Abstract
The recent discovery of bone flexoelectricity (strain-gradient-induced electrical polarization) suggests that flexoelectricity could have physiological effects in bones, and specifically near bone fractures, where flexoelectricity is theoretically highest. Here, we report a cytological study of the interaction between crack stress and bone cells. We have cultured MC3T3-E1 mouse osteoblastic cells in biomimetic microcracked hydroxyapatite substrates, differentiated into osteocytes and applied a strain gradient to the samples. The results show a strong apoptotic cellular response, whereby mechanical stimulation causes those cells near the crack to die, as indicated by live-dead and caspase staining. In addition, analysis two weeks post-stimulation shows increased cell attachment and mineralization around microcracks and a higher expression of osteocalcin –an osteogenic protein known to be promoted by physical exercise. The results are consistent with flexoelectricity playing at least two different roles in bone remodelling: apoptotic trigger of the repair protocol, and electro-stimulant of the bone-building activity of osteoblasts.
Highlights
The recent discovery of bone flexoelectricity suggests that flexoelectricity could have physiological effects in bones, and near bone fractures, where flexoelectricity is theoretically highest
In order to evaluate the survival of the osteocytes after crack generation, cell viability was analysed by Live/Dead staining before and after cracking in HA substrates with MC3T3-E1 osteoblasts cultured on the surface (Fig. 1)
The results show that mechanical loading of micro-fractures has two effects on bone cells: apoptosis of the osteocytes near the crack, and increased maturation and mineralization of osteoblasts over the subsequent differentiation days (Scheme 2)
Summary
The recent discovery of bone flexoelectricity (strain-gradient-induced electrical polarization) suggests that flexoelectricity could have physiological effects in bones, and near bone fractures, where flexoelectricity is theoretically highest. We have cultured MC3T3-E1 mouse osteoblastic cells in biomimetic microcracked hydroxyapatite substrates, differentiated into osteocytes and applied a strain gradient to the samples. Microcracking increases mineral delivery (principally calcium and inorganic phosphate ions) into the medium[11,12], having a strong effect on bone cells, stimulating osteoblast growth, differentiation and matrix mineralization in vitro[11,12,13,14]. The actual link between mechanical stress and bio-chemical effects, remains to be clarified This is where the electromechanical properties of bones (their ability to generate electric fields in response to mechanical stress) may play a role. A general property that allows materials of any symmetry (including non-piezoelectric ones) to generate a voltage in response to strain gradients[19,20]
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