title: A first vascularized skin equivalent as an alternative to animal experimentation.
abstract: Tissue-engineered skin equivalents mimic key aspects of the human skin, and can thus be employed as wound coverage for large skin defects or as in vitro test systems as an alternative to animal models. However, current skin equivalents lack a functional vasculature limiting clinical and research applications. This study demonstrates the generation of a vascularized skin equivalent with a perfused vascular network by combining a biological vascularized scaffold (BioVaSc) based on a decellularized segment of a porcine jejunum and a tailored bioreactor system. Briefly, the BioVaSc was seeded with human fibroblasts, keratinocytes, and human microvascular endothelial cells. After 14 days at the air-liquid interface, hematoxylin & eosin and immunohistological staining revealed a specific histological architecture representative of the human dermis and epidermis including a papillary-like architecture at the dermal-epidermal-junction. The formation of the skin barrier was measured non-destructively using impedance spectroscopy. Additionally, endothelial cells lined the walls of the formed vessels that could be perfused with a physiological volume flow. Due to the presence of a complex in-vivo-like vasculature, the here shown skin equivalent has the potential for skin grafting and represents a sophisticated in vitro model for dermatological research.
authors.affiliation: Translational Center Würzburg, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB) Würzburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Groeber
authors.affiliation: Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Engelhardt
authors.affiliation: Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Lange
authors.affiliation: Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Szymon
authors.initials: S
authors.lastname: Kurdyn
authors.affiliation: Translational Center Würzburg, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB) Würzburg, Germany.
authors.forename: Freia F
authors.initials: FF
authors.lastname: Schmid
authors.affiliation: Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Rücker
authors.affiliation: Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Mielke
authors.affiliation: Translational Center Würzburg, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB) Würzburg, Germany.|Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Walles
authors.affiliation: Translational Center Würzburg, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB) Würzburg, Germany.|Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Hansmann
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods*; D000818:Animals; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology; D042783:Endothelial Cells / Q000502:physiology*; D004817:Epidermis; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D007583:Jejunum / Q000098:blood supply*; D015603:Keratinocytes / Q000502:physiology*; D012867:Skin; D013552:Swine; D023822:Tissue Engineering
keywords: alternative to animal testing; skin equivalents; tissue engineering ; vascularization