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

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.

Harnessing HEK293 cell-derived exosomes for hsa-miR-365a-3p delivery: Potential application in hepatocellular carcinoma therapy

“…MiR-365a-3p has been reported as substantially downregulated in breast, gastric, and HCC cancers [ 33 , 34 ]. Delivering naked miRNA to target tissue is difficult due to endosomal entrapment, enzymatic degradation in body fluids, and immune surveillance [ [35] , [36] , [37] , [38] , [39] , [40] ]. Therefore, using proper carriers can enhance the stability, permeability, and efficiency of tumor suppressor microRNA transfection.…”

Developing hydrogels for gene therapy and tissue engineering

“…RNA loading into nanomaterials combined with hydrogels can improve the retention time around tumors and the uptake of RNA into cancer cells [ 173 ]. Qin et al [ 174 ] prepared miR-29b/GO-PEG-PEI@chitosan hydrogel that shows excellent miR-29b loading capacity and delivery efficiency. In vivo experiments showed that transfection of BMSCs significantly promoted their osteogenic differentiation and did not trigger inflammatory responses.…”

Advances and Trends of Photoresponsive Hydrogels for Bone Tissue Engineering

“…Research into novel methods for inducing bone regeneration has been prompted by the limited application of growth factors due to their short half-life, low bioactivity, and high production costs of recombinant proteins. , Nucleic acid provides an up-and-coming alternative for delivering the growth factors, including DNA , and RNA. , At the transcriptional and post-transcriptional levels, they can induce changes in gene expression. The cationic liposomes are the most common delivery systems for a nucleic acid.…”

“…168,169 Nucleic acid provides an up-and-coming alternative for delivering the growth factors, including DNA 170,171 and RNA. 172,173 At the transcriptional and posttranscriptional levels, they can induce changes in gene expression. The cationic liposomes are the most common delivery systems for a nucleic acid.…”