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15 pages, 1991 KB  
Review
Injectable Scaffolds for Adipose Tissue Reconstruction
by Valeria Pruzzo, Francesca Bonomi, Ettore Limido, Andrea Weinzierl, Yves Harder and Matthias W. Laschke
Gels 2026, 12(1), 81; https://doi.org/10.3390/gels12010081 - 17 Jan 2026
Viewed by 205
Abstract
Autologous fat grafting is the main surgical technique for soft tissue reconstruction. However, its clinical use with more extended volumes is limited by repeated procedures due to the little possibility of banking tissue, donor-site morbidity and unpredictable graft resorption rates. To overcome these [...] Read more.
Autologous fat grafting is the main surgical technique for soft tissue reconstruction. However, its clinical use with more extended volumes is limited by repeated procedures due to the little possibility of banking tissue, donor-site morbidity and unpredictable graft resorption rates. To overcome these problems, adipose tissue engineering has focused on developing injectable scaffolds. Most of them are hydrogels that closely mimic the biological, structural and mechanical characteristics of native adipose tissue. This review provides an overview of current injectable scaffolds designed to restore soft tissue volume defects, emphasizing their translational potential and future directions. Natural injectable scaffolds exhibit excellent biocompatibility but degrade rapidly and lack mechanical strength. Synthetic injectable scaffolds provide tunable elasticity and degradation rates but require biofunctionalization to support cell adhesion and tissue integration. Adipose extracellular matrix-derived injectable scaffolds are fabricated by decellularization of adipose tissue. Accordingly, they combine bio-mimetic structure with intrinsic biological cues that stimulate host-driven adipogenesis and angiogenesis, thus representing a translatable “off-the-shelf” alternative to autologous fat grafting. However, despite this broad spectrum of available injectable scaffolds, the establishment of clinically reliable soft tissue substitutes capable of supporting large-volume and long-lasting soft tissue reconstruction still remains an open challenge. Full article
(This article belongs to the Special Issue Hydrogels for Tissue Repair: Innovations and Applications)
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14 pages, 2178 KB  
Article
Autophagy Activation in Mesenchymal Stem Cells with Lithium Chloride and Trehalose: Implications for Regenerative Medicine
by Ali Fouad, Yasser ElSherbini, Elsayed Abdelhady and Mohamed Abdraboh
BioMed 2026, 6(1), 4; https://doi.org/10.3390/biomed6010004 - 16 Jan 2026
Viewed by 80
Abstract
Background/Objectives: Mesenchymal stem cells (MSCs) are deemed to be a highly safe model for autologous and allogeneic cellular therapy, owing to their inherent lack of HLA-DR expression, immunomodulatory properties, homing ability, and plasticity allowing differentiation into different cell types. The interest in [...] Read more.
