Time- and Concentration-Dependent Effects of Dissolution Products of 58S Sol–Gel Bioactive Glass on Proliferation and Differentiation of Murine and Human Osteoblasts

Abstract

Bone loss is a significant clinical problem, and treatments utilizing donated graft material are limited. To meet future demands in the healthcare industry, there has been a shift of outlook toward the use of bioactive materials for tissue regeneration. A number of in vivo and in vitro studies have highlighted the potential of the bioactive glass ceramic 45S5 Bioglass as a synthetic regenerative scaffold. The application of sol-gel processing techniques has led to the synthesis of mesoporous bioactive glasses with greater textural and compositional variety. In this study, we evaluated the effects of supplemented tissue culture medium containing up to 203 ppm silica prepared by static soaking of particles of 58S sol-gel bioactive glass (58% SiO(2), 33% CaO, 9% P(2)O(5)) on the in vitro proliferation and differentiation of murine and human primary osteoblasts. These extracts had a higher silica content than those used previously in studies of 45S5 Bioglass, because of the faster rates of ion exchange permitted by the higher surface area-to-volume ratio of mesoporous glass. We found that osteoblasts from both species increased their proliferation in response to the glass-conditioned medium. In addition, the extent to which supplemented medium could alter cell differentiation varied with time in culture. Proliferation induced by supplemented medium paralleled effects induced by treatment with basic fibroblast growth factor, a known mitogenic growth factor for osteoblasts. Bone nodule formation was also increased by exposure to the glass-conditioned medium and this effect was positively correlated with the dose of glass used to prepare the medium. Apoptosis was stimulated by glass-conditioned medium in murine osteoblasts, but inhibited in human osteoblasts. These data demonstrate the bioactive effects of dissolution products derived from sol-gel materials on primary osteoblasts and complements in vivo studies that indicate the suitability of this material as a bone graft substitute.

Bioactive Glass and Glass-Ceramic Scaffolds for Bone Tissue Engineering

“…Key mechanisms leading to enhanced new bone growth are now known to be related to the controlled release of ionic dissolution products from the degrading bioactive glass, especially critical concentrations of biologically active, soluble silica and calcium ions [8,191]. Recent studies have shown that bioactive (partially) resorbable glasses and their ionic dissolution products enhance osteo-genesis by regulating osteoblast proliferation, differentiation, and gene expression [7,41,51,191,192,193,194,195,196,197,198]. …”

“…It has been hypothesized, but to the authors’ knowledge not proven as yet, that the high silicon concentration from bioactive glass could be a major factor in stimulating osteoblasts to grow fast, which might be effective for melt-derived bioactive glasses [7,36,196]. However, Bielby et al [192] found no significant differences in the proliferation of human primary osteoblasts grown in conditioned cell culture media containing similar Ca, P, and Na ions but different Si ion concentrations (164 and 203 ppm) released from 58S sol-gel derived glass. Clearly, more fundamental investigations and further studies are required to gain quantitative knowledge and to confirm the conditions and the mechanisms leading to glass degradation and ion dissolution products affecting gene expression in bone cells.…”

Twenty-first century challenges for biomaterials

“…Bone biology and gene array analyses of five different in vitro models using four different sources of inorganic ions provide the experimental evidence for a genetic theory of osteogenic stimulation (Maroothynaden & Hench 2001;Xynos et al 2001;Hench 2003;Bielby et al 2004Bielby et al , 2005Gough et al 2004;Christodoulou et al 2005a,b;Jones et al 2007). The cell and organ culture models used in these studies are summarized in table 2.…”

“…For example, growth on a bioactive substrate (45S5 Bioglass) enhances derivation of osteogenic cells from ES cells. Bielby et al (2004) showed that soluble ionic extracts containing Si and Ca cations obtained from 58S bioactive gel glasses enhance differentiation of the osteoblast-specific lineage from murine ES cells (Bielby et al 2004). Differentiation of ES cells into osteogenic cells was characterized by the formation of multi-layered, mineralized bone nodules.…”

Bioactive Glass Nanoparticles: From Synthesis to Materials Design for Biomedical Applications

“…Bioactive glasses have been shown to be osteo-inductive, their dissolution products enhancing osteoblasts differentiation, upregulating the expression of genes playing a role in osteoblasts metabolism, proliferation and adhesion [48,49,50,51,52]. Bioactive glasses nanoparticles are thus highly attractive for bone tissue repair and regeneration.…”