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.
Keywords: 3D bio-printing; Liver cancer; personalized medicine; precision medicine; three-dimensional bio-printing models.
Primary liver cancer is a serious illness with two main types: hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Studying these cancers in the lab has been difficult because conventional methods like flat cell cultures and animal models fail to fully mimic how tumor cells grow and interact with their environment. However, recent advances in 3D bio-printing technology now enable scientists to build tiny, complex models of liver tumors that better replicate their real structure and environment. This review article summarizes the latest progress in creating 3D bio-printed liver cancer models that include different types of cells, primary blood vessel structures, and the surrounding microenvironment that supports tumor growth. These models not only provide a more accurate and personalized way to understand the cancer development and treatment response but also serve as powerful tools to study of liver tissue repair and tissue regeneration. By combining new materials and advanced printing techniques, researchers can produce patient-specific models that help predict that which medication will work better for individual patients. This technology promises to improve drug testing outcomes and accelerate the discovery of effective therapies.