Construction of a Microstructured Collagen Membrane Mimicking the Papillary Dermis Architecture and Guiding Keratinocyte Morphology and Gene Expression

A papillary‐structured collagen fibril membrane is created, mimicking the 3D‐architecture of the human papillary dermis. Primary human keratinocytes cultured to confluency on papillar‐structured films are compared to keratinocytes cultured on flat membranes. Microscopical evaluation reveals the presence of morphologically distinct cells at the base of the papillar structures that are not observed on flat membranes. Gene expression microarrays and RT‐qPCR indicate that these cells are in a more proliferative/migrational state, whereas cells on flat membranes have a more differentiated expression profile. Immunohistochemical stainings confirm these results. In conclusion, specific collagen architecture can direct keratinocyte behavior, and this may be used to further improve skin regeneration. Tissue‐engineered skin often lacks the architecture of the papillary dermis that is present in normal skin. Therefore, the construction of a fibrillar collagen membrane mimicking the 3D‐architecture of the human papillary dermis is described. Evaluation with cultured keratinocytes shows that cell morphology, gene and protein expression are directed by this membrane structure.