Bioactive decellularized adipose matrix prepared using a rapid, nonchemical/enzymatic method for adipogenesis.

Recent developments in the field of regenerative surgeries and medical applications have led to a renewed interest in adipose tissue-enriched mesenchymal stem cell scaffolds. Various advantages declared for the decellularized adipose matrix (DAM) have caused its extensive use in the transfer of stem cells or growth factors for soft tissue regeneration induction. Meanwhile, the long-term application of detergents toward DAM regeneration has been assumed as a risky obstacle in this era. Herein, a rapid, mechanical protocol was developed to prepare DAM (M-DAM) without chemicals/enzymes and was comprehensively compared with the ordinary DAM (traditional chemical method). Accordingly, this method could effectively hinder oils and cells, sustain the structural and biological elements, and contain a superior level of collagen content. In addition, more protein numbers, as well as higher basement membrane elements, glycoproteins, and extracellular matrix-related proteins were detected in the regenerated M-DAM. Also, superior adipogenesis and angiogenesis proteins were distinguished. The noncytotoxicity of the M-DAM was also approved, and a natural ecological niche was observed for the proliferation and differentiation of stem cells, confirming its great potential for vascularization and adipogenesis in vivo. The suggested technique could effectively prepare the modified DAM in variant constructions of tablets, powders, emulsions, hydrogels, and different three-dimensional-printed structures. Hence, this rapid, mechanical process can produce bioactive DAM, which has the potential to be widely used in various research fields of regenerative medicine.

Immediate SVF-Gel Injection Reduced Incision Scar Formation: A Prospective, Double-Blind, Randomized, Self-control Trial.

BACKGROUND: Skin incision scars are cosmetically displeasing; the effects of current treatments are limited, and new methods to reduce scar formation need to be found. OBJECTIVE: We sought to determine whether immediate postoperative injection of stromal vascular fraction gel (SVF-gel) could reduce scar formation at skin incision sites. METHODS: A prospective, randomized, double-blind, self-controlled trial was conducted in patients who underwent breast reduction. SVF-gel was intradermally injected into the surgical incision on one randomly selected side, with the other side receiving saline as a control. At the 6-month follow-up, the incision scars were evaluated using the Vancouver scar scale (VSS) and visual analog scale (VAS). Antera 3D camera was used for objective evaluation. RESULTS: The VSS score and VAS score were significantly different between the SVF-gel-treated side (3.80 ± 1.37, 3.37±1.25) and the control side (5.25 ± 1.18, 4.94 ± 1.28). Moreover, the SVF-gel-treated side showed statistically significant improvements in scar appearance, based on evidences from Antera 3D camera. LIMITATIONS: This was a single-center, single-race, and single-gender study. Furthermore, the results were available only for the 6-month interim follow-up period. CONCLUSION: Postoperative immediate SVF-gel injection in surgical incisions can reduce scar formation, and exert a preventive effect on scars. LEVEL OF EVIDENCE I: Evidence obtained from at least one properly designed randomized controlled trial. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Dual Network Hydrogels Based on PRP and SA Promote the Retention Rate and Vascularization of Transplanted Fat.

BACKGROUND: Autologous adipose tissue often experiences ischemia and hypoxia after transplantation, leading to low retention rates and unstable operative impacts due to necrotic absorption. Platelet-rich plasma (PRP) can enhance fat regeneration and increase the fat retention rate after transplantation. However, the quick release of growth factors (GFs) in PRP decreases therapeutic efficiency. This study aimed to achieve a slow release of PRP to promote fat retention. METHODS: We prepared a dual-network hydrogel (DN gel) based on FDA-approved PRP and sodium alginate (SA) through a simple "one-step" activation process. In vivo study, adipose tissue with saline (control group), SA gel (SA gel group), PRP gel (PRP gel group), and DN gel (DN gel group) was injected subcutaneously into the dorsum of nude mice. At 4 and 12 weeks after injection, tissues were assessed for volume and weight. Hematoxylin and eosin staining (HE) and immunofluorescence staining were performed for histological assessment. RESULTS: DN gel exhibits long-lasting growth factor effects, surpassing conventional clinical PRP gel regarding vascularization potential. In fat transplantation experiments, DN gel demonstrated improved vascularization of transplanted fat and increased retention rates, showing promise for clinical applications. CONCLUSIONS: DN gel-assisted lipofilling can significantly improve the retention rate and quality of transplanted fat. DN gel-assisted lipofilling, which is considered convenient, is a promising technique to improve neovascularization and fat 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.

