MicroRNA-29b/graphene oxide-polyethyleneglycol-polyethylenimine complex incorporated within chitosan hydrogel promotes osteogenesis

Han Qin; Yujie Ji; Guangyue Li; Xiaohui Xu; Chuangwei Zhang; Wenjie Zhong; Shihan Xu; Yuanyuan Yin; Jinlin Song

doi:10.3389/fchem.2022.958561

MicroRNA-29b/graphene oxide-polyethyleneglycol-polyethylenimine complex incorporated within chitosan hydrogel promotes osteogenesis

Front Chem. 2022 Jul 22:10:958561. doi: 10.3389/fchem.2022.958561. eCollection 2022.

Authors

Han Qin^{1

2

3}, Yujie Ji^{1

2

3}, Guangyue Li^{1

2

3}, Xiaohui Xu^{1

2

3}, Chuangwei Zhang^{1

2

3}, Wenjie Zhong^{1

2

3}, Shihan Xu^{1

2

3}, Yuanyuan Yin^{1

2

3}, Jinlin Song^{1

2

3}

Affiliations

¹ College of Stomatology, Chongqing Medical University, Chongqing, China.
² Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China.
³ Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China.

Abstract

MicroRNAs (miRNAs) play a pivotal role in regulating a number of physiologic and pathologic processes including bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation, making them a candidate used to promote osteogenesis. However, due to intrinsic structure and characteristics, "naked" miRNAs are unstable in serum and could not pass across the cellular membrane. Nano delivery systems seem to be a solution to these issues. Recently, graphene oxide (GO)-based nanomaterials are considered to be promising for gene delivery due to their unique physiochemical characteristics such as high surface area, biocompatibility, and easy modification. In this work, a GO-based nanocomplex functionalized by polyethyleneglycol (PEG) and polyethylenimine (PEI) was prepared for loading and delivering miR-29b, which participates in multiple steps of bone formation. The nanocomplex revealed good biocompatibility, miRNA loading capacity, and transfection efficiency. The miR-29b/GO-PEG-PEI nanocomplex was capsulated into chitosan (CS) hydrogel for osteogenesis. In vitro and in vivo evaluation indicated that miR-29b/GO-PEG-PEI@CS composite hydrogel was able to promote BMSC osteogenic differentiation and bone regeneration. All these results indicate that PEG/PEI functionalized GO could serve as a promising candidate for miRNA cellular delivery, and the miR-29b/GO-PEG-PEI@CS hydrogel has the potential for repairing bone defects in vivo.

Keywords: chitosan hydrogel; functionalization; gene delivery system; graphene oxide; miR-29b; osteogenesis; polyethyleneglycol; polyethylenimine.