Extracellular vesicles derived from nucleus pulposus mesenchymal stem cells combined with hydrogels promote bone defect repair

Abstract

In the case of large bone defects, the bone tissues cannot regenerate by themselves without extra surgical interventions. Recent studies showed that exosomes are a promising and relatively safe therapeutic tool for bone tissue engineering. Gelatin methacryloyl (GelMA)-based biomaterials can be used as a multifunctional matrix for bone tissue engineering scaffolds through various strategies to overcome major obstacles such as insufficient mechanical properties and uncontrollable degradation. Herein, we investigated the role and mechanism of human nucleus pulposus mesenchymal stem cells (hNPSCs) derived small extracellular vesicles (hNPSCs-EVs) on bone regeneration. EVs from the hNPSCs were initially extracted and identified. GelMA hydrogels were used to deliver hNPSCs-EVs, and the potential of hNPSCs-EVs in bone defect repair was investigated through in vivo and in vitro experiments on rat bone marrow-derived mesenchymal stem cells (BMSCs). In vitro results showed that hNPSCs-EVs offered substantial advantages in promoting BMSCs proliferation, migration, and angiogenesis. They significantly augmented the osteogenic ability of BMSCs by activating the mitogen-activated protein kinase signaling pathway, especially the extracellular regulated protein kinases 1/2 (ERK1/2) signaling pathway. In vivo results showed that hNPSCs-EVs containing GelMA hydrogel (hNPSCs-EVs/GelMA) effectively promoted bone regeneration. These results indicated that hNPSCs-EVs/GelMA offers a potential therapeutic option for bone defect management, and also provided valuable data for understanding the role and mechanism of hNPSCs-sEVs in bone regeneration.