Bioactive glasses (BG) which contain strontium have the potential to combine the known bone regenerative properties of BG with the anabolic and anti-catabolic effects of strontium cations. Here we created a BG series (SiO 2 -P 2 O 5 -Na 2 O-CaO) in which 0 to 100% of the calcium was substituted by strontium and tested their effects on osteoblasts and osteoclasts in vitro. We show that ions released from strontiumsubstituted BG enhance metabolic activity in osteoblasts. They also inhibit osteoclast activity by both reducing tartrate resistant acid phosphatase activity and inhibiting resorption of calcium phosphate films in a dose-dependent manner. Additionally, osteoblasts cultured in contact with BG show increased proliferation and alkaline phosphatase activity with increasing strontium substitution, while osteoclasts adopt typical resorption morphologies. These results suggest that similarly to the osteoporosis drug strontium ranelate, strontium-substituted BG may promote an anabolic effect on osteoblasts and an anti-catabolic effect on osteoclasts. These effects, when combined with the advantages of BG such as controlled ion release and delivery versatility, may make strontium-substituted BG an effective biomaterial choice for a range of bone regeneration therapies.

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Bioactive glasses are able to bond to bone through the formation of hydroxy-carbonate apatite in body fluids while strontium (Sr)-releasing bioactive glasses are of interest for patients suffering from osteoporosis, as Sr was shown to increase bone formation both in vitro and in vivo. A melt-derived glass series (SiO 2 -P 2 O 5 -CaO -Na 2 O) with 0 -100% of calcium (Ca) replaced by Sr on a molar base was prepared. pH change, ion release and apatite formation during immersion of glass powder in simulated body fluid and Tris buffer at 378C over up to 8 h were investigated and showed that substituting Sr for Ca increased glass dissolution and ion release, an effect owing to an expansion of the glass network caused by the larger ionic radius of Sr ions compared with Ca. Sr release increased linearly with Sr substitution, and apatite formation was enhanced significantly in the fully Sr-substituted glass, which allowed for enhanced osteoblast attachment as well as proliferation and control of osteoblast and osteoclast activity as shown previously. Studying the composition -structure-property relationship in bioactive glasses enables us to successfully design next-generation biomaterials that combine the bone regenerative properties of bioactive glasses with the release of therapeutically active Sr ions.

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