Pyroptosis-related lncRNA prognostic signatures for cutaneous melanoma and tumor microenvironment status.

Aims: To explore whether the expression of pyroptosis-related lncRNAs makes a difference in the prognosis and antitumor immunity of cutaneous melanoma (CM) patients. Methods: A series of analyses were conducted to establish a prognostic risk model and validate its accuracy. Immune-related analyses were performed to further assess the associations among immune status, tumor microenvironment and the prognostic risk model. Results: Eight pyroptosis-related lncRNAs relevant to prognosis were ascertained and applied to establish the prognostic risk model. The low-risk group had a higher overall survival rate. Conclusion: The established prognostic risk model presents better prediction ability for the prognosis of CM patients and provides new possible therapeutic targets for CM.

Rare Recurrent Giant Frontal Osteoma With Skin Multiple Keratinous Cysts and Multinucleated Giant Cell Granulomas.

BACKGROUND: Osteoma is the most common benign tumor of the craniomaxillofacial region. Its etiology remains unclear, and the computed tomography and histopathologic examination contribute to its diagnosis. There are very rare reports of recurrence and malignant transformation after surgical resection. Furthermore, giant frontal osteomas that occurred repeatedly and were accompanied by skin multiple keratinous cysts and multinucleated giant cell granulomas have not been reported in previous literature. METHODS: The previous cases of recurrent frontal osteoma in the literature and all cases of frontal osteoma in our department in the last 5 years were reviewed. RESULTS: A total of 17 cases of frontal osteoma (mean age 40 y, all female) were reviewed in our department. All patients underwent open surgery to remove the frontal osteoma, and no evidence of complications was found during postoperative follow-up. Two patients underwent 2 or more operations due to the recurrence of osteoma. CONCLUSIONS: Two cases of recurrent giant frontal osteoma were reviewed emphatically in this study, including 1 case of giant frontal osteoma with skin multiple keratinous cysts and multinucleated giant cell granulomas. As far as we know, this is the first giant frontal osteoma that occurred repeatedly and was accompanied by skin multiple keratinous cysts and multinucleated giant cell granulomas.

Hyaluronic acid-based hydrogels: As an exosome delivery system in bone regeneration.

Exosomes are extracellular vesicles (EVs) containing various ingredients such as DNA, RNA, lipids and proteins, which play a significant role in intercellular communication. Numerous studies have demonstrated the important role of exosomes in bone regeneration through promoting the expression of osteogenic-related genes and proteins in mesenchymal stem cells. However, the low targeting ability and short circulating half-life of exosomes limited their clinical application. In order to solve those problems, different delivery systems and biological scaffolds have been developed. Hydrogel is a kind of absorbable biological scaffold composed of three-dimensional hydrophilic polymers. It not only has excellent biocompatibility and superior mechanical strength but can also provide a suitable nutrient environment for the growth of the endogenous cells. Thus, the combination between exosomes and hydrogels can improve the stability and maintain the biological activity of exosomes while achieving the sustained release of exosomes in the bone defect sites. As an important component of the extracellular matrix (ECM), hyaluronic acid (HA) plays a critical role in various physiological and pathological processes such as cell differentiation, proliferation, migration, inflammation, angiogenesis, tissue regeneration, wound healing and cancer. In recent years, hyaluronic acid-based hydrogels have been used as an exosome delivery system for bone regeneration and have displayed positive effects. This review mainly summarized the potential mechanism of HA and exosomes in promoting bone regeneration and the application prospects and challenges of hyaluronic acid-based hydrogels as exosome delivery devices in bone regeneration.

Exosomal Lnc NEAT1 from endothelial cells promote bone regeneration by regulating macrophage polarization via DDX3X/NLRP3 axis.

