A Highly Adaptable Hydrogen Bond Re-Orientation (HyBRO) Strategy for Multiscale Vasculature Fabrication

Abstract

Three-dimensional printing of microchannel networks mimicking native vasculature provides essential functions for biomedical applications. However, developing a highly “adaptable” technique – that can adjust to diverse materials choices, high shape accuracy, and broad size ranges – for producing physiologically responsive vasculature remains challenging. Here, an innovative hydrogen bond re-orientation (HyBRO) strategy for microchannel network fabrication is reported. By identifying interfacial instability of sacrificial material (SM) during embedding as a core limitation, this strategy prints the SM into an optimal “nonsolvent” to shape the desirable channel structure. In this process, the nonsolvent instantaneously switches the SM from forming hydrogen bonds with exterior water to forming interior linkages inside it. This transition protects the SM from external solvent “erosion” upon re-exposure to embedding material, inhibiting deformation. Consequently, this approach enables the creation of accurate (>90%), multiscale (10-fold), hierarchical microchannel networks, accommodating accurate printing of a wide range of ink materials – extending from typical hydrophilic polymers into non-typical hydrophobic ones. Further biological tests demonstrate that HyBRO-produced vasculature recapitulates not only essential endothelial barrier function but also delicate ion-channel responses to varying shear stresses, highlighting its potential for engineering physiologically responsive vasculature in broad applications.