Qiang Wang1, Xiaoying Wang2, Paloma Valverde3, Dana Murray3, Michel M Dard4, Thomas Van Dyke5, Qiaobing Xu6, Xin Xu7, Nadeem Karimbux8, Qisheng Tu9, Jake Chen10. 1. Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, USA; Jinan Stomatological Hospital, Jinan, 250001, Shandong, China; Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School and Hospital of Stomatology, Shandong University, 44-1Wenhuaxi Road, Jinan, 250012, Shandong, China. 2. Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, USA; Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School and Hospital of Stomatology, Shandong University, 44-1Wenhuaxi Road, Jinan, 250012, Shandong, China. 3. Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, USA. 4. Division of Oral, Diagnostic and Rehabilitation Sciences, College of Dental Medicine, Columbia University, New York, NY, 10032, USA. 5. Clinical and Translational Research, Forsyth Institute, Cambridge, MA, 02142, USA; Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA. 6. Department of Biomedical Engineering, School of Engineering, Tufts University, Medford, MA, USA. 7. Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School and Hospital of Stomatology, Shandong University, 44-1Wenhuaxi Road, Jinan, 250012, Shandong, China. 8. Department of Periodontology, School of Dental Medicine, Tufts University, Boston, MA, USA. 9. Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, USA. Electronic address: Qisheng.tu@tufts.edu. 10. Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, USA; Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, School of Graduate Biomedical Sciences, Boston, MA, USA. Electronic address: jk.chen@tufts.edu.
Abstract
OBJECTIVE: In this study, we aimed to investigate the therapeutic potential of miR-335-5p lipidoid nanocomplexes coated on Titanium (Ti) SLActive surface by lyophilization. DESIGN: In our model, we coated miR-335-5p/Lipidoid nanoparticles on titanium implant, seeded GFP-labelled mouse bone marrow stromal cells (BMSCs) onto the functionalized Ti implant surface, and analyzed the transfection efficiency, cell adhesion, proliferation, and osteogenic activity of the bone-implant interface. RESULTS: The Ti SLActive surface displayed a suitable hydrophilicity ability and provided a large surface area for miRNA loading, enabling spatial retention of the miRNAs within the nanopores until cellular delivery. We demonstrated a high transfection efficiency of miR-335-5p lipidoid nanoparticles in BMSCs seeded onto the Ti SLActive surface, even after 14 days. Alkaline phosphatase (ALP) activity and cell vitality were significantly increased in BMSCs transfected with miR-335-5p at 7 and 14 days as opposed to cells transfected with negative controls. When miR-335-5p transfected BMSCs were induced to undergo osteogenic differentiation, we detected increased mRNA expression of osteogenic markers including Alkaline phosphatase (ALP), collagen I (COL1), osteocalcin (OCN) and bone sialoprotein (BSP) at 7 and 14 days as compared with negative controls. CONCLUSION: MiR-335-5p lipidoid nanoparticles could be used as a new cost-effective methodology to increase the osteogenic capacity of biomedical Ti implants.
OBJECTIVE: In this study, we aimed to investigate the therapeutic potential of miR-335-5p lipidoid nanocomplexes coated on Titanium (Ti) SLActive surface by lyophilization. DESIGN: In our model, we coated miR-335-5p/Lipidoid nanoparticles on titanium implant, seeded GFP-labelled mouse bone marrow stromal cells (BMSCs) onto the functionalized Ti implant surface, and analyzed the transfection efficiency, cell adhesion, proliferation, and osteogenic activity of the bone-implant interface. RESULTS: The Ti SLActive surface displayed a suitable hydrophilicity ability and provided a large surface area for miRNA loading, enabling spatial retention of the miRNAs within the nanopores until cellular delivery. We demonstrated a high transfection efficiency of miR-335-5p lipidoid nanoparticles in BMSCs seeded onto the Ti SLActive surface, even after 14 days. Alkaline phosphatase (ALP) activity and cell vitality were significantly increased in BMSCs transfected with miR-335-5p at 7 and 14 days as opposed to cells transfected with negative controls. When miR-335-5p transfected BMSCs were induced to undergo osteogenic differentiation, we detected increased mRNA expression of osteogenic markers including Alkaline phosphatase (ALP), collagen I (COL1), osteocalcin (OCN) and bone sialoprotein (BSP) at 7 and 14 days as compared with negative controls. CONCLUSION: MiR-335-5p lipidoid nanoparticles could be used as a new cost-effective methodology to increase the osteogenic capacity of biomedical Ti implants.
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