Silicon substitution in the calcium phosphate bioceramics

doi:10.1016/j.biomaterials.2007.05.003

Biomaterials

Volume 28, Issue 28, October 2007, Pages 4023-4032

https://doi.org/10.1016/j.biomaterials.2007.05.003 Get rights and content

Abstract

Silicon (Si) substitution in the crystal structures of calcium phosphate (CaP) ceramics such as hydroxyapatite (HA) and tricalcium phosphate (TCP) generates materials with superior biological performance to stoichiometric counterparts. Si, an essential trace element required for healthy bone and connective tissues, influences the biological activity of CaP materials by modifying material properties and by direct effects on the physiological processes in skeletal tissue. The synthesis of Si substituted HA (Si-HA), Si substituted α-TCP (Si-α-TCP), and multiphase systems are reviewed. The biological performance of these Si substituted CaP materials in comparison to stoichiometric counterparts is discussed. Si substitution promotes biological activity by the transformation of the material surface to a biologically equivalent apatite by increasing the solubility of the material, by generating a more electronegative surface and by creating a finer microstructure. When Si is included in the TCP structure, recrystallization to a carbonated HA is mediated by serum proteins and osteoblast-like cells. Release of Si complexes to the extracellular media and the presence of Si at the material surface may induce additional dose-dependent stimulatory effects on cells of the bone and cartilage tissue systems.

Introduction

Due to the high demand for synthetic biomaterials to assist and replace skeletal tissues, and the high failure rate of these medical implants, a great deal of research focuses on improving the strength of the implant–tissue interface, and in the design of implants that degrade in concert with the natural healing process [1].

Hard skeletal tissue is a complex composite consisting of cells embedded within a mineralized organic matrix. Bone mineral is calcium phosphate (CaP) based with a structural similarity to hydroxyapatite (HA; Ca₅(PO₄)₃OH) [2]. On account of this similarity, synthetic stoichiometric HA has been extensively utilized as a skeletal replacement material. However stoichiometric HA has a limited ability to form an interface with, and to stimulate the development of, new bone tissue. Also, stoichiometric HA does not degrade significantly but rather remains as a permanent fixture susceptible to long-term failure [3]. In contrast, the mineral found in bone is not a stoichiometric compound, but exhibits variable deficiencies in Ca, P and OH [2]. Various substitutions exist in bone mineral, in particular carbonate ions that are found at up to 8 wt%, as well as elements such as Na, Mg, K, Sr, Zn, Ba, Cu, Al, Fe, F, Cl and silicon (Si) that occur at trace (<1 wt%) levels [1], [4]. These substitutions in the apatite structure play important roles in the biological activity of both bone mineral and CaP-based implant materials that incorporate elemental substitutions, by influencing the solubility, surface chemistry and morphology of the material. Si in particular has been found to be essential for normal bone and cartilage growth and development. Synthetic CaP-based materials that include trace levels of Si in their structures demonstrate markedly increased biological performance in comparison to stoichiometric counterparts [5]. This increase in biological performance can be attributed to Si-induced changes in the material properties and also to the direct effects of Si in physiological processes of the bone and connective tissue systems.

Section snippets

Si in bone and cartilage physiology

Apart from oxygen, Si is the most abundant element in the earth's crust. The presence of Si in mammalian systems is quite variable. Si is present at a level of ∼1 ppm in the serum, 2–10 ppm in the liver, kidney, lung and muscle, 100 ppm in the bone and ligaments and 200–600 ppm in cartilage and other connective tissues [6]. In the examination of a variety of connective tissues using chemical methods, Si was found in high levels of 200–550 ppm bound to extracellular matrix compounds such as

Si substitution in CaPs

The synthesis and characterization of Si substituted HA (Si-HA) and Si substituted α-tricalcium phosphate (Si-α-TCP) has been the focus of many research efforts [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42]. Both Si-HA and Si-TCP based materials exhibit enhanced bone apposition, bone in-growth and cell-mediated degradation in comparison to stoichiometric HA controls. The synthesis of Si-HA and Si-α-TCP has focused on wet chemical methods where Si

Theoretical studies of Si substitution in CaPs

The nature of the structure of CaPs, in which covalently bound PO₄³⁻ units are stacked in a columnar form and ionically bonded to Ca²⁺_, has allowed theoretical computation of their structures using density functional theory (DFT) [49], [50], [51]. These are notable studies that use first principles or so-called ab initio methods based on density functional theory and pseudopotentials [52], [53]. These studies have been used to simulate bulk and surface properties, and the effects of Si doping

Comparative biological activity of Si substituted CaP bioceramics

Given the significant roles of Si in the enhancement of bone growth, it is not surprising that bioceramics that incorporate Si into their composition realize higher bioactivity. These include materials with very high Si levels such as Bioglass (Na–Ca–P–Si glasses of variable composition) [55] and Pseudowollastonite (CaSiO₃) [25], [56] as well as CaP-based materials with trace levels of Si doping such as Si-HA and Si-TCP [57], [58].

