Silicon: The evolution of its use in biomaterials

doi:10.1016/j.actbio.2014.09.025

Acta Biomaterialia

Volume 11, 1 January 2015, Pages 17-26

https://doi.org/10.1016/j.actbio.2014.09.025 Get rights and content

Abstract

In the 1970s, several studies revealed the requirement for silicon in bone development, while bioactive silicate glasses simultaneously pioneered the current era of bioactive materials. Considerable research has subsequently focused on the chemistry and biological function of silicon in bone, demonstrating that the element has at least two separate effects in the extracellular matrix: (i) interacting with glycosaminoglycans and proteoglycans during their synthesis, and (ii) forming ionic substitutions in the crystal lattice structure of hydroxyapatite. In addition, the dissolution products of bioactive glass (predominantly silicic acids) have significant effects on the molecular biology of osteoblasts in vitro, regulating the expression of several genes including key osteoblastic markers, cell cycle regulators and extracellular matrix proteins. Researchers have sought to capitalize on these effects and have generated a diverse array of biomaterials, which include bioactive glasses, silicon-substituted hydroxyapatites and pure, porosified silicon, but all these materials share similarities in the mechanisms that result in their bioactivity. This review discusses the current data obtained from original research in biochemistry and biomaterials science supporting the role of silicon in bone, comparing both the biological function of the element and analysing the evolution of silicon-containing biomaterials.

Graphical abstract

Introduction

Silicon is the eighth most abundant element in the solar system [1], and makes up 27.7% of the Earth’s crust by weight, second only to oxygen (46.6%) [2]. Despite this geological abundance, silicon is rarely found in biology, occurring as a trace element in higher animals and forming <0.01% by weight of the human body [3]. Indeed, most naturally occurring forms of silicon are indigestible by higher animals, limiting the degree to which silicon can enter the diet.

Silicon is found in greater abundance in plants (in which silica is often used to strengthen cell walls in the form of phytoliths; Fig. 1A) and in the frustules surrounding marine algae, diatoms and radiolarians [4], [5], [6] (Fig. 1B). The biochemical processing of silicon can be investigated easily in these simpler organisms, leading to fascinating observations regarding the molecular interactions between silicate species and biochemicals [7], [8], some of which (such as silicate interactions with ascorbic acid) also have implications in the biology of higher animals [9].

Silicon occurs in a variety of natural and synthetic forms: as small molecular species (e.g. silicic acid and silane); as silicon-based macromolecules (e.g. silicones); as silicates (e.g. dicalcium silicate); as silica (e.g. quartz and amorphous silicon dioxide); as ceramics (e.g. silicon carbide and silicon nitride) and in its pure elemental solid form as the semiconductor Si (both crystalline Si and hydrogenated amorphous silicon). This review brings together data from such disparate classes of materials to summarize knowledge on silicon-based molecules, compounds and composites that are receiving increasing attention from the biomaterials community. An emphasis is placed on the orthopaedic applications, although other medical uses for silicon are also under investigation.

Section snippets

Dietary silicon

Orthosilicic acid is the only dietary form of silicon that is biologically available to higher animals [10]. It is formed in nature by the action of acidified water on silica and silicate rocks, such as those exposed to rain and terrestrial groundwater or by the action of seawater on marine rock and animal debris, and can also be produced by the action of acidified water on pure silica such as quartz or glass.

Soluble silicic acids are absorbed by omnivores from four main sources: directly from

Polymerization of silicic acids into silica

Polymerization of soluble orthosilicic acid into larger polysilicic acids occurs through condensation of silanol groups, the formation of connecting siloxane bonds and partial dehydration, as illustrated in Fig. 2B. Polymerization continues to form increasingly higher-weight polysilicic acids that have correspondingly lower solubility, with silicic acid octomers being effectively insoluble in water [17]. Insoluble polysilicic acids condense to form colloidal particles of hydrated silica that

The role of silicon in bone biology

Silicon was found to be an essential element for normal development by Carlisle [23], [24], [25] and Schwarz [26], with the main effects of silicon-deficient diets being abnormal bone and cartilage formation. Similarly, Carlisle also demonstrated that chicks fed a silicon-supplemented diet (28 μg ml⁻¹ silicon as sodium metasilicate) had enhanced bone growth, increased amounts of articular cartilage, increased bone water content and biochemical changes in the mineral, hexosamine and collagen

Silicon substitution in hydroxyapatite

While bone mineral is generally referred to as hydroxyapatite (HA), the molar calcium/phosphorus ratios found in bone are slightly different from phase pure HA [42]. This results from the ionic substitutions for calcium and phosphate in the matrix with numerous other atoms and small molecules, such as magnesium and strontium for Ca²⁺ [43] with the majority of substitutions found in healthy bone being carbonate (0.79 mmol g⁻¹), sodium (0.32 mmol g⁻¹) and magnesium (0.17 mmol g⁻¹) [44]. In addition to

Silicon in the extracellular matrix

Research by Schwarz [25] demonstrated that silicon is essential to the normal development of the glycosaminoglycan network in the extracellular matrix, helping to stabilize complex polysaccharide structures and forming crosslinks via silanolate (R–O–Si–O–R and R–O–Si–O–Si–O–R) bonds that regulate the structure and function of these molecules. Almost concurrently, Carlisle demonstrated that Si-supplemented embryonic chick bones showed a 100% increase in collagen content over silicon-low bones

