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Microfluidic artery-on-a-chip model with unidirectional gravity-driven flow for high-throughput applications.

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Developing new cardiovascular disease (CVD) therapies requires better in vitro models. This study presents a novel microfluidic platform that accurately mimics healthy and diseased arteries, improving preclinical research for CVD treatments.

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Area of Science:

  • Biomedical Engineering
  • Cardiovascular Research
  • Microfluidics

Background:

  • Cardiovascular disease (CVD) remains a leading global cause of death.
  • Existing preclinical models for CVD lack predictive clinical efficacy.
  • There is a critical need for advanced in vitro models that better replicate human cardiovascular physiology.

Purpose of the Study:

  • To develop and validate a novel microfluidic platform for modeling human coronary arteries.
  • To investigate the impact of different flow conditions on vascular cell behavior and function.
  • To establish a more physiologically relevant in vitro system for cardiovascular research and drug screening.

Main Methods:

  • Utilized the OrganoPlate® 2-lane-48 UF microfluidic device with monocultures or cocultures of human coronary artery endothelial cells (HCAECs) and human coronary artery smooth muscle cells (HCASMCs).
  • Applied unidirectional and bidirectional fluid flow conditions via interval rocking and capillary forces.
  • Assessed endothelial cell alignment, fibronectin deposition, smooth muscle cell phenotype, ICAM-1 staining, and lipid deposits.
  • Induced vascular inflammation using TNFα and IL-1β.

Main Results:

  • Unidirectional flow promoted endothelial cell alignment and reduced fibronectin, mimicking healthy arteries.
  • Bidirectional flow induced features of early endothelial dysfunction, including contractile morphology, increased fibronectin, ICAM-1 staining, and lipid deposits.
  • The platform successfully replicated key characteristics of both healthy and diseased arteries and allowed for induction of vascular inflammation.

Conclusions:

  • The OrganoPlate® 2-lane-48 UF is a high-throughput, flow-controlled platform for creating physiologically relevant in vitro artery models.
  • This model accurately replicates features of healthy and diseased arteries, offering potential for improved cardiovascular drug screening.
  • The platform's compatibility with lab automation makes it a valuable tool for advancing cardiovascular disease therapeutic development.