A Prospective Investigation of Patient Satisfaction and Psychosocial Status Following Facial Bone Contouring Surgery using the Face-Q.

OBJECTIVE: The objective of this study was to assess satisfaction and psychosocial status before and after facial bone contouring surgery using the Face-Q. METHODS: The Face-Q, a multimodular patient-reported outcome (PRO) instrument, comprises independently functioning scales and checklists designed to assess outcomes in facial aesthetic patients. A prospective cohort study was conducted from November 2020 to May 2022. Participants undergoing facial bone contouring surgery (reduction mandibuloplasty and/or malarplasty) were asked to complete the Face-Q preoperatively and 12 months postoperatively. Comparative analyses were conducted using normative Face-Q data from 534 matched normal individuals. Face-Q scores were evaluated for each domain on a scale of 0 to 100, with higher scores indicating greater satisfaction with appearance or a superior quality of life. RESULTS: A total of 284 patients (274 female and 10 male) completed the Face-Q preoperatively and 12 months postoperatively. Of these, 146 underwent reduction mandibuloplasty, 18 underwent malarplasty, and 120 underwent both procedures. Post-surgery, patients experienced significant improvements in overall appearance, features altered by surgery, and quality of life, excluding the patient-perceived age. Preoperatively, patients demonstrated significantly lower scores compared to normative data, with scores significantly increasing postoperatively to levels representative of the general population. Satisfaction with outcome was significantly correlated with postoperative Face-Q measurements but not preoperatively. CONCLUSION: Facial bone contouring surgery significantly improves the satisfaction and quality of life in patients with square faces, reaching a level at least equivalent to the normative population. The use of Face-Q should be highlighted in the clinic practice. LEVEL OF EVIDENCE IV: 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.

Enhancing Fat Transplantation Efficiency in a Mouse Model through Pretreatment of Adipose-Derived Stem Cells with RIP3 Inhibitors.

BACKGROUND: Autologous fat transplantation, widely used in cosmetic and reparative surgery for volumetric enhancements, faces challenges with its inconsistent long-term survival rates. The technique's efficacy, crucial for its development, is hindered by unpredictable outcomes. Enriching fat grafts with adipose-derived stem cells (ADSCs) shows promise in improving survival efficiency. OBJECTIVES: This study aimed to explore the potential of receptor-interacting protein kinase 3 (RIP3) kinase inhibitors as a pretreatment for ADSCs in enhancing autologous fat graft retention over a long term. METHODS: ADSCs were isolated, cultured under normal or oxygen-glucose deprivation conditions, and mixed with particulate fat grafts to form distinct experimental groups in female nude mice. Fat graft mass and volume, along with underlying mechanisms, were evaluated using quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunohistochemistry, and Western blot analysis. RESULTS: The experimental group, pretreated with RIP3 kinase inhibitors, had higher graft mass and volume, greater adipocyte integrity, and increased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA levels than control groups. Furthermore, the experimental group demonstrated lower expression of necroptosis pathway proteins in the short term and an ameliorated inflammatory response as indicated by interleukin-1 beta (IL-1ß), interleukin-10 (IL-10) mRNA levels, and histological analyses. Notably, enhanced neovascularization was evident in the experimental group. CONCLUSIONS: These findings suggest that RIP3 kinase inhibitor pretreatment of ADSCs can improve fat graft survival, promote adipocyte integrity, potentially decrease inflammation, and enhance neovascularization. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Lower Gluteal Liposuction Combined With Upper Gluteal and Infragluteal Region Fat Grafting: A Novel Concept to Improve Gluteal Ptosis.

BACKGROUND: Gluteal ptosis results in a severe disturbance of gluteal aesthetics. Currently, satisfactory procedures for improving gluteal ptosis are lacking. OBJECTIVES: To improve gluteal ptosis, the authors propose a novel concept of combined liposuction of the lower gluteal region and fat grafting to the upper gluteal and infragluteal regions, and verify its efficacy and safety. METHODS: Patients who underwent liposuction of the lower gluteal region combined with fat grafting to the upper gluteal and infragluteal regions between January 2020 and July 2023 were retrospectively reviewed. Postoperative changes in the gluteal ptosis grade, complications, and patient satisfaction were evaluated. RESULTS: A total of 28 patients were enrolled in this study; 21 (75.0%) patients had gluteal ptosis grade 4 and 7 (25.0%) patients had gluteal ptosis grade 5. The median fat removal volume was 210 mL, and the median fat graft injected volume was 355 mL in the gluteal region and 180 mL in the infragluteal region. All patients showed improvement in gluteal ptosis; 16 (57.1%) patients improved by 1 grade and 12 (42.9%) patients showed a 2-grade improvement. All patients were satisfied with their posttreatment outcomes. Only 1 patient showed lateral translocation of the fat graft. No other complications were observed. CONCLUSIONS: Liposuction of the lower gluteal region combined with fat grafting to the upper gluteal and infragluteal regions is effective in improving gluteal ptosis, with a low risk of complications and high patient satisfaction.

