3D bioprinting strategies for recapitulation of hepatic structure and function in bioengineered liver: A state-of-the-art review

Abstract

3D bioprinting has recently emerged as a successful biofabrication strategy for replicating the complex in vivo hepatic milieu. Significant research advances in this field have allowed for the fabrication of biomimetic hepatic tissues with potential applications in the healthcare (regeneration, transplantation, drug discovery) and diagnostic sectors (in vitro disease models). This article initially delves into describing the hepatic tissue architecture and function, followed by a rational exposition of how 3D bioprinting potentiates the better development of functional liver tissue compared to traditional tissue engineering approaches and 3D cell culture platforms. This review then highlights the recent breakthroughs and reliable strategies for replicating liver structure and function through bioprinting approaches. In this context, we have systematically described the current landscape of hepatic bioprinting, initially focusing on the cell sources used, followed by the biomaterials and strategies implemented to prolong their in vitro viability. Proceeding forward, we have critically highlighted essential aspects of hepatic bioprinting, such as developing tissue-specific bioinks, strategies to induce vascularization within bioprinted liver constructs, and replication of native liver tissue heterogeneity through spatial distribution of multiple cell types in predetermined patterns. In our concluding remarks, we discuss the existing bottlenecks that prevail in this field and provide our viewpoint regarding possible future directions to overcome them.