title: Effect of ion release from Cu-doped 45S5 Bioglass® on 3D endothelial cell morphogenesis.
abstract: Both silicate-based bioactive glasses and copper ions have demonstrated angiogenic activity and therefore represent promising bioinorganic agents for the promotion of vascularization in tissue-engineered scaffolds. This study examined the effect of ionic release products from 45S5 Bioglass® doped with 0 and 2.5 wt.% CuO (BG and Cu-BG respectively) on the formation of capillary-like networks by SVEC4-10 endothelial cells (ECs) seeded in a three-dimensional (3D) type I collagen matrix. Copper and silicon release following 24h dissolution increased non-proportionally with Cu-BG concentration in cell culture medium, while calcium levels were decreased below the initial medium concentration. EC network length, connectivity, branching, quantified by means of a 3D morphometric image analysis method, as well as proliferation and metabolic activity were reduced in a dose-dependent fashion by BG and Cu-BG ionic release products. This reduction was less prominent for BG compared to an equivalent concentration of Cu-BG, which was attributed to a lower extent of silicon release and calcium consumption. Moreover, a CuCl2 dose equivalent to the highest concentration of Cu-BG exhibited no effect on ECs. In conclusion, while the previously reported pro-angiogenic activity of both Bioglass® and copper may not be reflected in a direct response of ECs, this study provides a maximum glass concentration for non-harmful angiogenic stimulation to be examined in future work.
authors.affiliation: Department of Mining and Materials Engineering, McGill University, 3610 University Street, Montreal, QC H3A 0C5, Canada. Electronic address: christoph.staehli@mail.mcgill.ca.
authors.forename: Christoph
authors.initials: C
authors.lastname: Stähli
authors.affiliation: Department of Mining and Materials Engineering, McGill University, 3610 University Street, Montreal, QC H3A 0C5, Canada. Electronic address: mark.james-bhasin@mail.mcgill.ca.
authors.forename: Mark
authors.initials: M
authors.lastname: James-Bhasin
authors.affiliation: Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Cauerstrasse 6, 91058 Erlangen, Germany. Electronic address: alexander.hoppe@ww.uni-erlangen.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoppe
authors.affiliation: Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Cauerstrasse 6, 91058 Erlangen, Germany. Electronic address: aldo.boccaccini@ww.uni-erlangen.de.
authors.forename: Aldo R
authors.initials: AR
authors.lastname: Boccaccini
authors.affiliation: Department of Mining and Materials Engineering, McGill University, 3610 University Street, Montreal, QC H3A 0C5, Canada. Electronic address: showan.nazhat@mcgill.ca.
authors.forename: Showan N
authors.initials: SN
authors.lastname: Nazhat
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002516:Ceramics / Q000737:chemistry* / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005898:Glass / Q000737:chemistry*; D007477:Ions / Q000494:pharmacology; D008422:Materials Testing; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects / Q000502:physiology*; D054457:Tissue Scaffolds
chemical_list: D007477:Ions; C425330:bioactive glass 45S5; D003300:Copper
keywords: Angiogenesis; Bioactive glass; Bioinorganics; Capillary-like network; Copper