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Updated: Jan 10, 2026
A Biomimetic Model for Liver Cancer to Study Tumor-Stroma Interactions in a 3D Environment with Tunable Bio-Physical Properties
Published on: August 7, 2020
Three-dimensional bio-printed microtissues: precision medicine approach in primary liver cancer
Hani Keshavarz Alikhani1, Homeyra Seydi1, Kosar Nouri1
1Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Abstract:
Despite remarkable progress in the clinical management of hepatocellular carcinoma (HCC), complications such as heterogenicity of HCC cells and characteristics of cancer stem cells (CSCs) contribute to frequent relapse and treatment resistance. Lack of proper in vitro models has limited developing novel approaches to evaluate innovative therapeutic settings to overcome these challenges. To address current limitations for mimicking cancer microenvironments; various three-dimensional (3D) platforms have been developed, such as tumoroids, patient-derived xenograft (PDX) models, microfluidics-based cancer chip devices, and bio-printed microtissues. Notably, 3D bio-printing technology has enabled researchers to produce scalable complex multicellular tissue models with accurate matrix composition and cellular organization. These microtissues provide precise platforms studying liver regeneration pathways, fibrosis reversal, and cellular responses to therapeutic interventions. This paper, a systematic literature search of databases covering publications from 2000 to 2025, uniquely highlights how these advances enable precise recapitulation of tumor heterogeneity and microenvironmental complexity, thereby offering transformative platforms for personalized drug screening and elucidating mechanisms of liver tissue repair and regeneration. We discussed current challenges and future directions for translating 3D bio-printed liver models into clinically relevant tools, potentially accelerating therapeutic advances and their potential applications in regenerative medicine in terms of personalized medicine and drug screening.
Insights
Three-dimensional bio-printing creates advanced liver cancer models that mimic tumor complexity. These innovative models improve personalized medicine and drug screening for hepatocellular carcinoma (HCC).
Area of Science:
- Biotechnology
- Regenerative Medicine
- Oncology
Background:
- Hepatocellular carcinoma (HCC) relapse and treatment resistance are linked to tumor heterogeneity and cancer stem cells (CSCs).
- Current in vitro models inadequately replicate the tumor microenvironment, hindering the development of novel therapies.
- Three-dimensional (3D) platforms like tumoroids, PDX models, microfluidics, and bio-printed microtissues offer improved in vitro modeling capabilities.
Purpose of the Study:
- To systematically review advancements in 3D bio-printing for creating complex liver tissue models.
- To highlight the potential of these models for studying HCC, liver regeneration, and therapeutic responses.
- To discuss challenges and future directions for clinical translation of 3D bio-printed liver models.
Main Methods:
- Systematic literature search of databases for publications from 2000 to 2025.
- Analysis of 3D bio-printing technologies for recapitulating tumor heterogeneity and microenvironmental complexity.
- Evaluation of applications in personalized drug screening and liver tissue repair research.
Main Results:
- 3D bio-printing enables scalable, complex multicellular tissue models with precise cellular organization and matrix composition.
- These advanced models accurately mimic tumor heterogeneity and microenvironmental complexity.
- 3D bio-printed liver models show promise for studying liver regeneration, fibrosis reversal, and therapeutic interventions.
Conclusions:
- 3D bio-printed liver models represent a transformative platform for personalized drug screening and understanding liver disease mechanisms.
- These models can accelerate therapeutic advances in hepatocellular carcinoma treatment and regenerative medicine.
- Further development is needed to translate these sophisticated in vitro tools into clinically relevant applications.
