2. Literature Review
2.4. The Role of Silicon in the Body and its Effects upon Bone
2.4.1. Toxicity
For decades silicon has been considered in terms of its toxicity and has previously been thought to be an environmental contaminant, rather than an essential ultra7 trace element. Oral ingestion of silicon is unlikely to result in toxic effects [99], however this may lead to conditions such as renal calculi, which has been associated with excessive silicon intake. Stewart et al. [100] showed by feeding rats 2700 mg of Si/kg urolithiasis could be induced. Subsequently, a reduction in silicon lowered this effect. The Food and Nutrient Board have no recommended adequate silicon intake for humans, although silicon requirement is estimated to be between 2720 mg day71 [99, 101].
2.4.2. Metabolism
Many dietary forms of silicon are known to exist; silica, tetraethylorthosilicate, monosilicic acid, sodium zeolite A and metasilicate. These are often derived from plant foods such as cereals, cereal products (especially beer), green beans and some mineral waters [102]. Dietary intake appears to have large affect on the amount of silicon absorbed into the body. Studies have shown that orthosilicic acid is the most readily available source of silicon to humans. It is unclear how much silicon is absorbed but research has shown this to be low amounts [103]. Silicon is broken down into monomeric silicon in the gastrointestinal tract and then absorbed, however the majority of ingested silicon is excreted in the urine typically within 3 7 8 h of ingestion. The mechanism of absorption is unknown and may be either by passive diffusion or active uptake. The degree of silicon polymerisation has been shown to influence the uptake of silicon with monomeric silicon being most easily absorbed and polymeric silicon most poorly absorbed [104].
2.4.3. Silicon and its effects on Growth and Bone Development
Silicon may be beneficial for healthy arteries [105], hair, nails and skin [106]. In general, silicon has been linked with the development and regulation of connective tissues of which most significantly bone and skeletal development [102]. The role of silicon within the skeletal system was first noted by Carlisle [107] who found abnormalities in bone and cartilage [110]. It has been suggested that the original studies of Carlisle and Schwarz and Milne may additionally have been depleted in other essential nutrients thus having cumulative adverse effects on growth and making the results difficult to interpret [102]. Alternatively, due to the ubiquity of silicon in the environment, low level silicon diets can be difficult to achieve and this may explain why no change in growth in chicks and rats was observed in subsequent studies [102]. Multiple studies have shown that increased silicon levels have beneficial effects on collagen synthesis [111] and that deficiency causes a reduction in connective tissue formation [112]. Silicon seems to affect the extracellular matrix formation of bone but may also have a role in the mineralisation events with accelerated mineralisation shown in rats [113]. Not only is silicon related to osteoblast up7regulation but studies have shown it to have a negative effect on bone resorption by a reduction of osteoclast numbers [114, 115].While there are much data available concerning the role of silicon in animal models, research in humans is less prevalent. Work has shown that administering
mg/day for four months to osteoporotic subjects increased trabecular bone volume when compared to untreated controls [116]. Subsequently, the bone mass density of femoral heads in osteoporotic women significantly increased after receiving 50 mg of monomethyl trisilanol twice weekly via intramuscular injection for 4 months [117]. A recent study by Jugdaohsingh et al. [118] reported higher dietary silicon intake resulting in higher bone mineral density at the hip of men and pre7menopausal women, but surprisingly not in post7menopausal women.
A number of authors have reported the positive effect which silicon has on osteoblast and chrondrocyte cells. Reffitt et al. [119] added orthosilicic acid at 107 20 bM concentrations to MG763 human osteosarcoma cells, fibroblasts and bone marrow stromal cells. In all cases collagen type I production was significantly higher than in unsupplemented cells. Furthermore, the MG763 cells exhibited increased differentiation as measured by osteocalcin and alkaline phosphatase activity.
Evidently there is a great deal of proof that silicon plays a beneficial role in the increased proliferation and differentiation of osteoblasts both in vitro and in vivo.
Therefore, silicon could be used as a cheap solution to aid the success of implant fixation and improve the quality of the surrounding bone tissue leading to a reduction in revision surgery. The following section will discuss this use of silicon in materials which could be suitable for orthopaedic applications.
2.4.4. Silicon in Biomaterials
The use of silicon in materials for bone repair is well established. Most notable is the bioceramic Bioglass®, which was discovered by Hench in 1969 and first used clinically in 1985. The material led to the concept of bioactive materials [120] and is available in multiple compositions but is mainly comprised approximately within
the ranges of 30755 wt % SiO2, 19.5724.5 wt % Na2O, 14.7724.5 wt % CaO and 6 wt % P2O5. The bioactivity of these materials, which are characterised by the ability of the material to form interfacial bonding with bone tissues, is in part due to the silicon content of the material. In the sequential interface reactions that
6 Adsorption of biological moieties in hydroxyl carbonated apatite layer 5 Crystallisation of hydroxyl carbonate apatite
4 Adsorption of amorphous Ca2+ + PO437 + CO327
3 Polycondensation of SiOH + SiOH 77> ≡Si7O7Si≡
Log time (Hours)
1 and 2 Formation of SiOH bonds
Figure 2013. The interfacial reactions involved in forming a direct bond between tissue and bioactive glasses . Taken from [121].
Silicon in these materials has been shown to have other advantages; Xynos et al.
[122] dissolved Bioglass® 45S5 in cell culture medium, which was shown to have an 88 fold increase in silicon content. Subsequently it was demonstrated that 190 genes out of 1,176 osteoblast genes were present at higher levels than the control cells. Upregulated genes included CD44, mitogen activated protein (MAP), kinase7 activated protein kinase 2, integrin β1 and RCL growth7related c7myc responsive gene. Only 5 genes were found to be downregulated. Although calcium and phosphate ions were present at increased levels, it was postulated that gene upregulation was related to the silicon ion content. Keeting et al. [123] showed osteoblasts to significantly increase their degree of proliferation and differentiation
compound, Zeolite A. Moreover, it was found that silicon induced the release of transforming growth factor β1 (TGF7β1). This topic is expanded in section 2.5, however silicon substituted HA is exclusively discussed rather than biomaterials generally.