Bubble casting strategy to construct multifurcated hydrogel microtubes with adjustable dimensions and endothelialization.

Abstract

The reconstruction of human tubular structures-characterized by adjustable small diameters (<6 mm), multifurcated morphologies, and biomimetic functionality-remains a significant challenge, particularly for researchers lacking specialized fabrication skills. In this work, we present a simple and effective strategy to fabricate freestanding, multifurcated hydrogel microtubes with tunable diameters, perfusability, and endothelialization capability by integrating stimuli-responsive hydrogels with a bubble casting technique. Leveraging the adhesive interaction between hydrogels and silicone molds, this method enables the formation of multifurcated hydrogel microtubes with uniform thickness and interconnected structures within modularly assembled molds. The integration of temperature-sensitive gelatine and photo-crosslinkable methacrylated gelatin (GelMA) permits the rapid and irreversible formation of robust hydrogel microtubes. A wide range of 2D structures including straight, L-shaped, T-shaped, bifurcated, and trifurcated microtubes can be readily produced, and further assembled into interconnected 3D microtube network using Lego-like assembly with the assistance of T- or Y-shaped adhesive connectors. The experimental results prove that the fabricated microtubes exhibit favorable physiological stability, mechanical strength, semi-permeability, hemocompatibility, cytocompatibility and anti-thrombogenicity. Moreover, the successful perfusion of whole rabbit blood and endothelialization with human umbilical vein endothelial cells (HUVECs) demonstrate their functional potential as biomimetic vascular scaffolds. Overall, our work introduces a robust, accessible, and modular strategy for generating multifurcated hydrogel microtubes featuring adjustable fine diameters. The technique is particularly suited for applications in tissue engineering and vascular modeling, and can be easily adopted by researchers across disciplines without the need for specialized equipment or training.