after trauma and injury require precise reconstruction to regain function. Hence, there is a great demand for clinically translatable approaches with materials that are both biocompatible and biodegradable. They should also be able to adequately integrate within the tissue through sufficient vascularization. Adipose tissue is abundant and easily accessible. It is a valuable tissue source in regenerative medicine and tissue engineering, especially with regard to its angiogenic potential. Derivatives of adipose tissue, such as microfat, nanofat, microvascular fragments, stromal vascular fraction and stem cells, are commonly used in research, but also clinically to enhance the vascularization of implants and grafts at defect sites. In plastic surgery, adipose tissue is harvested via liposuction and can be manipulated in three ways (macro-, micro- and nanofat) in the operating room, depending on its ultimate use. Whereas macro- and microfat are used as a filling material for soft tissue injuries, nanofat is an injectable viscous extract that primarily induces tissue remodeling because it is rich in growth factors and stem cells. In contrast to microfat that adds volume to a defect site, nanofat has the potential to be easily combined with scaffold materials due to its liquid and homogenous consistency and is particularly attractive for blood vessel formation. The same is true for microvascular fragments that are easily isolated from adipose tissue through collagenase digestion. In preclinical animal models, it has been convincingly shown that these vascular fragments inosculate with host vessels and subsequently accelerate scaffold perfusion and host tissue integration. Adipose tissue is also an ideal source of stem cells. It yields larger quantities of cells than any other source and is easier to access for both the patient and doctor compared with other sources such as bone marrow. They are often used for tissue regeneration in combination with biomaterials. Adipose-derived stem cells can be applied unmodified or as single cell suspensions. However, certain pretreatments, such as cultivation under hypoxic conditions or three-dimensional spheroids production, may provide substantial benefit with regard to subsequent vascularization in vivo due to induced growth factor production. In this narrative review, derivatives of adipose tissue and the vascularization of biomaterials are addressed in a comprehensive approach, including several sizes of derivatives, such as whole fat flaps for soft tissue engineering, nanofat or stem cells, their secretome and exosomes. Taken together, it can be concluded that adipose tissue and its fractions down to the molecular level promote, enhance and support vascularization of biomaterials. Therefore, there is a high potential of the individual fat component to be used in regenerative medicine.
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Affiliation(s)
- Pranitha Kamat
- Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland; Department of Plastic Surgery and Hand Surgery, University of Zurich, Zurich, Switzerland
| | - Florian S Frueh
- Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland
| | - Michelle McLuckie
- Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland
| | - Nadia Sanchez-Macedo
- Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland
| | - Petra Wolint
- Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland
| | - Nicole Lindenblatt
- Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland
| | - Jan A Plock
- Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland; Department of Plastic Surgery and Hand Surgery, University of Zurich, Zurich, Switzerland
| | - Maurizio Calcagni
- Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland
| | - Johanna Buschmann
- Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland.
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Nanofat Cell Aggregates: A Nearly Constitutive Stromal Cell Inoculum for Regenerative Site-Specific Therapies. Plast Reconstr Surg 2020; 144:1079-1088. [PMID: 31454336 PMCID: PMC6818980 DOI: 10.1097/prs.0000000000006155] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Supplemental Digital Content is available in the text. Recent technology developed by Tulip Medical Products allows clinicians to mechanically disaggregate fat tissue into small fat particles known as nanofat. The present study aimed to evaluate the cell yield obtained from nanofat generation in comparison to traditional methods involving enzymatic dissociation (stromal vascular fraction).
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Discussion: Nanofat Cell Aggregates: A Nearly Constitutive Stromal Cell Inoculum for Regenerative Site-Specific Therapies. Plast Reconstr Surg 2020; 144:1089-1090. [PMID: 31688755 DOI: 10.1097/prs.0000000000006186] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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Grünherz L, Sanchez-Macedo N, Frueh FS, McLuckie M, Lindenblatt N. Nanofat applications: from clinical esthetics to regenerative research. CURRENT OPINION IN BIOMEDICAL ENGINEERING 2019. [DOI: 10.1016/j.cobme.2019.07.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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