title: Use of an in vitro model of tissue-engineered human skin to study keratinocyte attachment and migration in the process of reepithelialization.
abstract: To produce a stable epidermis, keratinocytes need to be firmly attached to the basement membrane. However, following wounding, keratinocytes are required to develop a migratory phenotype in order to reepithelialize the wound. To investigate some of the issues underlying reepithelialization, we have developed a three-dimensional in vitro model of tissue-engineered skin, comprising sterilized human dermis seeded with human keratinocytes and dermal fibroblasts. Using this model, we have shown that the inclusion of fibroblasts within the model increases the stability of keratinocyte attachment. We have also demonstrated that keratinocyte migration occurs most effectively in the absence of a basement membrane and following the inclusion of fibroblasts in the model. In addition, subjecting the keratinocyte layer to mechanical trauma induces a migratory phenotype. We conclude that this three-dimensional in vitro wound model can be used to increase our understanding of the factors that enhance keratinocyte migration and hence wound healing in vivo.
authors.affiliation: Skin Research Unit, Section of Human Metabolism, Division of Clinical Sciences, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Harrison
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Heaton
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Layton
authors.forename: Sheila
authors.initials: S
authors.lastname: Mac Neil
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000502:physiology*; D051379:Mice; D012879:Skin Physiological Phenomena; D023822:Tissue Engineering / Q000379:methods*; D014945:Wound Healing / Q000502:physiology*