BACKGROUND: Bone regeneration is a complex procedure that involves an interaction between osteogenesis and inflammation. Macrophages in the microenvironment are instrumental in bone metabolism. Amount evidence have revealed that exosomes transmitting lncRNA is crucial nanocarriers for cellular interactions in various biotic procedures, especially, osteogenesis. However, the underlying mechanisms of the regulatory relationship between the exosomes and macrophages are awaiting clarification. In the present time study, we aimed to explore the roles of human umbilical vein endothelial cells (HUVECs)-derived exosomes carrying nuclear enrichment enriched transcript 1 (NEAT1) in the osteogenesis mediated by M2 polarized macrophages and elucidate the underlying mechanisms. RESULTS: We demonstrated HUVECs-derived exosomes expressing NEAT1 significantly enhanced M2 polarization and attenuated LPS-induced inflammation in vitro. Besides, the conditioned medium from macrophages induced by the exosomes indirectly facilitated the migration and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Mechanically, Exos carrying NEAT1 decreased remarkably both expression of dead-box helicase 3X-linked (DDX3X) and nod-like receptor protein 3 (NLRP3). The level of NLRP3 protein increased significantly after RAW264.7 cells transfected with DDX3X overexpression plasmid. Additionally, the knockdown of NEAT1 in exosomes partially counteracted the aforementioned effect of Exos. The results of air pouch rat model demonstrated that HUVECs-derived exosomes increased anti-inflammatory cytokines (IL-10) and decreased pro-inflammatory cytokines (IL-1ß and IL-6) significantly in vivo, contributing to amelioration of LPS-induced inflammation. Afterwards, we further confirmed that the HUVECs-derived exosomes encapsulated in alginate/gelatin methacrylate (GelMA) interpenetrating polymer network (IPN) hydrogels could promote the bone regeneration, facilitate the angiogenesis, increase the infiltration of M2 polarized macrophages as well as decrease NLRP3 expression in the rat calvarial defect model. CONCLUSIONS: HUVECs-derived exosomes enable transmitting NEAT1 to alleviate inflammation by inducing M2 polarization of macrophages through DDX3X/NLRP3 regulatory axis, which finally contributes to osteogenesis with the aid of alginate/GelMA IPN hydrogels in vivo. Thus, our study provides insights in bone healing with the aid of HUVECs-derived exosomes-encapsulated composite hydrogels, which exhibited potential towards the use of bone tissue engineering in the foreseeable future.

HLA-DRB1: A new potential prognostic factor and therapeutic target of cutaneous melanoma and an indicator of tumor microenvironment remodeling.

Cutaneous melanoma (CM) is the most common skin cancer and one of the most aggressive cancers and its incidence has risen dramatically over the past few decades. The tumor microenvironment (TME) plays a crucial role in the occurrence and development of cutaneous melanoma. Nevertheless, the dynamics modulation of the immune and stromal components in the TME is not fully understood. In this study, 471 CM samples were obtained from TCGA database, and the ratio of tumor-infiltrating immune cells (TICs) in the TME were estimated using the ESTIMATE algorithms and CIBERSORT computational method. The differently expressed genes (DEGs) were applied to GO and KEGG function enrichment analysis, establishment of protein-protein interaction (PPI) network and univariate Cox regression analysis. Subsequently, we identified a predictive factor: HLA-DRB1 (major histocompatibility complex, class II, DR beta 1) by the intersection analysis of the hub genes of PPI network and the genes associated with the prognosis of the CM patients obtained by univariate Cox regression analysis. Correlation analysis and survival analysis showed that the expression level of HLA-DRB1 was negatively correlated with the Stage of the patients while positively correlated with the survival, prognosis and TME of melanoma. The GEPIA web server and the representative immunohistochemical images of HLA-DRB1 in the normal skin tissue and melanoma tissue from the Human Protein Atlas (HPA) database were applied to validate the expression level of HLA-DRB1. CIBERSORT analysis for the ratio of TICs indicated that 9 types of TICs were positively correlated with the expression level of HLA-DRB1 and only 4 types of TICs were negatively correlated with the expression level of HLA-DRB1. These results suggested that the expression level of HLA-DRB1 may be related to the immune activity of the TME and may affect the prognosis of CM patients by changing the status of the TME.

Identification and validation of a prognostic model for melanoma patients with 9 ferroptosis-related gene signature.

