A multiphysics/multiscale 2D numerical simulation of scaffold-based cartilage regeneration under interstitial perfusion in a bioreactor

Abstract

In vitro tissue engineering is investigated as a potential source of functional tissue constructs for cartilage repair, as well as a model system for controlled studies of cartilage development and function. Among the different kinds of devices for the cultivation of 3D cartilage cell colonies, we consider here polymeric scaffold-based perfusion bioreactors, where an interstitial fluid supplies nutrients and oxygen to the growing biomass. At the same time, the fluid-induced shear acts as a physiologically relevant stimulus for the metabolic activity of cells, provided that the shear stress level is appropriately tuned. In this complex environment, mathematical and computational modeling can help in the optimal design of the bioreactor configuration. In this perspective, we propose a computational model for the simulation of the biomass growth, under given inlet and geometrical conditions, where nutrient concentration, fluid dynamic field and cell growth are consistently coupled. The biomass growth model is calibrated with respect to the shear stress dependence on experimental data using a simplified short-time analysis in which the nutrient concentration and the fluid-induced shear stress are assumed constant in time and uniform in space. Volume averaging techniques are used to derive effective parameters that allow to upscale the microscopic structural properties to the macroscopic level. The biomass growth predictions obtained in this way are significant for long times of culture.

A poroelastic mixture model of mechanobiological processes in biomass growth: theory and application to tissue engineering

“…We refer to [63] and the literature cited therein for a similar treatment of the oxygen consumption term in the framework of a multi-phase growing mixture.…”

“…These values are characteristic of a culture in a perfusion bioreactor where an external hydrodynamic shear stress is applied [55,58,63]. The first investigated question is the effect of the input model parameter amount A of cell density at the beginning of the culture process (t ¼ 0) and at the pore wall (x ¼ 0).…”

“…Table 1). These two values are selected by comparison with the maximum specific cell growth rate k g0 used in [63] in such a way that k g \k g0 corresponds to ''low growth regime'' whereas k g [ k g0 corresponds to ''high growth regime''.…”

Tissue Engineering and Regenerative Medicine Technologies in the Treatment of Articular Cartilage Defects

“…Перфузия жидкости через КИК в условиях in vitro обуславливает два типа физических воздейс-твий одновременно -силу сдвига и гидростатиче-ское давление [110].…”

Effect of ocular shape and vascular geometry on retinal hemodynamics: a computational model

“…Interestingly, various modeling approaches have been proposed to model retinal blood flow [2,23,39,44], and leverage information from fundus images to improve physically based models [19,20,33].…”