Surgical Treatment for Benign Lymphangioendothelioma After Two Incomplete Excisions: A Case Report and Literature Review.

Benign lymphangioendothelioma (BL) is a rare, poorly identified, slow-growing benign vascular lesion characterized by asymptomatic, solitary, well-demarcated macules, or by mildly infiltrated plaque. We report a case of an atypical BL that arose as a tender, protuberant, flesh-colored mass with cyanotic vesicles, and then progressed to a persistent exudative wound after two incomplete excisions. The patient was also diagnosed with thoracic duct narrowing. Although the stenosis was removed by surgery, the right lower extremity ulceration and exudation did not improve. Thus, we performed a thorough excision and split-thickness skin graft transplant following vacuum sealing drainage, and eventually the patient had a favorable functional and cosmetic outcome. A biopsy revealed irregular, dilated vascular spaces lined with a single layer of flat endothelial cells extending from the superficial dermis to the subcutis that did not reach the striated muscles. Additionally, by reviewing the literature on BL, in this paper we summarize the diverse pathogenic, morphological, and immunohistochemical presentations for this rare disease, as well as the histopathological differential diagnosis of lymphangiomatosis, Kaposi's sarcoma, and angiosarcoma.

The Effect of Various Temperatures on the Inflammatory Profile of Fat Graft Storage: An Experimental Study.

Fat tissue has been widely used as a filler material during plastic surgery, but unpredictable fat retention remains a significant concern. Fat tissue is vulnerable to ischemia and hypoxia, but it always has waiting time before injection in the operation theater. Apart from transferring fat tissue as quickly as possible after harvesting, washing the aspirate with cool normal saline is often used. However, the mechanisms of cool temperature acting on adipose tissue have yet to be fully elucidated. Herein, this study aims to explore the effect of preservation at different temperatures on the inflammatory profile of adipose tissue. Inguinal adipose tissue of rats was collected and cultured in vitro under 4°C, 10°C, and room temperature for 2 hours. The proportion of damaged adipocytes and an array of cytokines were determined. We observed that the damage rate of the adipocyte membrane was slightly higher at room temperature, but there was no significant difference, while we noticed increased IL-6 and MCP-1 levels in adipose tissue at room temperature ( P ＜0.01). The 4°C and 10°C cool temperatures may offer protection against proinflammatory states during the adipose tissue preserved in vitro.

The histologic reaction and permanence of hyaluronic acid gel, calcium hydroxylapatite microspheres, and extracellular matrix bio gel.

BACKGROUND: The filling materials on the beauty market can be classified into three types: natural biological materials, synthetic polymer materials, and composites containing bioactive substances. However, comparative experimental data is lacking to compare their biological responses and permanence. AIMS: The main object of this study was to evaluate the biological response of these three types of fillers to provide a theoretical basis for clinical application. METHODS: Six-week-old female mice were injected subcutaneously with hyaluronic acid (HA) gel, calcium hydroxylapatite (CaHA) microspheres, and extracellular matrix (ECM) bio gel to observe the body reaction and permanence. At 1, 4, 8, and 16 weeks, the test sites were excised and analyzed by histopathology and proteomics. RESULTS: Extracellular matrix had a minimal foreign body response. HA had a good volume effect at the early stage but the volume retention rate was lower than CaHA in the long term. CaHA could stimulate neo-collagen formation. CONCLUSION: This study has proven the effectiveness and safety of these fillers and could provide clinical guidance for the plastic surgeon.

Chondrogenic Differentiation of Adipose-Derived Stromal Cells Induced by Decellularized Cartilage Matrix/Silk Fibroin Secondary Crosslinking Hydrogel Scaffolds with a Three-Dimensional Microstructure.

