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23 pages, 4821 KB  
Article
Histological Remodeling of Irradiated Postmastectomy Breast Tissue After Autologous Fat Grafting: A Prospective Paired Tru-Cut Biopsy Study
by Razvan George Bogdan, Alina Helgiu, Anca Maria Cimpean, Mara Nicolau, Rodica Elena Heredea and Zorin Petrisor Crainiceanu
Med. Sci. 2026, 14(2), 180; https://doi.org/10.3390/medsci14020180 - 2 Apr 2026
Viewed by 333
Abstract
Background/Objectives: Radiotherapy following mastectomy induces persistent structural alterations in the chest wall, including fibrosis, extracellular matrix disorganization, and vascular changes that compromise reconstructive outcomes. Although autologous fat grafting is widely used to improve tissue quality in irradiated breasts, direct human histological evidence [...] Read more.
Background/Objectives: Radiotherapy following mastectomy induces persistent structural alterations in the chest wall, including fibrosis, extracellular matrix disorganization, and vascular changes that compromise reconstructive outcomes. Although autologous fat grafting is widely used to improve tissue quality in irradiated breasts, direct human histological evidence remains limited. The aim of this prospective pilot study was to evaluate intra-patient histological remodeling in irradiated postmastectomy breast tissue before and 4 months after autologous fat grafting using paired core needle biopsies. This study should be considered a hypothesis-generating histological pilot study. Methods: Five female patients with prior mastectomy and adjuvant radiotherapy underwent Tru-Cut core needle biopsy of irradiated chest wall tissue before lipofilling and at approximately four months (range between 3 and 12 months) post-procedure. Specimens were processed using formalin fixation, paraffin embedding, and hematoxylin and eosin staining. Histological assessment focused on collagen density, stromal organization, vascular structures, inflammatory infiltrate, and adipocyte integration. Comparative intra-patient analysis was performed descriptively. Results: Baseline biopsies demonstrated consistent post-radiation alterations, including collagen compaction, stromal disorganization, perivascular fibrosis, and variable inflammatory infiltrate. Post-lipofilling specimens showed heterogeneous remodeling characterized by focal collagen fiber insertion between adipocytes, areas of immature connective tissue formation, and variable preservation of adipose architecture. The extent and pattern of remodeling differed among patients. Inflammatory activity decreased or remained mild in most cases. Conclusions: Autologous fat grafting in irradiated postmastectomy tissue is associated with measurable histological remodeling. Structural adaptation appears heterogeneous and patient-specific, suggesting a dynamic multi-stage process rather than uniform regeneration. Further studies incorporating quantitative and molecular analyses are required to clarify the mechanisms underlying these changes. Full article
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18 pages, 2693 KB  
Article
Rubus fruticosus Fruit Extract Enhances the Pro-Adipogenic Program During Adipocyte Differentiation
by Emilio Rubio, Silvia Benito-Martínez, Manuel Reina, Claudia Müller-Sánchez, Jordi Bosch, David Manzano and Miguel Perez-Aso
Cosmetics 2026, 13(2), 82; https://doi.org/10.3390/cosmetics13020082 - 1 Apr 2026
Viewed by 476
Abstract
Although blackberries are associated with health benefits, their impact on adipocyte biology remains poorly understood. Here, we investigated the effect of a blackberry extract (Rubus fruticosus fruit extract, RFE) on adipogenesis and lipolysis in the 3T3-L1 cell model and characterized its transcriptomic [...] Read more.
Although blackberries are associated with health benefits, their impact on adipocyte biology remains poorly understood. Here, we investigated the effect of a blackberry extract (Rubus fruticosus fruit extract, RFE) on adipogenesis and lipolysis in the 3T3-L1 cell model and characterized its transcriptomic response. Adipogenesis and lipolysis were assessed by Oil Red O and AdipoRed™ staining and glycerol release, respectively. RNA-Seq analysis was processed with the PIGx pipeline, and differential gene expression was evaluated with edgeR. RFE strongly promoted adipogenesis, increasing Oil Red O staining by 29% (n = 3, p < 0.01), and showed anti-lipolytic activity, reducing glycerol release by 51% (n = 3, p < 0.05). Whole-transcriptome analysis revealed that RFE significantly regulated 4904 genes, enhancing the adipogenic program. Functional profiling identified metabolic pathways influenced by RFE, including those related to lipid biosynthesis. Notably, RFE also modulated extracellular matrix (ECM) pathways, suggesting a shift toward a less fibrotic microenvironment. These findings indicate that RFE promotes subcutaneous adipose tissue expansion while supporting ECM remodeling, favoring healthy adipose growth and reduced fibrosis. To our knowledge, this is the first evidence that RFE simultaneously stimulates adipocyte differentiation and ECM remodeling. Overall, RFE emerges as a promising active ingredient for lipofilling cosmetic applications aimed at improving adipose tissue volume and quality. Full article
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19 pages, 996 KB  
Article
Bleomycin-Induced Subcutaneous Fibrosis and Autologous Fat Graft Remodeling Assessed by Ultrasonography in a Rat Experimental Model
by Razvan George Bogdan, Anca Maria Cimpean, Alina Helgiu, Mara Nicolau, Ioan Cătălin Bodea, Rodica Elena Heredea and Zorin Petrisor Crainiceanu
Bioengineering 2026, 13(4), 390; https://doi.org/10.3390/bioengineering13040390 - 27 Mar 2026
Viewed by 464
Abstract
Radiation-associated soft tissue fibrosis represents a progressive structural remodeling process characterized by extracellular matrix accumulation, septal thickening, and reduced tissue compliance, which complicates reconstructive interventions. Reliable longitudinal experimental frameworks capable of non-invasive structural monitoring remain limited. This study aimed to develop and implement [...] Read more.
