A 3D printable perfused hydrogel vascular model to assay ultrasound-induced permeability.

Abstract

The development of an in vitro model to study vascular permeability is vital for clinical applications such as the targeted delivery of therapeutics. This work demonstrates the use of a perfusion-based 3D printable hydrogel vascular model as an assessment for endothelial permeability and its barrier function. Aside from providing a platform that more closely mimics the dynamic vascular conditions in vivo, this model enables the real-time observation of changes in the endothelial monolayer during the application of ultrasound to investigate the downstream effect of ultrasound-induced permeability. We show an increase in the apparent permeability coefficient of a fluorescently labeled tracer molecule after ultrasound treatment via a custom MATLAB algorithm, which implemented advanced features such as edge detection and a dynamic region of interest, thus supporting the use of ultrasound as a non-invasive method to enhance vascular permeability for targeted drug therapies. Notably, live-cell imaging with VE-cadherin-GFP HUVECs provides some of the first real-time acquisitions of the dynamics of endothelial cell-cell junctions under the application of ultrasound in a 3D perfusable model. This model demonstrates potential as a new scalable platform to investigate ultrasound-assisted delivery of therapeutics across a cellular barrier that more accurately mimics the physiologic matrix and fluid dynamics.