BACKGROUND: Melanoma is a highly heterogeneous and aggressive cutaneous malignancy. Ferroptosis, a new pathway of cell death depending on the intracellar iron, has been shown to be significantly associated with apoptosis of a number of tumors, including melanoma. Nevertheless, the relationship between ferroptosis-related genes (FRGs) and the melanoma patients' prognosis needs to be explored. METHODS: Download expression profiles of FRGs and clinical data from The Cancer Genome Atlas (TCGA) database. 70% data were randomly selected from the TCGA database and utilized the univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression model to create a prognostic model, and the remaining 30% was used to validate the predictive power of the model. In addition, GSE65904 and GSE22153 date sets as the verification cohort to testify the predictive ability of the signature. RESULTS: We identified nine FRGs relating with melanoma patients' overall survival (OS) and established a prognostic model based on their expression. During the research, patients were divided into group of high-risk and low-risk according to the results of LASSO regression analysis. Survival time was significantly longer in the low-risk group than that of in the high-risk group (P < 0.001). Enrichment analysis of different risk groups demonstrated that the reasons for the difference were related to immune-related pathways, and the degree of immune cell infiltration in the low-risk group was significantly higher than that in the high-risk group. CONCLUSIONS: The FRG prognostic model we established can predict the prognosis of melanoma patients and may further guide subsequent treatment.

Antioxidant biocompatible composite collagen dressing for diabetic wound healing in rat model.

Associated with persistent oxidative stress, altered inflammatory responses, poor angiogenesis and epithelization, wound healing in diabetic patients is impaired. N-acetylcysteine (NAC) is reported to resist excess reactive oxygen species (ROS) production, prompt angiogenesis and maturation of the epidermis. Studies have revealed that graphene oxide (GO) can regulate cellular behavior and form cross-links with naturally biodegradable polymers such as collagen (COL) to construct composite scaffolds. Here, we reported a COL-based implantable scaffold containing a mixture of GO capable of the sustained delivery of NAC to evaluate the wound healing in diabetic rats. The morphological, physical characteristics, biocompatibility and NAC release profile of the GO-COL-NAC (GCN) scaffold were evaluated in vitro. Wound healing studies were performed on a 20 mm dorsal full-skin defect of streptozotocin (STZ)-induced diabetic rats. The injured skin tissue was removed at the 18th day post-surgery for histological analysis and determination of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) activity. In diabetic rats, we confirmed that the GCN scaffold presented a beneficial effect in enhancing the wound healing process. Additionally, due to the sustained release of NAC, the scaffold may potentially induce the antioxidant defense system, upregulating the expression levels of the antioxidant enzymes in the wound tissue. The findings revealed that the antioxidant biocompatible composite collagen dressing could not only deliver NAC in situ for ROS inhibition but also promote the wound healing process. This scaffold with valuable therapy potential might enrich the approaches for surgeon in diabetic wound treatment in the future.

Sustained delivery of alendronate by engineered collagen scaffold for the repair of osteoporotic bone defects and resistance to bone loss.

Researches of biomaterials for osteoporotic bone defects focus on the improvement of its anti-osteoporosis ability, due to osteoporosis is a kind of systemic and long-range bone metabolism disorder. Nevertheless, how to steadily deliver anti-osteoporosis drugs in osteoporotic bone defects is rarely studied. Reported evidences have shown that alendronate (Aln) is known to not only restrain osteoclasts from mediating bone resorption but also stimulate osteoblasts to regenerate bone tissue. Here, we developed an engineered implantable scaffold that could sustainably release Aln for osteoporotic bone defects. Briefly, Aln was added into 2% collagen (Col) solution to form a 5 mg/ml mixture. Then the mixture was filled into pre-designed round models (diameter: 5 mm, height: 2 mm) and crosslinked to obtain engineered Col-Aln scaffolds. The release kinetics showed that Aln was released at an average rate of 2.99 µg/d in the initial 8 days and could sustainably release for 1 month. To detect the repair effects of the Col-Aln scaffolds for osteoporotic defects, the Col and Col-Aln scaffolds were implanted into 5 mm cranial defects in ovariectomized rats. After 3 months, the cranial defects implanted with Col-Aln scaffolds achieved more bone regeneration in defect area (11.74 ± 3.82%) than Col scaffold (5.12 ± 1.15%) (p < .05). Moreover, ovariectomized rats in Col-Aln scaffold group possessed more trabecular bone in femur metaphysis than Col scaffold group as analyzed by Micro-CT. This study demonstrated the engineered Col-Aln scaffold has the potential to repair osteoporotic bone defects and resist bone loss in osteoporosis.

