Abstract

Calcium phosphate glasses have a high potential for use as biomaterials because their composition is similar to that of the mineral phase of bone. Phosphate glasses can dissolve completely in aqueous solution and can contain various elements owing to their acidity. Thus, the glass can be a candidate for therapeutic ion carriers. Recently, we focused on the effect of strontium ions for bone formation, which exhibited dual effects of stimulating bone formation and inhibiting bone resorption. However, large amounts of strontium ions may induce a cytotoxic effect, and there is a need to control their releasing amount. This work reports fundamental data for designing quaternary CaO-SrO-P2O5-TiO2 glasses with pyro- and meta-phosphate compositions to control strontium ion-releasing behavior. The glasses were prepared by substituting CaO by SrO using the melt-quenching method. The SrO/CaO mixed composition exhibited a mixed cation effect on the glassification degree and ion-releasing behavior, which showed non-linear properties with mixed cation compositions of the glasses. Sr2+ ions have smaller field strength than Ca2+ ions, and the glass network structure may be weakened by the substitution of CaO by SrO. However, glassification degree and chemical durability of pyro- and meta-phosphate glasses increased with substituted all CaO by SrO. This is because titanium groups in the glasses are closely related to their glass network structure by SrO substitution. The P-O-Ti bonds in pyrophosphate glass series and TiO4 tetrahedra in metaphosphate glass series increased with substitution by SrO. The titanium groups in the glasses were crosslink and/or coordinate phosphate groups to improve glassification degree and chemical durability. Sr2+ ion releasing amount of pyrophosphate glasses with >83% SrO substitution was larger than 0.1 mM at day seven, an amount that reported enhanced bone formation by stimulation of osteogenic markers.

Highlights

  • Therapeutic inorganic ions such as silicate, phosphate, magnesium, calcium, and strontium ions have been reported to stimulate tissue regeneration [1,2]

  • Strontium ions downregulate receptor activators of nuclear factor kappa B (RANK) ligand expression, which relates to the differentiation of pre-osteoblasts by upregulation of osteoprotegerin (OPG; known as an osteoclastogenesis inhibitory factor) [10]

  • The oxygen density, which is an index of the compactness of the glass network structure [40,41], of PIG-xSr and MPG-ySr, decreased with an increase in SrO substitution percentage

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Summary

Introduction

Therapeutic inorganic ions such as silicate, phosphate, magnesium, calcium, and strontium ions have been reported to stimulate tissue regeneration [1,2]. Phosphate ions are the main components of bones and stimulate the expression of matrix Gla protein to improve bone formation [5]. Calcium ions upregulate the expression of IGF-I and IGF-II [7] and stimulate the formation of extracellular matrix for calcification [8]. The ions contribute to an improvement in cell proliferation by upregulating c-fos and egr-1, promoting osteoblast metabolism by activating calcium-sensing receptors, and stimulating ALP and osteopontin, which are markers for osteoblast differentiation [7,11,12,13,14]. The strontium-substituted hydroxyapatite scaffolds with an 0.05 of Sr/(Ca + Sr) molar ratio enhanced cell proliferation, ALP activity, calcification, and OPG.

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