Finding an ideal scaffold is always an important issue in the field of cartilage tissue engineering. Both decellularized extracellular matrix and silk fibroin have been used as natural biomaterials for tissue regeneration. In this study, a secondary crosslinking method of γ irradiation and ethanol induction was used to prepare decellularized cartilage extracellular matrix and silk fibroin (dECM-SF) hydrogels with biological activity. Furthermore, the dECM-SF hydrogels were cast in custom-designed molds to produce a three-dimensional multi-channeled structure to improve internal connectivity. The adipose-derived stromal cells (ADSC) were seeded on the scaffolds, cultured in vitro for 2 weeks, and implanted in vivo for another 4 and 12 weeks. The double crosslinked dECM-SF hydrogels exhibited an excellent pore structure after lyophilization. The multi-channeled hydrogel scaffold presents higher water absorption ability, surface wettability, and no cytotoxicity. The addition of dECM and a channeled structure could promote chondrogenic differentiation of ADSC and engineered cartilage formation, confirmed by H&E, safranin O staining, type II collagen immunostaining, and qPCR assay. In conclusion, the hydrogel scaffold fabricated by the secondary crosslinking method has good plasticity and can be used as a scaffold for cartilage tissue engineering. The multi-channeled dECM-SF hydrogel scaffolds possess a chondrogenic induction activity that promotes engineered cartilage regeneration of ADSC in vivo.

Efficacy and Safety of Perioral Mound Region Liposuction-A Novel Concept to Improve Perioral Mound Fullness.

BACKGROUND: Fullness of the perioral mound is considered a dissatisfying aspect of premature aging and has become a common complaint of patients seeking facial rejuvenation. OBJECTIVES: The authors propose a novel concept of improving perioral mound fullness by liposuction and verify its safety and efficacy through cadaver and clinical studies. METHODS: A cadaver study was conducted to discover the soft tissue structure of the perioral mound region and identify a vital use for liposuction. For clinical evaluation, 37 patients with perioral mound fullness who underwent liposuction were retrospectively reviewed. RESULTS: The cadaver study results showed moderate fatty tissue in the subcutaneous layer of the perioral mound region. The liposuction manipulation was limited to the subcutaneous fat layer. Among the 37 patients (including 74 perioral mound regions), the median fat removal volume per perioral mound region was 2.0 (1.2, 2.3) mL. After liposuction, the subcutaneous fat thickness significantly decreased (median 5.0 [3.9, 6.6] mm vs 0.7 [0.4, 1.0] mm per perioral mound region, P < .001). All patients were satisfied with their posttreatment outcomes. Two patients (5.4%) had slight skin hyperpigmentation in the liposuction area after treatment and recovered naturally in 3 months without any intervention. No other complications were noted. CONCLUSIONS: Liposuction is effective in improving perioral mound fullness with a low risk of complications.

Optical characteristics of the skin with dark circles using pump-probe imaging.

Pump-probe imaging was first used for quantitative analysis of melanin in dark circles' skin to improve the ability to diagnose and treat dark circles on human skin. This study aimed to compare the distribution characteristics in melanin of lower eyelid skin tissues and to determine whether pump-probe imaging has potential for the classification of dark circles in vivo. Specimens obtained from 15 patients undergoing blepharoplasty were examined using pump-probe imaging. Furthermore, adjacent slices were respectively treated with hematoxylin-eosin (HE) and ferrous sulfate (FeSO4) staining for cross-references. Subsequently, the melanin content index (MCI) and mean fluorescence intensity (MFI) were quantitatively analyzed by the pump-probe imaging. The distribution of melanin granules in the pump-probe image and FeSO4 staining was consistent. Meanwhile, the tissues of the skin with dark circles and normal skin demonstrated significant differences in MCI and MFI. These differences can be used to distinguish the skin with dark circles from the normal skin. Pump-probe imaging could be used for the analysis of the microstructure and spectral characteristics of melanin granules in skin with dark circles. Significant differences were noted between the pigmented type of dark circles and the other two groups (normal skin and the vascular type of dark circles), while no significant differences were found between normal skin and the vascular type of dark circles.

Identification of hub genes regulating the cell activity and function of adipose-derived stem cells under oxygen-glucose deprivation.

