Sacrificial microgel-laden bioink-enabled 3D bioprinting of mesoscale pore networks

Abstract

Three-dimensional (3D) bioprinting is a powerful approach that enables the fabrication of 3D tissue constructs that retain complex biological functions. However, the dense hydrogel networks that form after the gelation of bioinks often restrict the migration and proliferation of encapsulated cells. Herein, a sacrificial microgel-laden bioink strategy was designed for directly bioprinting constructs with mesoscale pore networks (MPNs) for enhancing nutrient delivery and cell growth. The sacrificial microgel-laden bioink, which contains cell/gelatin methacryloyl (GelMA) mixture and gelled gelatin microgel, is first thermo-crosslinked to fabricate temporary predesigned cell-laden constructs by extrusion bioprinting onto a cold platform. Then, the construct is permanently stabilized through photo-crosslinking of GelMA. The MPNs inside the printed constructs are formed after subsequent dissolution of the gelatin microgel. These MPNs allowed for effective oxygen/nutrient diffusion, facilitating the generation of bioactive tissues. Specifically, osteoblast and human umbilical vein endothelial cells encapsulated in the bioprinted large-scale constructs (≥ 1 cm) with MPNs showed enhanced bioactivity during culture. The 3D bioprinting strategy based on the sacrificial microgel-laden bioink provided a facile method to facilitate formation of complex tissue constructs with MPNs and set a foundation for future optimization of MPN-based tissue constructs with applications in diverse areas of tissue engineering.