  Mechanical properties of the tissue engineering scaffolds are known to play a
crucial role in tissue regeneration. Here, we have utilized discrete network
and finite element models to study fibrous scaffold mechanics and its
dependence on structure. We have considered two loading conditions, first,
uniaxial elongation (macroscopic), and second, localized cellular forces
(microscopic). Using these two scenarios, we have tried to establish a link
between scaffold micromechanics and its macroscopic mechanical properties. We
have demonstrated that the macroscopic elastic modulus of fibrous scaffold is
dependent on the sample shape, size and the degree of fiber fusion. Under
microscopic loading conditions the deformation of the fibrous scaffolds is
anisotropic with an orientation dependent decay with distance. Further, we
explored the stiffness sensing under the conditions of fixed stress or fixed
strain application by the cells. With fixed strain, we found that the stiffness
sensed by a cell is proportional to scaffold's macroscopic Young's modulus.
However, for fixed stress application, it also depends on cell's elasticity
with stiffness experienced by stiff and soft cells differing by an order of
magnitude. The analyses demonstrate that there exists a gap between mechanical
properties of the fibrous scaffolds as measured from the macroscopic testings
and those sensed by the cells. This warrants a need for extreme care during the
designing and reporting of experiments involving cell-scaffold interactions.
The insights from this work will help in the designing of tissue engineering
scaffolds for applications where mechanical stimuli are a critical factor
