Abstract

LAPONITE® clay nanoparticles are known to exert osteogenic effects on human bone marrow stromal cells (HBMSCs), most characteristically, an upregulation in alkaline phosphatase activity and increased calcium deposition. The specific properties of LAPONITE® that impart its bioactivity are not known. In this study the role of lithium, a LAPONITE® degradation product, was investigated through the use of lithium salts and lithium modified LAPONITE® formulations. In contrast to intact particles, lithium ions applied at concentrations equivalent to that present in LAPONITE®, failed to induce any significant increase in alkaline phosphatase (ALP) activity. Furthermore, no significant differences were observed in ALP activity with modified clay structures and the positive effect on osteogenic gene expression did not correlate with the lithium content of modified clays. These results suggest that other properties of LAPONITE® nanoparticles, and not their lithium content, are responsible for their bioactivity.

Highlights

  • A growing number of studies have reported the ability of clay nanoparticles to enhance osteogenic differentiation of skeletal stem and osteoprogenitor cell populations, even in the absence of traditional osteogenic supplements such as dexamethasone, ascorbate-2-phosphate and β-glycerophosphate

  • Our goal in this study was to explore the role of lithium in the modulation of LAPONITE® nanoclay bioactivity

  • In discussions of potential mechanisms in the literature it is frequently suggested that nanoclay bioactivity could be attributed to LAPONITE® degradation products.[2,3,4,5,6,7,8,31]

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Summary

Introduction

A growing number of studies have reported the ability of clay nanoparticles to enhance osteogenic differentiation of skeletal stem and osteoprogenitor cell populations, even in the absence of traditional osteogenic supplements such as dexamethasone, ascorbate-2-phosphate and β-glycerophosphate. The mechanism(s) behind this osteogenic bioactivity remain poorly understood.[1] Relatively little attention has been given, for example, to the question of which specific properties of clay structure and composition play a role in imparting nanoclay bioactivity. Answering these questions is key for the successful control and manipulation of this exciting new class of biomaterial for therapeutic application. Clay degradation products have been proposed as playing a role in clay osteogenic bioactivity.[2,3,4,5,6,7,8] For example, it has been suggested that following cellular uptake, clay nanoparticles may undergo degradation within the low pH endosomal or lysosomal intracellular compartments to release dissolution products known to influence osteogenic cell function.[2,3,4,5,6,7,8] In the case of LAPONITE®, these degradation products include orthosilicic acid Si(OH)[4], magnesium Mg2+, and lithium Li+

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