3D Microfluidic Approach to Mechanical Stimulation of Osteocyte Processes

Abstract

It has been well recognized that bone adapts its structure to best meet its mechanical environment. However, the cellular mechanism underlying bone adaptation is not well understood. Significant research efforts have been made towards understanding the cellular mechanotransduction mechanism in bone by studying cells in monolayer. These in vitro studies have indeed shown that bone cells are mechanosensitive and contributed critical insights into the mechanism of transduction. However, the monolayer approach may be limited in that it does not reflect the interaction of the osteocyte with its extracellular environment. It is in this context, we developed a microchamber system to mimic the in vivo extracellular environment in bone. Specifically, the osteocyte process appears to have unique ultrastructural characteristics which are potentially the molecular sites of cellular mechanosensitivity. In this study we describe a microfluidics approach aimed at replicating the bone canalicular system both in terms of geometry and fluid flow driven by exogenous loading. We demonstrate that individual osteocytes can be successfully cultured in this system for extended periods and extend processes similar to those observed in vivo. Our hope is that this approach will allow the role of flow over the osteocyte process to be better delineated.