Innovative biofabrication: integrating microfluidics, nanotechnology, and multiphysics simulations in tissue engineering

Abstract

The escalating cost of medicine production and ethical concerns surrounding animal testing have driven the need for alternative approaches in drug development. Tissue engineering, organ-on-a-chip technology, bioprinting, and advanced cell culture techniques have emerged as innovative strategies to improve the predictability and relevance of in vitro models while reducing reliance on traditional methods. One such approach is bioprinting with cell spheroids, which allows for precise placement of cells and biomaterials to fabricate intricate tissue constructs. However, challenges remain in accurately representing the fusion process of cell aggregates and expediting tissue fusion. To address these challenges, this study aims to achieve two objectives. Firstly, a multiphysical stochastic phase field model is proposed to accurately represent the fusion process of cellular spheroids. This model incorporates stochastic elements and phase field principles to capture the inherent variability and complexities of the fusion behavior. The model exhibits an average error of 6% when compared to experimental results, demonstrating its effectiveness in simulating and predicting the fusion behavior of spheroids. Secondly, the study explores the application of magnetic fields to accelerate the fusion process of cell aggregates. Magnetite nanoparticles are incorporated into the spheroids to magnetize them, enhancing the interaction and fusion of the cell aggregates. The rapid magnetization of the spheroids is facilitated by the translocating effect of the Buforin-II peptide, allowing for effective and quick penetration of nanoparticles throughout the entire spheroid. The application of a magnetic field significantly reduces the fusion time from 7 days to 2 days, leading to expedited maturation of bioprinted tissues. Increasing the number of magnetic spheroids further enhances the speed of the fusion process.The use of the proposed multiphysical stochastic phase field model and magnetite-assisted bioprinting technique holds great promise for tissue engineering and regenerative medicine. These advancements have the potential to revolutionize tissue engineering by improving the efficiency and reliability of the tissue development process, while also reducing the need for animal testing in drug development. Further investigations are recommended to ensure the safety and viability of cells under the stress exerted by the magnetic field.