Fabrication of topographically controlled electrospun scaffolds to mimic the stem cell microenvironment in the dermal-epidermal junction

The use of microfabrication techniques for the development of innovative constructs for tissue regeneration is a growing area of research. This area comprises both manufacturing and biological approaches for the development of smart materials aiming to control and direct cell behavior to enhance tissue healing. Many groups have focused their efforts on introducing complexity within these innovative constructs via the inclusion of nano- and microtopographical cues mimicking physical and biological aspects of the native stem cell niche. Specifically, in the area of skin tissue engineering, seminal work has reported replicating the microenvironments located in the dermal-epithelial junction, which are known as rete ridges. The rete ridges are key for both stem cell control and the physiological performance of the skin. In this work, we have introduced complexity within electrospun membranes to mimic the morphology of the rete ridges in the skin. We designed and tested three different patterns, characterized them, and explored their performance in vitro, using 3D skin models. One of the studied patterns (pattern B) was shown to aid in the development of an in vitro rite-ridgelike skin model that resulted in the expression of relevant epithelial markers such as collagen IV and integrin β1. In summary, we have developed a new skin model including synthetic rete-ridgelike structures that replicate both morphology and function of the native dermal-epidermal junction and that offer new insights for the development of smart skin tissue engineering constructs.