Multiscale Modeling in Vascular Disease and Tissue Engineering - Multiscale Computer Modeling in Biomechanics and Biomedical Engineering - page 246

adopt quiescent and contractile characteristics, following this initial proliferative
phase whereby the cells populate and remodel the scaffold, gives rise to the most
significant long-term limitation of vascular grafts and tissue engineered vessels,
namely intimal hyperplasia (IH).
The elasticity of the tissue engineering scaffolds, usually referred to as
''compliance'' in the context of vascular conduits, plays a key role in regulation of
the proliferative capacity of VSMCs and hence prevention of intimal hyperplasia.
The amplitude of cyclic strain which is dictated by the compliance of scaffolds has
an anti-proliferative influence on VSMCs and also increases their apoptosis rate
[ 46 - 49 ]. In addition, physiological cyclic strain upregulates synthesis of ECM
products, such as collagen and elastin, which enhances the remodelling of vascular
scaffolds [ 48 ]. On the other hand, it is necessary for cells within the scaffold to
receive nutrients and discard waste material in order to maintain their viability, a
property governed by interstitial fluid flow which is dependent on the scaffold
permeability. Interstitial fluid flow in a scaffold is also influenced by cyclic strain
[ 50 ], however, and is therefore also dependant on the elasticity of the scaffold.
Clearly therefore, there are numerous interlinked mechanobiological parameters
which need to be considered in the design and development of viable tissue
engineered blood vessels. Multiscale in-silico models provide the ideal platform to
explore and optimize the mechanics of such vascular scaffolds.
Towards this goal, in a recent study the authors presented a multiscale
mechanobiological framework which enabled investigation of the role of
mechanical factors, such as scaffold compliance and loading regimes during cell
culture, on the growth of cells within vascular scaffolds and their remodelling [ 10 ].
As previously discussed, cyclic strain and pore fluid flow are two key mechanical
regulators of VSMC growth in a vascular tissue-engineered construct. As a result,
cyclic strain and pore fluid flow velocity were adopted as the main regulators of
VSMC growth in these models of cell and tissue growth within a TEBV. The
mechanobiological modelling framework comprised two main coupled modules,
(i) a module based on the finite element method (FEM) that quantified cyclic strain
(e cyc ) and pore fluid velocity (V fluid ) as the main regulators of VSMC growth in
TEBVs and (ii) a biological module based on ABM that simulated migration,
proliferation, apoptosis and ECM synthesis by VSMCs under the influence of the
mechanical stimuli quantified in the FE module, see Fig. 5 .
The FE model employed in these simulations was an axisymmetric poro-
hyperelastic FE model of a tubular scaffold which could quantify cyclic strain (e cyc )
and pore fluid flow velocity (V fluid ) in the tissue engineered construct. Pressure and
pore pressure boundary conditions were applied to the luminal surface of the tissue-
engineered construct while the two ends were longitudinally tethered and the
pressure was set to zero at the abluminal surface.
Following remodelling by cells, the mechanical properties of the scaffolds, such
as elasticity and permeability, should ideally mimic that of the native artery. Several
scaffolds such as woven polyglactin 910 grafts and Poly(Trimethylene Carbonate)
scaffolds have shown this response following remodelling by cells [ 51 , 52 ].
Therefore, remodelling of the mechanical properties of the scaffolds was represented