No abstract

Small extracellular vesicles (sEVs) secreted by mesenchymal stem cells (MSCs) have been extensively studied in recent years. sEV contents change with the secreting cell state. When MSCs are exposed to an inflammatory environment, they release more functional growth factors, exosomes, and chemokines. Herein, MSCs are stimulated to alter sEV cargos and functions to regulate the inflammatory microenvironment and promote tissue regeneration. Sequencing of sEV miRNAs shows that certain RNAs conducive to cell function are upregulated. In this study, in vitro cell function experiments show that both inflammation‐stimulated adipose‐derived MSC (ADSC)‐derived sEV (IAE) and normal ADSC‐derived sEV (AE) promote cell proliferation; IAE also significantly improves cell migration. Regarding macrophage polarization regulation, IAE significantly promotes M2 macrophage differentiation. RNA‐sequencing analysis indicates that high miR‐27b‐3p expression levels in IAE may regulate macrophages by targeting macrophage colony‐stimulating factor‐1 (CSF‐1). In vivo, a rabbit temporomandibular joint (TMJ) condylar osteochondral defect model shows that both AE and IAE promote TMJ regeneration, with IAE having the most significant therapeutic effect. Therefore, the authors confirm that exposing MSCs to an inflammatory environment can feasibly enhance sEV functions and that modified sEVs achieve better therapeutic effects.

No abstract

Chronic diabetic wounds have become a significant cause of disability worldwide. It is highly desired to develop effective therapies that can promote the rapid healing of diabetic wounds. Owing to the outstanding hydrophilic and water-retaining properties, hydrogels could accelerate the healing process. Extracellular vesicles (EVs) have shown the ability to promote cell regeneration and angiogenesis. In this study, we chose a gelatin methacryloyl (GelMA) hydrogel, a kind of biomaterial characteristic of good biocompatibility, to load the EVs derived from umbilical cord mesenchymal stem cells (UCMSCs) in order to have a long-lasting effect by consistent release of EVs. Then, the hydrogel with EVs was used to treat diabetic wounds in rat models. Nuclear magnetic resonance spectroscopy and scanning electron microscopy were used to characterize the synthesis of the hydrogel; cell experiments, animal experiments, and histological staining were used to evaluate the function of the hydrogel with EVs. The results show that the GelMA hydrogel incorporated with the UCMSC-derived EVs exhibits unique physicochemical properties, excellent biocompatibility, and much enhanced therapeutic effects for diabetic wounds.