While oxygen-glucose deprivation (OGD) has been widely utilized in many cell lines to mimic certain biological changes, it has yet to be validated in mesenchymal stem cells. We performed RNA sequencing on adipose-derived stem cells (ADSCs) under hypoxic and glucose-free conditions after 4 h and 8 h. A total of 335 common differentially expressed genes (DEGs) were identified in the two OGD groups compared with the normal control group, consisting of 292 upregulated and 43 downregulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that DEGs are mainly involved in metabolic processes, programmed cell death, and DNA-binding transcription activator activity. Protein‒protein interaction and hub gene analysis revealed various potential hub genes, in which response to oxygen levels, the IL-17-related biological function and the hypoxia-inducible factor 1 signaling pathway have been of vital importance. In summary, changes in transcription factor activity may play pivotal roles in oxygen-glucose deprivation. Through RNA sequencing, we have a deeper understanding of the changes in ADSCs after OGD treatment, providing more precise insight into predicting and regulating the stemness of ADSCs.

Breast Augmentation with Autologous Fat Grafting Immediately after Removal of Polyacrylamide Hydrogel and Fibrotic Capsule in 162 Patients.

Objective: In this study, we investigated the feasibility and efficacy of immediate breast augmentation with autologous fat grafting after removal of polyacrylamide hydrogel (PAAG) and fibrotic capsule. Methods: A retrospective study was conducted on 162 female patients who underwent removal of breast filler PAAG and the fibrotic capsule which produced after injection of PAAG via areola omega-shaped incision. Then autologous fat grafting was immediately performed evenly and radially around the areola via the same incision into different layers (subcutaneous, submammary tissue, pectoralis major intramuscular, and inferior pectoralis major space) except the empty cavity. The cavity left by removal of PAAG and fibrous capsule was closed with negative pressure drainage tube and slight external pressure. Results: All patients recovered well without severe complications. The average score of postoperative satisfaction with physical well-being: chest was 99.83 (total score: 100) compared with the average satisfaction score of 71.69 (total score: 100) preoperatively by means of BREAST-Q™ evaluation (p < 0.01). All patients were satisfied with their postoperative breast shape. Conclusions: Removing as much as possible is critical for patients who underwent the PAAG injection. Our experience in immediate breast augmentation with autologous fat grafting after removal of PAAG and fibrotic capsule proved useful and effective to maintain the balance between removing the PAAG as much as possible and retaining soft tissue to reshape breasts. Level of Evidence: IV.

Comprehensive Analysis of Novel Genes and Pathways Associated with Osteogenic Differentiation of Adipose Stem Cells.

Background: Adipose-derived stem cells (ADSCs) are an important alternative source of mesenchymal stem cells (MSCs) and show great promise in tissue engineering and regenerative medicine applications. However, identifying the novel genes and pathways and finding the underlying mechanisms regulating ADSCs osteogenic differentiation remain urgent. Methods: We downloaded the gene expression profiles of GSE63754 and GSE37329 from the Gene Expression Omnibus (GEO) Database. We derived differentially expressed genes (DEGs) before and after ADSC osteogenic differentiation, followed by Gene Ontology (GO) functional and KEGG pathway analysis and protein-protein interaction (PPI) network analysis. 211 differentially expressed genes (142 upregulated genes and 69 downregulated genes) were aberrantly expressed. GO analysis revealed that these DEGs were associated with extracellular matrix organization, protein extracellular matrix, and semaphorin receptor binding. Conclusions: Our study provides novel genes and pathways that play important roles in regulating ADSC osteogenic differentiation, which may have potential therapeutic targets for clinic.

Paranasal Augmentation: A Viable and Simplified Modality With Diced Expanded Polytetrafluoroethylene.

A flat or concave lower midface profile is generally considered less attractive. Paranasal augmentation is usually performed to move paranasal deficiency to relative convexity. Herein, we present a viable and simplified modality with diced expanded polytetrafluoroethylene to correct paranasal deficiency. Between February of 2020 and April of 2021, 19 patients underwent procedures to correct paranasal deficiency. Paranasal augmentation was performed with diced expanded polytetrafluoroethylene. All procedures were performed via intranasal approach. Preoperative and postoperative photographs were taken. Of these 19 patients (18 women and 1 man), deficiency of 18 patients were caused by congenital factors and 1 by cleft deformities. All but 1 procedures were carried out bilaterally. Procedures were performed in conjunction with additional operations mainly including rhinoplasty and minimally invasive midface lift. Age of patients ranged from 19 to 57 years, with a mean of 37 years. Follow-up time ranged from 8 to 22 months, with a mean of 12.6 months. All patients were satisfied with esthetic improvement and facial holistic profile. No severe complications and reoperation arisen in any of the patients. Temporary discomfort involved foreign body sensation in 1 case and numbness in 2 cases. The present technique provides a viable and simplified method to give the face a more balanced appearance and achieves esthetically superior results.

