New Software Tools for Hydrogel-Based Bioprinting

Tissue engineering seeks to solve the problem of donor organ shortage by building tissues and organs in the laboratory. A powerful approach to tissue engineering is three-dimensional (3D) bioprinting-a numerically controlled deposition of cells and biomaterials. The outcome of bioprinting, however, depends on subsequent cell movements governed by mechanisms known from developmental biology. This work presents new informatics tools for predicting post-printing structure formation in bioprinted constructs. We extended the SIMMMC application, developed for simulating cell rearrangements in scaffold-based tissue engineering, with new modules for modeling and simulating the evolution of bioprinted tissue constructs, composed of cells, hydrogels, and cell culture medium. We adapted the Metropolis Monte Carlo algorithm, which lies at the basis of our simulations, such that it takes into consideration the energies of interaction between all the elements of the system. We also created a module that generates automatically the 3D models of fabricated tissue constructs, after loading an XYZ file. Thus, we have the possibility to integrate in our platform many architectures of bioprinted tissue constructs. To validate our new software components, we generated two models used in experiments and simulated their evolution, finding a qualitative agreement between experiments and simulations. The software packages presented here might be used to optimize extrusion-based bioprinting by testing various paths of the print head and diverse cell-cell and cell-hydrogel interactions.