3D Bioprinting of Graphene Oxide-Incorporated Hydrogels for Neural Tissue Regeneration

Abstract

Bioprinting has emerged as a powerful manufacturing platform for tissue engineering, enabling the fabrication of 3D living structures by assembling living cells, biological molecules, and biomaterials into these structures. Among various biomaterials, hydrogels have been increasingly used in developing bioinks suitable for 3D bioprinting for diverse human body tissues and organs. In particular, hydrogel blends combining gelatin and gelatin methacryloyl (GelMA; ‘‘GG hydrogels’’) receive significant attention for 3D bioprinting owing to their many advantages, such as excellent biocompatibility, biodegradability, intrinsic bioactive groups, and polymer networks that combine the thermoresponsive gelation feature of gelatin and chemically crosslinkable attribute of GelMA. However, GG hydrogels have poor electroactive properties, which hinder their applications in neural tissue engineering where electrical conductivity is required. To overcome this problem, in this study, a small amount of highly electroactive graphene oxide (GO) was added in GG hydrogels to generate electroactive hydrogels for 3D bioprinting in neural tissue engineering. The incorporation of GO nanoparticles slightly improved mechanical properties and significantly increased electrical conductivity of GG hydrogels. All GO/ GG composite hydrogels exhibited shear thinning behavior and sufficient viscosity and hence could be 3D printed into 3D porous scaffolds with good shape fidelity. Furthermore, bioinks combining rat bone marrow-derived mesenchymal stem cells (rBMSCs) with GO/GG composite hydrogels could be 3D bioprinted into GO/ GG constructs with high cell viability. GO nanoparticles in the constructs provided ultraviolet (UV) shading effect and facilitated cell survival during UV exposure after bioprinting. The GO/GG composite hydrogels appear promising for 3D bioprinting applications in repairing damaged neural tissues.