Abstract

Fluid flow shear stresses are strong regulators for directing the organization of vascular networks. Knowledge of structural and flow dynamics information within complex vasculature is essential for tuning the vascular organization within engineered tissues, by manipulating flows. However, reported investigations of vascular organization and their associated flow dynamics within complex vasculature over time are limited, due to limitations in the available physiological pre-clinical models, and the optical inaccessibility and aseptic nature of these models. Here, we developed laser speckle contrast imaging (LSCI) and side-stream dark field microscopy (SDF) systems to map the vascular organization, spatio-temporal blood flow fluctuations as well as erythrocytes movements within individual blood vessels of developing chick embryo, cultured within an artificial eggshell system. By combining imaging data and computational simulations, we estimated fluid flow shear stresses within multiscale vasculature of varying complexity. Furthermore, we demonstrated the LSCI compatibility with bioengineered perfusable muscle tissue constructs, fabricated via molding techniques. The presented application of LSCI and SDF on perfusable tissues enables us to study the flow perfusion effects in a non-invasive fashion. The gained knowledge can help to use fluid perfusion in order to tune and control multiscale vascular organization within engineered tissues.

Highlights

  • Fluid flow shear stresses are strong regulators for directing the organization of vascular networks

  • More recent studies showed that vascular cells can display plasticity with respect to local cues such as hemodynamics, especially blood flow shear stresses, meaning that the organization is influenced by the ­environment[4]

  • Perturbation of blood flow within the naturally formed vascular network of the chick embryo has been used to observe the effect of hemodynamic changes on vascular ­organization[4,5,6]

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Summary

Introduction

Fluid flow shear stresses are strong regulators for directing the organization of vascular networks. By combining imaging data and computational simulations, we estimated fluid flow shear stresses within multiscale vasculature of varying complexity. As fluid flow shear stresses is one of the key regulators of vascular organization and ­remodeling[1,2], it is important to understand the blood flow within developing vascular networks of varying complexity. Even though the importance of fluid flow related mechanical signals in a wide range of in vitro cellular organizational phenomena has been shown, it has not been possible so far to completely elucidate the physiological significance of these mechanical signals, largely due to a lack of accessible angiogenesis models and integrated imaging platforms fit for long-term culture

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