Bioprinted high cell density liver model with improved hepatic metabolic functions

IF 12.8 1区 医学 Q1 ENGINEERING, BIOMEDICAL Biomaterials Pub Date : 2025-03-11 DOI:10.1016/j.biomaterials.2025.123256
Ting-Yu Lu , Yichun Ji , Cheng Lyu , Erin Nicole Shen , Yazhi Sun , Yi Xiang , Tobias Meng-Saccoccio , Gen-Sheng Feng , Shaochen Chen
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Abstract

In vitro liver tissue models are valuable for studying liver function, understanding liver diseases, and screening candidate drugs for toxicity and efficacy. While three-dimensional (3D) bioprinting shows promise in creating various types of functional tissues, current efforts to engineer a functional liver tissue face challenges in replicating native high cell density (HCD) and maintaining long-term cell viability. HCD is crucial for establishing the cell-cell interactions necessary to mimic the liver's metabolic and detoxification functions. However, HCD bioinks exacerbate light scattering in light-based 3D bioprinting. In this study, we incorporated iodixanol into our bioink formulation to minimize light scattering, enabling the fabrication of hepatic tissue constructs with an HCD of 8 × 107 cells/mL while maintaining high cell viability (∼80 %). The printed dense hepatic tissue constructs showed enhanced cell-cell interactions, as evidenced by increased expression of E-cadherin and ZO-1. Furthermore, these constructs promoted albumin secretion, urea production, and P450 metabolic activity. Additionally, HCD hepatic tissue inactivated the YAP/TAZ pathway via cell-cell interactions, preserving primary hepatocyte functions. Further screening revealed that hepatocytes in the dense model were more sensitive to drug treatments than those in a lower-density hepatic model, highlighting the importance of HCD in recapitulating the physiological drug responses. Overall, our approach represents a significant advancement in liver tissue engineering, providing a promising platform for the development of physiologically relevant in vitro liver models for drug screening and toxicity testing.
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来源期刊
Biomaterials
Biomaterials 工程技术-材料科学:生物材料
CiteScore
26.00
自引率
2.90%
发文量
565
审稿时长
46 days
期刊介绍: Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.
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