In-Depth Investigation of Electrostatic Interaction-Based Hydrogel Shrinking for Volumetric Printing and Tissue Engineering Applications

Three-dimensional printing of hydrogels enables the fabrication of complex structures for tissue engineering. Postprinting shrinking via electrostatic interactions offers a promising strategy to better replicate the size and intricacy of native tissues. This study explores hyaluronic acid (HA)-based hydrogels that undergo shrinking upon polycation penetration and complexation focusing on the influence of the HA macromer concentration, molecular weight, cross-linking density, hydrogel initial volume, and polycation properties on shrinking efficiency. To support cell adhesion, RGD peptides were incorporated into the HA network. The polycation concentration strongly affected cell viability: a high concentration of 1 wt % resulted in reduced viability, while 0.1 wt % preserved it with effective shrinkage. Volumetrically printed structures were reduced up to 9 times in volume, achieving features as small as 42 ± 6 μm. This shrinking approach enables the fabrication of hydrogel structures with significantly reduced dimensions, making it a powerful tool for developing high-precision hydrogel structures for tissue engineering.