Background/Objectives: Mesenchymal stem cells (MSCs) are deemed to be a highly safe model for autologous and allogeneic cellular therapy, owing to their inherent lack of HLA-DR expression, immunomodulatory properties, homing ability, and plasticity allowing differentiation into different cell types. The interest in activating autophagic signaling in MSCs has recently grown due to its significant potential in maintaining stemness, enhancing paracrine signaling, and providing therapeutic benefits for cancer and neurodegenerative diseases. This study aimed to explore the impact of autophagy induction on enhancing the therapeutic potential of MSCs by maintaining their plasticity and to assess different induction agents. Methods: In this study, MSCs were first extracted from the fat tissue of Sprague–Dawley (SD) rats and characterized phenotypically and molecularly by their positive expression of stemness markers CD29, CD106, and CD44, and their negative expression of hematopoietic surface markers CD14, CD34, and CD45, using a flow cytometry approach. Isolated MSCs were then treated separately with two FDA-approved autophagy inducers: Lithium Chloride and Trehalose, following assessment of autophagy activity. Results: Treated MSCs showed significant increases in autophagic activity at both the transcriptional and translational levels. The successful induction of autophagy in MSCs was confirmed through the elevated expression of autophagy-related genes such as ATG3, ATG13, ATG14, P62, and ULK1. These data were confirmed by the significant upregulation in LC3 protein expression and the formation of autophagosomes, which was detected using a transmission electron microscope. Furthermore, the expression of Oct4, Sox2, and Nanog genes was significantly enhanced after treatment with Trehalose and Lithium Chloride compared with untreated control MSCs which may indicate an upregulation of pluripotency. Meanwhile, Lithium Chloride and Trehalose did not significantly induce cellular apoptosis, indicated by the Bax/Bcl-2 expression ratio, and significantly decreased the expression of the antioxidant markers SOD and GPx. Conclusions: Treatment of MSCs with Trehalose and, in particular, Lithium Chloride significantly activated autophagic signaling, which showed a profound effect in enhancing cells’ pluripotency, reinforcing the usage of treated MSCs for autologous and/or allogenic cellular therapy. However, further in vivo studies for activating autophagy in cellular grafts should be conducted before their use in clinical trials. Full article
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10 pages, 1406 KB  
Article
Breast Reconstruction Using the Axillary-Approach Endoscopic Extended Latissimus Dorsi (Ax-eeLD) Flap
by Shinsuke Akita, Yoshihisa Yamaji, Haruka Maei, Kahoko Yamada, Nobuhiro Ando, Kentaro Kosaka, Hiroshi Fujimoto and Nobuyuki Mitsukawa
J. Clin. Med. 2026, 15(2), 703; https://doi.org/10.3390/jcm15020703 - 15 Jan 2026
Viewed by 99
Abstract
Background/Objectives: Although the endoscopic extended latissimus dorsi (eeLD) flap avoids dorsal scarring, a lateral thoracic incision is still required. We developed an axillary-approach endoscopic extended latissimus dorsi (Ax-eeLD) flap enabling harvest through a single 40-mm axillary incision and two 5-mm ports. This [...] Read more.
Background/Objectives: Although the endoscopic extended latissimus dorsi (eeLD) flap avoids dorsal scarring, a lateral thoracic incision is still required. We developed an axillary-approach endoscopic extended latissimus dorsi (Ax-eeLD) flap enabling harvest through a single 40-mm axillary incision and two 5-mm ports. This study evaluated its safety and feasibility and compared outcomes with conventional eeLD. Methods: Patients who underwent Ax-eeLD flap (study group) were retrospectively analyzed and compared with the patients who underwent conventional eeLD flap (control group, n = 15). The flap was elevated endoscopically via a single 40-mm axillary incision and two 5-mm ports, harvesting the entire latissimus dorsi muscle with its surrounding adipose tissue. Outcomes included incision length, operative time, complications, secondary fat grafting, and BREAST-Q scores. Results: Fifteen patients (post-mastectomy, n = 13; congenital hypoplasia, n = 2) underwent Ax-eeLD flap. All procedures used only the planned incisions without intraoperative complications. The study group had significantly shorter incisions than the control group (39 ± 1 mm vs. 89 ± 9 mm, p < 0.01). Operative times were similar between the groups. Eight patients developed seromas, all of which were resolved by outpatient aspiration. The frequency of postoperative cases requiring fat grafting did not differ significantly between the study and control groups (4 vs. 8; p = 0.26). BREAST-Q scores improved postoperatively and were similar between groups. Conclusions: Ax-eeLD flap enables minimally invasive harvest of the latissimus dorsi without lateral thoracic scarring. This retrospective case series supports technical feasibility and safety; further prospective studies with objective volume assessment are required. Full article
(This article belongs to the Special Issue New Clinical Advances in Breast Reconstruction)
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14 pages, 3646 KB  
Article
Mastectomy Reconstruction Techniques for Gender Diverse Breast Cancer and High Risk Patients: A Case Series and Literature Overview
by Thais Calderon, James T. Antongiovanni, Danielle J. Eble, Alisha L. Nguyen, Chizoba A. Mosieri, Andreea Gavrilescu, Sarah R. Goldsberry-Long, Rachel B. Lentz and Suzanne M. Inchauste
J. Clin. Med. 2026, 15(2), 441; https://doi.org/10.3390/jcm15020441 - 6 Jan 2026
Viewed by 261
Abstract
Background/Objectives: Assigned female at birth (AFAB) individuals who identify as transgender or gender-diverse (TGD) with concurrent breast cancer or high-risk genetic mutations represent a unique population, requiring consideration of oncologic and aesthetic goals. These patients sought chest masculinization with oncologic gender-affirming mastectomy [...] Read more.
