Development of a novel bioreactor to apply shear stress and tensile strain simultaneously to cell monolayers

Abstract

To date many bioreactor experiments have investigated the cellular response to isolated in vitro forces. However, in vivo, wall shear stress ͑WSS͒ and tensile hoop strain ͑THS͒ coexist. This article describes the techniques used to build and validate a novel vascular tissue bioreactor, which is capable of applying simultaneous wall shear stress and tensile stretch to multiple cellular substrates. The bioreactor design presented here combines a cone and plate rheometer with flexible substrates. Using such a combination, the bioreactor is capable of applying a large range of pulsatile wall shear stress ͑−30 to + 30 dyn/ cm 2 ͒ and tensile hoop strain ͑0%-12%͒. The WSS and THS applied to the cellular substrates were validated and calibrated. In particular, curves were produced that related the desired WSS to the bioreactor control parameters. The bioreactor was shown to be biocompatible and noncytotoxic and suitable for cellular mechanical loading studies in physiological condition, i.e., under simultaneous WSS and THS conditions.

HUVEC ICAM-1 and VCAM-1 Synthesis in Response to Potentially Athero-Prone and Athero-Protective Mechanical and Nicotine Chemical Stimuli

“…This validation approach also considered the shallow indents on the plate surface. These shallow indents did affect the flow at the localized edge regions of the shallow indent, but his effect was minimal and had an insignificant effect on the over WSS applied to the cellular samples (see Breen et al 9 for further details).…”

“…However, in the experimental study reported here, involving unsteady flow, varying WSS waveforms were desired, each requiring a corresponding CAV profile. The linear relationship determined in Breen et al 9 for steady flow (and the resulting master curve) were insufficient to directly determine the appropriate CAV profiles due to the unsteady nature of the flow and the inertia and momentum effects associated with mimicking physiological (mechanical) stimuli. In order to account for momentum/inertia effects, the CFD preprocessor flow state within Ansys-CFX was set to ''transient flow.''…”

“…9 However, the human vasculature is exposed to a range of pulsatile and sometimes oscillatory WSS levels. In this study, we implemented two contrasting physiological WSS waveforms, these were determined in a study by Dai et al 19 using MRI and ultrasound techniques.…”

Novel mechanical bioreactor for concomitant fluid shear stress and substrate strain

“…Unfortunately, the amount of shear stress on the cells through the perturbation of the media was unable to be measured. Other bioreactors include the compression of a media-filled substrate with loadinduced flow (Tanaka et al, 2005) and a cone-and-plate viscometer with additional tension (Breen et al, 2006). Although these bioreactors, in some way, apply two different types of loading, they are not designed to examine the effects of these loading modes individually or to quantify these loads explicitly.…”

Fluid Flow Shear Stress Stimulation on a Multiplex Microfluidic Device for Rat Bone Marrow Stromal Cell Differentiation Enhancement

“…Research in cell chemotaxis can be easily performed while further integrating a microfluidic gradient generator [22]. In mechanical stress stimulation experiments, a conventional bioreactor uses a compressive loading cylinder [23], rotating cone [24,25], or parallel plate chamber [26] to generate hydrostatic pressure or shear stress on cells. With a microfluidic device, on the other hand, physical shear stress can be simply created by fluid flow induction from laminar microflow behavior [27], and hydrostatic pressure can be created by a vortex in the PDMS chamber [28].…”