A fluid–structure interaction model to characterize bone cell stimulation in parallel-plate flow chamber systems

Abstract

Bone continuously adapts its internal structure to accommodate the functional demands of its mechanical environment and strain-induced flow of interstitial fluid is believed to be the primary mediator of mechanical stimuli to bone cells in vivo. In vitro investigations have shown that bone cells produce important biochemical signals in response to fluid flow applied using parallel-plate flow chamber (PPFC) systems. However, the exact mechanical stimulus experienced by the cells within these systems remains unclear. To fully understand this behaviour represents a most challenging multi-physics problem involving the interaction between deformable cellular structures and adjacent fluid flows. In this study, we use a fluid-structure interaction computational approach to investigate the nature of the mechanical stimulus being applied to a single osteoblast cell under fluid flow within a PPFC system. The analysis decouples the contribution of pressure and shear stress on cellular deformation and for the first time highlights that cell strain under flow is dominated by the pressure in the PPFC system rather than the applied shear stress. Furthermore, it was found that strains imparted on the cell membrane were relatively low whereas significant strain amplification occurred at the cell -substrate interface. These results suggest that strain transfer through focal attachments at the base of the cell are the primary mediators of mechanical signals to the cell under flow in a PPFC system. Such information is vital in order to correctly interpret biological responses of bone cells under in vitro stimulation and elucidate the mechanisms associated with mechanotransduction in vivo.

Multiscale fluid–structure interaction modelling to determine the mechanical stimulation of bone cells in a tissue engineered scaffold

“…More importantly, due to the high resolution of our local sub-scaffold FSI model, it was shown that the WSS was amplified significantly at the cell level when compared to the predicted WSS from the global model, with certain cases exhibiting a five-fold increase. Interestingly, similar cell level amplification effects of WSS have been observed for 2D cell perfusion systems (Anderson et al 2006;Vaughan et al 2013). However, in 2D cell perfusion systems, the WSS magnitudes to stimulate a biochemical response of cells in osteogenic and chondrogenic differentiation were much higher than the levels of WSS in our study.…”

“…This approach allows deformable structures and resulting fluid flow fields to be predicted. By using the two-way FSI and multilevel methodologies, Vaughan et al (2013) predicted with high resolution flow fields and cellular deformation, and revealed the influence of WSS and fluid pressure on the bone cells that were cultured in a parallel-plate flow chamber system. Verbruggen et al (2013) applied a two-way FSI to precisely obtain the WSS and strain of the osteocytes in vivo environment.…”

“…In recent studies, advanced two-way fluid structure interaction (FSI) methods have been applied to model the complex interaction between soft cells and tissues and extracellular fluid flow (Birmingham et al 2013;Vaughan et al 2013, Verbruggen et al 2013). This approach allows deformable structures and resulting fluid flow fields to be predicted.…”

Mechanical Analysis of a Pneumatically Actuated Concentric Double-Shell Structure for Cell Stretching

“…In most studies, the computational models of the devices for cellular mechanical stimulation have aimed for predicting the mechanical behavior of the device and quantifying the mechanical stimulation [17][18][19][20]. For instance, Thompson et al [17] developed a fluid structure interaction model for a commercial device (FX-4000) to quantify the fluid shear stress and biaxial mechanical strain of the substrate.…”

“…Zhao et al [19] modeled a microfluidic platform of tunable microlens arrays (with a deformable PDMS cover) to generate mechanical strains on cells. Furthermore, Vaughan et al [20] characterized parallel-plate flow chamber systems, which utilised FSS to stimulate cells by a mutiscale fluid-structure interaction modeling approach. However, in this study, the computational model is developed not only for predicting mechanical behavior of the cell stretching device, but also for determining the elastic modulus of the material of the device (PDMS) by parametric variation study.…”