Mechanically Tunable Biofabricated Channels Enable Mimicking Arterial Pulsatility and Dynamic Tissue Actuation.

Abstract

Dynamic alteration of blood vessel geometry is an inherent feature of the circulatory system. However, while the engineering of multiscale, branched, and interconnected blood vessels has been well explored, mimicking the dynamic behavior (e.g., pulsatile blood flow) of native arterial vessels has remained understudied. This is surprising because the natural pulsatile flow and subsequent dynamic deformation of arteries provide physiologically relevant mechanical actuation to proximal cells and tissues, contributing to both tissue homeostasis and disease progression. Yet, many tissue engineering efforts and Organ-on-Chip developments have focused on replicating vessel structure, while overlooking the native mechanical dynamicity that governs arterial tissue function. Here, the development of an on-demand tunable elastic hydrogel is reported, composed of tyramine-conjugated alginate, offering controlled, reversible dilation under physiologically relevant flow. Exploring casted and 3D bioprinted channels, how vessel dilation influences shear stresses in relation to vessel compliance is investigated. This approach is demonstrated to allow for hydrodynamic mechanodeformation and stimulation of engineered tissues. Moreover, it is revealed that pulsatile flow deformation alters compound penetration rates (e.g., nutrients and pharmaceuticals) into surrounding tissues. Finally, the spatially controlled stiffening of engineered blood vessels is demonstrated to locally limit the dilation, modeling blood vessel diseases such as stenosis or aneurysm.