(692b) Nanoengineered Ionic-Covalent Entanglement (NICE) Bioinks for 3D Bioprinting

Three-dimensional (3D) bioprinting is emerging as a promising method for rapid fabrication of biomimetic cell-laden constructs for tissue engineering using cell-containing hydrogels, called bioinks, that can be crosslinked to form a hydrated matrix for encapsulated cells. However, extrusion based 3D bioprinting has hit a bottleneck in progress due to the lack of available bioinks with high printability, mechanical strength, and biocompatibility. Here, we introduce an enhanced nanoengineered ionic covalent entanglement (NICE) bioink for the fabrication of mechanically stiff and elastomeric 3D biostructures. NICE bioink formulations combine nanocomposite and ionic covalent entanglement (ICE) strengthening mechanisms to print customizable cell-laden constructs for tissue engineering with high structural fidelity and mechanical stiffness. Nanocomposite and ICE strengthening mechanisms complement each other through their synergistic interactions, improving mechanical strength, elasticity, toughness, and flow properties beyond the sum of the effects of both reinforcement techniques alone. Herschel-Bulkley flow behavior shields encapsulated cells from excessive shear stresses during extrusion. The encapsulated cells readily proliferate and maintain high cell viability over 120 days within the 3D-printed structure, which is vital for long-term tissue regeneration. The unique aspect of the NICE bioink is its ability to print much taller and higher aspect ratio structures than conventional bioinks without requiring secondary supports. We envision that NICE bioinks can be used to bioprint complex, large-scale, cell-laden constructs for tissue engineering with high structural fidelity and mechanical stiffness for applications in custom bioprinted scaffolds and tissue engineered implants.