Biological characteristics of adipose-derived stem cells from patients with progressive hemifacial atrophy: An in vivo study.

OBJECTIVE: In this study, we investigate the biological characteristics of ADSCs from patients with progressive hemifacial atrophy (PHA) in vivo and try to explore the theoretical support for cell-assisted lipotransfer in treating patients with PHA. METHODS: ADSCs and exosomes were respectively extracted from patients with PHA and healthy ones. PHA-ADSC was detected the differentiation ability, phenotype, and anoxic resistance. NTA particle size, electron microscopy (TEM), and WB for CD63 and TSG10 were used to detect the exosomes. ADSCs of PHA (PHA-ADSCs) and healthy ones (NORM-ADSCs) mixed with their granular fat, exosomes mixed with PHA-granular fat, and PBS mixed with PHA-granular fat as the control group. The four groups of different grafts were, respectively, transplanted into nude mice, and the fat grafts were dissected and weighed at 2, 4, 8 and 12 w. Weight and volume retention were calculated for each of the four groups. Then, the four groups of fat grafts were tested for hematoxylin-eosin (HE) and immunohistochemical stainings, CD31 for blood vessel formation, CD68 for macrophage infiltration, and perilipin for fat formation, RT-PCR analysis of the APRC5, ATG5, ATG7, ATG12, BAX, PPARG, CDKN1A, and CDKN2A genes. RESULTS: ADSCs in the PHA group had typical phenotypes and multidirectional abilities. The PHA-ADSCs -assisted lipotransfer group, exhibited a weaker droplet formation and lower volume retention rate than the NORM-ADSCs-assisted lipotransfer group but much better than the non-cell-assisted lipotransfer group. Exosome-assisted lipotransfer group showed benefits, too. CONCLUSIONS: The PHA-ADSCs-assisted lipotransfer and the exosome-assisted lipotransfer improved the fat survival rate after fat filling in patients with hemifacial atrophy. Cell-assisted and exosome-assisted lipotransfer is an effective method to treat hemifacial atrophy.

In Vitro Study on the Biological Characteristics of Adipose-Derived Stem Cells from Liposuction Area in Patients with Progressive Hemifacial Atrophy.

OBJECTIVE: In this study, we investigate the biological characteristics of ADSCs from the liposuction area in patients with hemifacial atrophy in vitro. METHODS: ADSCs were respectively extracted from the donor site of patients with hemifacial atrophy and healthy ones. ADSCs of two groups were respectively tested for proliferation ability, phenotype, multipotency, migration ability, self-repair ability, apoptosis, and autophagy. Exosomes extracted from the supernatant of two groups were detected by NTA particle size, electron microscopy (TEM), and WB for CD63 and TSG10, respectively. RESULTS: CCK-8 showed a statistically less increase in cell proliferation in PHA-ADSCs after the sixth day. ADSCs in both groups had typical phenotypes and multidirectional abilities. PHA-ADSCs exhibited weaker droplet formation. The cell migration ability in PHA-ADSCs was weaker tested by Transwell assay. The live/dead proportion calculated by ImageJ following calcein-AM/PI double staining revealed live cells in PHA-ADSCs was 46.11% compared with 54.21% in NORM-ADSCs after OGD treatment. A significant down-regulation of ATG7 and ATG12 and a higher percentage of apoptosis were found in PHA-ADSCs. A significant up-regulation of BAX occurred in PHA-ADSCs.ARPC5 expression in the PHA group was extremely distinct down-regulated.CDKN1A and CDKN2A expression in the PHA group was significantly up-regulated.WB analyses confirmed that both groups' ADSCs-Exosomes surface markers CD63 and TSG101 were positively expressed but varied significantly. CONCLUSIONS: PHA-ADSCs exhibited a poorer proliferation ability, higher apoptosis percentage, weaker lipid droplets formation, weaker cell migration, poorer intolerance to OGD, aging earlier, and weaker self-renewal and repairability.PHA-ADSCs-Exosomes showed low expressions of CD63 and TSG101.This study provides strong evidence that the addition of exosomes with specific cytokines can improve the fat survival rate after fat filling in patients with hemifacial atrophy. NO LEVEL ASSIGNED: This journal requires that authors 42 assign a level of evidence to each submission to which 43 Evidence-Based Medicine rankings are applicable. This 44 excludes Review Articles, Book Reviews, and manuscripts 45 that concern Basic Science, Animal Studies, Cadaver 46 Studies, and Experimental Studies. For a full description of 47 these Evidence-Based Medicine ratings, please refer to the 48 Table of Contents or the online Instructions to Authors 49 https://www.springer.com/00266 .

