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Title: Does copper ion release from hydroxyapatite bioceramics mediate angiogenisis?
Author: Imrie, Flora Elisabeth
ISNI:       0000 0004 5916 4835
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2015
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Copper ions are widely reported to have pro-angiogenic properties and can be incorporated into bone substitute bioceramics as bio-instructive cues to stimulate infiltration of blood vessels into the material after implantation. By this, the viability of bone forming cells within the scaffold (which decreases rapidly with increasing depth from the surface) could be enhanced, and the healing process (resorption and replacement of the scaffold with new, natural bone) hastened. Pure-phase copper-doped hydroxyapatite (CuHA) materials with x = 0 - 1 in the nominal formula Ca10(PO4)6CuxOy(H)z were prepared by solid state synthesis at 1100 °C. Attempted preparation of compositions with y = 0.1 and 0.5 in the nominal formula Ca10−yCuy(PO4)6(OH)2 by an aqueous precipitation method led to formation of biphasic products containing considerable amounts of β-tricalcium phosphate. Dissolution tests in TRIS buffer, cell culture medium and citric acid buffer indicated that copper ions are released from CuHA materials at concentrations that increase with copper content in the materials and soaking time, and are in a physiologically-relevant range. This offers the potential to tune copper ion release by controlling the copper content of CuHA materials. In vitro in cultures of human osteoblast-like cells and human mesenchymal stem cells (hMSCs), copper ions released from CuHA downregulated ALP expression in both cell types and (particularly for hMSCs) upregulated VEGF expression. In vivo, the prepared copper-containing materials had pro-angiogenic and possible inflammatory effects in the chick embryo yolk sac membrane and chorioallantoic membrane angiogenesis assays. Copper ions released from beads grafted into the developing chick limb affected the integrity of developing blood vessels in the graft vicinity, causing haemorrhaging. The results suggest that the coupling of angiogenesis and osteogenesis, perhaps through the hypoxia and NO pathways, are important for copper's biological effects, and with further investigation and careful control of dose and timing these effects may be better understood and controlled.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Copper ions ; Hydroxyapatite ; Ceramics in medicine ; Neovascularization