Bioprinting for Liver Transplantation

Abstract

Bioprinting techniques can be used for the in vitro fabrication of functional complex bio-structures. Thus, extensive research is being carried on the use of various techniques for the development of 3D cellular structures. This article focuses on direct writing techniques commonly used for the fabrication of cell structures. Three different types of bioprinting techniques are depicted: Laser-based bioprinting, ink-jet bioprinting and extrusion bioprinting. Further on, a special reference is made to the use of the bioprinting techniques for the fabrication of 2D and 3D liver model structures and liver on chip platforms. The field of liver tissue engineering has been rapidly developed, and a wide range of materials can be used for building novel functional liver structures. The focus on liver is due to its importance as one of the most critical organs on which to test new pharmaceuticals, as it is involved in many metabolic and detoxification processes, and the toxicity of the liver is often the cause of drug rejection.

Innovative Human Three-Dimensional Tissue-Engineered Models as an Alternative to Animal Testing

“…Recently, the combination of several techniques of production or maturation, such as induced pluripotent stem cells, organoids, bioprinting, composite hydrogels, organ-on-chip, microphysiological systems, mechanical stimuli, innervation etc., (e.g., [ 312 , 313 , 314 , 315 , 316 ]), gave us the opportunity to produce a large spectra of complex organs. These organs could also be used for various applications such as potential transplantation (e.g., [ 317 ]) or disease modeling (e.g., [ 318 , 319 , 320 ]). For example, after demonstrating the functionality of hepatic cells bioprinted on collagen gels to drug screening [ 321 ], a mini-liver was produced using iPSC which differentiated into hepatocyte and self-organized into acini [ 322 ].…”

“…For example, after demonstrating the functionality of hepatic cells bioprinted on collagen gels to drug screening [ 321 ], a mini-liver was produced using iPSC which differentiated into hepatocyte and self-organized into acini [ 322 ]. The basis of the production of liver substitute for transplantation has been laid: such a tissue required not only the right differentiation and organization of hepatocyte but also irrigation by a vascular network and potential reconnection to the host [ 317 ]. Another example: a gut-on-chip platform has been established to study various physiological aspect of this complex organ which is the gastrointestinal tract [ 323 ].…”

Biofabrication of Hepatic Constructs by 3D Bioprinting of a Cell‐Laden Thermogel: An Effective Tool to Assess Drug‐Induced Hepatotoxic Response

“…Thus, several research groups have adapted different AM techniques to direct the assembly of extracellular matrix (ECM) materials with multiple cell types, and to obtain heterogeneous distribution of drugs and growth factors within controlled 3D architectures. [2,3] Furthermore, viable cell-laden constructs have been successfully fabricated and proposed as in vitro cellular models for pathogenetic and drug discovery studies; the reported applications of cell bioprinting include, among the others, the biofabrication of adipose tissue, [4] bone tissue, [5] liver tissue, [6,7] and cervical tumor models. [8] Targeting bioprinting applications, hydrogels have to meet specific requirements of viscosity and gelation rate to achieve an accurate match of the designed architecture, therefore limiting the number of formulations that can be processed by bioprinting.…”

Challenges for Deriving Hepatocyte-Like Cells from Umbilical Cord Mesenchymal Stem Cells forIn VitroToxicology Applications

“…The perivenous hepatocytes have less access to oxygen supplies and are characterized by a higher xenobiotic metabolism, being exposed to physiologic conditions similar to the ones observed around the inner cells [3,7]. Moreover, hepatocytes are not the only cells present in the liver as they interact with mesenchymal cells, stellate cells, Küpffer cells, macrophages, and lymphocytes, and are exposed, in vivo, to a fluid perfusion [105]. Hence, in vitro liver function may be optimized by resorting to microfluidic technologies.…”