Multiscale 3D Printing of Nanoporous Scaffolds with Surface Topography for Guiding 3D Cell Alignment

Engineering biomaterial scaffolds with hierarchical structures that integrate macroscale architecture with micro/nanoscale features is essential for directing cellular organization and tissue regeneration. However, fabricating such multiscale scaffolds remains a challenge due to the limitations of conventional techniques and the speed-resolution trade-off in current 3D printing methods. Here, a multiscale micro-continuous liquid interface production (MµCLIP) method is presented, combined with polymerization-induced phase separation, to enable rapid, one-step 3D printing of centimeter-scale scaffolds featuring microscale surface topography and nanoscale porosity. MµCLIP achieves unprecedented structural resolution across five orders of magnitude (20 nm-1 cm) at high printing speed of up to 1.85 mm min^-1. As a proof of concept, a 1cm-long tubular scaffold with interconnected nanopores (20-260 nm) and dual surface topographies: 15 µm circumferential rings on outer surface and 20 µm longitudinal grooves on luminal surface is fabricated. These topographies directed orthogonal alignment of vascular smooth muscle cells and endothelial cells, closely recapitulating the architecture of native arteries. Additionally, surface grooves significantly enhanced endothelial cell migration within scaffolds, suggesting a promising approach for accelerating re-endothelialization. This study establishes MµCLIP as a versatile platform for integrating distinct topographies into 3D scaffolds, opening new opportunities for regenerative implants and biomimetic tissue models.