Three-dimensional bioprinted hiHeps hepatorganoids with enhanced hepatic functions for the treatment of liver failure and promotion of liver regeneration
Year: 2025
Type: article
Abstract: The intricate architecture of the liver, combined with its limited regenerative ability in severe injury, has spurred the development of innovative approaches for hepatic repair and functional restoration. Three-dimensional (3D) bioprinting provides a unique platform to reconstruct biomimetic liver tissues through spatially orchestrated cellular and extracellular matrix integration. Here, we developed 3D bioprinted hepatorganoids derived from human induced hepatocytes (hiHeps), which faithfully recapitulate the native lobular zonation crucial for spatially segregated metabolic functions in vivo. 3D bioprinted hiHeps hepatorganoids (3DP-HHO) exhibited markedly enhanced metabolic performance, including improved glucose and lipid regulation and elevated albumin synthesis, highlighting their potential as advanced liver models. The hepatorganoids demonstrated robust regenerative potential, which reversed chronic liver fibrosis (CLF) by resolving pathological collagen deposition, rescued acute liver failure (ALF) through rapid functional compensation, and accelerated liver regeneration in partial hepatectomy models by stimulating endogenous hepatocyte proliferation. Preclinical validation of post-hepatectomy liver failure (PHLF) model revealed that the implantation of 3DP-HHO significantly improved survival outcomes and promoted liver regeneration, compared to controls. In the future, by integrating patient-specific cells with regulable 3D microenvironments, our platform will achieve superior functional integration and regenerative efficacy over conventional approaches. This work establishes a paradigm for bioengineered liver grafts that actively drive tissue repair and regeneration. As a scalable and physiologically relevant approach, these bioprinted hepatic units pioneer a transformative strategy in regenerative hepatology, addressing critical challenges in treating liver failure and post-resection recovery while illuminating microenvironmental factors essential for organ-level regeneration.
Source: Bioactive Materials
Authors: Zhichao Ye, Jianing Yan, Yuheng Wang, Yuheng Wang, Yiheng Lin, Chao Wang, Quan Yang, Tong Ji, Enjie Zhou, Qiang Zheng, Danyang Zhong, Yuyang Yuan, Tingting Yan, Ziyuan Wang, Jun Yin, Xiujun Cai, Yifan Wang, Yifan Wang
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $2,200
OpenAlex ID: W7116040404