Topography-mediated apical guidance in epidermal wound healing

Abstract

Topographic modifications of the substrate of a cell culture have the potential to guide cell polarization and migration, through which epidermal wound healing may be accelerated. Classic topographic contact guidance is based on the interaction between cells and a supporting scaffold that interferes with the establishment of focal adhesions, thereby influencing the organization of the actin cytoskeleton. Using soft lithography techniques on PDMS, we engineered gratings with groove and ridge widths of 1 μm and a groove depth of 0.6 μm. These gratings were applied to the apical free surface of human dermal fibroblasts during in vitro wound healing. Gratings oriented perpendicularly to the wound induced a significant enhancement of cell polarization, migration speed and directionality which resulted in faster wound coverage. The apically applied texture influenced the deposition of the extracellular matrix into the wound yielding homogeneously distributed fibronectin fibers. Apical guidance was not mediated by the establishment of focal adhesions between cells and the topographically modified patch, thus allowing for removal of the latter after complete healing. Altogether, our results demonstrate an alternative guidance scheme based on the apical, adhesion-free interaction between migrating cells and an anisotropic surface topography, which leads to faster healing in an in vitro wound model.