The superior biological performance of Si-HA and Si-TCP implant

Influence of Si in the biological response to an implant

When a biomaterial is implanted into a biological system, dynamic reactions occur at the material–tissue interface that have been shown to determine the degree and conformation of specific proteins which influence recruitment and activation of cells and the stimulation of new tissue development [55], [64], [65]. Precipitation of a biologically equivalent carbonated HA (biomimetic precipitation) at the surface of an implant has been consistently associated with the bioactivity [66] of a wide

Conclusions

It is clear that Si plays important and significant roles in the bone and cartilage systems, acting on the physiological system most prominently during the growth and development of the skeletal system of higher organisms. Si has also been shown to influence cartilage synthesis and the integrity of the extracellular matrix. Direct effects of Si on the biomineralization process are also observed. Si has also shown to have effects on the differentiation, proliferation and collagen synthesis of

Acknowledgements

Work supported by the Natural Sciences and Research Council of Canada and Millenium Biologix Corporation through a Cooperative Research and Development Grant. Discussions with Roope Astala are also gratefully acknowledged.

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ReviewSilicon substitution in the calcium phosphate bioceramics

Abstract

Introduction

Section snippets

Si in bone and cartilage physiology

Si substitution in CaPs

Theoretical studies of Si substitution in CaPs

Comparative biological activity of Si substituted CaP bioceramics

Influence of Si in the biological response to an implant

Conclusions

Acknowledgements

Bone

Biomaterials

Biomaterials

Biomaterials

Biomaterials

Sol State Ionics

Mater Lett

Biomaterials

Solid State Sci

Biomaterials

Biomaterials

Biomaterials

Biomaterials

Biomaterials

Micron

Biomaterials

Biomaterials

Biomaterials

Biomaterials

Biomaterials

Biomineralization of calcium phosphates

Agnew Chem Int Ed

Tissue engineering of bone: search for a better scaffold

Orthod Craniofacial Res

Structure and chemistry of the apatites and other calcium orthophosphates

Silicon substituted hydroxyapatites: a method to upgrade calcium phosphate based implants

J Mater Chem

A bound form of Si in glycosaminoglycans and polyuronides

Proc Nat Acad Sci USA

Si: a possible factor in bone calcification

Science

Effects of silicate ions on the formation and transformation of calcium phosphates in neutral aqueous solutions

J Chem Soc Faraday Trans

Silica-induced precipitation of calcium phosphate in the presence of inhibitors of hydroxyapatite formation

J Dent Res

Si: an essential element for the chick

Science

Biochemical and morphological changes associated with long bone abnormalities in Si deficiency

J Nutr

Growth promoting effects of Si in rats

Nature

Si depravation decreases collagen formation in wounds, bone and ornithine transaminase enzyme activity in liver

Biol Trace Elem Res

The nutritional essentiality of silicon

Nutr Rev

Silicon as an essential trace element in animal nutrition

Ciba Found Symp

Silicon as a trace nutrient

Sci Total Environ

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

J Bone Miner Res

Supplementation of calves with stabilized orthosilicic acid. Effect on the Si, Ca, Mg and P concentrations in serum and the collagen conventration in skin and cartilage

Biol Trace Elem Res

Short term effects of organic silicon on trabecular bone in mature ovariectomized rats

Cal Tiss Inter

Dietary Si affects bone turnover and differentiation in overiectomized and sham operated growing rats

J Trace Elements Exp Med

Zeolite A increases proliferation, differentiation and TGF-beta production in normal adult human osteoblast-like cells in vitro

J Biomed Mater Res

Gene-expression profiling of human osteblasts following treatment with the ionic products of Bioglass 45S5 dissolution

J Biomed Mater Res

Morphological and structural study of pseudowollastonite implants in bone

J Microsc

The role of silicon in Si-TCP bioceramics: a material and biological characterization

Silicon doped hydroxyapatite

J Aust Ceram Soc

Chemical characterization of silicon substituted hydroxyapatite

J Biomed Mater Res

Review
Silicon substitution in the calcium phosphate bioceramics