Delayed two steps PRP injection strategy for the improvement of fat graft survival with superior angiogenesis.

Platelet-rich plasma (PRP) has been widely used to improve the fat retention rate in autologous fat transplantation since it possesses a good angiogenesis capability in vivo. However, due to the short half-life of growth factors released from PRP and its uneven distribution in injected fat tissue, the strategy of PRP in fat transplantation needs further improvement. Since the capillaries started to grow into fat grafts in 1 week and vascular growth peaks in the second week after transplantation, we hypothesized that delayed two-steps PRP injection into the interior of grafts, accompanied with the extent of neovascularization might theoretically promote microvessel growth inside transplanted adipose tissue. 24 nude mice were divided into three groups: Blank group (0.35 mL fat mixed with 0.15 mL saline, N = 8), Single step group (0.35 mL fat mixed with 0.15 mLPRP, N = 8), and Two steps group (0.35 mL fat (day 0) + 0.075 mL PRP (day 7) + 0.075 mL PRP (day 14), N = 8). At 6 and 14 weeks post-transplantation, grafts were dissected, weighted, and assessed for histology, angiogenesis, fat regeneration and inflammation level. The weight and volume of the fat samples revealed no statistical difference among the three groups at 6 weeks after fat transplantation. The weight and volume of the Two steps group fat samples showed significantly higher compared to that in Blank and Single step groups at 14 weeks after fat transplantation (weight: 137.25 ± 5.60 mg versus 87.5 ± 3.90 mg,106.75 ± 2.94 mg, respectively; volume: 0.13 ± 0.01 mL versus 0.08 ± 0.01 mL, 0.09 ± 0.01 mL, respectively). Histological assessments indicated that delayed two-steps PRP injection strategy helps to improve adipose tissue content and reduce the composition of fibrous connective tissue at 14 weeks after fat transplantation. At 6 weeks and 14 weeks after transplantation, CD31 immunofluorescence indicated that delayed two-steps PRP injection strategy helps to improve angiogenesis and significantly higher compared to that in Blank and Single step groups (6 weeks: 28.75 ± 4.54 versus 10.50 ± 2.06, 21.75 ± 1.85; 14 weeks: 21.75 ± 2.86 versus 9.87 ± 2.08, 11.75 ± 1.47, respectively). Preadipocyte count indicated delayed two-steps PRP injection strategy might promote fat regeneration and significantly higher compared to that in Blank and Single step groups at 14 weeks (129.75 ± 6.57 versus 13.50 ± 3.50, 17.12 ± 6.23, respectively). In this study, we demonstrated that the novel delayed two-steps PRP injection strategy remarkably enhanced the long-term fat retention rate and improved the neovascularization extent in the interior of the fat graft. Platelet-rich plasma, Delayed two-steps injection, Angiogenesis, Fat transplantation.

Experimental models for cutaneous hypertrophic scar research.

Human skin wound repair may result in various outcomes with most of them leading to scar formation. Commonly seen in many cutaneous wound healing cases, hypertrophic scars are considered as phenotypes of abnormal wound repair. To prevent the formation of hypertrophic scars, efforts have been made to understand the mechanism of scarring following wound closure. Numerous in vivo and in vitro models have been created to facilitate investigations into cutaneous scarring and the development of antiscarring treatments. To select the best model for a specific study, background knowledge of the current models of hypertrophic scars is necessary. In this review, we describe in vivo and in vitro models for studying hypertrophic scars, as well as the distinct characteristics of these models. The choice of models for a specific study should be based on the characteristics of the model and the goal of the study. In general, in vivo animal models are often used in phenotypical scar formation analysis, development of antiscarring treatment, and functional analyses of individual genes. In contrast, in vitro models are chosen to pathway identification during scar formation as well as in high-throughput analysis in drug development. Besides helping investigators choose the best scarring model for their research, the goal of this review is to provide knowledge for improving the existing models and development of new models. These will contribute to the progress of scarring studies.

