Shape changes of bioprinted tissue constructs simulated by the Lattice Boltzmann method

Abstract

Tissue engineers seek to build living tissue constructs for replacing or repairing damaged tissues. Computational methods foster tissue engineering by pointing out dominant mechanisms involved in shaping multicellular systems. Here we apply the Lattice Boltzmann (LB) method to study the fusion of multicellular constructs. This process is of interest in bioprinting, in which multicellular spheroids or cylinders are embedded in a supportive hydrogel by a computer-controlled device. We simulated post-printing rearrangements of cells, aiming to predict the shape and stability of certain printed structures. To this end, we developed a two-dimensional LB model of a multicellular system in a hydrogel. Our parallel computing code was implemented using the Portable Extensible Toolkit for Scientific Computation (PETSc). To validate the LB model, we simulated the fusion of multicellular cylinders in a contiguous, hexagonal arrangement. Our two-dimensional LB simulation describes the evolution of the transversal cross section of the construct built from three-dimensional multicellular cylinders whose length is much larger than their diameter. Fusion eventually gave rise to a tubular construct, in qualitative agreement with bioprinting experiments. Then we simulated the time course of a defect in a bioprinted tube. To address practical problems encountered in tissue engineering, we also simulated the evolution of a planar construct, as well as of a bulky, perfusable construct made of multicellular cylinders. The agreement with experiments indicates that our LB model captures certain essential features of morphogenesis, and, therefore, it may be used to test new working hypotheses faster and cheaper than in the laboratory.