Radiation-associated soft tissue fibrosis represents a progressive structural remodeling process characterized by extracellular matrix accumulation, septal thickening, and reduced tissue compliance, which complicates reconstructive interventions. Reliable longitudinal experimental frameworks capable of non-invasive structural monitoring remain limited. This study aimed to develop and implement a standardized ultrasonographic protocol for the evaluation of bleomycin-induced subcutaneous fibrosis and to assess remodeling dynamics following autologous fat grafting in a rat model. Twenty-two adult female Wistar rats were included. Subcutaneous fibrosis was induced using submaximal bleomycin administration (1 mg/kg/day for three consecutive days). High-frequency ultrasonography (12 MHz) was performed at baseline (Day 0), post-bleomycin (Day 17), and post-lipofilling (Day 31). A predefined semi-quantitative 0–3 scoring system was applied to characterize global echogenicity, septal thickening, and architectural organization. At Day 17, all animals demonstrated structural alteration with a mean score of 2.15 ± 0.58. At Day 31, the mean score decreased to 1.50 ± 0.50, with complete disappearance of high-grade architectural disorganization (score 3). Focal hypoechoic areas consistent with graft integration were observed in 88.9% of animals without ultrasonographic signs of necrosis or fluid collection. This standardized imaging-based framework enables reproducible longitudinal monitoring of early-stage subcutaneous fibrotic remodeling and provides a non-invasive tool for evaluating regenerative interventions in translational soft tissue engineering research. Full article
(This article belongs to the Section Regenerative Engineering)
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13 pages, 1113 KB  
Article
Hybrid Breast Reconstruction Revisited: Patient-Reported Outcomes Following Fat Grafting
by Ioan Constantin Pop, Maximilian Vlad Muntean, Vlad Alexandru Gata, Radu Alexandru Ilies, Delia Nicoara, Claudiu Ioan Filip, Vasile Pop and Patriciu Andrei Achimas-Cadariu
J. Clin. Med. 2026, 15(3), 1158; https://doi.org/10.3390/jcm15031158 - 2 Feb 2026
Cited by 1 | Viewed by 410
Abstract
Background/Objectives: Hybrid breast reconstruction (HBR), which combines implant-based reconstruction with autologous fat grafting (lipofilling), has emerged as a promising approach for improving both aesthetic and functional outcomes following mastectomy. This study aimed to evaluate patient-reported outcomes using the BREAST-Q questionnaire before and [...] Read more.
Background/Objectives: Hybrid breast reconstruction (HBR), which combines implant-based reconstruction with autologous fat grafting (lipofilling), has emerged as a promising approach for improving both aesthetic and functional outcomes following mastectomy. This study aimed to evaluate patient-reported outcomes using the BREAST-Q questionnaire before and after lipofilling, focusing on aesthetic satisfaction, physical well-being, and quality of care. Methods: This before–after study included patients who underwent prepectoral implant-based reconstruction followed by one session of lipofilling between November 2024 and May 2025. The BREAST-Q questionnaire was administered preoperatively and at three months postoperatively. Statistical analyses were conducted to compare changes across aesthetic, functional, and care-related domains. Results: A total of 96 patients completed both pre- and postoperative questionnaires. Statistically significant improvements (p < 0.01) were observed in most aesthetic and psychosocial parameters, including satisfaction with breast appearance (Q1), psychosocial well-being (Q2), sexual well-being (Q4), and satisfaction with surgical outcomes (Q5). Physical symptoms such as discomfort (Q3) decreased significantly postoperatively. Satisfaction with medical care remained high, with minor improvements noted. No oncologic recurrences were reported. Conclusions: Hybrid breast reconstruction using fat grafting after implant placement offers significant benefits in terms of aesthetics, symptom relief, and patient satisfaction. It is a safe and effective procedure that can be widely integrated into clinical practice, provided that patient selection and technique are carefully considered. Full article
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10 pages, 991 KB  
Article
Is Lipofilling Predictable? Factors Associated with Delayed Lipofilling for Rippling After Prepectoral Direct-to-Implant Breast Reconstruction
by Marco Franchello, Gianluca Marcaccini, Claudia Chiarini, Roberto Cuomo and Diletta Maria Pierazzi
Surgeries 2026, 7(1), 18; https://doi.org/10.3390/surgeries7010018 - 26 Jan 2026
Viewed by 501
Abstract
Background/Objectives: Prepectoral direct-to-implant reconstruction is widely used, but implant rippling often necessitates lipofilling. This study aimed to identify preoperative and perioperative factors associated with delayed lipofilling. Methods: A retrospective cohort of consecutive patients who underwent immediate prepectoral implant reconstruction (April 2023–September 2024) was [...] Read more.
