Development of photocrosslinkable bioinks with improved electromechanical properties for 3D bioprinting of cardiac BioRings

Abstract

Three-dimensional (3D) bioprinting is an advanced fabrication technique to build biomimetic constructs for different biomedical applications. Here, we developed composite bioinks based on photocrosslinkable natural polymers, gelatin methacryloyl (GelMA) and alginate methacrylate (AlgMA), and electroconductive reduced graphene oxide (rGO) nanomaterials. The photocrosslinked hydrogels indicated interconnected porous microarchitecture with detectable rGO nanosheets on the pore walls. The addition of AlgMA and rGO to GelMA bioinks significantly enhanced tensile and compressive mechanical properties, improved the rheological properties and printability of inks, and controlled the degradation profile of the constructs. The optimization was done based on the suitable electromechanical properties for cardiac tissue engineering applications. The ring-shaped cardiac constructs were further 3D bioprinted with different cardiac cell types (neonatal rat cardiomyocytes, cardiac fibroblasts, and HL-1 cells). The optimized bioink supported a high level of cardiac cell viability, proliferation, spreading, elongation, and alignment with functional hallmarks (e.g., calcium transient and cellular spontaneous beating). Proof-of-concept validation was demonstrated for utilizing this platform as a 3D bioprinted heart-on-a-chip model with automated high-throughput in the 12-well plates. The developed bioprinted cardiac model could be used for different applications, including drug screening and disease modeling.