title: Microarc-oxidized titanium surfaces functionalized with microRNA-21-loaded chitosan/hyaluronic acid nanoparticles promote the osteogenic differentiation of human bone marrow mesenchymal stem cells.
abstract: Dental implants have been widely used for the replacement of missing teeth in the clinic, but further improvements are needed to meet the clinical demands for faster and tighter osseointegration. In this study, we fabricated safe and biocompatible chitosan (CS)/hyaluronic acid (HA) nanoparticles to deliver microRNA-21 (miR-21) and thereby accelerate osteogenesis in human bone marrow mesenchymal stem cells (hBMMSCs). The CS/HA/miR-21 nanoparticles were cross-linked with 0.2% gel solution onto microarc oxidation (MAO)-treated titanium (Ti) surfaces to fabricate the miR-21-functionalized MAO Ti surface, resulting in the development of a novel coating for reverse transfection. To characterize the CS/HA/miR-21 nanoparticles, their particle size, zeta potential, surface morphology, and gel retardation ability were sequentially investigated. Their biological effects, such as cell viability, cytotoxicity, and expression of osteogenic genes by hBMMSCs on the miR-21-functionalized MAO Ti surfaces, were evaluated. Finally, we explored appropriate CS/HA/miR-21 nanoparticles with a CS/HA ratio of 4:1 and N/P ratio 20:1 for transfection, which presented good spherical morphology, an average diameter of 160.4±10.75 nm, and a positive zeta potential. The miR-21-functionalized MAO Ti surfaces demonstrated cell viability, cytotoxicity, and cell spreading comparable to those exhibited by naked MAO Ti surfaces and led to significantly higher expression of osteogenic genes. This novel miR-21-functionalized Ti implant may be used in the clinic to allow more effective and robust osseointegration.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Zhongshan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, People's Republic of China ; Qingdao First Sanatorium, Jinan Military Region, Qingdao, Shandong Province, People's Republic of China.
authors.forename: Guangsheng
authors.initials: G
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Shizhu
authors.initials: S
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002469:Cell Separation; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D035683:MicroRNAs / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010012:Osteogenesis / Q000187:drug effects*; D010084:Oxidation-Reduction; D013499:Surface Properties; D014025:Titanium / Q000494:pharmacology*; D014162:Transfection
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C009495:titanium dioxide; D006820:Hyaluronic Acid; D048271:Chitosan; D014025:Titanium
keywords: human bone marrow MSCs; microRNA; microarc oxidation; nanoparticles; osteogenic differentiation; titanium implants