Bioactive glass and the response of osteoblasts to silicate biomaterials

Since the discovery by Hench in the 1960s that certain glass compositions can form a strong chemical bond to living bone (comprehensively reviewed in Hench [48] and Jones [49]), research has focused on the properties of these materials that are responsible for their biocompatibility [49]. Having a low silica content of <60% and a calcium/phosphorous ratio similar to HA, 45S5 Bioglass supports the attachment and proliferation of osteoblasts, resulting in the incorporation of the Bioglass into

Silica sol–gels and porous silica nanoparticles

Melt-derived bioactive glasses lose their bone-bonding ability when the silica ratio exceeds 60% of the material, leading researchers to conclude that the silica phase is paramount in conferring osteogenic effects. By precipitating sol–gels composed purely of silica, the effects on osteoblasts of glass-like materials could be determined without the confounding influences of other ionic constituents found in Bioglass. Anderson et al. [65] found that osteoblasts adhered to silica gels, and while

Porous silicon

Porous silicon (pSi) was discovered by accident in 1956 at the Bell laboratories in the US as an undesired product of electrochemical methods for polishing and shaping silicon surfaces for use as semiconductors [73], [74]. Under certain conditions, the combination of acid etching under an anodic current resulted in the formation of a thick black, red or brown film on the material’s surface. As this was regarded as a failure for the electropolishing of silicon wafers, the discovery was not

Silicon-substituted HA

HA has been used extensively as a bone-filler in vivo, and many metal articular prostheses are now coated with HA with the aim of improving osseointegration, although clinical data is inconclusive as to the effectiveness of these coatings [94], [95]. In bioactive glasses, the spontaneous formation of silicon-substituted and carbonate-substituted HA in vivo is a major factor in their bone-bonding ability, and so several research groups have directly incorporated silicon into synthetic HA as a

Established Si-based biomaterials

Although clinicians have been using electronic implants and hence silicon technology since the 1960s, the semiconductor device has been sealed away from the biological environment in titanium packaging. The silicon compounds that have undoubtedly received the most extensive clinical use as biomaterials are the silicone polymers [43], which have been used safely for decades in catheters, drains, shunts, small joint implants and aesthetic implants. Extensive literature (and litigation) exists

Discussion

There is now a sufficient wealth of data available from studies of dietary supplementation and biomaterials research to be able to unpick some of the biological roles of silicon, silica and resorbable glass/ceramics, despite the relative lack of information on the detailed biomolecular interactions. High concentrations of polymerized silicic acids and silica gel are shown to have effects primarily at the surface of materials and the extracellular matrix by binding serum proteins, increasing

Conclusions

Considerable research has demonstrated that silicon has several biological functions in the human body, and many of these can be exploited therapeutically to improve bone health and accelerate healing. The many biomaterials that contain silicon all share the same fundamental property of providing a localized source of bioavailable silicon in the form of silicic acid, which both directly affects cell molecular biology and has numerous direct and indirect effects on the extracellular matrix.

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ReviewSilicon: The evolution of its use in biomaterials

Abstract

Graphical abstract

Introduction

Section snippets

Dietary silicon

Polymerization of silicic acids into silica

The role of silicon in bone biology

Silicon substitution in hydroxyapatite

Silicon in the extracellular matrix

Bioactive glass and the response of osteoblasts to silicate biomaterials

Silica sol–gels and porous silica nanoparticles

Porous silicon

Silicon-substituted HA

Established Si-based biomaterials

Discussion

Conclusions

Anal Biochem

Am J Clin Nutr

Sci Total Environ

J Nutr

Bone

Am J Clin Nutr

Gastroenterology

J Ultrastruct Res

J Nutr

Acta Biomater

Biomaterials

Bone

Biomaterials

Biomaterials

Acta Biomater

Biomaterials

J Lumin

Biomaterials

Adv Drug Deliv Rev

Biomaterials

Biomaterials

Mater Sci Eng, C

Acta Biomater

Thin Solid Films

Abundances of the elements

Rev Modern Phys

Essentials of geology

Functional characterization of a silicon transporter gene implicated in silicon distribution in barley

Plant Physiol

A family of diatom-like silicon transporters in the siliceous loricate choanoflagellates

Proc Biol Sci

Characterization of a silicon transporter gene family in Cylindrotheca fusiformis: sequences, expression analysis, and identification of homologs in other diatoms

Mol Gen Genet

An overview of silica in biology: its chemistry and recent technological advances

Prog Mol Subcell Biol

Cell reactivity to different silica

Prog Mol Subcell Biol

Ascorbic acid-pretreated quartz enhances cyclo-oxygenase-2 expression in RAW 264.7 murine macrophages

FEBS J

Dietary silicon and bone health

Nutr Bull

The silicon content of beer and its bioavailability in healthy volunteers

Br J Nutr

Silicon content of Italian mineral waters and its contribution to daily intake

J Food Sci

Dietary silicon intake is positively associated with bone mineral density in men and premenopausal women of the Framingham Offspring cohort

J Bone Min Res

The chemistry of silica and its potential health benefits

J Nutr Health Aging

Silicon balance in human volunteers: a pilot study to establish the variance in silicon excretion versus intake

Nutr Metab

The chemistry of silica

Silica chemistry and reverse osmosis

Ultrapure Water

Silica reduction in reverse osmosis desalting plants

The 6th Saudi Engineering Conference

Biofabrication of biosilica-glass by living organisms

Nat Prod Rep

Biogenic silica patterning: simple chemistry or subtle biology

ChemBioChem

Silicon: an essential element for the chick

Science

Silicon as an essential element

Review
Silicon: The evolution of its use in biomaterials