Background/Objectives: Assigned female at birth (AFAB) individuals who identify as transgender or gender-diverse (TGD) with concurrent breast cancer or high-risk genetic mutations represent a unique population, requiring consideration of oncologic and aesthetic goals. These patients sought chest masculinization with oncologic gender-affirming mastectomy (OGAM) or non-binary reconstruction to alleviate gender dysphoria and treat their breast cancer. There is limited literature on surgical techniques in this patient population. Methods: A retrospective chart review of AFAB TGD adults (>18 years of age) who underwent OGAM or non-binary reconstruction at the University of Washington between 2019 and 2023 was conducted. All patients had a consultation with a plastic surgeon for reconstruction and a minimum of one year follow-up. Demographic data, oncologic status, post-operative complications, and revision surgical history were collected. Results: Eight AFAB TGD individuals met the inclusion criteria. The mean age at the time of mastectomy was 35.13 years (SD = 8.04), and the mean BMI was 29.88 (SD = 6.40). Indications for mastectomy included a breast cancer diagnosis (N = 4) or a strong family history of breast cancer or genetic predisposition (N = 4). Two (25%) patients underwent nipple-sparing mastectomies (NSM), two patients (25%) underwent skin-sparing mastectomy with Goldilocks reconstruction, and four patients (50%) underwent simple mastectomy (oncologic gender-affirming mastectomy), flat closure with free nipple graft (FNG). Two patients had staged nipple mastectomy with secondary nipple reduction and fat grafting. Six patients had immediate reconstruction, four (50%) patients underwent immediate double-incision OGAM with FNG, and two (25%) patients underwent Goldilocks procedures—one with and one without FNG. One patient (12.5%) experienced a surgical site infection, and three patients (37.5%) underwent revision surgery. No patients had positive margins following their mastectomy. Conclusions: This case series highlights the importance of a multidisciplinary and highly personalized approach for AFAB and TGD individuals undergoing oncologic gender-affirming mastectomy or non-binary reconstruction. We reviewed reconstructive options performed at our institution, demonstrating safe oncologic and reconstructive techniques that emphasized collaboration between breast and plastic surgeons. Full article
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19 pages, 8732 KB  
Article
Hypoxic Preconditioned Nanofat at 1% O2 for 24 h Loses Its Regenerative In Vivo Vascularization Capacity
by Francesca Bonomi, Ettore Limido, Andrea Weinzierl, Caroline Bickelmann, Emmanuel Ampofo, Yves Harder and Matthias W. Laschke
Cells 2026, 15(2), 100; https://doi.org/10.3390/cells15020100 - 6 Jan 2026
Viewed by 134
Abstract
Hypoxic preconditioning is increasingly explored to enhance the survival and vascularization of fat grafts. In this study, nanofat from donor mice was exposed to hypoxia (1% O2) for 24 h to investigate the effects of this preconditioning protocol on the viability, [...] Read more.
