Behavior of Dermal Fibroblasts on Microdot Arrays Yields Insight into Wound Healing Mechanisms

The behavior of fibroblasts on patterned substrates was examined in order to elucidate the role of dermal structure in wound healing. Dermal fibroblasts were cultured on micro-patterned silicone elastomer substrates designed to enforce cell adhesion only to fibronectin microdots. The morphology, expression of α-smooth muscle actin (α-SMA), proliferation, apoptotic cells, and soluble collagen production of cells were measured. Cells grown on patterned substrates showed some signs of a scar-fibroblast phenotype such as: elongated pseudopodia, enhanced expression of alpha smooth muscle actin (α-SMA), and increased collagen/pre-collagen, in comparison to unpatterned controls. Cells also showed low proliferation rates and high apoptotic index. The results showed that the microdot arrays, acting as a grid of limited focal adhesion sites, could force cells to adopt constrained morphologies and limited adhesion areas, which affect the cytoskeleton, ultimately leading to expression of a scar-tissue fibroblast phenotype. This study provides insight into the regulatory mechanisms of micro-topology on cell behavior in wound healing.