Nanoengineered Granular Hydrogel Bioinks with Preserved Interconnected Microporosity for Extrusion Bioprinting.

ABSTRACT

3D bioprinting of granular hydrogels comprising discrete hydrogel microparticles (microgels) may overcome the intrinsic structural limitations of bulk (nanoporous) hydrogel bioinks, enabling the fabrication of modular thick tissue constructs. The additive manufacturing of granular scaffolds has predominantly relied on highly jammed microgels to render the particulate suspensions shear yielding and extrudable. This inevitably compromises void spaces between microgels (microporosity), defeating rapid cell penetration, facile metabolite and oxygen transfer, and cell viability. Here, this persistent bottleneck is overcome by programming microgels with reversible interfacial nanoparticle self-assembly, enabling the fabrication of nanoengineered granular bioinks (NGB) with well-preserved microporosity, enhanced printability, and shape fidelity. The microporous architecture of bioprinted NGB constructs permits immediate post-printing 3D cell seeding, which may expand the library of bioinks via circumventing the necessity of bioorthogonality for cell-laden scaffold formation. This work opens new opportunities for the 3D bioprinting of tissue engineering microporous scaffolds beyond the traditional biofabrication window.