Three-dimensional bioprinted hiHeps hepatorganoids with enhanced hepatic functions for the treatment of liver failure and promotion of liver regeneration

Sep 29, 2026

Uploaded by Adam

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 hiHeps that preserve native lobular zonation and show enhanced metabolic performance, regenerative potential, and improved outcomes in preclinical liver failure models.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages24

Reading Time1 h 0 min

AccessFree to download

Introduction

Liver injury and regenerative limitations

Current therapies and unmet needs

Hepatocyte transplantation background

Bioactive Materials 58 (2026) 550–573 Contents lists available at ScienceDirect Bioactive Materials journal [homepage:](homepage: www.keaipublishing.com/en/journals/bioactive-materials)[ www.keaipublishing.com/en/journals/bioactive-materials](homepage: www.keaipublishing.com/en/journals/bioactive-materials) | Three-dimensional bioprinted hiHeps hepatorganoids with enhanced hepatic functions for the treatment of liver failure and promotion of liver regeneration | | | | | --- | --- | --- | --- | | Zhichao Ye a,b,c,1, Jianing Yan a,b,c,1, Yuheng Wang a,b,c,1,
Yiheng Lina,b,c,1, Chao Wang b,c, Quan Yang b,c, Tong Jib,c, Enjie Zhou a,b,c,
Qiang Zheng a,b,c, Danyang Zhong a,b,c, Yuyang Yuan a,b,c, Tingting Yan b,c, Ziyuan Wang b,c, Jun Yin d,e,*, Xiujun Cai a,b,c,**, Yifan Wang a,b,c,***
a Department of General Surgery, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, 310016, China b National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments, Hangzhou, 310016, China
c Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, 310016, China
d The State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310028, China
e Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310028, China | | | | | A R T I C L E I N F O | | A B S T R A C T | | | Keywords: Hepatorganoids 3D bioprinting Liver regeneration
Liver failure | | 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 posthepatectomy 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 patientspecific 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. | | Peer review under the responsibility of editorial board of Bioactive Materials. * Corresponding author. The State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310028, China. ** Corresponding

FAQs

What problem does the study target?

It addresses liver failure caused by severe injury, where the liver’s intrinsic regenerative capacity is insufficient, leading to irreversible damage and organ dysfunction.

How are the hepatorganoids created and what do they model?

The work develops 3D bioprinted hepatorganoids derived from human induced hepatocytes, recapitulating native lobular zonation that supports spatially segregated metabolic functions.

What therapeutic and functional effects are demonstrated?

The hepatorganoids show enhanced metabolic regulation and albumin synthesis, reverse chronic liver fibrosis, rescue acute liver failure via rapid functional compensation, and accelerate regeneration in partial hepatectomy models.

Sep 29, 2026

Uploaded by Adam