Hypoxic preconditioning is increasingly explored to enhance the survival and vascularization of fat grafts. In this study, nanofat from donor mice was exposed to hypoxia (1% O2) for 24 h to investigate the effects of this preconditioning protocol on the viability, gene expression and vascularization capacity of this mechanically processed fat derivative. Ex vivo analyses revealed that hypoxic preconditioning does neither affect apoptotic nor necrotic cell death within nanofat but significantly upregulates the expression of hypoxia-inducible factor (HIF)-1α and stromal cell-derived factor (SDF)-1 compared to non-preconditioned nanofat. Moreover, preconditioned nanofat exhibited a pro-angiogenic protein expression profile. For in vivo analyses, dermal substitutes were either seeded with preconditioned or non-preconditioned nanofat and transferred into dorsal skinfold chambers of mice to assess their vascularization by intravital fluorescence microscopy. Unexpectedly, implants seeded with preconditioned nanofat exhibited a significantly reduced functional microvessel density when compared to non-preconditioned controls. Immunohistochemical analyses also confirmed a lower microvessel density within the implants of the preconditioned group. These findings suggest that hypoxic preconditioning at 1% O2 for 24 h cannot be recommended for enhancing the regenerative in vivo vascularization capacity of nanofat. Therefore, milder preconditioning protocols with shorter periods of hypoxia or higher oxygen levels should be alternatively tested in future studies. Full article
(This article belongs to the Section Tissues and Organs)
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51 pages, 2219 KB  
Review
Integrative Migraine Therapy: From Current Concepts to Future Directions—A Plastic Surgeon’s Perspective
by Cristian-Sorin Hariga, Eliza-Maria Bordeanu-Diaconescu, Andrei Cretu, Dragos-Constantin Lunca, Catalina-Stefania Dumitru, Cristian-Vladimir Vancea, Florin-Vlad Hodea, Stefan Cacior, Vladut-Alin Ratoiu and Andreea Grosu-Bularda
Medicina 2026, 62(1), 50; https://doi.org/10.3390/medicina62010050 - 26 Dec 2025
Viewed by 438
Abstract
Migraine is a prevalent and disabling neurological disorder with multifactorial origins and complex clinical manifestations. While pharmacologic therapies remain the cornerstone of management, a growing body of evidence highlights the role of extracranial peripheral nerve compression as a significant contributor to migraine pathophysiology [...] Read more.
Migraine is a prevalent and disabling neurological disorder with multifactorial origins and complex clinical manifestations. While pharmacologic therapies remain the cornerstone of management, a growing body of evidence highlights the role of extracranial peripheral nerve compression as a significant contributor to migraine pathophysiology in selected patients. This recognition has expanded the therapeutic role of plastic surgery, offering anatomically targeted interventions that complement or surpass traditional medical approaches for refractory cases. From a plastic surgeon’s perspective, optimal migraine care begins with accurate identification of clinical patterns, trigger-site mapping, and the judicious use of diagnostic tools such as nerve blocks and botulinum toxin. Surgical decompression techniques, including endoscopic and open approaches, address compression of the supraorbital, supratrochlear, zygomaticotemporal, greater and lesser occipital, auriculotemporal, and intranasal contact-point trigger sites. Adjunctive strategies such as autologous fat grafting further enhance outcomes by providing neuroprotective cushioning and modulating local inflammation through adipose-derived stem cell activity. Recent advances, including neuromodulation technologies, next-generation biologics, and innovations in surgical visualization, underscore the ongoing shift toward precision-based, mechanism-driven therapy. As understanding of migraine heterogeneity deepens, the integration of surgical expertise with modern neuroscience offers a comprehensive and personalized therapeutic framework. Plastic surgeons, equipped with detailed knowledge of peripheral nerve anatomy and minimally invasive techniques, play an increasingly pivotal role in the multidisciplinary management of refractory migraine. Full article
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17 pages, 289 KB  
Systematic Review
Biomarkers of Sarcopenia and Sarcopenic Obesity in Renal Transplant Recipients: A Systematic Review and Evidence Quality Assessment
by Ioanna Soukouli, Thomas Karagkounis, Konstantinos S. Mylonas, Theofanis Kalathas, Kalliopi-Anna Poulia, Alexander Kokkinos and Smaragdi Marinaki
J. Clin. Med. 2025, 14(24), 8943; https://doi.org/10.3390/jcm14248943 - 18 Dec 2025
Viewed by 338
Abstract
Background: Sarcopenia and sarcopenic obesity are increasingly recognized in kidney transplant recipients (KTRs), yet their molecular underpinnings remain poorly defined. We sought to synthesize current evidence on biomarker associations with muscle loss and function in the post renal transplant setting. Methods: A comprehensive [...] Read more.
