Functional impairment
of vascular cells is associated with cardiovascular
pathologies. Recent literature clearly presents evidence relating
cell microenvironment and their function. It is crucial to understand
the cell-material interaction while designing a functional tissue
engineered vascular graft. Natural silk biopolymer has shown potential
for various tissue-engineering applications. In the present work,
we aimed to explore the combinatorial effect of variable innate physicochemical
properties and topographies of silk films on functional behavior of
vascular cells. Silk proteins from different varieties (mulberry Bombyx mori, BM; and non-mulberry Antheraea assama, AA) possess unique inherent amino acid composition that leads to
variable surface properties (roughness, wettability, chemistry, and
mechanical stiffness). In addition, we engineered the silk film surfaces
and printed a microgrooved pattern to induce unidirectional cell orientation
mimicking their native form. Patterned silk films induced unidirectional
alignment of porcine vascular cells. Regardless of alignment, endothelial
cells (ECs) proliferated favorably on AA films; however, it suppressed
production of nitric oxide (NO), an endogenous vasodilator. Unidirectional
alignment of smooth muscle cells (SMCs) encouraged contractile phenotype
as indicated by minimal cell proliferation, increment of quiescent
(G0) phase cells, and upregulation of contractile genes. Moderately
hydrophilic flat BM films induced cell aggregation and augmented the
expression of contractile genes (for SMCs) and endothelial nitric
oxide synthase, eNOS (for ECs). Functional studies further confirmed
SMCs’ alignment improving collagen production, remodeling ability
(matrix metalloproteinase, MMP-2 and MMP-9 production) and physical
contraction. Altogether, this study confirms vascular cells’
functional behavior is crucially regulated by synergistic effect of
their alignment and cell–substrate interfacial properties.