posted on 2024-03-15, 14:08authored byLi Wang, Xinbo Wei, Xi He, Shengzhao Xiao, Qiusheng Shi, Peng Chen, Jesse Lee, Ximin Guo, Haifeng Liu, Yubo Fan
Stem cell-derived extracellular vesicles (EVs) show great
potential
for promoting bone tissue regeneration. However, normal EVs (Nor-EVs)
have a limited ability to direct tissue-specific regeneration. Therefore,
it is necessary to optimize the osteogenic capacity of EV-based systems
for repairing extensive bone defects. Herein, we show that hydrogels
loaded with osteoinductive dental pulp stem cell-derived EVs (Ost-EVs)
enhanced bone tissue remodeling, resulting in a 2.23 ± 0.25-fold
increase in the expression of bone morphogenetic protein 2 (BMP2)
compared to the hydrogel control group. Moreover, Ost-EVs led to a
higher expression of alkaline phosphatase (ALP) (1.88 ± 0.16
of Ost-EVs relative to Nor-EVs) and the formation of orange-red calcium
nodules (1.38 ± 0.10 of Ost-EVs relative to Nor-EVs) in vitro. RNA sequencing revealed that Ost-EVs showed significantly
high miR-1246 expression. An ideal hydrogel implant should also adhere
to surrounding moist tissues. In this study, we were drawn to mussel-inspired
adhesive modification, where the hydrogel carrier was crafted from
hyaluronic acid (HA) and polyethylene glycol derivatives, showcasing
impressive tissue adhesion, self-healing capabilities, and the ability
to promote bone growth. The modified HA (mHA) hydrogel was also responsive
to environmental stimuli, making it an effective carrier for delivering
EVs. In an ectopic osteogenesis animal model, the Ost-EV/hydrogel
system effectively alleviated inflammation, accelerated revascularization,
and promoted tissue mineralization. We further used a rat femoral
condyle defect model to evaluate the in situ osteogenic
ability of the Ost-EVs/hydrogel system. Collectively, our results
suggest that Ost-EVs combined with biomaterial-based hydrogels hold
promising potential for treating bone defects.