Modeling of flow‐induced shear stress applied on 3D cellular scaffolds: Implications for vascular tissue engineering

Abstract

Novel tissue-culture bioreactors employ flow-induced shear stress as a means of mechanical stimulation of cells. We developed a computational fluid dynamics model of the complex three-dimensional (3D) microstructure of a porous scaffold incubated in a direct perfusion bioreactor. Our model was designed to predict high shear-stress values within the physiological range of those naturally sensed by vascular cells (1-10 dyne/cm(2)), and will thereby provide suitable conditions for vascular tissue-engineering experiments. The model also accounts for cellular growth, which was designed as an added cell layer grown on all scaffold walls. Five model variants were designed, with geometric differences corresponding to cell-layer thicknesses of 0, 50, 75, 100, and 125 microm. Four inlet velocities (0.5, 1, 1.5, and 2 cm/s) were applied to each model. Wall shear-stress distribution and overall pressure drop calculations were then used to characterize the relation between flow rate, shear stress, cell-layer thickness, and pressure drop. The simulations showed that cellular growth within 3D scaffolds exposes cells to elevated shear stress, with considerably increasing average values in correlation to cell growth and inflow velocity. Our results provide in-depth analysis of the microdynamic environment of cells cultured within 3D environments, and thus provide advanced control over tissue development in vitro.

Design concepts and strategies for tissue engineering scaffolds

“…Smooth muscle cells are a critical component of a number of cardiovascular, gastrointestinal, and urological tissues residing in mechanically dynamic in vivo environments. Thus, the development of scaffolds that can maintain their mechanical integrity and transfer the mechanical signals to adhering cells during long-term cyclic mechanical strain is necessary to engineer viable smooth muscle that can be applied to various tissue applications [83][84][85][86]. Then, the most important property of the scaffold for those applications is its elasticity and capability of withstanding cyclic mechanical strain for extended periods of time without cracking or significant permanent deformation.…”

A Computational Based Design and Optimization Study of Scaffold Architectures

“…1a), based on the geometry of a polymeric scaffold obtained by particulate leaching. On the other hand, Lesman et al [12], proposed a more complicated 3D structure, namely the face-centered cubic lattice (FCC) model (Fig. 1b).…”

“…In order to test and validate the considered scheme, the SC and FCC models were designed and the analysis results were compared to those published by Boschetti et al [11] and Lesman et al [12], respectively. Figure 2 shows the shear stress distribution on the walls of the central pore for porosities and pore sizes shown in Table 1.…”

“…Moreover, as the microstructure of the scaffold does not allow the measurement of the shear stress experimentally, this can be done only through CFD calculations. In this field many researchers, using either simple [11] or more complex [12,13] geometries, demonstrated the great dependence of the shear stress on the pore size and the porosity. The target of the present study is to examine through CFD simulations the shear stress distribution and the Darcian permeability factor to different regular scaffold architectures with a variety of geometrical characteristics.…”

Review: Mechanotransduction in ovarian cancer: Shearing into the unknown

“…72 (d) Porous perfusion scaffold bioreactor; cells were seeded onto a perfused particle leached PLLA/PLGA scaffold. 73 (e) 3D microfluidic device providing three unique shear rates; cells seeded on a Collagen Type I scaffold experienced shear over the surface of the scaffold. 74 cancer ECM stiffness investigations and contradictory evidence, further studies are needed to deepen our understanding of the role of substrate stiffness in ovarian cancer mechanotransduction.…”