A Phase-separating Thiol-ene Photoresin for Volumetric Bioprinting of Macroporous Hydrogels

Abstract

AbstractMacroporous hydrogels facilitate solute transport and cell-cell communication in 3D, but materials allowing for in situ pore formation and 3D-printing in aqueous solutions are scarce. Here, a phase-separating thiol-ene photoresin is developed for light-assisted 3D-printing of hierarchical macroporous hydrogels that support 3D cell growth. The resin consists of norbornene-functionalized polyvinyl alcohol, di-thiol crosslinker and dextran sulfate, which can rapidly form a hydrogel with interconnected pores by photopolymerization-induced phase separation (PIPS). The pore size is tunable in the range of 2-40 μm as quantified by fast Fourier transformation of confocal imaging data and depends on light intensity, polymer composition and molecular charge. After 3D photoencapsulation, high cell viability (>90%) is achieved and cell spreading in the macroporous hydrogels is significantly higher than in conventional nanoporous hydrogels. The incorporation of a thermo-reversible gelatin network enables its printability for tomographic volumetric bioprinting in the presence of human mesenchymal stem cells. A cm-scale cell-laden hydrogel construct with vasculature-like channels and interconnected pores can be 3D-printed in 12 seconds. The materials are cell-compatible, low-cost, easy-to-make and highly efficient for PIPS and light-based 3D-printing, which is unachievable with conventional 3D-printable hydrogels. Such materials are promising for future photofabrication of complex tissues with a hierarchical porosity within seconds.