Embedded 3D bioprinting - An emerging strategy to fabricate biomimetic & large vascularized tissue constructs

Three-dimensional bioprinting is an advanced tissue fabrication technique that allows printing complex structures with precise positioning of multiple cell types layer-by-layer. Compared to other bioprinting methods, extrusion bioprinting has several advantages to print large-sized tissue constructs and complex organ models due to large build volume. Extrusion bioprinting using sacrificial, support and embedded strategies have been successfully employed to facilitate printing of complex and hollow structures. Embedded bioprinting is a gel-in-gel approach developed to overcome the gravitational and overhanging limits of bioprinting to print large-sized constructs with a micron-scale resolution. In embedded bioprinting, deposition of bioinks into the microgel or granular support bath will be facilitated by the sol-gel transition of the support bath through needle movement inside the granular medium. This review outlines various embedded bioprinting strategies and the polymers used in the embedded systems with advantages, limitations, and efficacy in the fabrication of complex vascularized tissues or organ models with micron-scale resolution. Further, the essential requirements of support bath systems like viscoelasticity, stability, transparency and easy extraction to print human scale organs are discussed. Additionally, the organs or complex geometries like vascular constructs, heart, bone, octopus and jellyfish models printed using support bath assisted printing methods with their anatomical features are elaborated. Finally, the challenges in clinical translation and the future scope of these embedded bioprinting models to replace the native organs are envisaged.