Improving the osteogenesis of rat mesenchymal stem cells by chitosan-based-microRNA nanoparticles

• CTH NPs were prepared to deliver antimiR-138 to enhance the osteogenesis of MSCs.
• The highest encapsulation efficiency of CTH NPs for antimiR-138 was 92.6%.
• CTH/antimiR-138 NPs were able to transfect MSCs efficiently.
• CTH/antimiR-138 NPs obviously enhanced the osteogenic genes and protein of MSCs.

MicroRNAs (miRNAs) play important roles in the osteogenic differentiation of stem cells. However, the application of miRNA in bone regeneration has been limited by its poor stability, low cellular uptake, and undesired immune response. In this study, chitosan (CS)/tripolyphosphate (TPP)/Hyaluronic Acid (HA) nanoparticles (CTH NPs) were prepared to deliver antimiR-138 to bone marrow mesenchymal stem cells (MSCs). The particle size, polydispersity index, and zeta potential of CTH NPs were related to the weight ratio of CS:TPP:HA. At optimum N/P ratio (20:1), the highest encapsulation efficiency was obtained. Both blank CTH NPs and CTH/antmiR-138 NPs exhibited no cytotoxicity to MSCs. A high transfection efficiency (nearly 70%) and significant enhancement of the osteogenesis of MSCs were observed. Above results demonstrated that CTH NPs was a potential candidate as an efficient non-viral miRNA vector to regulate the osteogenic differentiation of MSCs.