Micro-to-Macro Scale Hydrogel Microchannel Networks by Twisted Wire Templating

Abstract

The human vasculature is a complex, multiscale system comprising hierarchical networks of macroscale to microscopic vessels. Existing in vitro fabrication techniques often fail to bridge these disparate scales, as high-resolution methods like multiphoton ablation are too slow for replicating larger vessels, while 3D printing lacks the resolution for fine microscale features. Here, we report a "twisted wire templating" strategy capable of generating perfusable bifurcating hydrogel networks that seamlessly transition from the macro- to the micro-scale (2.3 mm to 140 {micro}m) through seven orders of bifurcations. By optimizing wire-twisting geometries and polyurethane dip-coating, we overcame instability-driven bead formation to ensure replication fidelity across the networks. Fabrication rigs were reconfigured from existing 2D planar layouts to 3D reconfigurable architectures to better replicate 3D vessel geometries which simultaneously reducing the laboratory footprint and fabrication times by 47%. Using a Taguchi orthogonal array, we further optimized surface chemistry and hydrogel composition to inhibit structural failure during template extraction, resulting in fully patent, perfusable networks. This method provides a robust, low-cost, and scalable foundation for creating physiologically representative vascular models for investigating multiscale disease mechanisms and organ-level tissue engineering.