Background/Objectives: Prepectoral direct-to-implant reconstruction is widely used, but implant rippling often necessitates lipofilling. This study aimed to identify preoperative and perioperative factors associated with delayed lipofilling. Methods: A retrospective cohort of consecutive patients who underwent immediate prepectoral implant reconstruction (April 2023–September 2024) was analyzed. Demographic data, BMI, smoking, comorbidities, oncologic treatments, surgical factors, and tumor location were recorded. Patients were divided according to whether delayed lipofilling was required. Univariate analysis was performed using Mann–Whitney U and Fisher’s exact tests. Results: Fifty-eight patients were included; approximately one-third required lipofilling. Patients who underwent lipofilling were younger and had lower BMI than those who did not. Tumor location was strongly associated with the outcome: upper inner quadrant tumors were consistently linked to delayed lipofilling, whereas upper outer quadrant tumors were more frequently observed in the group not requiring revision. Smoking history and planned radiotherapy showed nonsignificant trends toward higher lipofilling rates. No differences were found for diabetes or corticosteroid therapy. Conclusions: Younger age, low BMI, and tumor location, particularly in the upper inner quadrant, were key factors associated with delayed lipofilling after prepectoral reconstruction. These variables may support preoperative counseling and follow-up planning to better anticipate secondary procedures and optimize aesthetic outcomes. Full article
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11 pages, 562 KB  
Article
Symptomatic Outcomes After Autologous Fat Grafting in Irradiated Postmastectomy Chest Wall
by Razvan George Bogdan, Mara Nicolau, Alina Helgiu and Zorin Petrisor Crainiceanu
Healthcare 2026, 14(2), 281; https://doi.org/10.3390/healthcare14020281 - 22 Jan 2026
Cited by 1 | Viewed by 362
Abstract
Background/Objectives: Radiotherapy of the chest wall after mastectomy frequently leads to fibrosis, reduced tissue elasticity, erythema, pain and chronic skin-related symptoms that complicate reconstructive strategies. Autologous fat grafting has been proposed as a regenerative option for radiation induced soft tissue damage, but clinical [...] Read more.
Background/Objectives: Radiotherapy of the chest wall after mastectomy frequently leads to fibrosis, reduced tissue elasticity, erythema, pain and chronic skin-related symptoms that complicate reconstructive strategies. Autologous fat grafting has been proposed as a regenerative option for radiation induced soft tissue damage, but clinical data focused on patient-reported symptoms remain limited. The objective of this study was to describe symptomatic and clinical changes after autologous fat grafting in irradiated postmastectomy chest wall tissue. Methods: This pilot observational study included five female patients with a history of mastectomy followed by adjuvant chest wall radiotherapy. All patients underwent a single session of standard autologous fat grafting without adipose derived stem cell enrichment. Patient-reported symptoms, including pruritus, local discomfort, burning sensation and erythema, were recorded preoperatively and at six months using a standardized 0 to 5 scale. Scar pliability was assessed by two experienced physicians using the same scale. Only descriptive statistical analysis was performed. Results: All patients demonstrated lower postoperative symptom scores at six months. Mean reductions were observed for erythema (71.4 percent), burning sensation (61.1 percent) and pruritus (57.1 percent). Local discomfort decreased by 33.3 percent. Mean scar pliability scores increased from 2.2 to 3.2. No postoperative complications, such as infection, fat necrosis or oil cyst formation, were recorded. All patients completed the six month follow up. Conclusions: In this small pilot observational study, autologous fat grafting was well tolerated and associated with descriptive improvement of patient-reported symptoms and scar pliability in irradiated postmastectomy chest wall tissue. These findings suggest a potential symptomatic benefit of fat grafting, while larger studies with objective imaging and histological correlation are required to confirm efficacy and durability. Full article
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12 pages, 243 KB  
Article
Long-Term Outcome in Implant Breast Reconstruction and Radiotherapy: The Role of Fat Grafting
by Alessia De Col, Francesco Buttarelli, Melissa Akuma, Ferruccio Paganini and Anna Scevola
J. Clin. Med. 2025, 14(21), 7569; https://doi.org/10.3390/jcm14217569 - 25 Oct 2025
Cited by 3 | Viewed by 1365
Abstract
Background: Capsular contracture remains one of the most challenging complications of implant-based breast reconstruction, particularly in patients undergoing postmastectomy radiotherapy (PMRT). Autologous fat grafting has been proposed as a regenerative strategy to mitigate radiation-induced damage, but long-term data are limited. Methods: We retrospectively [...] Read more.
