A major objective of scaffold fabrication for tissue-engineering applications in wound healing is to understand the relationship between scaffold topography and cell behaviour. Recently, researchers have focused on arrays of cell adhesion protein styled in linear-grid micropatterns; however, these linear-grid patterns hardly reflect the topographical features of a natural extracellular matrix (ECM). In order to clarify the relationship between substrate adhesion points and cell behaviour, changes of dermal fibroblasts cultured on triangular microdot arrays were investigated. Micropatterns were micro-printed by silicone substrate stamps with collagen, while regions outside of the microdots were functionalized to block cellular adhesion. Cell morphology, expression of α-SMA, cell viability and hydroxyproline levels were examined for dermal fibroblasts cultured on the microdot substrates and on non-patterned control substrates. On patterned substrates, the expression of α-SMA significantly decreased, cell vitality increased and hydroxyproline content decreased with increasing vertex angles of the triangular array. Significantly more hydroxyproline was observed in all experimental groups in comparison to the control group. The results indicate that small vertex angles of the triangular array were detrimental to cell survival, likely due to constraint of the cell to a small adhesion area. We hypothesize that cells actively adapt to this situation by attempting to remodel their microenvironments with secretion of hydroxyproline. This illustrates the existence of feedback between cells and their microenvironments, such that when surroundings are unfavourably altered, the cells attempt to reconstruct the environment with secretion of ECM.
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