Fluid flow‐induced cell stimulation in bone tissue engineering changes due to interstitial tissue formation in vitro

Abstract

In tissue engineering experiments in vitro, bioreactors have been used for applying wall shear stress (WSS) on cells to regulate cellular activities. To determine the loading conditions within bioreactors and to design tissue engineering products, in silico models are used. Previous in silico studies in bone tissue engineering (BTE) focused on quantifying the WSS on cells and the influence on appositional tissue growth. However, many BTE experiments also show interstitial tissue formation (i.e., tissue infiltrated in the pores rather than growing on the struts ‐ appositional growth), which has not been considered in previous in silico studies. We hereby used a multiscale fluid‐solid interaction model to quantify the WSS and mechanical strain on cells with interstitial tissue formation, taken from a reported BTE experiment. The WSS showed a high variation among different interstitial tissue morphologies. This is different to the situation under appositional tissue growth. It is found that a 35% filling of the pores results (by mineralised bone tissue) when the average WSS increases from 1.530 (day 0) to 5.735 mPa (day 28). Furthermore, the mechanical strain on cells caused by the fluid flow was extremely low (at the level of 10−14‐10−15), comparing to the threshold in a previous mechanobiological theory of osteogenesis (eg, 10−2). The output from this study offers a significant insight of the WSS changes during interstitial tissue growth under a constant perfusion flow rate in a BTE experiment. It has paved the way for optimising the local micro‐fluidic environment for interstitial tissue mineralisation.

Porous Geometry Guided Micro-mechanical Environment Within Scaffolds for Cell Mechanobiology Study in Bone Tissue Engineering

“…In reality, however, interstitial formation, in which the tissue is infiltrated within the pores rather than being attached on the struts surfaces is also observed in many cases ( Li et al, 2009 ) (as illustrated in Figure 3C ). The resultant WSS on cells under interstitial tissue formation was quantified and compared to appositional tissue formation ( Zhao et al, 2020b ). Distinct difference in WSS between two cases were found, even if the same amount of newly formed tissue was present.…”

“…5. The WSS (τ) FIGURE 3 | Illustrations of (A) cells within the scaffold in computational model, re-produced from (Jungreuthmayer et al, 2009); (B) appositional tissue growth in computational model, re-produced from (Zhao et al, 2020a); (C) interstitial tissue within unit scaffold in computational model, re-produced from (Zhao et al, 2020b).…”

Scaffold pore geometry guides gene regulation and bone-like tissue formation in dynamic cultures

“…WSS) on cells [55]. Moreover, the tissue morphologies had a distinct influence on the resultant WSS on cells [55].…”

“…Recent computational studies have shown that cell/tissue growth within a scaffold can change the mechanical stimulation (e.g. WSS) on cells [55]. Moreover, the tissue morphologies had a distinct influence on the resultant WSS on cells [55].…”

Challenges in computational fluid dynamics applications for bone tissue engineering

“…Alongside the CFD analysis, a number of studies also implement a fluid structure interaction (FSI) analysis [26,33,34]. This method is used to obtain a better understanding of how differences in scaffolds (such as different geometries or pore sizes) influence the shear stress on scaffold surfaces and consequently the cell adhering to those surfaces.…”