Leveraging Particle Dispersion in Porous Biomaterials to Reprogram Cells

The dispersive property of liquid flow in porous media is a well-studied phenomenon that has made significant impact in the fields of water science, oil exploration, and semiconductors. More recently, our lab has demonstrated the therapeutic potential of porous biomaterials as a platform to reprogram cells and produce gene therapies. Cells are reprogrammed when a liquid suspension containing cells and gene carriers (like viruses and lipid nanoparticles) is absorbed into a macroporous medium. In this study, we have used computational modeling and in vitro experimentation to develop a fluid dynamic understanding of how liquid flow through porous media enhances cell-virus interaction at the microscale level. We developed a representative pore geometry of the biomaterial from X-ray computed tomography and simulated liquid and particle flow inside the pores using computational fluid dynamics and discrete element modeling. Our results show that liquid flow in stochastic pores promotes an order of magnitude greater number of collisions between cells and viruses than in uniform pores or unbounded flow. The number of cell-virus collisions increases with the increase in flow velocity indicating the crucial role of convection in cell-virus interaction. Our study concludes that hydrodynamic dispersion of the liquid flow in stochastic pores induces particle diffusion at the macroscale level, which plays an important role in particle mixing and particle-particle interaction in porous media.