Challenges and perspectives in using finite element modeling to advance 3D bioprinting.

As an emerging additive manufacturing technique, three-dimensional bioprinting enables precise control over the fabrication of tissue replacements, surpassing the limitations of conventional biofabrication methods. However, the successful production of functional bioprinted constructs remains challenging due to the complex interplay of numerous process parameters. The finite element method (FEM) has proven to be a powerful computational tool in biomedical research, offering a means to simulate and optimize various aspects of the bioprinting process. This review systematically examines the diverse applications of FEM across the three key stages of extrusion-based bioprinting-pre-printing, printing, and post-printing-one of the most widely adopted bioprinting technologies. FEM enables the prediction and optimization of tissue construct properties before fabrication by simulating bothandloading conditions, providing valuable insights into critical yet experimentally inaccessible parameters, such as internal stress distributions and mechanical deformations. By enhancing the understanding of these factors, FEM contributes to the development of mechanically stable and biologically functional bioprinted structures. Additionally, FEM-driven simulations facilitate the optimization of bioprinting parameters, reducing material consumption, improving reproducibility, and accelerating the design process. Despite its significant contributions, existing FEM tools remain constrained in their ability to capture the highly dynamic and multi-scale nature of bioprinting completely. Future advancements should enhance the accurate representation of real-time cell-matrix interactions, bioink dynamics, and the progressive maturation of bioprinted constructs. By refining FEM simulations and embedding them into adaptive bioprinting workflows, this computational approach has the potential to drive transformative innovations in tissue engineering, regenerative medicine, and organ fabrication.