A Novel Bioreactor System for the Assessment of Endothelialization on Deformable Surfaces.

Björn J Bachmann,Dimos Poulikakos,Edoardo Mazza,Julian Marschewski,Aldo Ferrari,Paolo Ermanni,Christian Loosli,Laura Bernardi,Martin Ehrbar,Michela Perrini

doi:10.1038/srep38861

Abstract

The generation of a living protective layer at the luminal surface of cardiovascular devices, composed of an autologous functional endothelium, represents the ideal solution to life-threatening, implant-related complications in cardiovascular patients. The initial evaluation of engineering strategies fostering endothelial cell adhesion and proliferation as well as the long-term tissue homeostasis requires in vitro testing in environmental model systems able to recapitulate the hemodynamic conditions experienced at the blood-to-device interface of implants as well as the substrate deformation. Here, we introduce the design and validation of a novel bioreactor system which enables the long-term conditioning of human endothelial cells interacting with artificial materials under dynamic combinations of flow-generated wall shear stress and wall deformation. The wall shear stress and wall deformation values obtained encompass both the physiological and supraphysiological range. They are determined through separate actuation systems which are controlled based on validated computational models. In addition, we demonstrate the good optical conductivity of the system permitting online monitoring of cell activities through live-cell imaging as well as standard biochemical post-processing. Altogether, the bioreactor system defines an unprecedented testing hub for potential strategies toward the endothelialization or re-endothelialization of target substrates.

Highlights

Statistical predictions for the ageing population of Western Countries foresee a dramatic increase of cardiovascular patients in the two decades, which will manifest itself as a rapidly growing public health issue with significant economic impact[1]
The realized concomitant and time-variable wall deformation (WD) and wall shear stress (WSS), are representative of a variety of conditions experienced by endothelial cells (ECs) in heart ventricles, large vessels, and cardiovascular devices
The various elements of the work substantiate the introduced novel reactor system as a valuable platform to test the endothelialization of artificial materials under physiological and supraphysiological conditions of mechanical loading

Summary

Introduction

Statistical predictions for the ageing population of Western Countries foresee a dramatic increase of cardiovascular patients in the two decades, which will manifest itself as a rapidly growing public health issue with significant economic impact[1]. Several strategies have been proposed to address the process of endothelialization of artificial materials (i.e. metal alloys, plastic polymers, and elastomers) These include the chemical modification of synthetic interfaces in contact with blood[10], the surface structuring with rationally engineered topography[11,12,13], or the biological functionalization with intervening layers of basal matrix components or biological molecules promoting the binding and proliferation of ECs14. The common goal of these approaches is to promote specific endothelial activities, overall supporting the generation and long-term maintenance of a functional monolayer, in order to support the establishment of local homeostasis and prevent the direct contact between blood and artificial materials[15,16]. EC polarization is dictated by the direction of flow and of substrate deformation[27]

Methods

Results

Conclusion