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CERIUM, ZIRCONIUM AND COPPER DOPED ZINC OXIDE NANOPARTICLES FOR BONE REGENERATION AND ANGIOGENESIS
H Akhtar1, J A Darr2, T Ashton2 , AA Chaudhry3, and I U Rehman4 & GC Reilly1
hakhtar2@sheffield.ac.uk, j.a.darr@ucl.ac.uk, t.ashton@ucl.ac.uk, aqifanwar@cuilahore.edu.pk, i.u.rehman@lancaster.ac.uk, g.reilly@sheffield.ac.uk.
1 INSIGNEO institute for in silico Medicine, University of Sheffield, UK, 2 Clean Materials Technology Group, University College London (UCL), UK, 3 Interdisciplinary Research Centre in Biomedical Materials (IRCBM), Pakistan, 4 Bioengineering, Engineering Department Lancaster University, UK.
Introduction: Bone tissue engineering (TE) is a therapeutic strategy to induce bone repair. Bone TE scaffolds often combine ceramic and polymeric materials to capture the advantages of each to create strong, tough and bioactive materials. However most current bone TE strategies still suffer from insufficient bone vessel recruitment into the defect region. Zinc Oxide has recently caught attention in the field of nanomaterials for its ability to induce upregulation of fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) while improving the scaffold surface properties. In this research, we propose synthesis of novel composite materials made from polyurethane, hydroxyapatite and doped zinc oxide nanoparticles.
Methods: ZnO and doped ZnO nanoparticles (cerium, copper and zirconium doped nanoparticles) were synthesised using a hydrothermal flow system. The nanoparticles were characterised and the most viable doped ZnO nanoparticles were selected for scaffold synthesis. The freeze extraction salt leaching technique was used to fabricate porous polyurethane foams substituted with nano hydroxyapatite and zinc oxide or doped ZnO. Human Embryonic Stem Cell-Mesenchymal progenitors (hES-MPs) and Bone Marrow Stromal cells Y201 were used to evaluate the cell metabolic activity, cell adhesion and cell seeding efficiency.
Results: The ZnO_2 and ZrZnO5 incorporated scaffolds improved the tensile strength from 0.3MPa (PU porous scaffold) to 0.87MPa and 0.81MPa respectively. The cell culture data suggested the ZrZnO5 incorporated scaffolds likely stimulated the cells to proliferate at a faster rate as compared to cells on CeZnO5 and CuZnO5 containing scaffolds. Overall, the doped ZnO incorporated nanoparticles stimulated the Y201 cells to attach and proliferate better on scaffolds as compared to controls. The copper doped ZnO and cerium Doped ZnO incorporated scaffolds were found to be the most efficient when it comes to cell attachment as the highest cell metabolic activity was recorded after 16hours of cell seeding.
Figure 1: Cell Seeding Efficiency after 16 hours incubation with Y201 cells. A) The metabolic activity assay was performed to identify viable cells attached on scaffolds and Tissue Culture plastic(TCP). B) the percentage cell attachment is shown with control being considered 100%(cells on TCP). CuZnO5 incorporated scaffolds showed 80% cell attachment. Data represents mean±S.D, n= 3, N=3
Conclusions: The ability of doped ZnO nanoparticles to support Y201 cell attachment and proliferation is better than HA alone, combined with previous data indicating their ability to enhance angiogenesis, indicates their potential for use in improved bone bone tissue engineering scaffolds.
Acknowledgements: Prof. P Genever, University of York for Y201 cells. European Union’s Horizon 2020 research and innovation programme H2020-MSCA-RISE under grant agreement No 777926 and Doctoral academy, University of Sheffield for the funding.
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