A Novel Microfluidic Device for Modeling an Artery-on-a-Chip and Cardiovascular Diseases

Abstract: Cardiovascular disease (CVD) remains a predominant global health challenge, with a noticeable decline in the approval of new therapeutic interventions. Current treatments, notably statins, demonstrate limited efficiency. The challenge of translating preclinical models to clinical efficacy underscores the urgent need for enhanced in vitro models that more accurately mirror human disease processes. This study introduced and characterized the OrganoPlate® Uniflow 2-lane, a novel microfluidic device designed to simulate vascular inflammation and the impacts of fluid flow on arterial vessels, offering a more precise platform for drug development.
The OrganoPlate® Uniflow 2-lane, a gravity-driven microfluidic device, has 48 chips per plate. Passive leveling of fluid reduces system complexity and ensures compatibility with lab automation through its open well architecture. When used with the OrganoFlow rocker system it is possible to use 16 plates simultaneously (768 chips).
I these experiments, monocultures of human coronary artery endothelial cells (HCAECs) or cocultures of HCAECs with human coronary artery smooth muscle cells (HCASMCs) were established. These cultures underwent either unidirectional or bidirectional flow conditions. Investigations into cellular alignment, marker expression, extracellular matrix secretion, and vascular inflammatory responses were conducted. Results indicated that under unidirectional flow, endothelial cells aligned with the flow direction, there was less fibronectin deposition and smooth muscle cells presented a non-contractile phenotype, emulating the characteristics of healthy arteries. Conversely, bidirectional flow elicited features of endothelial dysfunction, such as disrupted actin alignment and augmented fibronectin secretion; in coculture, bidirectional flow led to a contractile morphology and disruption of the tube.
In conclusion, the OrganoPlate® Uniflow 2-lane offers a unique, medium-throughput, and physiologically relevant model that bridges the gap between traditional in vitro and in vivo models. Its ability to reduce inflammation signals and replicate key features of arterial health and disease, combined with its adaptability for drug screening and compatibility with lab automation, makes it an invaluable tool for researchers aiming for more accurate and efficient therapeutic development in CVD.