Hydrogel-Based Bioinks for Cell Electrowriting of Well-Organized Living Structures with Micrometer-Scale Resolution

Abstract

Bioprinting has become an important tool for fabricating regenerative implants and in vitro cell culture platforms. However, until today, extrusion-based bioprinting processes are limited to resolutions of hundreds of micrometers, which hamper the reproduction of intrinsic functions and morphologies of living tissues. This study describes novel hydrogel-based bioinks for cell electrowriting (CEW) of well-organized cell-laden fiber structures with diameters ranging from 5 to 40 μm. Two novel photoresponsive hydrogel bioinks, that is, based on gelatin and silk fibroin, which display distinctly different gelation chemistries, are introduced. The rapid photomediated cross-linking mechanisms, electrical conductivity, and viscosity of these two engineered bioinks allow the fabrication of 3D ordered fiber constructs with small pores (down to 100 μm) with different geometries (e.g., squares, hexagons, and curved patterns) of relevant thicknesses (up to 200 μm). Importantly, the biocompatibility of the gelatin- and silk fibroin-based bioinks enables the fabrication of cell-laden constructs, while maintaining high cell viability post printing. Taken together, CEW and the two hydrogel bioinks open up fascinating opportunities to manufacture microstructured constructs for applications in regenerative medicine and in vitro models that can better resemble cellular microenvironments.