Nanoengineered Osteoinductive Bioink for 3D Bioprinting Bone Tissue

Bioprinting is an emerging additive manufacturing approach to the
fabrication of patient-specific, implantable three-dimensional (3D)
constructs for regenerative medicine. However, developing cell-compatible
bioinks with high printability, structural stability, biodegradability,
and bioactive characteristics is still a primary challenge for translating
3D bioprinting technology to preclinical and clinal models. To overcome
this challenge, we developed a nanoengineered ionic covalent entanglement
(NICE) bioink formulation for 3D bone bioprinting. The NICE bioinks
allow precise control over printability, mechanical properties, and
degradation characteristics, enabling custom 3D fabrication of mechanically
resilient, cellularized structures. We demonstrate cell-induced remodeling
of 3D bioprinted scaffolds over 60 days, demonstrating deposition
of nascent extracellular matrix proteins. Interestingly, the bioprinted
constructs induce endochondral differentiation of encapsulated human
mesenchymal stem cells (hMSCs) in the absence of osteoinducing agent.
Using next-generation transcriptome sequencing (RNA-seq) technology,
we establish the role of nanosilicates, a bioactive component of NICE
bioink, to stimulate endochondral differentiation at the transcriptome
level. Overall, the osteoinductive bioink has the ability to induce
formation of osteo-related mineralized extracellular matrix by encapsulated
hMSCs in growth factor-free conditions. Furthermore, we demonstrate
the ability of NICE bioink to fabricate patient-specific, implantable
3D scaffolds for repair of craniomaxillofacial bone defects. We envision
development of this NICE bioink technology toward a realistic clinical
process for 3D bioprinting patient-specific bone tissue for regenerative
medicine.