Zwitterionic in situ-gelling hydrogel-based bioinks for tissue regeneration applications

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Despite the tremendous promise of 3D bioprinting for revolutionizing our ability to regenerate diseased tissues and/or create cell-based therapeutics for managing chronic diseases, the rapid development of 3D bioprinting technologies has greatly outpaced the development of new functional commercially-available bioinks to leverage those technologies. In particular, the availability of a bioink that can enable free-form bioprinting using multiple types of 3D printers and meet the key physical and biological requirements of a functional tissue scaffold (i.e. targeted mechanics, tunable degradation, well-defined porosity, cell adhesivity, and anti-fibrotic properties) is essential to address key translational challenges in tissue engineering and cell therapy. Toward meeting this challenge, we have developed an in situ-gelling zwitterionic hydrogel based on mixing hydrazide and aldehyde and/or ketone functionalized pre-polymers to form a reversible hydrazone-crosslinked gel network. These hydrogels can facilitate ultra-fast gelation upon mixing (<1 s), highly tunable degradation times (ranging from a few days to several months), extremely high lubricity (beneficial for 3D printing cartilage for joint regeneration), very low cell/protein adsorption, anti-fibrotic tissue responses, and a capacity to support both the viability and expansion of encapsulated cells, a suite of properties highly relevant to a 3D bioink. While these materials have already attracted interest from potential company partners in the 3D bioprinting industry, proof-of-concept demonstrations around practically implementing our in situ gelation crosslinking chemistry on commercial 3D printers to achieve required shape fidelities and mechanics, printing clinically-relevant primary human cells or stem cells, and ensuring the scalable manufacturing of chemically pure and biologically inert bioink components are required prior to investment being feasible. The work proposed in this I2I grant is designed to answer these key proof-of-concept questions, aiming to produce at least one 3D bioink "kit" that could be licensed for distribution and/or internal development use at one or more leading 3D printing companies by the end of the I2I project period.