Background: Sarcopenia and sarcopenic obesity are increasingly recognized in kidney transplant recipients (KTRs), yet their molecular underpinnings remain poorly defined. We sought to synthesize current evidence on biomarker associations with muscle loss and function in the post renal transplant setting. Methods: A comprehensive search of PubMed/MEDLINE and Cochrane databases was conducted according to PRISMA guidelines. Studies evaluating biomarkers related to sarcopenia or sarcopenic obesity in adult and pediatric KTRs were included. Quality assessment was performed with the NHLBI tool. Results: Seven studies were included, encompassing 548 KTRs. Myostatin levels predicted sarcopenia in KTRs (cut-off: 390 pg/mL) and inversely correlated with Metabolic equivalent of Tasks (METs), handgrip strength (HGS), and graft performance. Although adiponectin was negatively correlated with body fat, its high-molecular-weight isoform was linked to lower muscle mass and long-term graft decline. Leptin was associated with sarcopenic obesity and lower estimated Glomerular Filtration Rate (eGFR). Insulin like Growth Factor-1 (IGF-1) independently predicted HGS but not muscle mass. Brain-derived neurotrophic factor (BDNF) levels predicted sarcopenia (cut off: 17.8 ng/mL) and reflected physical activity levels. Visfatin showed no association with sarcopenia but it was positively correlated with eGFR. Lastly, certain polymorphisms of Alpha-actinin-3 (ACTN3) were shown to genetically predispose to post-transplant sarcopenia. Conclusions: These emerging candidate biomarkers provide promising mechanistic insight into post-transplant muscle decline and may ultimately support more personalized risk assessment. Further validation is needed, and functional measures remain the most reliable clinical tools at present. Full article
6 pages, 2818 KB  
Interesting Images
Pulmonary Fat Embolism After Fat Grafting
by Xin Lu, Huadong Zhu and Yi Li
Diagnostics 2025, 15(24), 3214; https://doi.org/10.3390/diagnostics15243214 - 16 Dec 2025
Viewed by 372
Abstract
Fat embolism syndrome (FES) is a clinical syndrome in which the obstruction of small blood vessels by fat emboli triggers a systemic inflammatory response, leading to organ dysfunction. Due to a lack of specific laboratory tests and physical examination, FES is clinically underdiagnosed. [...] Read more.
Fat embolism syndrome (FES) is a clinical syndrome in which the obstruction of small blood vessels by fat emboli triggers a systemic inflammatory response, leading to organ dysfunction. Due to a lack of specific laboratory tests and physical examination, FES is clinically underdiagnosed. We report a case of a 39-year-old woman who presented with dyspnea that had developed after augmentation mammaplasty and vaginal tightening with autologous fat. Bedside transthoracic echocardiography (TTE) carried out in our emergency department evidently revealed right heart embolic material presumed to be fat. Based on echocardiography findings, combined with medical history and computed tomography pulmonary angiography images, a diagnosis of pulmonary fat embolism was made. This case presents valuable echocardiographic images and emphasizes the availability of bedside TTE in the diagnosis of fat embolism in a patient with dyspnea after plastic surgery, highlighting the value of bedside TTE in rapidly identifying pulmonary fat embolism. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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15 pages, 2974 KB  
Article
Augmenting Bone Formation by Implanting Dedifferentiated Fat Cell-Loaded Cotton-like Graft Materials in a Rat Bone Defect Model
by Jin Inoue, Tomohiko Kazama, Takahisa Okubo, Daisuke Akita, Yoshinori Arai, Yoshiyuki Hagiwara, Koichiro Kano, Masaki Honda and Taro Matsumoto
Bioengineering 2025, 12(12), 1364; https://doi.org/10.3390/bioengineering12121364 - 16 Dec 2025
Viewed by 398
Abstract
Bone graft materials frequently employed in dental implant placement procedures, including hydroxyapatite and β-tricalcium phosphate (β-TCP), are typically granular in form, which complicates their manipulation and contributes to extended treatment durations. A tissue engineering approach utilizing readily manageable biomaterials in conjunction with mesenchymal [...] Read more.