Background: Capsular contracture remains one of the most challenging complications of implant-based breast reconstruction, particularly in patients undergoing postmastectomy radiotherapy (PMRT). Autologous fat grafting has been proposed as a regenerative strategy to mitigate radiation-induced damage, but long-term data are limited. Methods: We retrospectively reviewed women who underwent two-stage implant-based breast reconstruction followed by PMRT (50 Gy in 25 fractions) between 2010 and 2021 at Ospedale Sant’Anna, Como. Eligible patients subsequently received at least one session of autologous fat grafting after radiotherapy. Primary outcome was the incidence and severity of capsular contracture; secondary outcomes included the need for salvage autologous reconstruction, oncologic safety, and patient-reported satisfaction. Results: Thirty-two patients met inclusion criteria. The mean age was 56.1 years, and mean BMI was 23.8 kg/m2. All underwent submuscular two-stage reconstruction with anatomically shaped implants (mean volume 336 cc). Patients received an average of 1.7 fat grafting sessions (mean cumulative volume 180 cc). At a mean follow-up of 7.7 years, capsular contracture occurred in 6 patients (18.8%): 4 with Baker grade III and 2 with Baker grade II. No cases of severe (grade IV) contracture were observed. Importantly, no patient required salvage autologous reconstruction, and no local recurrences were recorded. Minor donor-site complications (transient edema or ecchymosis) occurred in 18.7% of patients. Subjective satisfaction was uniformly high, with reported improvements in breast softness and contour. Conclusions: Fat grafting appears to be a safe and effective adjunct in maintaining implant-based breast reconstruction after radiotherapy. In this long-term series, lipofilling was associated with a lower incidence of capsular contracture compared with historical rates, absence of severe contracture, and no oncologic events. For selected patients who are not candidates for autologous reconstruction, fat grafting may represent a valuable strategy to preserve implant viability, improve tissue quality, and reduce the need for salvage procedures. Full article
15 pages, 1446 KB  
Systematic Review
Histological and Immunohistochemical Characteristics of Mechanically Processed Adipose Tissue: A Systematic Review and Meta-Analysis
by Tom Schimanski, Rafael Loucas, Marios Loucas, Vanessa Brébant, Alexandra Anker, Silvan Klein, Sophia Theresa Diesch, Andrea Pagani and Lukas Prantl
Cells 2025, 14(21), 1664; https://doi.org/10.3390/cells14211664 - 23 Oct 2025
Viewed by 1255
Abstract
Background: Mechanical processing techniques are commonly employed to prepare adipose tissue for clinical applications in reconstructive and aesthetic procedures. However, their histological and immunohistochemical impact on adipose tissue remains incompletely characterized. Purpose: This systematic review aims to investigate the impact of mechanical processing [...] Read more.
