Photoclick Phase-separating Hydrogels for 3D Cell Culture and Volumetric Bioprinting

Abstract

Macroporous scaffolds facilitate solute transport and cell-cell communication, but materials allowing for in situ pore formation and 3D printing in aqueous solutions are scarce. Here, we introduce an efficient thiol-ene photoclick resin for light-assisted fabrication of cell-compatible macroporous hydrogels via photopolymerization-induced phase separation (PIPS). This resin consists of norbornene-functionalized polyvinyl alcohol, di-thiol crosslinker and dextran sulfate, which can rapidly form a hydrogel with interconnected pores by PIPS. The pore size is tunable in the range of 2-40 m as a function of light intensity, polymer composition and molecular charge. Unlike conventional methods to porous materials, PIPS uniquely allows in situ pore formation in the presence of living cells, thereby enabling 3D cell culture and bioprinting applications. We demonstrate fast 3D photoencapsulation of living cells, enhanced cell spreading in macroporous hydrogels, and tomographic volumetric bioprinting of cm-scale hydrogel constructs with hierarchical pores within 20 seconds. Collectively, this resin is cell-compatible, low-cost, easy-to-make and highly efficient for PIPS, offering promises for fast photofabrication of living tissues with complex porous structures.