Bone graft materials frequently employed in dental implant placement procedures, including hydroxyapatite and β-tricalcium phosphate (β-TCP), are typically granular in form, which complicates their manipulation and contributes to extended treatment durations. A tissue engineering approach utilizing readily manageable biomaterials in conjunction with mesenchymal stem cells (MSCs) represents the most promising approach in dentistry. This study assessed the bone-augmenting capacity at bone defect sites in inbred rats by seeding dedifferentiated fat (DFAT) cells onto a cotton-like bone graft scaffold composed of β-TCP and poly(L-lactic-co- glycolide) (PLGA), which was subsequently wrapped around titanium. As a control, cotton-like bone graft material without cells was used and wrapped around and transplanted. Four weeks post-implantation, computed tomography (CT) images of the DFAT group revealed a 1.25-fold enhancement in hard tissue formation compared to the control group. Histological analysis revealed compact structure in a dark red color surrounding the cotton-like bone graft material was observed on the titanium surface of DFAT group. Histomorphometric analysis revealed that the amount of hard tissue generated in the DFAT group was approximately 2.5 times higher than that observed in the control group. Moreover, this mineralized tissue demonstrated properties analogous to those observed in cortical bone. Collectively, these findings indicate that the composite of DFAT cells and cotton-like bone graft material holds potential for bone augmentation applications and represents a promising approach for regenerative therapies within the orofacial region. Full article
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16 pages, 963 KB  
Review
Recent Advances in Localized Scleroderma
by Toshiya Takahashi, Takehiro Takahashi and Yoshihide Asano
Sclerosis 2025, 3(4), 40; https://doi.org/10.3390/sclerosis3040040 - 2 Dec 2025
Viewed by 1261
Abstract
Localized scleroderma (LSc), or morphea, is an autoimmune connective tissue disease causing inflammation and fibrosis of the skin and underlying tissues. While distinct from systemic sclerosis, its clinical presentation is highly diverse. This review summarizes recent advances in the understanding and management of [...] Read more.
Localized scleroderma (LSc), or morphea, is an autoimmune connective tissue disease causing inflammation and fibrosis of the skin and underlying tissues. While distinct from systemic sclerosis, its clinical presentation is highly diverse. This review summarizes recent advances in the understanding and management of LSc. Pathophysiological insights have evolved significantly; the somatic mosaicism hypothesis is now supported by the observation of all six of Happle’s classic lesion patterns in LSc. Furthermore, recent single-cell RNA sequencing has elucidated key cellular mechanisms, revealing an IFN-γ-driven pro-fibrotic crosstalk between T cells, dendritic cells, and specific inflammatory fibroblast subpopulations. The discovery of a rare monogenic form of LSc caused by a STAT4 gain-of-function mutation provides a powerful human model, solidifying the critical role of the JAK-STAT pathway. Clinically, LSc is classified into subtypes such as circumscribed, linear, and generalized morphea. Extracutaneous manifestations are common, particularly in juvenile LSc, and are associated with higher disease activity and reduced quality of life, necessitating a multidisciplinary approach. Management is becoming standardized, with methotrexate as the first-line systemic therapy for severe disease. For refractory cases, targeted treatments including abatacept, tocilizumab, and JAK inhibitors are emerging as promising options. In addition, reconstructive therapies like autologous fat grafting are crucial for managing atrophic sequelae. These recent advances are paving the way for more effective, targeted therapies to improve outcomes for patients with this complex disease. Full article
