PTEN-knockdown modified T2DM ADSCs-derived extracellular vesicles promote T2DM implant osseointegration by enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells.

How to improve implant osseointegration in type 2 diabetes mellitus (T2DM) represents a severe challenge worldwide. Currently, extracellular vesicles (EVs) play an essential role in intercellular communication and the execution of various biological functions, and are often employed as an ideal natural endogenous nanomedicine for repairing the structure and function of damaged tissues. Accumulating evidence suggests that exosomes derived from genetically modified ADSCs play an important role in tissue repair and regeneration, particularly in the context of bone healing. However, the role of EVs derived from genetically modified T2DM ADSCs (mTADSCs-EVs) in T2DM implant osseointegration remains largely unknown, with limited research being conducted on this aspect. In the present study, we investigated the effects of exosomes derived from TADSCs of Pten low expression on TBMSCs and the underlying molecular mechanisms, as well as the potential application of mTADSCs-EVs in T2DM implant osseointegration. Our results demonstrated that mTADSCs-EVs significantly enhanced the proliferation and osteogenic differentiation of TBMSCs in vitro. Furthermore, mTADSCs-EVs promoted implant osseointegration in T2DM rats, which is likely attributable to the effect of mTADSCs-EVs in promoting the expression of key osteogenic proteins in TBMSCs. In conclusion, our findings reveal the crucial role of mTADSCs-EVs in promoting TBMSCs proliferation and osteogenic differentiation during T2DM implant osseointegration. Moreover, this study proposes a novel strategy to enhance T2DM implant osseointegration by utilizing extracellular vesicles extracted from genetically modified TADSCs.