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School of Metallurgy and Materials Engineering, Iran University of Science and ... National Cell Bank of Iran, Pasteur Institute of Iran, P.O. Box 131...
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Bio-interactions and Biocompatibility

Incorporation of Nano-Alumina Improves Mechanical Properties and Osteogenesis of Hydroxyapatite Bioceramics Hossein Tavassoli, Jafar Javadpour, Mahdiar Taheri, Morteza Mehrjou, Newsha Koushki, Farzin Arianpour, Mohammad Majidi, Jalal Izadi-Mobarakeh, Babak Negahdari, Peggy Pui Yik Chan, Majid Ebrahimi Warkiani, and Shahin Bonakdar ACS Biomater. Sci. Eng., Just Accepted Manuscript • DOI: 10.1021/ acsbiomaterials.7b00754 • Publication Date (Web): 05 Mar 2018 Downloaded from http://pubs.acs.org on March 10, 2018

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ACS Biomaterials Science & Engineering

Incorporation of Nano-Alumina Improves Mechanical Properties and Osteogenesis of Hydroxyapatite Bioceramics

Hossein Tavassoli1,2,7,8, Jafar Javadpour1, Mahdiar Taheri1,3, Morteza Mehrjou2, Newsha Koushki4, Farzin Arianpour1, Mohammad Majidi2, Jalal Izadi-Mobarakeh5, Babak Negahdari6, Peggy Pui Yik Chan7, Majid Ebrahimi Warkiani9* and Shahin Bonakdar2*

1. School of Metallurgy and Materials Engineering, Iran University of Science and Technology, P.O. Box 16846-13114, Tehran, Iran. 2. National Cell Bank of Iran, Pasteur Institute of Iran, P.O. Box 13169-43551, Tehran, Iran 3. ANU College of Engineering & Computer Science, The Australian National University, Canberra, ACT 2601, Australia 4. Department of Bioengineering, McGill University, Montreal Canada H3A 0C3 5. Physiology and Pharmacology Department, Pasteur Institute of Iran, P.O. Box 13169-43551, Tehran, Iran 6. School of Advanced Technologies in Medicine, Department of Medical Biotechnology, Tehran University of Medical Sciences, Tehran, Iran 7. Department of Biomedical Engineering, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia 8. School of Mechanical and Manufacturing Engineering, University of New South Wales, Sydney, NSW 2052, Australia 9. School of Biomedical Engineering, University of Technology Sydney, 2007 Australia

* Contact: Majid Ebrahimi Warkiani ([email protected]) School of Biomedical Engineering, University of Technology Sydney, 2007 Australia Australian Centre for NanoMedicine, Sydney, NSW 2033, Australia Shahin Bonakdar ([email protected]) National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran.

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Abstract A handful of work focused on improving the intrinsic low mechanical properties of hydroxyapatite (HA) by various reinforcing agents.  However, the big challenge regarding improving mechanical properties is maintaining bioactivity. To address this issue, we report fabrication of apatite-based composites by incorporation of alumina nanoparticles (n-Al2O3). Although numerous studies have used micron or submicron alumina for reinforcing hydroxyapatite, only few reports are available about the use of n-Al2O3. In this study, spark plasma sintering (SPS) method was utilized to develop HA-nAl2O3 dense bodies. Compared to the conventional sintering, decomposition of HA and formation of calcium aluminates phases are restricted using SPS. Moreover, n-Al2O3 acts as a bioactive agent while its conventional form is an inert bioceramics. The addition of n-Al2O3 resulted in 40% improvement in hardness along with a 110% increase in fracture toughness, while attaining nearly full dense bodies. The in-vitro characterization of nanocomposite demonstrated improved bone-specific cell function markers as evidenced by cell attachment and proliferation, alkaline phosphatase activity, calcium and collagen detection and nitric oxide production. Specifically, gene expression analysis demonstrated that introduction of n-Al2O3 in HA matrix resulted in accelerated osteogenic differentiation of osteoblast and mesenchymal stem cells, as expression of Runx-2 and OSP showed 2.5 and 19.6 fold increase after 2 weeks (p