Surface properties and ion release from fluoride-containing bioactive glasses promote osteoblast differentiation and mineralization in vitro

Abstract

1 IntroductionBioactive glasses (BG) have the ability to bond directly with living tissue via the formation of a hydroxycarbonate apatite-like layer on their surface, and are therefore utilised in a variety of dental and orthopaedic applications [1,2]. However, this is not their only mechanism of action. BG can also be designed to release ions that stimulate specific cell behaviour. Indeed, we have recently reported on BG that release strontium ions, the active component of the osteoporosis drug strontium ranelate, which act to both promote osteoblast activity and inhibit osteoclast activity [3].Fluoride is widely recognised for its ability to prevent dental caries as it inhibits dentine and enamel demineralisation [4], however, it also affects the axial skeleton. That is, clinical examinations of osteoporotic patients have demonstrated that fluoride treatment stimulates bone formation [5]. Nevertheless, in placebocontrolled, double-blind clinical trials, sodium fluoride (NaF) was found not to be efficacious in preventing osteoporosis-related fractures [6,7]. In subsequent detailed analyses of these trials, fluoride's lack of efficacy was attributed to its substitution into bone apatite, creating structurally and mechanically inferior bone, as mineral crystal size and crystallinity increased [8]. Consequently, fluoride's use as an osteoporosis treatment was largely dismissed. Moreover, this seemed judicious as osteomalacia was reported in patients treated with NaF [9], and skeletal fluorosis, which is endemic in areas with high levels of fluoride in the ground water, is known to cause a range of skeletal abnormalities [10].As clinical trials with fluoride failed to demonstrate clear anti-fracture efficacy, other osteoporosis drugs have come into favour. Anti-catabolic agents such 2 as bisphosphonates, which block osteoclast-mediated bone resorption via inhibition of the mevalonate pathway [11] are widely prescribed. However, anti-catabolic agents only prevent further bone resorption and do not promote bone formation.Furthermore, long-term bisphosphonate use has been associated with osteonecrosis of the jaw [12] and atypical, low-energy femur fractures [13], which has created reluctance among some clinicians to prescribe them. Anabolic agents such as recombinant parathyroid hormone (PTH), which stimulate osteoblast-mediated bone matrix formation [14], are also often administered. However, PTH is expensive and requires daily subcutaneous injections. As a result, alternative treatments, such as inexpensive NaF, have recently been re-examined [15].In vitro studies point towards a small dosing range for NaF that will successfully promote osteoblast activity [16], and recent meta-analyses have shown that fluoride is efficacious in preventing osteoporosis-related fractures when administered at doses lower than those used in the widely reported clinical trials [17].Furthermore, in vitro studies have demonstrated that fluoride has an anabolic effect on bone, enhancing osteoblast proliferation [18, 19] and alkaline phosp...

Novel nanocomposite biomaterials with controlled copper/calcium release capability for bone tissue engineering multifunctional scaffolds

“…Both inorganic and organic biomaterials (such as ceramics and polymers, respectively) have been widely used to prepare scaffolds with those requirements [3,[5][6][7][8][9]. Among ceramics, bioactive glasses-particularly Bioglass w 45S5-exhibit interesting properties for BTE [7,8,[10][11][12][13][14], such as the promotion of the formation of bone-like hydroxyapatite (HA) layers on the biomaterial surface [15,16], and their osteoconductive and osteoinductive characteristics [6,17,18]. In addition, reports indicate that dissolution products from bioactive glasses upregulate the expression of genes that control osteogenesis [13,[17][18][19] and induce proangiogenic effects by stimulating the production of vascular endothelial growth factor (VEGF) [20,21], the secretion of angiogenic growth factors in fibroblasts [22,23], the proliferation of endothelial cells [22][23][24] and the formation of endothelial tubules [22].…”

Long term effects of bioactive glass particulates on dental pulp stem cells in vitro

“…Previously Hench et al showed that approximately 17-21 ppm of soluble Si and 60-88 ppm of soluble Ca ions were required for osteoblasts to grow, differentiate and form a mineralized extracellular matrix and create bone nodules [40]. In a study by Chen et al [41], it was shown that the exposure of 50 mg/mL bredigite extracts had a profound effect in delaying cell senescence, stimulating pluripotency-related gene expression and enhancing odontogenic and adipogenic differentiation.…”

The role of fluoride in the nanoheterogeneity of bioactive glasses

“…In vitro cell culture results on fluoride--containing bioactive glasses showed contradictory results with regard to cell proliferation, toxicity and bone mineralisation (26,57) . These differences may be related to the use of different cell lines or experimental design (particulate vs. monolith bioactive glass), but they may also be related to differences in glass design and resulting structure: As in some of the studies the silicate network polymerisation changed upon incorporation of fluoride (57) , and as changes in silicate polymerisation are known to be linked to bioactivity (8,43) , results from in vitro cell tests may have been affected by changes in bioactive glass degradation and bioactivity (17) .…”

“…Bioactive glasses are typically multicomponent systems, often containing two network formers (SiO2 and smaller amounts of P2O5 (8) ) besides large concentrations of various network modifiers (CaO and Na2O mostly, but also SrO (22) , K2O (23) , MgO (24) or Li2O (25) ) as well as other components such as fluorides (26) or chlorides (27) , making the occurrence of heterogeneities at a nano--scale more likely. Heterogeneities are understood to be important factors in effects such as phase separation, nucleation and crystallisation (28) or density and rigidity (29) in glasses, but are also likely to affect degradation and ion release (30) .…”