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
negative influence on fibrotic fibroblasts with poor adhesion and
spreading capability. Decrease in vimentin, fibronectin expression,
and cytoskeleton reorganization justify the poor stability of later
cells on the optimized substrate, thereby allowing selective modulation
of normal and fibrosis associated fibroblasts under the synergistic
influence of honey concentration, topography, and rigidity of HSF
substrates. The work highlights the possible therapeutic efficacy
of honey based micropatterned substrates as smart patches for fast
wound healing and in minimizing the chances of recurrence of precancer
post oral tumor resection surgeries.