Functionalization of SF/HAP Scaffold with GO-PEI-miRNA inhibitor Complexes to Enhance Bone Regeneration through Activating Transcription Factor 4

利用 GO-PEI-miRNA 抑制剂复合物对 SF/HAP 支架进行功能化,通过激活转录因子 4 来增强骨再生

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作者:Lingling Ou, Yong Lan, Zhiqiang Feng, Longbao Feng, Junjie Yang, Yu Liu, Liming Bian, Jiali Tan, Renfa Lai, Rui Guo

Conclusion

This technology is used to increase osteogenic differentiation and mineralized bone formation in bone defects, which helps to achieve cell-free scaffold-based miRNA-inhibitor therapy for bone tissue engineering.

Methods

Here, we show that a polyethyleneimine (PEI)-functionalized graphene oxide (GO) complex efficiently loaded with the miR-214 inhibitor is assembled into silk fibroin/hydroxyapatite (SF/HAP) scaffolds that spatially control the release of the miR-214 inhibitor.

Results

SF/HAP/GO scaffolds with nanosized GO show high mechanical strength, and their hierarchical microporous structures promote cell adhesion and growth. The SF/HAP/GO-PEI scaffolds loaded with mir-214 inhibitor (SF/HAP/GPM) were tested for their ability to enhance osteogenic differentiation by inhibiting the expression of miR-214 while inversely increasing the expression of activating transcription factor 4 (ATF4) and activating the Akt and ERK1/2 signaling pathways in mouse osteoblastic cells (MC3T3-E1) in vitro. Similarly, the scaffolds activated the osteoblastic activity of endogenous osteoblast cells to repair critical-sized bone defects in rats without the need for loading osteoblast cells.

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