Architecture-Dependent Transition from Quasi-2D to 3D Cell-Scaffold Interactions in Ultrafine Electroprinted Cellulose Scaffolds

Abstract

Precise control over scaffold microarchitecture is critical for engineering cell-instructive biomaterials and for understanding how structural cues regulate cell-material interactions. In this study, ultrafine cellulose-based scaffolds fabricated by near-collector electroprinting (NCE) were used as a model platform to investigate how scaffold architecture influences the transition between quasi-2D and 3D cell-scaffold interactions. Cellulose acetate scaffolds with micrometer-scale fiber diameters, tunable fiber spacing, and defined multilayer geometries were systematically evaluated to determine the effects of scaffold dimensionality and pore architecture on human mesenchymal stem cell behavior. Low-layer scaffolds functioned primarily as quasi-2D topographical patterns, where cells adhered predominantly to the underlying substrate while aligning along the printed fibers in a spacing-dependent manner. Increasing scaffold height generated a 3D microenvironment that promoted direct cell-scaffold interaction and enabled inter-fiber bridging. Quantitative analysis of nuclear orientation and actin organization revealed that scaffold dimensionality and fiber spacing jointly govern the transition between topographical guidance and bridging-mediated cellular organization. To further demonstrate material versatility, lignosulfonate was incorporated into the printing ink to fabricate composite scaffolds while retaining print fidelity and cytocompatibility. Together, these findings demonstrate how scaffold architecture can be used to govern cell-material interactions across multiple dimensional regimes.