(440b) Fiber-Based Hydrogels As 3D Printable Granular Materials with Unique Properties for Addressing Challenges in Biofabrication

Particle-based (granular) hydrogels are dynamic systems that can transition from a solid- to a liquid-like state under applied stress and back, upon the removal of stress, in the absence of interparticle crosslinking. As a function of this property alone, these materials have emerged as attractive (bio)inks and support baths in state-of-the-art 3D bioprinting processes. While these materials are typically formed from spherical particles, next-generation systems with new potential for engineering functionality are emerging in the form of fiber-based granular hydrogels. Here, we present granular hydrogels formed either partially or completely from discrete hydrogel microfibers that are ~1-2 microns in diameter but that can be 100s of microns in length. Compared to spherical particles, nanofiber particles’ aspect ratios result in long-range interparticle interactions that give rise to new viscoelastic properties. Additionally, nanofibers can support high porosity in granular materials. We have created hydrogel nanofibers from both hyaluronic acid and poly(ethylene glycol) backbones. After electrospinning, fibers were dry-crosslinked, hydrated, and then segmented by homogenization to form the discrete microfiber particles. These were suspended in aqueous medium with or without cells, and then centrifuged to concentrate the hydrogel microfibers (and cells, if present) into macroscale granular hydrogels. Rheological and extensibility testing showed that, like traditional granular hydrogels, microfiber-based hydrogels exhibited a yield stress and can transition between solid- and liquid-like behaviors depending on applied stresses. Unlike traditional particle-based hydrogels, however, they were highly extensible (stretching to > 2000% bulk length). These materials also exhibited rapid stress relaxation, on the order of 10s of seconds, that can be controlled in part through formulation. In extrusion-based applications, such as bioprinting, the long-range entanglements stabilize printed filaments, even absent interfiber crosslinking. Interparticle crosslinking can be introduced within these systems to stabilize 3D structures. By introducing fibers into highly-porous granular hydrogels based on spherical particles, long-range fiber-mediated crosslinking can stabilize granular systems that would otherwise degrade by erosion. The new material functionalities enabled by these systems enable cell behaviors, such as spreading or the formation of microvascular network-like structures, without the need to design the hydrogel chemistry to support for degradation or yielding. We have seen that fiber-based granular materials support embedded printing, including allowing channels to formed by the removal of fugitive inks. Taken together, we believe fiber-based granular systems will present new opportunities for designing 3D materials for biomedical applications.