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

Abstract

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.

In Vitro Human Umbilical Vein Endothelial Cells Response to Ionic Dissolution Products from Lithium-Containing 45S5 Bioactive Glass

“…However, the angiogenic effects of Li + released from biomaterials have not yet been assessed. The studies that have examined the effect of the addition of Li + into different biomaterials have focused on the evaluation of the physicochemical and structural properties as well as on the osteogenic potential of some of them [ 18 , 19 , 22 , 23 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. In particular, the incorporation of Li + into bioactive glasses was first described by Khorami et al, who partially substituted Na 2 O by variable amounts of Li 2 O (3, 7, and 12 wt %) in a bioactive glass in the SiO 2 -CaO-Na 2 O-P 2 O 5 (45S5) system [ 30 ].…”

“…These results are in agreement with the recent findings of Bruckner et al using 45S5 microparticles (<38 µm) with 6.1 to 24.4% (mol %) of Li 2 O [ 33 ], as well as with the data reported by Miguez-Pacheco et al for glass-ceramic scaffolds derived from the 45S5 bioactive glass with 2.5, 5, and 10 wt % of Li 2 O, which showed that a content of up to 5 wt % of Li 2 O keeps the bioactive behavior and thermal characteristics of the 45S5 glass [ 34 ]. On the other hand, it has been demonstrated that ion release from lithium-substituted BG can be tailored to induce an appropriate biological response [ 41 ]; for example, the partial replacement of Na 2 O by up to 5 wt % of Li 2 O in the 45S5 bioactive glass [ 34 ] ensures the release of Li + within therapeutic levels for humans (0.5–1.2 mmol) [ 13 , 14 ].…”

Guest editors’ preface

“…Several papers deal with the investigation of novel compositions of silicate and phosphate bioactive glasses, in particular glasses with therapeutic ion delivery capability to enhance cellular response, an area highlighted in one of the most recent papers authored by Larry Hench in 2015 [6], which reflects the importance of this topic for applications of bioactive glasses in regenerative medicine and as antibacterial agent. For example, novel bioactive silicate glasses (both melt-derived and solgel produced) incorporating B [7,8], bivalent ions such as Mg, Zn, Sr and Cu [9], Li [10], Ce [11], Sr [12,13], Cu, Zn [14], Mn [15], are discussed. The release of ''classical'' ions in bioactive glasses, namely Si, Ca, P, is the subject of the studies of Houreh et al [16] and Obata et al [17] in the context of dental pulp stem cells and osteoblast cell responses, respectively.…”

Effect of chloride ions in Tris buffer solution on bioactive glass apatite mineralization

“…Bioactive glasses degrade when in contact with body fluids, release ions and mineralize a surface layer of biomimetic apatite . In the last years, one main focus in bioactive glass research was the incorporation of therapeutically active ions such as strontium, lithium, or cobalt for controlled release. One key part of early‐stage bioactive glass characterization is immersion in simulated physiological solutions, to investigate in vitro ion release and apatite surface mineralization.…”