Microfluidic principles for designing vascular-like supply networks for large three-dimensional human tissue models*

In vitro models of tissues are created by providing suitable microphysiological conditions to the cells. In larger human tissue models, a vascular-like supply network is required to ensure sufficient transport of metabolic species (such as oxygen, glucose, and carbon dioxide) to and from cells. In this work, the species transport in human tissue models with an artificial supply network of porous-wall microfluidic channels in Cartesian grid structure is analyzed numerically and analytically. The species diffusion and metabolic activity in the space occupied by the cellular matrix (outside the supply network) is considered in combination with the diffusive and advective transport of the species in the culture medium inside the supply network. Thereby, correlations between the dimensionless groups characterizing the transport processes and the biological parameters indicating the type of tissue cells are derived, as well as principles for designing the artificial supply network. In addition to metabolic aspects, the resilience of the network to clogging of channels and the ease of fabrication of the network using 3D printing are analyzed. In sum, this study addresses key microfluidic problems to be solved when creating the next generation of large three-dimensional tissue models.