Effect of ion release from Cu-doped 45S5 Bioglass® on 3D endothelial cell morphogenesis

Christoph Stähli; Mark James-Bhasin; Alexander Hoppe; Aldo R Boccaccini; Showan N Nazhat

doi:10.1016/j.actbio.2015.03.009

Effect of ion release from Cu-doped 45S5 Bioglass® on 3D endothelial cell morphogenesis

Acta Biomater. 2015 Jun:19:15-22. doi: 10.1016/j.actbio.2015.03.009. Epub 2015 Mar 12.

Authors

Christoph Stähli¹, Mark James-Bhasin², Alexander Hoppe³, Aldo R Boccaccini⁴, Showan N Nazhat⁵

Affiliations

¹ Department of Mining and Materials Engineering, McGill University, 3610 University Street, Montreal, QC H3A 0C5, Canada. Electronic address: [email protected].
² Department of Mining and Materials Engineering, McGill University, 3610 University Street, Montreal, QC H3A 0C5, Canada. Electronic address: [email protected].
³ Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Cauerstrasse 6, 91058 Erlangen, Germany. Electronic address: [email protected].
⁴ Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Cauerstrasse 6, 91058 Erlangen, Germany. Electronic address: [email protected].
⁵ Department of Mining and Materials Engineering, McGill University, 3610 University Street, Montreal, QC H3A 0C5, Canada. Electronic address: [email protected].

PMID: 25770928
DOI: 10.1016/j.actbio.2015.03.009

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.

Keywords: Angiogenesis; Bioactive glass; Bioinorganics; Capillary-like network; Copper.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Cell Proliferation / drug effects
Cell Proliferation / physiology
Ceramics / chemistry*
Ceramics / pharmacology*
Copper / chemistry*
Copper / pharmacology*
Endothelial Cells / cytology
Endothelial Cells / drug effects
Endothelial Cells / physiology*
Glass / chemistry*
Ions / pharmacology
Materials Testing
Mice
Morphogenesis / drug effects
Morphogenesis / physiology*
Tissue Scaffolds

Substances

Ions
bioactive glass 45S5
Copper