Bioactive Glass Stimulates the Secretion of Angiogenic Growth Factors and Angiogenesis in Vitro

Abstract

Neovascularization of tissue-engineered constructs remains a limiting factor for the engineering of larger tissue constructs. Attempts to stimulate neovascularization, using recombinant protein or gene transfer of angiogenic growth factors, have been proposed; however, these approaches have been associated with problems regarding the delivery and duration of exposure of the growth factor. This study was performed to determine the ability of biologically active glass to stimulate the secretion of angiogenic growth factors from human stromal cells and subsequent angiogenesis. CCD18Co human fibroblasts were cultured on tissue culture surfaces coated with specific quantities of 45S5 Bioglass particles. At 24-, 48-, and 72-h intervals the gene expression of vascular endothelial growth factor (VEGF) and the protein secretion of VEGF and basic fibroblast growth factor (bFGF) from fibroblasts were measured. The effect of conditioned medium collected from Bioglass-stimulated fibroblasts on human dermal microvascular endothelial cells was assessed using in vitro angiogenesis assays. Results showed that surfaces coated with Bioglass produced a significant increase in the secretion of VEGF and bFGF. Conditioned medium from stimulated fibroblasts significantly increased the proliferation of human dermal microvascular endothelial cells and induced a significant increase in the formation of anastomosed networks of human endothelial cell tubules. It is concluded that the ability of 45S5 Bioglass to stimulate the release of angiogenic growth factors and to promote angiogenesis provides a novel alternative approach for stimulating neovascularization of tissue-engineered constructs.