Particles of Different Sizes Affect the Retention Pattern of the Fat Grafts in a Mouse Model.

BACKGROUND: Autologous fat grafting is an effective form of soft tissue regeneration. However, the optimal fat particle size and graft retention pattern need more research. METHODS: The mouse inguinal fat pad was harvested and cut into fat particles of different diameters: ≥ 5 mm, 3-4 mm, 2-3 mm, 1-2 mm and 1 mm (micro-fat). A volume of 0.2 ml fat was transplanted into another mouse dorsum. Volume and retention rate were measured at 1, 4, 8 and 12 weeks. Histology analysis was performed. Immunofluorescence staining was used to evaluate M1 and M2 macrophage infiltration and graft angiogenesis. RESULTS: Fat retention was highest in the "> 5 mm" group and lowest in the "micro-fat" group. Large vacuoles were more common in larger-diametered fat particles. There was less collagen accumulation in the well-vascularized connective tissue in the "1-2 mm" group. The infiltrated nucleated cells peak at week 4 in groups of fat particles under 3 mm and at week 8 in in groups with fat particles above 3 mm. The number of M1 macrophages peaked at week 1 and then declined in all groups except for the "5 mm" group. The number of M2 macrophages peaked at week 4 and gradually decreased through 12 weeks in the groups below 3 mm, but increased through 12 weeks in the groups above 3 mm. Vascular intensity was similar to M2 macrophage prevalence. CONCLUSIONS: Fat particles of different sizes may posses different retention patterns. Larger grafts have higher retention rate but worse quality. Meanwhile, smaller grafts have better quality with lower retention rate. 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 .

Meta-Analysis of the Oncological Safety of Autologous Fat Grafting After Breast Cancer on Basic Science and Clinical Studies.

BACKGROUND: The purpose of the present study was to comprehensively evaluate the oncological safety of autologous fat grafting after breast cancer by combining experimental and clinical studies. METHODS: All studies published before August 2021 were collected by searching PubMed, Cochrane, Embase, Web of Science, SINOMED, and China National Knowledge Infrastructure. After screening the research and extracting the data, RevMan was used to perform the meta-analysis. RESULTS: Five basic science studies and 26 clinical studies, involving a total of 10,125 patients, were eventually included. In the basic science studies, adipose-derived stem cells promoted breast cancer growth, but fat grafting and adipose-derived stem cells plus fat grafting were not associated with breast cancer growth. An overall analysis of clinical studies showed that autologous fat grafting does not increase the risk of breast cancer recurrence. Subgroup analyses indicated that autologous fat grafting did not increase the risk of breast cancer recurrence in Asian or Caucasian patients, in patients undergoing breast-conserving surgery or modified radical mastectomy, in patients with in situ carcinomas or invasive carcinomas, or in patients undergoing postoperative radiotherapy. CONCLUSION: This study combined experimental and clinical studies to conclude that autologous fat grafting does not increase the risk of breast cancer recurrence. However, the experimental results suggest that adipose-derived stem cells should be used with caution after breast cancer surgery. LEVEL OF EVIDENCE III: 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 .

Oral squamous cell carcinoma gene patterns connected with RNA methylation for prognostic prediction.

OBJECTIVES: To determine whether m6A/m1A/m5C/m7G/m6Am/Ψ-related genes influence the prognosis of a patient with oral squamous cell carcinoma. MATERIALS AND METHODS: We investigated the changes in regulatory genes using publicly available data from The Cancer Genome Atlas. Consensus clustering by RNA methylation-related regulators was used to describe oral squamous cell carcinomas (OSCCs). Then, we developed the prediction model. The tumor microenvironment was investigated using ESTIMATE. Gene set enrichment analysis was used to determine whether pathways or cell types were enriched in different groups. The association between the model and immune-related risk scores was investigated using correlation analysis. RESULTS: We found 22 gene signatures in this analysis and then developed a predictive model that reveals the genes that are highly connected to the overall survival of OSCC patients. The survival and death rates were substantially different in the two groups (high and low risk) classified by the risk scores. The validation cohort verified the phenotypic diversity and prognostic effects of these genes. CONCLUSION: Our data reveal that immune cell infiltration, genetic mutation, and survival potential in OSCC patients are linked to m6A/m1A/m5C/m7G/m6Am/Ψ-related genes, and we constructed a dependable prognostic model for OSCC patients.

