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-1β 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.

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.

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.

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. 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. 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. 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.

The development of various osteogenic biomaterials has not only promoted the development of bone tissue engineering but also provided more possibilities for bone defect repair.

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.