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Computational simulation for a perfusion bioreactor project


Bioprinting of tissues and organs can be defined as a computer-aided, layer-by-layer, additive biofabrication of functional 3D tissue and organs constructs based on a digital model using tissues spheroids as self-assembling building blocks (Mironov et al., 2008). Tissue spheroids are cell agglomerate that acquires the most stabilized form of a sphere. The diameter is limited since all mass transfer occurs by diffusion and the cells cannot be farther then 200μm of the flow of capillaries (Muschler et al., 2004).
The product of the 3D printing process is not a fully operational organ and must be maturated. During the maturation the tissue spheroids will fuse and the cells can start a sequence of process to form the tissue. This process will occur in a bioreactor, a device in which biological and biochemical process develop under closely monitored and tightly controlled environmental and operating conditions (e.g. pH, temperature, pressure) (Martin et al., 2004).
Because of the limitation of the diffusion range and the lack of circulatory system to improve the distribution of nutrients and oxygen for the agglomerate of cells, the size of tissue is limited. An alternative to help solve this problem is discussed in this project, the application of porous needles in a perfusion bioreactor to nourish the center of the tissue. The needles behave as an artificial circulatory system.

Objetivos - Metodologia - Resultados - Discussão dos Resultados/Objectives - Methodology - Results - Discussion of Results/Objetivos - Metodología - Resultados - Discusión de los resultados

The objective of the project is to simulate 3 parameters: temperature, shear stress and diffusion to compound a perfect environment for a tissue in a bioreactor. To validate the simulations the values will be compared with biological values.
The cell produces energy (metabolism) which increase the temperature of the system. The needles will refrigerate the tissue, keeping it in a viable temperature for the cell survival. With higher the velocity, more fluid flows through the tissue, increasing the quantity of nutrient and oxygen and the refrigerated area, but it also generates a higher shear stress in the cells.
The software for the study were Rhinoceros 5.0® for design and Ansys/CFX® for simulation. The first model study the shear stress. The goal is to test different velocities of a flow through an agglomeration of spheres to find the maximum velocity that causes the maximum allowable shear stress. This velocity is applied to the second model consisting of a rectangular box (the tissue) and a needle (0.47mm of diameter and 0.04mm of diameter pores). This model will help determine the number of needles a tissue will need based on the volume a needle can refrigerate and nourish. The box is a porous model producing a metabolism, its cross-sectional area increase until the temperature reaches a value higher than allowed by the conditions imposed.
The simulations concluded so far shows that different tissues need different numbers of needles since they depend on different conditions. The accuracy of the information of this conditions is essential for the precision of the simulations.

Considerações Finais/Final considerations/Consideraciones finales

In the future others parameters will be considerate to create a prototype. All the analyzes contribute to avoid large expenses with laboratory tests.

Martin, I., et al. The role of bioreactors in tissue engineering. TRENDS in Biotechnology ,22(2), 80, 2004
Mironov, V., et al. Organ printing: promises and challenges,2008
Muschler, G.F., et al. Engineering principles of clinical cell-based tissue engineering.JBJS, 86(7), 1541, 2004

Palavras-chave/Key words/Palabras clave

Bioreactor, CFD, Bioprinting, Biofabrication




JULIA ADAMI NOGUEIRA, Daniel Takanori Kemmoku, Pedro Yoshito Noritomi, Jorge Vicente Lopes da Silva, Janaina Dernowsek, Monize Caiado Decarli, Rodrigo Alvarenga Rezende, Fabio Vilalba