Background: Mechanical processing techniques are commonly employed to prepare adipose tissue for clinical applications in reconstructive and aesthetic procedures. However, their histological and immunohistochemical impact on adipose tissue remains incompletely characterized. Purpose: This systematic review aims to investigate the impact of mechanical processing on the histological and immunohistochemical properties of adipose tissue. Methods: A systematic search was conducted using PubMed, Ovid, and Cochrane Library databases, with publications up to December 2024, employing Boolean operators (“mechanically processed” OR “lipoaspirate” OR “fat graft” OR “gauze rolling” OR “decantation” OR “coleman fat” OR “celt” OR “nanofat” OR “lipofilling” OR “human fat”) AND (“histol*”). Included were English-language studies or studies with a recognized English translation which had been subject to peer review and reported quantitative or qualitative markers of mechanically processed human adipose tissue with histology or immunohistochemistry. Risk of Bias was assessed with the OHAT score. Results: A total of 15 studies (n = 15) were included. In 13 of 15 studies (87%), mechanically processed adipose tissue demonstrated an increased stromal vascular fraction (SVF) cell density compared to unprocessed fat. Twelve studies (80%) reported improved preservation of the extracellular matrix (ECM), while 11 studies (73%) observed a reduction in mature adipocytes. Immunohistochemical analyses in 10 studies (67%) revealed elevated expression of vascular markers (CD31, CD34) and perilipin. Adverse histological features such as oil cysts, fibrosis, and inflammatory infiltrates were reduced in 9 studies (60%). Considerable heterogeneity in processing techniques and staining protocols precluded meta-analysis. Conclusions: Mechanical processing of adipose tissue is associated with favorable histological and immunohistochemical profiles, including increased SVF cell density, improved ECM preservation, and reduced inflammatory and fibrotic features. These findings support the potential of mechanical processing to enhance graft quality; however, standardization of techniques and evaluation protocols is needed to strengthen clinical translation. Full article
(This article belongs to the Special Issue Adipose Tissue Functioning in Health and Diseases)
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15 pages, 2434 KB  
Article
Hybrid Fractional Laser and Autologous Lipofilling: A Synergistic Strategy for Functional and Aesthetic Scar Remodeling
by Gabriele Delia, Lucia Quattrocchi, Pietro Micieli, Damiano Tambasco, Roberta Albanese and Fabiana Battaglia
J. Clin. Med. 2025, 14(19), 6708; https://doi.org/10.3390/jcm14196708 - 23 Sep 2025
Cited by 1 | Viewed by 1192
Abstract
Background: Scar management remains a significant challenge in plastic and reconstructive surgery, particularly when addressing atrophic, retractile, or fibrotic scars. Autologous fat grafting and hybrid fractional laser therapy have independently shown efficacy in improving scar quality. This study aims to evaluate the synergistic [...] Read more.
Background: Scar management remains a significant challenge in plastic and reconstructive surgery, particularly when addressing atrophic, retractile, or fibrotic scars. Autologous fat grafting and hybrid fractional laser therapy have independently shown efficacy in improving scar quality. This study aims to evaluate the synergistic effect of their combination on clinical and functional scar outcomes. Methods: A prospective, comparative study was conducted on patients with cutaneous scars of various etiologies. Participants were treated with either hybrid fractional laser therapy alone (CO2 and 1570 nm Erbium-glass wavelengths) or a combined protocol of laser plus autologous lipofilling. Clinical outcomes were assessed at baseline and at 30, 60, and 90 days post-treatment using the Vancouver Scar Scale (VSS), patient satisfaction scores, and Visual Analog Scale (VAS) for pain and discomfort. Results: Patients receiving the combined treatment demonstrated significantly greater improvement in scar pigmentation, elasticity, pliability, and thickness compared to those treated with laser alone. Subjective symptoms, including pain and itching, were also more effectively alleviated. The volumetric and regenerative properties of adipose tissue, particularly its content of adipose-derived stem cells (ADSCs) and stromal vascular fraction (SVF), likely contributed to the enhanced outcomes observed. Conclusions: The combination of hybrid fractional laser therapy and autologous lipofilling offers a superior therapeutic strategy for scar remodeling compared to laser monotherapy. This integrated regenerative approach addresses both structural and biological aspects of scar tissue, making it a valuable protocol for personalized and effective scar management. Further randomized trials with larger sample sizes and histological validation are warranted to confirm these preliminary findings and refine therapeutic protocols. Full article
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14 pages, 1994 KB  
Article
Enhancing Breast Reconstruction with Bovine Pericardium: A Preliminary STEP (Surgical Techniques and Efficacy in Pericardium Use) Towards Improved Outcomes
by Donato Casella, Nicola Rocco, Gianluigi Luridiana, Marco Marcasciano, Irene Zerini, Silvia Sordi, Alessandro Neri, Giuseppe Catanuto, Pietro Maria Ferrando and Juste Kaciulyte
J. Clin. Med. 2025, 14(17), 6296; https://doi.org/10.3390/jcm14176296 - 6 Sep 2025
Cited by 1 | Viewed by 1267
Abstract
Background/Objectives: In pre-pectoral breast reconstruction, both synthetic meshes (SM) and acellular dermis or pericardium matrixes (ADM/APM) present drawbacks that can be prevented with targeted device choosing. In daily practice, the authors wrap the implant with a human-derived ADM (hADM) when they found [...] Read more.
