Differential Behavior of Normal and Fibrotic Fibroblasts under the Synergistic Influence of Micropillar Topography and the Rigidity of Honey/Silk-Fibroin Substrates

We report differential proliferation behavior of normal and fibrosis associated human oral fibroblasts on micropillar honey embedded silk fibroin substrates (HSF). Oral fibroblasts of different origins manifest differences in proliferation rate, morphology, and the cytoskeletal arrangement on HSF substrates with distinct topography (H, D, and S), stiffness, and honey concentration. It is observed that the proliferation rate is maximized for normal and inhibited for fibrosis associated fibroblasts on a HSF substrate surface with moderate height of ∼8.5 μm and 2% honey concentration. Molecular expression analysis reveals decrease in c-myc and p53 expression in later cells validating the inhibition of their proliferation rate, which is further correlated with the decreased Col I and Col III expression on this substrate. A substrate with enhanced interspacing and intermediate mechanical stiffness (0.57 ± 0.32 μN/nm) favors strong adhesion and stable cell–matrix interaction for normal cells, while exhibiting n...