Titanium Surfaces Functionalized with siMIR31HG Promote Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells.

Abstract

Titanium (Ti) implants are widely used in the clinic as bone substitutes and dental implants, but further improvements are needed to obtain high osteogenic ability and consequent osseointegration. Knockdown of long noncoding RNA MIR31HG promotes osteogenic differentiation and bone formation. In this study, we fabricated a Ti surface functionalized with siRNA targeting MIR31HG (siMIR31HG) and accelerated osteogenesis of bone marrow mesenchymal stem cells (BMSCs). Chitosan/siRNA complex was loaded onto the thermal alkali-treated Ti surface to fabricate the siMIR31HG-functionalized Ti surface. The surface morphology, siRNA loading and release efficiency, and transfection efficacy were investigated, and the biological effects, such as cell proliferation, cell morphology, and osteogenic activity, were determined. The results showed that the siMIR31HG-functionalized Ti implant generated an ∼50% knockdown of MIR31HG, with no apparent cytotoxicity, which consequently enhanced osteogenic differentiation of BMSCs, as indicated by the increase of ALP production, extracellular matrix mineralization, osteogenic gene expression, and ectopic bone formation in vivo. The siMIR31HG biofunctionalization can be used to obtain better osseointegration of Ti implant in the clinic.