3D printing of vascularized hepatic tissues with a high cell density and heterogeneous microenvironment

Abstract

Three-dimensional (3D) bioprinting has emerged as an appealing approach for creating functional tissues; however, a lack of suitable bioinks with high cell density and printability has greatly limited our ability to print functional tissues. We address this limitation by developing a granular cell aggregate-based biphasic (GCAB) bioink based on densely packed cell aggregates. The GCAB bioink exhibited the desired shear-thinning and shear-recovery properties for extrusion bioprinting and hyperelastic behaviors postprinting for modeling the mechanical characteristics of soft biological tissues. The GCAB bioink displayed a high cell density (~1.7×108 cells/cm3) without compromising viability (~83%). We printed dense hepatic tissue constructs with enhanced vascularization and metabolic functions by preorganization of GCAB bioink with a defined heterogeneous microenvironment. By simultaneously printing the GCAB bioink and an endothelial cell-laden gelatin bioink, we successfully produced functional hepatic tissues with a high cell density and a perfusable vascular network. The design of the generalizable GCAB bioink opens new avenues to create functional tissues for therapeutic applications.

iPSC-derived cells for whole liver bioengineering

“…Synthetic biomaterials (e.g., PCL, PEG, PLGA) yield more stable structures but may elicit immunogenic responses. Conversely, while natural bioinks (e.g., alginate, collagen, gelatin) are biocompatible and degradable, achieving optimal printability requires precise adjustment of bioprinting parameters (e.g., bioink concentration, printing time, crosslinking strategy) and often involves blending with other biomaterials ( Fang et al, 2023 ).…”

Advances in the construction of in vitro liver tissue models using 3D bioprinting technology

“…When compared to bioink composed of dispersed cells at the same density, GCAB bioink printed bodies exhibit higher liver function activity. Furthermore, the addition of HUVECs for co-printing results in enhanced vascularization effects when using GCAB bioink ( 12 ).…”