Circumferential Liposuction of the Thigh with Concomitant Fat Transplantation to the Infragluteal Region: A Promising Option for Preventing Postliposuction Gluteal Ptosis.

BACKGROUND: Gluteal ptosis is a common complication of circumferential liposuction of the thigh. The authors propose a novel concept of combining circumferential liposuction of the thigh with concomitant fat transplantation to the infragluteal/posterior thigh junction region to prevent postliposuction gluteal ptosis. METHODS: Patients underwent circumferential liposuction of the thigh with or without concomitant fat transplantation from 2015 to 2020 and were retrospectively reviewed. The postoperative changes in the grade of gluteal ptosis, length of hospitalization, time to recovery, postoperative complications, and patient satisfaction were evaluated. RESULTS: A total of 109 patients were enrolled in this study, including 46 patients in the liposuction-only group and 63 patients in the liposuction plus fat transplantation group. There was no significant difference in fat removal volume between the liposuction-only group and the liposuction plus fat transplantation group ( p = 0.152). Aggravation of gluteal ptosis occurred in 43 patients (93.5 percent) in the liposuction-only group and four patients (6.3 percent) in the liposuction plus fat transplantation group ( p < 0.001). The length of hospitalization and time to recovery was not significantly different between the two groups ( p = 0.402 and p = 0.423, respectively). Complications were rare in both groups. With a minimum evaluation time of 6 months, patients in the liposuction plus fat transplantation group showed significantly higher satisfaction ( p < 0.001). CONCLUSION: Concomitant fat transplantation to the infragluteal/posterior thigh junction region during circumferential liposuction of the thigh is effective in preventing postliposuction gluteal ptosis and improving patient satisfaction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

The Role of Verteporfin in Prevention of Periprosthetic Capsular Fibrosis: An Experimental Study.

BACKGROUND: Capsular contracture (CC) characterized by excessive fibrosis is one of the most common complications after silicone implant surgery. Verteporfin (VP), an inhibitor of Yes-associated protein 1 (YAP1), has recently been found to reduce the fibrotic process. OBJECTIVES: The aim of this study was to use an in vivo rabbit model to evaluate the efficacy of VP for the prevention of CC. METHODS: Twenty-four New Zealand rabbits received 10-cc smooth saline silicone implants inserted in the dorsal skin and were randomly divided into 2 groups to receive 2 mL VP (1.5 mg/mL) or 2 mL phosphate-buffered saline solution instillation in the implant pocket. When the animals were killed on Day 60, capsule formation was observed both macroscopically and microscopically. Histologic evaluation included capsule thickness, fibrosis degree, and myofibroblast (α smooth muscle actin positive) content. In addition, the YAP1 expression level was examined by immunofluorescence staining. Transforming growth factor ß1, collagen I, and connective tissue growth factor expression were measured by real-time quantitative polymerase chain reaction. RESULTS: The VP-treated group exhibited thinner, more transparent capsules and less fibrosis than the control group at 60 days postsurgery (P < 0.05). Moreover, the VP treatment significantly reduced α smooth muscle actin, YAP1, transforming growth factor ß1, collagen I, and connective tissue growth factor expression levels in the capsular tissues (P < 0.05). CONCLUSIONS: VP reduced capsule formation after silicone implantation by inhibiting YAP1-mediated mechanical signaling, thereby attenuating excessive collagen deposition in the rabbit model. This preclinical study may provide a feasible strategy to prevent periprosthetic capsular fibrosis in clinical application.

Quercetin May Improve Fat Graft Survival by Promoting Fat Browning Peripherally.

