Excluded Volume Effect-induced Shrinkage for Resolution Enhancement of Hydrogel Bioconstructs

Abstract

Biofabrication of hydrogel materials is usually constrained by process-specific resolution limits. Here, we introduce excluded volume effect-induced shrinkage (EVER), a dehydration-enabled resolution enhancement strategy that achieves dimensional refinement via post-processing. In this approach, we treat biofabricated constructs with hydrophilic macromolecular crowding agent bath, with poloxamer as a representative. With EVER treatment, gelatin-based constructs can reach a dimension reduction of up to ~49% with an estimated volumetric reduction of ~87%. Shape fidelity was well retained after shrinkage across different constructs and could be stabilized by introducing secondary crosslinking. In extrusion bioprinted cell-laden constructs, myoblasts retained a considerable cell viability right after the shrinkage treatment and recovered significantly by day 1, with subsequent cell spreading and increasing proliferation over 7 days. Without the need of continued immersion in the shrinkage bath, EVER provides a hardware-independent route for refining hydrogel structures while retaining encapsulated cell compatibility.