Background/Objectives: In pre-pectoral breast reconstruction, both synthetic meshes (SM) and acellular dermis or pericardium matrixes (ADM/APM) present drawbacks that can be prevented with targeted device choosing. In daily practice, the authors wrap the implant with a human-derived ADM (hADM) when they found mastectomy flaps thinner than 1 cm. When hADM is not available, an APM is used. Here, the authors present their results with APM utilisation. Methods: From January to September 2024, patients undergoing pre-pectoral breast reconstruction with mastectomy flaps thinner than 1 cm were selected. Specifically, implants were wrapped in bovine pericardium (Exaflex—MAGGI Srl, TO, Italy). During a minimum 6 months follow-up, outcomes were recorded; in particular, rippling incidence was assessed with indication for secondary fat grafting. Results: Nineteen patients met the inclusion criteria. Average age was 54.4 years (range: 39–70), three of them were smokers (15.8%) and three were affected from diabetes or hypertension (15.8%). With one case bilateral, a total of 20 mastectomies were performed. Intra-operative mastectomy flaps’ thickness mean measure was 0.75 cm (range: 0.5–0.8). All of them underwent two-stage pre-pectoral IBR with APM covering the implant. During a mean follow-up of 9.5 months (range: 6–13), no major post-operative complications occurred and five cases (25%) presented rippling. Conclusions: With no consensus on the superiority of either biologic matrixes or SMs, the authors extended their patients’ selection tool to aid in the choice of peri-prosthetic device. The bovine APM use showed capacity of reducing secondary lipofilling interventions in patients with thin mastectomy flaps. Full article
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20 pages, 72348 KB  
Article
Integrated Fluidic Platform for Washing and Mechanical Processing of Lipoaspirate for Downstream Fat Grafting and Regenerative Applications
by David Zalazar, Jiayi Feng, Derek A. Banyard, Marzieh Aliaghaei, Alan D. Widgerow and Jered B. Haun
Bioengineering 2025, 12(9), 918; https://doi.org/10.3390/bioengineering12090918 - 26 Aug 2025
Viewed by 2156
Abstract
Autologous fat grafting of human lipoaspirate (LA) is increasingly used in reconstructive and cosmetic surgery for lipofilling and stem cell-rich “nanofat” reinjection for regenerative medicine. While commercial devices (e.g., REVOLVE and Puregraft) are available, many surgeons use non-standardized manual washing techniques, leading to [...] Read more.
Autologous fat grafting of human lipoaspirate (LA) is increasingly used in reconstructive and cosmetic surgery for lipofilling and stem cell-rich “nanofat” reinjection for regenerative medicine. While commercial devices (e.g., REVOLVE and Puregraft) are available, many surgeons use non-standardized manual washing techniques, leading to inconsistent graft retention (20–80%). Moreover, no system can unite washing directly with mechanical processing to produce a nanofat-like product directly from raw LA. We developed a novel preparation device (PD) that is designed for peristaltic pump-driven washing of LA and can be seamlessly combined with our previously developed Emulsification and Micronization Device (EMD) into an automated closed-loop platform. Human LA samples were washed with the PD and compared to standard manual washing via visual colorimetric analysis. We then evaluated the mechanical processing of PD-washed LA using our EMD and assessed cell count, viability, and stromal vascular fraction-derived subpopulations (i.e., mesenchymal stem cells, endothelial progenitor cells (EPCs), pericytes, transit-amplifying (TA) progenitor cells, and supra-adventitial adipose stromal cells). Recirculating LA through the PD for at least one minute resulted in sufficient mixing, producing LA with equivalent color and quality to manual washing. Integrating the EMD within a platform enabled both washing and mechanical processing under peristaltic flow, enriching key subpopulations compared to manual methods. Thus, our fluidic platform effectively washes LA in a closed-loop system, minimizing LA tissue manipulation and opportunity for contamination while also simplifying the workflow for mechanical processing. Further refinement and automation of this platform would enhance the reproducibility and quality of small-volume fat grafts, cell-assisted lipotransfer, and stem/progenitor cell injections to promote wound healing and angiogenesis. Full article
(This article belongs to the Special Issue Regenerative Technologies in Plastic and Reconstructive Surgery)
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15 pages, 2310 KB  
Article
CELTPLUS Fat Increases the Metabolic Activity as Well as the SVF-Yield Significantly When Compared to CELT Fat, Even After Cryopreservation with DMSO
by Tom Schimanski, Lukas Prantl, Andreas Eigenberger, Oliver Felthaus, Rafael Loucas, Kirsten Utpatel and Kerstin Steer
Cells 2025, 14(16), 1270; https://doi.org/10.3390/cells14161270 - 17 Aug 2025
Cited by 1 | Viewed by 1309
Abstract
Lipofilling has far more applications than cosmetic surgery alone. Due to its high content of stromal vascular fraction (SVF) cells, lipoaspirate can also be used to treat wounds, as its cellular components may accelerate wound healing. Using our CELTPLUS protocol, we can [...] Read more.
