Liver bioengineering for regeneration: advances in liver disease modeling approaches and decellularization strategies

The global shortage of donor organs and the limitations of conventional in vitro models stress the urgent need for advanced liver tissue engineering and regenerative medicine strategies. These approaches aim to create physiologically relevant platforms for drug testing and develop transplantable tissues to restore liver function. Decellularization offers unique advantages by providing native extracellular matrix architecture and biochemical cues that support cell adhesion, differentiation, and vascularization. Complementary technologies such as three-dimensional (3D) bioprinting and microfluidics enable precise spatial organization of multiple cell types and dynamic perfusion, improving tissue functionality and disease modeling. Together, these innovations facilitate the development of high-fidelity liver constructs and organ-on-chip systems for studying pathologies like fibrosis and steatosis, as well as for preclinical drug screening. In this review we summarize current methods for liver decellularization and explore its role as a regenerative medicine strategy. We also examine applications in disease modeling, with emphasis on 3D bioprinting and microfluidic platforms, and discusses emerging vascularization techniques. Collectively, these insights highlight the progress and remaining challenges in engineering functional liver tissues for clinical and research applications.