Epidemiology and Prognostic Factors Analysis of Electrical Injuries in Shaanxi, China: A Single-Center Observational Study of 385 Cases.

The objective of this research is to investigate the epidemiological features of electrical injuries in Shaanxi Province, China, examine their prognosis, and ascertain the factors that impact the outcomes. Telephone follow-ups were conducted with electrical injury patients at our hospital between 2011 and 2021, yielding the following results: Most electrical injuries occur in males (94.3%) and younger or middle-aged individuals. The most common voltages involved are 220V and 380V. Since 2016, there has been a 20.1% annual decrease in electrical injuries, with most cases occurring from April to September. Patients typically undergo 1 surgical procedure (0,3), with a 14.8% amputation rate and an average hospital stay of 21 days (9,43). 1.8% of electrical injury patients have died, 17.1% have permanent nerve damage, and 10.8% need help with daily tasks. 18.5% have psychological issues and 9.6% have PTSD. 93.7% return to work in an average of 6 months (2,12). Amputation risk is influenced by voltage, muscle injury, and current pathway; skin grafting risk is mainly due to voltage. Heart injuries are affected by unconsciousness and current pathways; labor loss risk factors include voltage, falls from heights, and muscle injury; nerve damage is linked to muscle injury. Cataract development risk is associated with electric shock to the head and neck. It is crucial to address the psychological well-being of patients and provide necessary support. Patient input should be taken into account when deciding on treatment for non-functional limbs. Physicians should evaluate prognostic factors and provide appropriate treatment to enhance patient outcomes.

Identification of a polyamine-related signature and six novel prognostic biomarkers in oral squamous cell carcinoma.

Elevated polyamine levels are required for tumor transformation and development; however, expression patterns of polyamines and their diagnostic potential have not been investigated in oral squamous cell carcinoma (OSCC), and its impact on prognosis has yet to be determined. A total of 440 OSCC samples and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Consensus clustering was conducted to classify OSCC patients into two subgroups based on the expression of the 17 polyamine regulators. Polyamine-related differentially expressed genes (PARDEGs) among distinct polyamine clusters were determined. To create a prognostic model, PARDEGs were examined in the training cohorts using univariate-Lasso-multivariate Cox regression analyses. Six prognostic genes, namely, "CKS2," "RIMS3," "TRAC," "FMOD," CALML5," and "SPINK7," were identified and applied to develop a predictive model for OSCC. According to the median risk score, the patients were split into high-risk and low-risk groups. The predictive performance of the six gene models was proven by the ROC curve analysis of the training and validation cohorts. Kaplan-Meier curves revealed that the high-risk group had poorer prognosis. Furthermore, the low-risk group was more susceptible to four chemotherapy drugs according to the IC50 of the samples computed by the "pRRophetic" package. The correlation between the risk scores and the proportion of immune cells was calculated. Meanwhile, the tumor mutational burden (TMB) value of the high-risk group was higher. Real-time quantitative polymerase chain reaction was applied to verify the genes constructing the model. The possible connections of the six genes with various immune cell infiltration and therapeutic markers were anticipated. In conclusion, we identified a polyamine-related prognostic signature, and six novel biomarkers in OSCC, which may provide insights to identify new treatment targets for OSCC.

Integrative analysis of lysine acetylation-related genes and identification of a novel prognostic model for oral squamous cell carcinoma.

Introduction: Oral squamous cell carcinoma (OSCC), which accounts for a high proportion of oral cancers, is characterized by high aggressiveness and rising incidence. Lysine acetylation is associated with cancer pathogenesis. Lysine acetylation-related genes (LARGs) are therapeutic targets and potential prognostic indicators in various tumors, including oral squamous cell carcinoma. However, systematic bioinformatics analysis of the Lysine acetylation-related genes in Oral squamous cell carcinoma is still unexplored. Methods: We analyzed the expression of 33 Lysine acetylation-related genes in oral squamous cell carcinoma and the effects of their somatic mutations on oral squamous cell carcinoma prognosis. Consistent clustering analysis identified two lysine acetylation patterns and the differences between the two patterns were further evaluated. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to develop a lysine acetylation-related prognostic model using TCGA oral squamous cell carcinoma datasets, which was then validated using gene expression omnibus (GEO) dataset GSE41613. Results: Patients with lower risk scores had better prognoses, in both the overall cohort and within the subgroups These patients also had "hot" immune microenvironments and were more sensitive to immunotherapy. Disscussion: Our findings offer a new model for classifying oral squamous cell carcinoma and determining its prognosis and offer novel insights into oral squamous cell carcinoma diagnosis and treatment.

