Multiscale Modeling in Vascular Disease and Tissue Engineering - Multiscale Computer Modeling in Biomechanics and Biomedical Engineering - page 248

Fig. 6 Schematic of the modelled tubular scaffold (Image courtesy of [ 10 ] with permission)

The model predictions for these scenarios provided valuable insights into the
multiscale mechanobiological processes involved in vascular tissue engineering and
underscored the significance of mechanical factors. The study showed that any subtle
decrease of cyclic strain can ultimately lead to proliferation of VSMCs towards the
lumen and development of IH. Low cyclic strain contributed to more luminal ingrowth
which in turn reduced the cyclic strain further and thereby expedited patency loss.
Interestingly, the model predicted that under a hypertensive luminal pressure intimal
growth is higher compared to normotensive and hypotensive loading regimes which
corroborates findings from clinical studies which suggest that hypertension causes
thickening and stiffening of arteries [ 54 ]. This response is related to the stress-stiffening
mechanical response of vascular tissue which stiffens at higher pressures and therefore
undergoes approximately 20 % lower cyclic strain under the hypertensive pressure
regime compared to the normotenstive pressure, see Fig. 7 .
The influence of loading regime during culture was also simulated using the
model given that many in-vitro studies have shown that dynamic culture of VSMCs
on vascular scaffolds using pulsatile flow bioreactors results in a higher number of
VSMCs and improved mechanical properties compared to static culture [ 53 , 55 , 56 ].
The model also predicted that the amount of collagen produced in the vascular
scaffold would be higher where a pulsatile flow culture was used compared to a
static culture. Whilst the pulsatile flow maintained intimal growth at a considerably
lower level, the model predicted enhanced ECM synthesis and remodelling of the