BACKGROUND: Adipose browning occurs after white fat transfer. But its location and effects on fat graft survival remains controversial. This study was performed to locate the browning of fat grafts, and to explore the effects of quercetin on fat graft browning and fat graft survival. METHODS: Human fat granules were injected into the subcutaneous layer of 12 nude mice. Control group was injected with fat granules and 10% of normal saline, while quercetin group was injected with fat granules and 10% of quercetin. The graft samples (n = 6 for each group) were obtained in weeks 2, 4, 8 and 12. Weight retention rate of the grafts was calculated. Gene and protein expression of mitochondrial markers (silent information regulator 1, SIRT1; heat shock protein 60, HSP60), browning marker (uncoupling protein 1, UCP1), peroxisome proliferator-activated receptor-γ (PPAR-γ), vascular endothelial growth factor A (VEGF-A) were evaluated. Hematoxylin and eosin staining and anti-UCP1 staining were performed. RESULTS: Clusters of small multilocular beige adipocytes were observed in the periphery of fat grafts. Compared with control group, quercetin group had a higher weight retention rate, a higher gene/protein expression of SIRT1, HSP60, UCP1, PPAR-γ and VEGF-A, and a higher occurrence of peripheral adipose browning. CONCLUSIONS: Peripherally located adipose browning occurred after white fat transfer. It can be enhanced by the addition of quercetin through promoting mitochondrial function of fat cells, and may be one of the mechanisms that quercetin improves fat graft survival. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Creatine promotes the repair of peripheral nerve injury by affecting macrophage polarization.

The present study aimed to explore whether creatine promotes the repair of peripheral nerve injury and its possible mechanism. In vitro: RAW264.7 cells were used to investigate the role of proteins related to the JAK2/STAT1 pathway in the polarization of macrophages treated with creatine. In vivo: A sciatic nerve crush model was used. After the injury, IL-4 or creatine was injected. The recovery of motor function was assessed by the rotarod test and sciatic function index at 2, 6, 10, and 16 days after injury. At 16 days after injury, the ultrastructure of the nerve tissue was observed under a transmission electron microscope. Immunostaining were performed at 4 and 16 days to investigate the expression levels of macrophage-related markers as well as the distribution of macrophages after injury. Compared with the IFN-γ group, the group pretreated with creatine showed a significant decrease in p-JAK2 and p-STAT1 in vitro. The motor function of mice in the creatine group (CR1) and creatine 4 days group (CR2) was significantly improved compared to the control group (CON). The improvement in the CR2 group was more significant. Immunostaining showed that infiltrating macrophages mainly comprised M1 macrophages in the CON group and M2 macrophages in the CR group. Our study shows that creatine promotes the repair of peripheral nerve injury by affecting macrophage polarization, possibly through decreasing M1 polarization by inhibiting the JAK2/STAT1 pathway.

Inhibition of RIP3 increased ADSC viability under OGD and modified the competency of adipogenesis, angiogenesis, and inflammation regulation.

Adipose-derived stem cells (ADSCs) showed decreased cell viability and increased cell death under oxygen-glucose deprivation (OGD). Meanwhile, vital necroptotic proteins, including receptor-interacting protein kinase (RIP) 3 (RIP3) and mixed lineage kinase domain-like pseudokinase (MLKL), were expressed in the early stage. The present study aims to explore the effect of necroptosis inhibition on ADSCs. ADSCs were obtained from normal human subcutaneous fat and verified by multidirectional differentiation and flow cytometry. By applying cell counting kit-8 (CCK-8), calcein/propidium iodide (PI) staining and immunostaining, we determined the OGD treatment time of 4 h, a timepoint when the cells showed a significant decrease in viability and increased protein expression of RIP3, phosphorylated RIP3 (pRIP3) and phosphorylated MLKL (pMLKL). After pretreatment with the inhibitor of RIP3, necroptotic protein expression decreased under OGD conditions, and cell necrosis decreased. Transwell assays proved that cell migration ability was retained. Furthermore, the expression of the adipogenic transcription factor peroxisome proliferator-activated receptor γ (PPARγ) and quantitative analysis of Oil Red O staining increased in the inhibitor group. The expression of vascular endothelial growth factor-A (VEGFA) and fibroblast growth factor 2 (FGF2) and the migration test suggest that OGD increases the secretion of vascular factors, promotes the migration of human umbilical vein endothelial cells (HUVECs), and forms unstable neovascularization. ELISA revealed that inhibition of RIP3 increased the secretion of the anti-inflammatory factor, interleukin (IL)-10 (IL-10) and reduced the expression of the proinflammatory factor IL-1ß. Inhibition of RIP3 can reduce the death of ADSCs, retain their migration ability and adipogenic differentiation potential, reduce unstable neovascularization and inhibit the inflammatory response.