Extracellular Vesicles from Human Adipose-Derived Stem Cells for the Improvement of Angiogenesis and Fat-Grafting Application.

BACKGROUND: The efficacy of autologous fat transplantation is reduced by fat absorption and fibrosis that are closely related to unsatisfactory vascularization. Extracellular vesicles are key components of the cell secretome, which can mirror the functional and molecular characteristics of their parental cells. Growing evidence has revealed that adipose-derived mesenchymal stem cells have the ability to enhance vascularization, which is partly ascribed to extracellular vesicles. The authors evaluated whether adipose-derived mesenchymal stem cell-derived extracellular vesicles improved vascularization of fat grafts and increased their retention rate. METHODS: To test the angiogenesis ability of adipose-derived mesenchymal stem cell-derived extracellular vesicles, they were isolated from the supernatant of cultured human adipose-derived mesenchymal stem cells and incubated with human umbilical vein endothelial cells in vitro. Then, the vesicles were co-transplanted with fat into nude mice subcutaneously. Three months after transplantation, the retention rate and inflammatory reaction of the grafts were analyzed by histologic assay. RESULTS: The experimental group could significantly promote migration and tube formation at the concentration of 20 µg/ml. At 3 months after transplantation, the volume of the experimental group (0.12 ± 0.03 mm) was larger compared with the blank group (0.05 ± 0.01 mm). Histology and immunohistology results demonstrated significantly fewer cysts and vacuoles, less fibrosis, and more neovessels in the extracelluar vesicle group. CONCLUSIONS: The authors co-transplanted adipose-derived mesenchymal stem cell-derived extracellular vesicles with fat into a nude mouse model and found that the vesicles improved volume retention by enhancing vascularization and regulating the inflammatory response.

N-acetyl cysteine-loaded graphene oxide-collagen hybrid membrane for scarless wound healing.

Wound dressings composed of natural polymers, such as type I collagen, possess good biocompatibility, water holding capacity, air permeability, and degradability, and can be used in wound repair. However, due to the persistent oxidative stress in the wound area, the migration and proliferation of fibroblasts might be suppressed, leading to poor healing. Thus, collagen-containing scaffolds are not suitable for accelerated wound healing. Antioxidant N-acetyl cysteine (NAC) is known to reduce the reactive oxygen species (ROS) and has been widely used in the clinic. Theoretically, the carboxyl group of NAC allows loading of graphene oxide (GO) for sustained release and may also enhance the mechanical properties of the collagen scaffold, making it a better wound-dressing material. Herein, we demonstrated an innovative approach for a potential skin-regenerating hybrid membrane using GO incorporated with collagen I and NAC (N-Col-GO) capable of continuously releasing antioxidant NAC. Methods: The mechanical stability, water holding capacity, and biocompatibility of the N-Col-GO hybrid membrane were measured in vitro. A 20 mm rat full-skin defect model was created to evaluate the repair efficiency of the N-Col-GO hybrid membrane. The vascularization and scar-related genes in the wound area were also examined. Results: Compared to the Col only scaffold, N-Col-GO hybrid membrane exhibited a better mechanical property, stronger water retention capacity, and slower NAC release ability, which likely promote fibroblast migration and proliferation. Treatment with the N-Col-GO hybrid membrane in the rat wound model showed complete healing 14 days after application which was 22% faster than the control group. HE and Masson staining confirmed faster collagen deposition and better epithelization, while CD31 staining revealed a noticeable increase of vascularization. Furthermore, Rt-PCR demonstrated decreased mRNA expression of profibrotic and overexpression of anti-fibrotic factors indicative of the anti-scar effect. Conclusion: These findings suggest that N-Col-GO drug release hybrid membrane serves as a better platform for scarless skin regeneration.

Proton pump inhibitors therapy and risk of bone diseases: An update meta-analysis.

