Abstract
In the microvasculature, blood flow-derived forces are key regulators of vascular structure and function. Consequently, the development of hydrogel-based microvessel-on-chip systems that strive to mimic the in vivo cellular organization and mechanical environment has received great attention in recent years. However, despite intensive efforts, current microvessel-on-chip systems suffer from several limitations, most notably failure to produce physiologically relevant wall strain levels. In this study, a novel microvessel-on-chip based on the templating technique and using luminal flow actuation to generate physiologically relevant levels of wall shear stress and circumferential stretch is presented. Normal forces induced by the luminal pressure compress the surrounding soft collagen hydrogel, dilate the channel, and create large circumferential strain. The fluid pressure gradient in the system drives flow forward and generates realistic pulsatile wall shear stresses. Rigorous characterization of the system reveals the crucial role played by the poroelastic behavior of the hydrogel in determining the magnitudes of the wall shear stress and strain. The experimental measurements are combined with an analytical model of flow in both the lumen and the porous hydrogel to provide an exceptionally versatile user manual for an application-based choice of parameters in microvessels-on-chip. This unique strategy of flow actuation adds a dimension to the capabilities of microvessel-on-chip systems and provides a more general framework for improving hydrogel-based in vitro engineered platforms.
Highlights
In the vasculature, mechanical forces regulate blood vessel development, network architecture, wall remodeling, and arterio-venous specification [1, 2]
Despite the softness of the collagen hydrogel within which it is embedded, the microvessel lumen has a circular cross-section as determined by 3D reconstruction of confocal microscopy images (Figure 1aii, Movie 1) and Optical coherence tomography (OCT) imaging (Figure S1)
We show that combining specific design features with luminal flow actuation of a poroelastic collagen hydrogel constitutes a novel and highly effective strategy for overcoming these limitations
Summary
Mechanical forces regulate blood vessel development, network architecture, wall remodeling, and arterio-venous specification [1, 2]. Pulsatility has traditionally been assumed to be completely dampened by the time blood reaches the microvasculature, recent data challenge this consensus and have reported significant velocity and diameter oscillations even in the smallest capillaries [17,18,19,20,21]. In diseases such as hypertension, the higher pulse pressure penetrates deeper into the vascular tree, further increasing pulsatility in the microvasculature [7, 22]
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