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.

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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.