AIMS: Large observational studies have yielded conflicting results regarding whether the use of proton pump inhibitors (PPI) increases the risk of bone diseases. Here, we performed a meta-analysis to examine the link between PPI and risk of bone fractures, osteoporosis and bone mineral density (BMD) loss. MATERIALS AND METHODS: We systematically performed a search for published reports on PubMed, EMBASE and the Cochrane Library. We considered articles published in English, and restricted the search to studies on human participants. Studies that reported adjusted Hazard ratio (HR) estimates with 95% confidence intervals (CI) for the associations of interest were included. Data from the articles which can be used to estimate standardized mean difference (SMD) were also obtained and utilized to assess the risk of BMD loss. KEY FINDINGS: Compared with patients not taking PPI, those taking PPI, had the increased risk of developing any-site fractures (HR: 1.30; 95%CI: 1.16 to 1.45), hip fracture (HR:1.22; 95%CI:1.15 to 1.31), spine fracture (HR:1.49; 95%CI:1.31 to 1.68), and osteoporosis (HR:1.23; 95%CI:1.06 to 1.42) based on a random model, but there was no correlation with developing BMD loss in the femoral (SMD: -0.27; 95%CI: -0.62 to 0.09), or in the spine (SMD: -0.06; 95%CI: -0.54 to 0.41). SIGNIFICANCE: Results of this meta-analysis suggest that PPI may moderately increase the risk of any-site, hip, spine fracture. Due to the widespread use of PPI and the impact of fractures on human health, clinicians should carefully evaluate the patient condition before prescribing PPI therapy.

An in vivo comparative study of the gelatin microtissue-based bottom-up strategy and top-down strategy in bone tissue engineering application.

Tissue-engineered bone grafts (TEBGs) represent a promising treatment for bone defects. Nevertheless, drawbacks of the current construction strategy (top-down [TD] strategy) such as limited transmission of nutrients and nonuniform distribution of seeded cells, result in an unsatisfied therapeutic effect on large segmental bone defects. Theoretically, tissue-engineered microtissue (TEMT)-based bottom-up (BU) strategy is effective in preserving seed cells and vascularization, thus being regarded as a better alternative for TEBGs. Yet, there are few studies focusing on the comparison of the in vivo performance of TEBGs fabricated by TD or BU strategy. Here, we developed an ectopic bone formation rat model to compare the performance of these two construction strategies in vivo. TEBGs made from gelatin TEMT (BU strategy) and bulk tissue (BT; TD strategy) were seeded with equal number of rat bone marrow-derived mesenchymal stem cells and fabricated in 5 mm polydimethylsiloxane chambers. The grafts were implanted into subcutaneous pockets in the same rat. Four weeks after implantation, microcomputed tomography and hematoxylin and eosin staining results demonstrated that more bony tissue was formed in the microtissue (MT) group than in the BT group. CD31 staining further confirmed that there were more blood vessels in the MT group, indicating that the BU strategy was superior in inducing angiogenesis. This comparative study provides evidence that the BU construction strategy is more effective for in vivo application and bone defect treatment by bone tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 678-688, 2019.

Clinicopathologic Characteristics and Prognosis Analysis of Marjolin's Ulcer in 40 Cases.

Marjolin's ulcer (MU) is a rare but aggressive epidermoid carcinoma observed in scars or wounds. This article provides comprehensive characteristics and prognostic details of MU. Clinical data of 40 patients with MU between January 2010 and December 2017 were analyzed retrospectively. Squamous cell carcinoma was the most common pathological type (35/40, 87.5%). Extended resection was performed to treat all cases with skin grafting or flap grafting. Follow-up duration ranged from 6 to 96 months (median, 52 months) and recurrence was noted in 9 cases. The 1-, 3- and 5-year recurrence-free survival (RFS) rates were 87.2%, 87.2%, 83.2% respectively and the recurrence rate was 22.5%. Univariate analysis revealed that cause of scars (P=0.044), lesion appearance (P=0.036), ultraviolet radiation exposure (P=0.000), depth (P=0.001) and histological grade (P=0.027) had a statistically significant correlation with prognosis of MU. Multivariate analysis revealed that depth (P=0.034, RR=2.681, 95%CI: 1.077-6.674) and histological grade (P=0.008, RR=2.820, 95%CI: 1.315-6.050) were independent prognostic factors for RFS. In conclusion, superficial infiltration and high-grade differentiation predict more favorable prognosis. Careful follow-up of high-risk groups is strongly recommended to prevent recurrence and improve prognosis.

