Minimal essentials for humanized vessel-on-a-chip model for vascular research

During the last decade, in vitro 3D models based on organ-on-a-chip technology have been developed, representing a biotechnology research advance towards more physiologically relevant models that aim to provide more predictable and less costly preclinical models. We aimed to develop a vessel-on-a-chip using a biocompatible microfluidic device co-cultured with human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC).

VSMC and HUVEC were isolated from umbilical cords and co-cultured in a polydimethylsiloxane (PDMS) chip using specific growth media and tropoelastin-enriched media to favour extracellular matrix (ECM) synthesis, which was measured by gene expression (quantitative polymerase chain reaction) and deposition (immunofluorescence), to establish an organized structure. Then, using a microfluidic pump system, the functional relevance of the model was evaluated by fluidic and permeability studies after a 9-day- cell growth period.

Our vessel-on-a-chip model showed a bilayer structure, cell specific morphology and biomarkers phenotypes, and cell integrity. Gene and protein expression demonstrated the presence of ECM components, providing structural support and microenvironment control. It was observed that shear stress closer to the physiological range provided stability to the model and control of the permeability function.

Our 3D model may serve as a promising preclinical research tool that closely mimics the structural conformation of blood vessels and reflects essential physiological parameters, including cell maturity, shear stress, and functional permeability. Consequently, it could potentially be applied to cellular and molecular research to further elucidate vascular biology in cardiovascular diseases.