Advanced mimicry of physiological blood vessel haemodynamics in vitro

Abstract

Cardiovascular disease is a major contributor to the global health burden. Research to address the challenges of cardiovascular disease is currently dependent on simplistic in vitro models which do not replicate the three-dimensional, multicellular, mechanically dynamic environment of human blood vessels, and therefore are not predictive of human outcomes. Perfusion bioreactors allowing 3D culture of vascular cells under flow have emerged as a platform for studying pathological mechanisms and for biomaterial evaluation. Current bioreactors are limited by reliance on positive displacement pumps that do not adequately replicate the complex pulsatile pressure and flow conditions of human arteries. Here, a novel pumping system for accurately mimicking the haemodynamics of human blood vessels was developed and characterised.

The system was developed using a biologically inspired mechanism of pressure-driven flow rather than conventional geometric displacement. A flow circuit was developed from custom 3D-printed components to allow unidirectional flow by alternate pneumatic pressurisation of a pair of reservoirs. An automated control system coordinated the pressure in each reservoir and allowed independent regulation of both pressure and flow.

Comparative studies with typical positive displacement pump systems revealed the superior capabilities of the pneumatic system in replicating physiological parameters. The pneumatic system demonstrated precise control over pressure and flow conditions independently, offering a versatile platform for replicating specific waveforms relevant to peripheral and coronary arteries.

Cell culture experiments validated the compatibility of the pneumatic system with tissue engineering, revealing distinctive mechanobiological effects. Expression of adhesion molecules, endothelial nitric oxide synthase and metabolites was altered under combined pressure and flow stimulus compared to only flow stimulus.