Collagen Functionalized With Graphene Oxide Enhanced Biomimetic Mineralization and in Situ Bone Defect Repair.

Biomimetic mineralization using simulated body fluid (SBF) can form a bonelike apatite (Ap) on the natural polymers and enhance osteoconductivity and biocompatibility, and reduce immunological rejection. Nevertheless, the coating efficiency of the bonelike apatite layer on natural polymers still needs to be improved. Graphene oxide (GO) is rich in functional groups, such as carbonyls (-COOH) and hydroxyls (-OH), which can provide more active sites for biomimetic mineralization and improve the proliferation of the rat bone marrow stromal cells (r-BMSCs). In this study, we introduced 0%, 0.05%, 0.1%, and 0.2% w/v concentrations of GO into collagen (Col) scaffolds and immersed the fabricated scaffolds into SBF for 1, 7, and 14 days. In vitro environment scanning electron microscopy (ESEM), energy-dispersive spectrometry (EDS), thermogravimetric analysis (TGA), micro-CT, calcium quantitative analysis, and cellular analysis were used to evaluate the formation of bonelike apatite on the scaffolds. In vivo implantation of the scaffolds into the rat cranial defect was used to analyze the bone regeneration ability. The resulting GO-Col-Ap scaffolds exhibited a porous and interconnected structure coated with a homogeneous distribution of bonelike apatite on their surfaces. The Ca/P ratio of 0.1% GO-Col-Ap group was equal to that of natural bone tissue on the basis of EDS analysis. More apatites were observed in the 0.1% GO-Col-Ap group through TGA analysis, micro-CT evaluation, and calcium quantitative analysis. Furthermore, the 0.1% GO-Col-Ap group showed significantly higher r-BMSCs adhesion and proliferation in vitro and more than 2-fold higher bone formation than the Col-Ap group in vivo. Our study provides a new approach of introducing graphene oxide into bone tissue engineering scaffolds to enhance biomimetic mineralization.

Off-the-Shelf Biomimetic Graphene Oxide-Collagen Hybrid Scaffolds Wrapped with Osteoinductive Extracellular Matrix for the Repair of Cranial Defects in Rats.

Hydrogels such as type I collagen (COL) have been widely studied in bone tissue repair, whereas their weak mechanical strength has limited their clinical application. By adding graphene oxide (GO) nanosheets, researchers have successfully improved the mechanical properties and biocompatibility of the hydrogels. However, for large bone defects, the osteoinductive and cell adhesion ability of the GO hybrid hydrogels need to be improved. Mesenchymal stem cell (MSC) secreted extracellular matrix (ECM), which is an intricate network, could provide a biomimetic microenvironment and functional molecules that enhance the cell proliferation and survival rate. To synergize the advantages of MSC-ECM with GO-COL hybrid implants, we developed a novel ECM scaffold construction method. First, an osteoinductive extracellular matrix (OiECM) was created by culturing osteodifferentiated bone marrow mesenchymal stem cells (BMSCs) for 21 days. Then, the GO-COL scaffold was fully wrapped with the OiECM to construct the OiECM-GO-COL composite for implantation. The morphology, physical properties, biocompatibility, and osteogenic performance of the OiECM-GO-COL implants were assessed in vitro and in vivo (5 mm rat cranial defect model). Both gene expression and cell level assessments suggested that the BMSCs cultured on OiECM-GO-COL implants had a higher proliferation rate and osteogenic ability compared to the COL or GO-COL groups. In vivo results showed that the OiECM-GO-COL implants achieved better repair effects in a rat critical cranial defect model, whereas bone formation in other groups was limited. This study provides a promising strategy, which greatly improves the osteogenic ability and biocompatibility of the GO hydrogels without the procedure of seeding and culturing MSCs on scaffolds in vitro, demonstrating its potential as an off-the-shelf method for bone tissue engineering.

