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Tissue-engineered dermo-epidermal skin analogs exhibit de novo formation of a near natural neurovascular link 10weeks after transplantation

Biedermann, Thomas ; Klar, Agnieszka ; Böttcher-Haberzeth, Sophie ; Schiestl, Clemens ; Reichmann, Ernst ; Meuli, Martin

In: Pediatric Surgery International, 2014, vol. 30, no. 2, p. 165-172

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    Titre
    • Tissue-engineered dermo-epidermal skin analogs exhibit de novo formation of a near natural neurovascular link 10weeks after transplantation
    Auteur
    • Biedermann, Thomas. Tissue Biology Research Unit, University Children's Hospital Zurich, Zurich, Switzerland
    • Klar, Agnieszka. Tissue Biology Research Unit, University Children's Hospital Zurich, Zurich, Switzerland
    • Böttcher-Haberzeth, Sophie. Tissue Biology Research Unit, University Children's Hospital Zurich, Zurich, Switzerland
    • Schiestl, Clemens. Department of Surgery, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland
    • Reichmann, Ernst. Tissue Biology Research Unit, University Children's Hospital Zurich, Zurich, Switzerland
    • Meuli, Martin. Department of Surgery, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Pediatric Surgery International, 2014, vol. 30, no. 2, p. 165-172. Springer Berlin Heidelberg
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:325872
    Summary
    Purpose: Human autologous tissue-engineered skin grafts are a promising way to cover skin defects. Clearly, it is mandatory to study essential biological dynamics after transplantation, including reinnervation. Previously, we have already shown that human tissue-engineered skin analogs are reinnervated by host nerve fibers as early as 8weeks after transplantation. In this study, we tested the hypothesis that there is a de novo formation of a "classical” neurovascular link in tissue-engineered and then transplanted skin substitutes. Methods: Keratinocytes, melanocytes, and fibroblasts were isolated from human skin biopsies. After expansion in culture, keratinocytes and melanocytes were seeded on dermal fibroblast-containing collagen type I hydrogels. These human tissue-engineered dermo-epidermal skin analogs were transplanted onto full-thickness skin wounds on the back of immuno-incompetent rats. Grafts were analyzed after 3 and 10 weeks. Histological sections were examined with regard to the ingrowth pattern of myelinated and unmyelinated nerve fibers into the skin analogs using markers such as PGP9.5, NF-200, and NF-160. Blood vessels were identified with CD31, lymphatic vessels with Lyve1. In particular, we focused on alignment patterns between nerve fibers and either blood and/or lymphatic vessels with regard to neurovascular link formation. Results: 3weeks after transplantation, blood vessels, but no nerve fibers or lymphatic vessels could be observed. 10weeks after transplantation, we could detect an ingrowth of myelinated and unmyelinated nerve fibers into the skin analogs. Nerve fibers were found in close proximity to CD31-positive blood vessels, but not alongside Lyve1-positive lymphatic vessels. Conclusion: These data suggest that host-derived innervation of tissue-engineered dermo-epidermal skin analogs is initiated by and guided alongside blood vessels present early post-transplantation. This observation is consistent with the concept of a cross talk between neurovascular structures, known as the neurovascular link.