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.
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 mm3) was larger compared with the blank group (0.05 ± 0.01 mm3). 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.
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.
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