Expanded Paramedian Forehead Flaps for Nasal Defects: Beyond Aesthetic Subunits.

BACKGROUND: Reconstruction of nasal tip defects presents a significant challenge for plastic surgeons. The form, function, and aesthetic appeal of all nasal subunits must be addressed. The expanded paramedian forehead flap is a good choice for nasal reconstruction, providing similar texture, structure, and skin color, and high reliability. This article discusses the authors' modification of the expanded paramedian forehead flap in reconstructing defects on or around the nasal tip. METHODS: Twenty-two patients with nasal defects located on or around the nasal tip were treated in our institution. Sixteen patients underwent nasal reconstruction with expanded forehead flaps. The other 6 cases with cartilage defect underwent reconstruction with expanded forehead flaps and autogenous rib cartilage grafts. Functional and cosmetic results were assessed by surgeon, patient, and patient's relatives using a scale from 1 to 10. RESULTS: The aesthetic appearance of all patients was significantly improved after surgery. Two cases had mild hyperpigmentation. Two patients considered the flaps too thick. Three cases had minor brow elevation at the donor site. There were no obvious scars at the donor sites. There were no serious complications, such as infection, flap necrosis, deviation, or collapse. CONCLUSIONS: The expanded paramedian forehead flap is a safe and effective method for reconstructing defects located on or around the nasal tip. Moreover, this technique can result in good functional and cosmetic outcomes with very few complications.

Reducing Prominent Mandibular Angle Osteotomy Complications: 10-Year Retrospective Review.

BACKGROUND: Several methods are available for mandibular reduction, and each method is characterized by unique limitations and complications. However, only a few studies have systematically analyzed these complications. This study aimed to investigate the effects of the outcome of performing curved mandibular angle ostectomy and outer cortex grinding in 1-stage operation and to examine the causes of different types and characteristics of complications. METHODS: The subjects consisted of 528 patients who were subjected to curved mandibular angle ostectomy and outer cortex grinding in 1-stage operation through an intraoral approach. Surgical complications and related factors were recorded, and the rates of complication according to surgeons were simultaneously evaluated. RESULTS: The esthetic appearance of all of the patients was significantly improved, and they were satisfied with the results of the operation. The complication rate was 5.87%. No serious complications, such as subcondylar fracture, massive bleeding, permanent facial nerve, or asymmetry, occurred. Some complications, including 4 cases of hematoma, 4 cases of severe swelling, 2 cases of infection, and 1 case of sagging face, were detected. The absolute complication rate among faculty members ranged from 3.5% to 11.1%. CONCLUSIONS: Our protocol is an effective method for mandibular angle osteotomy with very few complications. The rate of complications can be effectively reduced, and some serious complications can be avoided because protective measures are improved.

Clinical Outcomes of Digital Three-Dimensional Hydroxyapatite in Repairing Calvarial Defects.

PURPOSE: The objective of this article is to present the long-term outcomes of digital three-dimensional (3D) hydroxyapatite (HA) implants used for calvarial defects. Porous HA provide good results and have many characteristics, making it suitable for calvarial defect reconstruction. However, using HA may be associated with potentially serious complications, including infection and exposure. The authors used digital 3D HA for cranioplasty for many years and accumulated considerable experience from using it. The authors found that digital 3D HA is an effective method for cranioplasty, showing low complication rate. METHODS: A total of 57 patients underwent calvarial defect reconstruction with 3D HA from June 2009 to August 2016. The follow-up period was 1 to 5 years. RESULTS: Most patients (91.2%) were greatly satisfied with the esthetic outcomes of the surgery. The highest rate of complication was seroma (8.8%). Two patients developed postoperative infections (3.5%). One patient with infections was successfully treated with antibiotic therapy. Another patient was required to undergo an extensive surgical debridement followed by delayed autogenous bone reconstruction. One patient suffered from implant exposure. No hematoma, unexpected fractures, asymmetry, and contour or implant abnormalities occurred. CONCLUSIONS: The digital 3D HA implant was highly biocompatible and durable for the reconstruction of calvarial defects. With appropriate treatment, the proposed method was able to achieve a functional and cosmetic reconstruction with lesser complications.