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 cross-linked to form a hydrated matrix for encapsulated cells. Bioprinting currently enables precise deposition of viable cells in 2 dimensions, however, their printability in the Z-axis is severely limited because the inks are too weak to support additional layers or do not have the flow properties necessary to fabricate stable many-layered structures. Thus, extrusion-based 3D bioprinting has hit a bottleneck in progress over the lack of suitable bioinks. My research has focused on overcoming this limitation by developing a bioink able to bioprint in all 3 dimensions. Nanoengineered Ionic-Covalent Entanglement (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 synergistic interactions, improving mechanical strength, elasticity, toughness, and flow properties beyond the sum of the effects of either reinforcement technique alone. 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. Next, we transform this platform technology into a specialized bioink for recreating missing bone tissue by testing bioink components to create a highly printable bioink with appropriate mechanical and degradation properties for osteogenic tissue formation. Then, bone marrow derived stem cells are encapsulated and bioprinted into custom structures using patient scans, and are closely followed for stem cell differentiation, proliferation, histological changes, and blood vessel ingrowth. The overall effect of this research is the development of a new range of bioinks capable of replicating large 3D tissue structures, and the demonstration of their use for rapidly fabricating cell-containing custom scaffolds for bone tissue regeneration. I envision my research's continued development towards a realistic clinical process for bioprinting patient-specific bone tissue.