(This article belongs to the Special Issue Advances in Systemic Sclerosis Research in Japan)
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16 pages, 9263 KB  
Article
Immunohistochemical Characterization and CT-Derived Volume of Epicardial Adipose Tissue in Patients with Coronary Artery Disease
by Matija Furtula, Igor Zivkovic, Slobodan Micovic, Zoran Tabakovic, Gorica Vidovic, Zelimir Antonic, Jelica Vukmirovic, David Savic, Milovan Bojic, Branko Beleslin, Milan Dobric and Jelena Rakocevic
Cells 2025, 14(22), 1760; https://doi.org/10.3390/cells14221760 - 11 Nov 2025
Cited by 1 | Viewed by 2447
Abstract
Background: Epicardial adipose tissue (EAT) is a visceral fat depot surrounding the myocardium. It contributes to coronary artery disease (CAD) through local inflammation, while its metabolic activity, including the expression of uncoupling protein-1 (UCP-1) and incretin receptors (GLP-1R, GIPR), may exert protective effects. [...] Read more.
Background: Epicardial adipose tissue (EAT) is a visceral fat depot surrounding the myocardium. It contributes to coronary artery disease (CAD) through local inflammation, while its metabolic activity, including the expression of uncoupling protein-1 (UCP-1) and incretin receptors (GLP-1R, GIPR), may exert protective effects. The relationship between EAT immunohistochemical features and imaging-derived volume remains unclear. Methods: We prospectively studied 50 patients undergoing cardiac surgery: 25 with CAD undergoing coronary artery bypass grafting and 25 without CAD undergoing valve replacement. EAT samples were immunohistochemically stained for CD3, CD68, MPO, UCP-1, GLP-1R, and GIPR. Preoperative CT was used to quantify EAT volume. Results: Patients with CAD more frequently had higher CD3 immunopositivity compared to the control group (84.0 vs. 58.3%, p = 0.047), with no difference in MPO and CD68 immunoexpression. UCP-1 expression was elevated in CAD patients (p = 0.004), whereas GLP-1R and GIPR immunopositivity were similar. EAT volume did not differ between CAD and non-CAD patients (102.87 cm3 vs. 99.38 cm3, p = 0.964) but correlated modestly with BMI (rs = 0.325, p = 0.021). UCP-1 and GLP-1R immunopositivity, as well as larger LVEDD (left ventricular end-diastolic diameter), were positively associated with greater EAT volume. Conclusions: EAT in CAD exhibits increased T-cell infiltration and elevated UCP-1 expression, indicating an inflammatory yet metabolically active profile. Larger EAT volume was associated with UCP-1 and GLP-1R expression, underscoring the immunometabolic role of EAT in CAD. Full article
(This article belongs to the Special Issue Ischemic Heart Disease: From Cellular Level to Clinical Approaches)
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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
Viewed by 908
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 828
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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10 pages, 452 KB  
Article
Identifying Plasma Biomarkers That Predict Patient-Reported Outcomes Following Treatment for Trapeziometacarpal Osteoarthritis Using Machine Learning
by Mauro Maniglio, Moaath Saggaf, Nupur Purohit, Daniel Antflek, Jason S. Rockel, Mohit Kapoor and Heather L. Baltzer
Int. J. Mol. Sci. 2025, 26(20), 9856; https://doi.org/10.3390/ijms26209856 - 10 Oct 2025
Viewed by 730
Abstract
Osteoarthritis (OA) in the trapeziometacarpal joint (TM) is a prevalent form of hand OA, yet research on biomarkers specific to hand OA remains limited. This study aims to identify systemic plasma biomarkers at baseline in TM OA patients that are associated with patient-reported [...] Read more.