Lipofilling has far more applications than cosmetic surgery alone. Due to its high content of stromal vascular fraction (SVF) cells, lipoaspirate can also be used to treat wounds, as its cellular components may accelerate wound healing. Using our CELTPLUS protocol, we can increase the number of SVF cells per volume. Unfortunately, some patients require more than one treatment to achieve an optimal outcome, but would unnecessarily suffer from repeated liposuction. Therefore, our objective was to test whether cryopreserving CELTPLUS fat could offer a solution, potentially avoiding the need for repeated liposuction procedures. DMSO was used as a cryoprotective agent for proof-of-principle testing, although other non-toxic cryoprotective agents should be considered in the future. The rest of our freezing protocol is a clinically friendly attempt to facilitate the translation into clinical practice. We tested the cryopreserved tissue using histological evaluation, metabolism measurement, SVF cell yield estimation, PCRs from both whole tissue and from cultured SVF cells, and Oil Red “O” staining. We found that freezing CELTPLUS fat with DMSO yields better results than without cryoprotection in all evaluated methods. Until non-toxic cryoprotective agents are tested on CELTPLUS fat, we do not recommend initiating animal or human testing. Full article
(This article belongs to the Special Issue Adipose-Derived Stem Cells for Tissue Regeneration)
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19 pages, 586 KB  
Systematic Review
Upper Eyelid Static Surgical Approaches for the Treatment of Facial Palsy-Induced Lagophthalmos: A Systematic Review
by Giovanni Ottonelli, Jacopo Celada Ballanti, Alessandro Gaeta, Gianmaria Barone, Novella Montericcio and Alessandra Di Maria
J. Clin. Med. 2025, 14(13), 4688; https://doi.org/10.3390/jcm14134688 - 2 Jul 2025
Cited by 2 | Viewed by 3745
Abstract
Background: Incomplete eyelid closure and lagophthalmos due to facial nerve palsy are significant functional and aesthetic concerns often requiring surgical correction. The aim of this systematic review is to quantitatively assess the efficacy, safety, and patient satisfaction associated with gold or platinum [...] Read more.
Background: Incomplete eyelid closure and lagophthalmos due to facial nerve palsy are significant functional and aesthetic concerns often requiring surgical correction. The aim of this systematic review is to quantitatively assess the efficacy, safety, and patient satisfaction associated with gold or platinum weight implantation, autologous fat grafting (lipofilling), and müllerectomy. Methods: A systematic review was performed following PRISMA guidelines, searching PubMed, Embase, Cochrane Library, Web of Science, and Scopus up to March 2025. Studies included clinical data on surgical correction for incomplete eyelid closure in facial palsy, reporting functional, anatomical, and satisfaction outcomes. Quality was assessed using the Newcastle–Ottawa Scale (NOS) and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: Twenty-six studies including a total of 1205 patients were included. Gold/platinum weight implantation achieved complete or near-complete eyelid closure in 83–92% of cases, with a reduction in lagophthalmos to <1 mm. Complication rates ranged from 5–15% (mainly extrusion/migration), and patient satisfaction averaged 7.9/10. Lipofilling showed persistent benefit in 77% of cases, with 9–20% requiring repeat procedures and 10–12% experiencing minor complications. Müllerectomy yielded symptomatic improvement or resolution in 92% of cases, with a mean lagophthalmos reduction of 1.18 mm. Conclusions: Gold or platinum weight implantation provides the most reliable improvement for severe upper eyelid dysfunction in facial palsy. Lipofilling is a viable autologous alternative, while müllerectomy is effective in selected cases. Further prospective comparative trials are needed to refine surgical selection and optimize outcomes. Full article
(This article belongs to the Section Ophthalmology)
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14 pages, 1059 KB  
Systematic Review
Role of Hyaluronic Acid in Post-Blepharoplasty Volume Restoration and Complication Management: A Systematic Review
by Alaa Safia, Uday Abd Elhadi, Shlomo Merchavy, Ramzy Batheesh and Naji Bathish
J. Clin. Med. 2025, 14(13), 4572; https://doi.org/10.3390/jcm14134572 - 27 Jun 2025
Viewed by 3106
Abstract
Background: Hyaluronic acid (HA) has emerged as a favored adjunct to restore volume after blepharoplasty and is very effective in the treatment of postoperative hollowness, sagging, and asymmetry. Its efficacy, rate of complications, and optimal injection technique are different in different clinical studies. [...] Read more.
