Theranostics 2019; 9(15):4525-4541. doi:10.7150/thno.34676

Research Paper

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

Lingling Ou1, Yong Lan2, Zhiqiang Feng1, Longbao Feng2, Junjie Yang1, Yu Liu3, Liming Bian4, Jiali Tan5, Renfa Lai1,✉, Rui Guo6,✉

1. The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China
2. Beogene Biotech (Guangzhou) CO., LTD, Guangzhou 510663, China
3. Guangzhou Chuangseed Biomedical Materials CO., LTD, Guangzhou 510663, China
4. Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, China
5. Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
6. Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China

Abstract

Evidence indicates that microRNAs (miRNAs) play vital roles in regulating osteogenic differentiation and bone formation.

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.

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.

Keywords: miRNA-214 inhibitor, GO-PEI, SF/HAP scaffold, activating transcription factor 4 (ATF4), bone regeneration

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How to cite this article:
Ou L, Lan Y, Feng Z, Feng L, Yang J, Liu Y, Bian L, Tan J, Lai R, Guo R. Functionalization of SF/HAP Scaffold with GO-PEI-miRNA inhibitor Complexes to Enhance Bone Regeneration through Activating Transcription Factor 4. Theranostics 2019; 9(15):4525-4541. doi:10.7150/thno.34676. Available from http://www.thno.org/v09p4525.htm