3D Bioprinting of Graphene Oxide-Incorporated Cell-laden Bone Mimicking Scaffolds for Promoting Scaffold Fidelity, Osteogenic Differentiation and Mineralization

Bioprinting is a promising technique for facilitating the fabrication of engineered bone tissues for patient-specific defect repair and for developing in vitro tissue/organ models for ex vivo tests. However, polymer-based ink materials often result in insufficient mechanical strength, low scaffold fidelity and loss of osteogenesis induction because of the intrinsic swelling/shrinking and bioinert properties of most polymeric hydrogels. In this work, we developed a novel human mesenchymal stem cell (hMSC)-laden graphene oxide (GO)/alginate/gelatin composite bioink to form 3D bone mimicking scaffolds. Our results showed that the GO composite bioinks with higher GO concentrations improved the bioprintability, scaffold fidelity, compressive modulus and cell viability. The higher GO concentration increased the cell body size and DNA content. The 1GO group had the highest osteogenic differentiation of hMSC with the upregulation of osteogenic-related gene expression at day 42. To mimic critical-sized calvarial bone defects in mice, 3D cell-laden GO defect scaffolds with complex geometries were successfully bioprinted. 1GO maintained the best scaffold fidelity and had the highest mineral volume after culturing in the bioreactor for 42 days. Finally, the 1GO bioink has been demonstrated great potential for 3D bioprinting in applications of bone model and bone tissue engineering.