Optimizing the tissue engineering of tubular organ structures by bio-printing

Abstract

Tissue engineering and regenerative medicine may help to save people’s lives by fabricating new organs. Towards this goal our objective is to optimize the conditions for cells to self assemble into functional structures, such as tissues and eventually organoids. To facilitate self-assembly we employ the technology of bioprinting. To maintain the extended cellular assemblies, they need to be vascularized. Thus we first concentrated on the fabrication of blood vessels. We prepared convenient bioink particles, multicellular units composed of the relevant cell types and we deposited them into a configuration, consistent with the shape of the vessel. Self-assembly and the maturation of the construct takes place post-printing in special-purpose bioreactors by the fusion of the bioink units and the rearrangement of the cells within them. The time to achieve near physiological biomechanical properties has so far been found by trial and error. We report the experimental part of an experimental-theoretical-computational framework to optimize the postprinting maturation process, in particular the fusion of the bioink units. The connection between experiments and computer simulations were guided by theory. Here we report the results of extended fusion experiments and on their comparison with predictions of the theory. The excellent agreement we found, on one hand, provided a verification of the theoretical component of the formalism, and, on the other hand, the input for the computational component of the formalism. Specifically, our experiments, together with the theory, allowed the calibration of the basic simulation parameters, which in turn allows the full implementation of the computational component of the formalism to optimize the fabrication of blood vessels through the bioprinting process.