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Optimizing the dispersion of calcium phosphate nanoparticles for cellular studies using statistical design of experiments
Affiliation:1. School of Mechanical Engineering, Shandong University of Technology, Zibo, 255000, China;2. School of Materials Science and Engineering, Shandong University of Technology, Zibo, 255000, China;3. Institute of Additive Manufacturing, Shandong University of Technology, Zibo, 255000, China;4. Shandong Industrial Ceramics Research & Design Institute Co., Ltd., Zibo, 255000, China;5. School of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo, 255000, China;1. Key Laboratory of Aero-engine Thermal Environment and Structure, Ministry of Industry and Information Technology, College of Energy and Power Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 210016, PR China;2. Jiangsu Province Key Laboratory of Aerospace Power System, College of Energy and Power Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 210016, PR China;3. State Key Laboratory of Mechanics and Control of Mechanical Structures, Nanjing University of Aeronautics and Astronautics, Nanjing, 210016, PR China;1. Key Laboratory of Electronic Functional Composite Materials of Guizhou Province, College of Big Data and Information Engineering, Guizhou University, Guiyang, 550025, PR China;2. School of Electronic and Communication Engineering, Guiyang University, Guiyang, 550005, PR China;1. University of Science and Technology of China, Hefei, 230026, China;2. Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, Shanghai, 201800, China;3. University of Chinese Academy of Sciences, Beijing, 100049, China;4. University of North Texas, Denton, 76201, USA
Abstract:The in vitro experimentation of ceramic nanoparticles often requires their dispersion in liquid media without causing particle clumps or deteriorating sample integrity. However, the dispersion of nanoparticles using the available protocols rarely leads to stable and uniform dispersions which, in turn, raises concerns about the validity, repeatability and comparability of the findings observed in vitro. Moreover, the ability to control the final dispersion quality of ceramic nanoparticles is an essential step to obtaining optimized nanoceramic materials with desired functionality and to enhancing their performance in subsequent applications. While the need to have a comprehensive guideline for the dispersion of nanoparticles has led to several published documents and protocols, the dispersion methodology of ceramic nanoparticles and the relative contribution of the experimental parameters to the quality of resulting dispersion are still not clear. Here, we employed the statistical design of experiment (DoE) approach to systematically assess the magnitude and source of variation in dispersion quality of two different ceramic nanoparticles, hydroxyapatite and tricalcium phosphate. Using the first-order Plackett-Burman Design (PBD), nanoparticle concentration, pH and the presence of an additive were identified as the most critical factors influencing the resulting hydrodynamic size and zeta potential of the ceramic nanoparticles. Optimization using a second-order Central Composite Design (CCD) yielded a set of quadratic regression equations that were used to predict the hydrodynamic size or zeta potential of ceramic nanoparticles with high accuracy (R2, 0.88–0.92). The results of PBD screening and CCD optimization experiments were employed to prepare nanoparticle dispersions of different quality, which were then used to compare the effect of aggregation on the viability of human osteosarcoma (SaOS-2) cells. Overall, the results of this study provided insight into the role that various experimental parameters play in the colloidal stability and dispersion of ceramic nanoparticles.
Keywords:Nanoparticles  Nanoceramics  Nano-powders  Dispersion  Optimization  Design of experiment
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