3D Liver Tissue Model with Branched Vascular Networks by Multimaterial Bioprinting

Abstract

Complicated vessels pervade almost all body tissues and influence the pathophysiology of the human body significantly. However, current fabrication strategies have limited success at multiscale vascular biofabrication. This study reports a methodology to fabricate soft vascularized tissue at centimeter scale using multimaterial bioprinting by a customized multistage-temperature-control printer. The printed constructs can be perfused via the branched endothelialized vasculatures to support the well-formed 3D capillary networks, which ensure cellular activities with sufficient nutrient supply and then mimic a mature and functional liver tissue in terms of synthesis of liver-specific proteins. Moreover, an inner and external pressure-bearing layer is printed to support the direct surgical anastomosis of the carotid artery to the jugular vein. In summary, a versatile platform to recapitulate the vasculature network is presented, in which case sustaining the optimal cellularization in engineered tissues is achievable.

Single-Cell Analysis Reveals Transcriptomic Reprogramming in Aging Cardiovascular Endothelial Cells

“…Human umbilical vein endothelial cells (HUVECs) ( 20 ) were cultured in the endothelial growth factor medium EGM™2 with BulletKit™ (Lonza, CC-4176) supplemented with 2% fetal bovine serum (FBS) under standard culture conditions (37°C, with 5% CO2) on 0.1% Gelatin-coated plates. Cells within 10 passages were used for all the experiments.…”

“…We thank Dr. Qi Gu and Wenhui Huang from the Institute of Zoology, Chinese Academy of Sciences for providing the HUVECs ( 20 ).…”

Vascularization in Bioartificial Parenchymal Tissue: Bioink and Bioprinting Strategies

“…However, although the engineered vessel has a diameter of 6 mm, primary patency rates of 63% at 6 months and 28% at 12 months indicate the need for improvements [ 38 ]. Cell-containing bioprinted products are yet to be developed [ 39 ]. On the other hand, microvascular capillaries enable gas exchange and protein and substrate transport to perivascular tissue [ 21 , 40 ].…”

“…While the biofabrication of macrovessels has already been successful in vitro, the engineering of the microvasculature remains challenging. The direct or indirect printing of vascular structures cannot be completely scaled down to reproduce a capillary bed and is mostly limited to the manufacture of structures larger than 100 µm [ 39 , 41 , 42 , 43 ]. Thus, biomaterials, or rather bioinks themselves, may need to provide cues that promote vessel formation.…”

3D printed controllable microporous scaffolds support embryonic development in vitro

“…3D printing has been increasingly applied in tissue engineering (Do et al, 2015; Raja & Yun, 2016). Complicated architectures of various tissues such as the liver (Liu et al, 2021; Yang et al, 2021), heart (Ma et al, 2014), blood vessels (Peng et al, 2021; Zhou et al, 2020), and tumors have been fabricated (Huang et al, 2014). 3D printing holds the advantage of building spatial structures mimicking the living environment of cells in vivo (Hossain et al, 2021).…”