Bone marrow mesenchymal stem cells enhance angiogenesis and promote fat retention in fat grafting via polarized macrophages.

BACKGROUND: Fat grafting is one of the most common soft tissue filling methods in plastic surgery. Bone marrow mesenchymal stem cell (BM-MSC) transplantation is an effective method for improving graft retention. However, the role of BM-MSCs in fat transplantation is not completely clear. METHODS: Human fat particles, together with BM-MSCs or PBS as a control, were subcutaneously transplanted into the backs of nude mice. Samples were taken on days 14, 30 and 90 post-grafting to calculate the fat graft retention rate, and tissue staining was evaluated. Furthermore, macrophages were treated with BM-MSC conditioned medium (BM-MSC-CM) to identify the beneficial component secreted by these stem cells. RESULTS: In this study, we found that BM-MSCs improved retention by enhancing angiogenesis in fat grafting. Further analysis revealed that BM-MSCs could significantly inhibit the expression of the proinflammatory M1 macrophage markers interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α) and IL-6 in the early stages of fat grafting and promote the expression of the anti-inflammatory M2 macrophage markers Arg1, IL-10 and VEGF. Furthermore, our results showed that IL-10 secreted by BM-MSCs induced M2 macrophage polarization in vitro. CONCLUSIONS: BM-MSC transplantation can improve the fat retention rate and promote angiogenesis, which may be related to M2 macrophages. These results help elucidate the role of BM-MSCs in fat grafting.

Innovative Application of Three-Dimensional-Printed Breast Model-Aided Reduction Mammaplasty.

Symptomatic macromastia places a severe physical and psychological burden on patients. Reduction mammaplasty is the primary treatment; however, conventional surgery may lead to postoperative nipple-areolar complex necrosis due to damage to the dominant supplying arteries. In this study, we designed and fabricated an innovative, three-dimensional-printed breast vascular model to provide surgical guidance for reduction mammaplasty. Preoperative computed tomography angiography scanning data of patients were collected. The data were then processed and reconstructed using the E3D digital medical modeling software (version 17.06); the reconstructions were then printed into a personalized model using stereolithography. The three-dimensional-printed breast vascular model was thus developed for individualized preoperative surgical design. This individualized model could be used to intuitively visualize the dominant supplying arteries' spatial location in the breasts, thereby allowing effective surgical planning for reduction mammaplasty. The three-dimensional-printed breast vascular model can therefore provide an individualized preoperative design and patient education, avoid necrosis of the nipple-areolar complex, shorten operation duration, and ensure safe and effective surgery in patients.

Pre-clinical evaluation of thermosensitive decellularized adipose tissue/platelet-rich plasma interpenetrating polymer network hydrogel for wound healing.

Wound healing remains a challenge worldwide, and an ideal wound dressing that promotes healing is urgently needed. In this study, we developed a thermosensitive injectable hydrogel known as the thermosensitive decellularized adipose tissue/platelet-rich plasma interpenetrating polymer network (t-DPI) hydrogel based on decellularized adipose tissue (DAT) and temperature-controlled platelet-rich plasma (t-PRP). Abundant platelets, growth factors (GFs), and bioactive substances from the decellularized extracellular matrix (dECM) in the t-DPI hydrogel had positive effects on wound healing. The morphology, thermosensitivity, and GFs release properties of the t-DPI hydrogel were studied. In vitro, the t-DPI hydrogel showed ideal cytocompatibility and the abilities to promote the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs). Moreover, M2 macrophage polarization was enhanced after treated with t-DPI hydrogel. In vivo, the t-DPI hydrogel notably accelerated the full-thickness wound healing. The positive role of the t-DPI hydrogel on pro-angiogenesis, macrophage polarization and collagen deposition were validated in the nude mouse full-thickness skin defect model. In addition, the clinical application potential was confirmed using a pre-clinical porcine full-thickness wound model. Overall, this study demonstrated that the t-DPI hydrogel achieves fast and ideal wound healing in full-thickness wound defects and provides a potential clinical treatment strategy.