Osteoarthritis (OA) in the trapeziometacarpal joint (TM) is a prevalent form of hand OA, yet research on biomarkers specific to hand OA remains limited. This study aims to identify systemic plasma biomarkers at baseline in TM OA patients that are associated with patient-reported outcomes one year post-treatment. Blood samples and clinical data were collected prospectively from 143 TM OA patients undergoing conservative therapy, fat grafting, or surgery, with one-year follow-up. Supervised machine learning with Lasso regularization analyzed associations among 10 systemic biomarkers related to cartilage turnover, bone remodeling, pain, or lipid metabolism. Generalized estimating equation models evaluated baseline biomarker associations with one-year outcomes. Patients averaged 61 years, were mostly female (69%), and were primarily treated conservatively (47%). The machine learning model identified associations between outcomes and biomarkers, including PIIANP, Visfatin, adiponectin, and leptin. Adjusted analyses revealed baseline PIIANP associated with VAS, QuickDASH, and TASD improvements, while Visfatin correlated with VAS worsening. We could identify two different plasma markers that could predict the clinical outcome of TM OA treatment. Baseline PIIANP is associated with improvement, while Visfatin is associated with worsening in TM OA outcomes up to one year post-treatment. Further prospective studies are needed to confirm and solidify these findings. Full article
(This article belongs to the Special Issue Recent Advances in Osteoarthritis Pathways and Biomarker Research)
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20 pages, 1677 KB  
Article
Changes in Body Composition Compartments After Kidney Transplantation: A One-Year Prospective Study
by Emilia Ferrer-López, Raúl López-Blasco, Francisco Javier Rubio-Castañeda, Víctor Cantín-Lahoz, Juan José Aguilón-Leiva, María García-Magán, Carlos Navas-Ferrer, Isabel Blázquez-Ornat, María Teresa Fernández-Rodrigo, Isabel Antón-Solanas and Fernando Urcola-Pardo
J. Clin. Med. 2025, 14(20), 7131; https://doi.org/10.3390/jcm14207131 - 10 Oct 2025
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Abstract
Background/Objectives: Weight gain after kidney transplantation is frequent but heterogeneous, often accompanied by changes in body composition that influence long-term outcomes. This study analysed one-year changes in body compartments and their demographic and clinical determinants. Methods: A prospective cohort of 112 [...] Read more.
Background/Objectives: Weight gain after kidney transplantation is frequent but heterogeneous, often accompanied by changes in body composition that influence long-term outcomes. This study analysed one-year changes in body compartments and their demographic and clinical determinants. Methods: A prospective cohort of 112 adult kidney recipients transplanted between September 2020 and June 2022 at a Spanish tertiary hospital was followed. Body weight, muscle mass, fat mass, visceral fat and total body water were assessed by multi-frequency bioelectrical impedance at discharge, and at 3, 6 and 12 months. Associations with sociodemographic, clinical and comorbidity variables were examined using repeated-measures ANOVA and comparative tests. Results: At 12 months, mean weight gain was 3.6 ± 6.5 kg (5.1%). Increases were greater in men, younger patients, non-dialysis candidates, those with previous transplantation and living donor grafts. Muscle mass rose during the first three months and then stabilised, with greater gains in men and haemodialysis patients. Fat mass decreased initially and then increased, particularly in women, younger recipients and living donor transplants. Visceral fat progressively increased after three months, with higher levels in men and older patients. Total body water declined in women, younger recipients and first transplant patients. Patients with new-onset diabetes gained less weight, while smokers gained more. Conclusions: Post-transplant body composition is shaped by sex, age, BMI, comorbidities and donor type. Monitoring compartments beyond body weight may allow early detection of adverse metabolic trajectories. Tailored nutritional and lifestyle interventions are needed to optimise long-term outcomes. Full article
(This article belongs to the Special Issue Recent Clinical Perspective in Kidney Transplantation)
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