title: MicroRNA functionalized microporous titanium oxide surface by lyophilization with enhanced osteogenic activity.
abstract: Developing biomedical titanium (Ti) implants with high osteogenic ability and consequent rigid osseointegration is a constant requirement from the clinic. In this study, we fabricate novel miRNA functionalized microporous Ti implants by lyophilizing miRNA lipoplexes onto a microporous titanium oxide surface formed by microarc oxidation (MAO). The microporous titanium oxide surface provides a larger surface area for miRNA loading and enables spatial retention of the miRNAs within the pores until cellular delivery. The loading of lipoplexes into the micropores on the MAO Ti surface is facilitated by the superhydrophilicity and Ti-OH groups gathering of the MAO surface after UV irradiation followed by lyophilization. A high miRNA transfection efficiency was observed in mesenchymal stem cells (MSCs) seeded onto the miRNA functionalized surface with no apparent cytotoxicity. When functionalizing the Ti surface with miR-29b that enhances osteogenic activity and antimiR-138 that inhibits miR-138 inhibition of endogenous osteogenesis, clear stimulation of MSC osteogenic differentiation was observed, in terms of up-regulating osteogenic expression and enhancing alkaline phosphatase production, collagen secretion and ECM mineralization. The novel miRNA functionalized Ti implants with enhanced osteogenic activity promisingly lead to more rapid and robust osseointegration of a clinical bone implant interface. Our study implies that lyophilization may constitute a versatile method for miRNA loading to other biomaterials with the aim of controlling cellular function.
authors: Department of Prosthetic Dentistry, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an 710032, China.
authors: Kaimin
authors: K
authors: Wu
authors: Wen
authors: W
authors: Song
authors: Lingzhou
authors: L
authors: Zhao
authors: Mengyuan
authors: M
authors: Liu
authors: Jun
authors: J
authors: Yan
authors: Morten Østergaard
authors: MØ
authors: Andersen
authors: Jørgen
authors: J
authors: Kjems
authors: Shan
authors: S
authors: Gao
authors: Yumei
authors: Y
authors: Zhang
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D010084:Oxidation-Reduction; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry* / Q000633:toxicity; D014162:Transfection; D014466:Ultraviolet Rays
chemical_list: D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; C009495:titanium dioxide; D003094:Collagen; D014025:Titanium; D000469:Alkaline Phosphatase