Background: Hyaluronic acid (HA) has emerged as a favored adjunct to restore volume after blepharoplasty and is very effective in the treatment of postoperative hollowness, sagging, and asymmetry. Its efficacy, rate of complications, and optimal injection technique are different in different clinical studies. Hyaluronidase has been studied by diverse methods in the treatment of HA complications, including chronic edema and surgical distortion. This study critically evaluated the efficacy, safety, and technical aspects of HA in the context of blepharoplasty outcomes. Methods: A systematic review was performed to evaluate the use of HA and hyaluronidase for post-blepharoplasty volume rejuvenation and the treatment of complications. Studies describing HA injection technique, time interval between blepharoplasty and injection, volumetric maintenance, complication rates, esthetic and functional results, and patient satisfaction scores were considered. Risk of bias was estimated with the ROBINS-I tool. Results: Sample sizes across the five included studies ranged from 5 to 109 patients, and follow-up intervals ranged from 1 month to 7 years. The age of patients ranged from 31 to 76 years, and females accounted for 86% of the participants in some studies. Injection of HA successfully restored meaningful volume, with retention persisting for over 12 months in the majority of cases. HA preoperative injection caused significant patient satisfaction in a short duration and was not associated with severe complications; delayed injection caused slight distortions in some revision operations. Lipofilling showed a reduced rate of complications (12%) compared with isolated blepharoplasty (20%), suggesting its utility as an adjuvant procedure of volume restoration. Hyaluronidase successfully treated recalcitrant edema, with improvements ranging from 50% to 100%, while the application of adjuvant RF microneedling caused complete remission (100%) in subjects with multiple treatments. The application of ultrasound imaging made measurements more precise, although methods of clinical assessment were significantly heterogeneous among the studies. Conclusions: HA displayed efficacy in terms of efficient volume restoration after blepharoplasty, especially when technique, time, and filler selection are meticulously optimized. In comparison to lipofilling, HA is seen as somewhat safer because of its reversibility and lower likelihood of adverse vascular events. Nonetheless, considerable variability in filler type, amount, timing of administration, and result evaluation constrains conclusive clinical recommendations. The use of hyaluronidase is an effective remedial approach for overcorrection or ongoing edema. Full article
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28 pages, 2589 KB  
Systematic Review
Histology and Immunohistochemistry of Adipose Tissue: A Scoping Review on Staining Methods and Their Informative Value
by Tom Schimanski, Rafael Loucas, Marios Loucas, Oliver Felthaus, Vanessa Brébant, Silvan Klein, Alexandra Anker, Konstantin Frank, Andreas Siegmund, Andrea Pagani, Sebastian Geis, Sophia Theresa Diesch, Andreas Eigenberger and Lukas Prantl
Cells 2025, 14(12), 898; https://doi.org/10.3390/cells14120898 - 14 Jun 2025
Cited by 6 | Viewed by 5325
Abstract
Background: Histological and immunohistochemical analyses of adipose tissue are essential for evaluating the quality and functionality of lipoaspirates in regenerative medicine and fat grafting procedures. These methods provide insights into tissue viability, cellular subtypes, and extracellular matrix (ECM) composition—all factors influencing graft retention [...] Read more.
Background: Histological and immunohistochemical analyses of adipose tissue are essential for evaluating the quality and functionality of lipoaspirates in regenerative medicine and fat grafting procedures. These methods provide insights into tissue viability, cellular subtypes, and extracellular matrix (ECM) composition—all factors influencing graft retention and clinical outcomes. Purpose: This scoping review aims to summarize the most commonly used staining methods and their applications in the histology and immunohistochemistry of adipose tissue. By exploring qualitative and quantitative markers, we seek to guide researchers in selecting the appropriate methodologies for addressing experimental and translational research. Methods: A systematic search was conducted using PubMed, Ovid, and the Cochrane Library databases from inception to 2024, employing Boolean operators (“lipoaspirate” OR “fat graft” OR “gauze rolling” OR “decantation” OR “coleman fat” OR “celt” OR “nanofat” OR “lipofilling” OR “human fat” AND “histol*”). Studies were included if they utilized histology or immunohistochemistry on undigested human adipose tissue or its derivatives. The inclusion criteria focused on peer-reviewed, English-language studies reporting quantitative and qualitative data on adipose tissue markers. Results: Out of 166 studies analyzed, hematoxylin–eosin (H&E) was the most frequently employed histological stain (152 studies), followed by Masson Trichrome and Sudan III. Immunohistochemical markers such as CD31, CD34, and perilipin were extensively used to distinguish stromal vascular fraction (SVF) cells, adipocytes, and inflammatory processes. Studies employing semiquantitative scoring demonstrated enhanced comparability, particularly for fibrosis, necrosis, and oil cyst evaluation. Quantitative analyses focused on SVF cell density, mature adipocyte integrity, and ECM composition. Methodological inconsistencies, particularly in preparation protocols, were observed in 25 studies. Conclusions: This review highlights the critical role of histological and immunohistochemical methods in adipose tissue research. H&E staining remains the cornerstone for general tissue evaluation in the clinical context, while specialized stains and immunohistochemical markers allow for detailed analyses of specific cellular and ECM components in experimental research. Standardizing preparation and evaluation protocols will enhance interstudy comparability and support advancements in adipose tissue-based therapies. Full article
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