Therapeutic Ion-Releasing Bioactive Glass Ionomer Cements with Improved Mechanical Strength and Radiopacity

Fuchs, Maximilian; Gentleman, Eileen; Shahid, Shamsuddin; Hill, Robert G.; Brauer, Delia S.

doi:10.3389/fmats.2015.00063

Cited by 28 publications

(16 citation statements)

References 48 publications

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“…Among the elements with potential therapeutic properties, strontium has received remarkable interest, due to its well-known role in bone metabolism [ 18 , 19 , 20 , 21 , 22 ] by exercising anabolic and anti-catabolic effects. Indeed, due to its chemical analogy to calcium, strontium is able to exploit the calcium sensing receptors present on both osteoblastic and osteoclastic cells to activate their downstream signalling pathways, leading to the promotion of osteoblast replication, differentiation and survival as well as downregulating osteoclast activities [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

The Incorporation of Strontium to Improve Bone-Regeneration Ability of Mesoporous Bioactive Glasses

et al. 2018

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Over the recent years, mesoporous bioactive glasses (MBGs) gained interest as bone regeneration systems, due to their excellent bioactivity and ability to release therapeutic molecules. In order to improve the bone regeneration ability of MBGs, the incorporation of Sr2+ ions, due to its recognized pro-osteogenenic potential, represents a very promising strategy. In this study, MBGs based on the SiO2–CaO system and containing different percentages (2 and 4 mol %) of strontium were prepared by two synthesis methods, in the form of microspheres and nanoparticles. Sr-containing MBGs were characterized by FE-SEM, XRD and N2 adsorption/desorption analysis. The in vitro bioactivity in SBF resulted excellent. The assessment of fibroblast cell (line L929) viability showed that Sr-containing MBGs were biocompatible both in form of micro- and nanoparticles. The osteogenic response of osteoblast-like SAOS-2 cells was investigated by analysing the expression of GAPDH, COL1a1, RANKL, SPARC, OPG and ALPL genes, as cell differentiation markers. The results indicate that the incorporation of Sr into MBG is beneficial for bone regeneration as promotes a pro-osteogenic effect, paving the way to the design of advanced devices enabled by these nanocarriers also in combination with drug release, for the treatment of bone pathologies, particularly in patients with osteoporosis.

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Section: Introductionmentioning

confidence: 99%

The Incorporation of Strontium to Improve Bone-Regeneration Ability of Mesoporous Bioactive Glasses

et al. 2018

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“…Similarly, modifying BG with strontium promotes an anabolic effect on osteoblasts and an anti-catabolic effect on osteoclasts [ 9 , 10 ], and surprisingly, strongly regulates the isoprenoid pathway in human mesenchymal stem cells [ 11 ]. BG can also be incorporated into other biomaterials, such as glass ionomer-type [ 12 , 13 ] and other bone cements [ 14 ], which will likewise release BG ions over time [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Optimisation of lithium-substituted bioactive glasses to tailor cell response for hard tissue repair

et al. 2017

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Bioactive glasses (BG) are used clinically because they can both bond to hard tissue and release therapeutic ions that can stimulate nearby cells. Lithium has been shown to regulate the Wnt/β-catenin cell signalling pathway, which plays important roles in the formation and repair of bone and teeth. Lithium-releasing BG, therefore, have the potential to locally regulate hard tissue formation; however, their design must be tailored to induce an appropriate biological response. Here, we optimised the release of lithium from lithium-substituted BG by varying BG composition, particle size and concentration to minimise toxicity and maximise upregulation of the Wnt target gene Axin2 in in vitro cell cultures. Our results show that we can tailor lithium release from BG over a wide therapeutic and non-toxic range. Increasing the concentration of BG in cell culture medium can induce toxicity, likely due to modulations in pH. Nevertheless, at sub-toxic concentrations, lithium released from BG can upregulate the Wnt pathway in 17IA4 cells, similarly to treatment with LiCl. Taken together, these data demonstrate that ion release from lithium-substituted BG can be tailored to maximise biological response. These data may be important in the design of BG that can regulate the Wnt/β-catenin pathway to promote hard tissue repair or regeneration.

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“…Cytotoxicity measurements were performed according to the ISO-10993-5 procedure, using MC3T3-E1 cells [ 35 ]. Liquid extracts from pSrBG and BG45S5 (n = 6) were obtained by incubating scaffolds in alpha-Minimum Essential Medium Eagle (alpha-MEM, Gibco) at 0.2 g/ml for 24 h at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

Multiscale analyses reveal native-like lamellar bone repair and near perfect bone-contact with porous strontium-loaded bioactive glass

et al. 2019

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The efficient healing of critical-sized bone defects using synthetic biomaterial-based strategies is promising but remains challenging as it requires the development of biomaterials that combine a 3D porous architecture and a robust biological activity. Bioactive glasses (BGs) are attractive candidates as they stimulate a biological response that favors osteogenesis and vascularization, but amorphous 3D porous BGs are difficult to produce because conventional compositions crystallize during processing. Here, we rationally designed a porous, strontium-releasing, bioactive glass-based scaffold (pSrBG) whose composition was tailored to deliver strontium and whose properties were optimized to retain an amorphous phase, induce tissue infiltration and encourage bone formation. The hypothesis was that it would allow the repair of a critical-sized defect in an ovine model with newly-formed bone exhibiting physiological matrix composition and structural architecture. Histological and histomorphometric analyses combined with indentation testing showed pSrBG encouraged near perfect bone-to-material contact and the formation of well-organized lamellar bone. Analysis of bone quality by a combination of Raman spectral imaging, small-angle X-ray scattering, X-ray fluorescence and focused ion beam-scanning electron microscopy demonstrated that the repaired tissue was akin to that of normal, healthy bone, and incorporated small amounts of strontium in the newly formed bone mineral. These data show the potential of pSrBG to induce an efficient repair of critical-sized bone defects and establish the importance of thorough multi-scale characterization in assessing biomaterial outcomes in large animal models.

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Therapeutic Ion-Releasing Bioactive Glass Ionomer Cements with Improved Mechanical Strength and Radiopacity

Cited by 28 publications

References 48 publications

The Incorporation of Strontium to Improve Bone-Regeneration Ability of Mesoporous Bioactive Glasses

The Incorporation of Strontium to Improve Bone-Regeneration Ability of Mesoporous Bioactive Glasses

Optimisation of lithium-substituted bioactive glasses to tailor cell response for hard tissue repair

Multiscale analyses reveal native-like lamellar bone repair and near perfect bone-contact with porous strontium-loaded bioactive glass

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