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 8 weeks 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: 3 weeks after transplantation, blood vessels, but no nerve fibers or lymphatic vessels could be observed. 10 weeks 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.
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 8 weeks 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: 3 weeks after transplantation, blood vessels, but no nerve fibers or lymphatic vessels could be observed. 10 weeks 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.
Authors: Sophie Böttcher-Haberzeth; Thomas Biedermann; Clemens Schiestl; Fabienne Hartmann-Fritsch; Jörg Schneider; Ernst Reichmann; Martin Meuli Journal: Pediatr Surg Int Date: 2012-02 Impact factor: 1.827
Authors: Thomas Biedermann; Sophie Böttcher-Haberzeth; Agnieszka S Klar; Luca Pontiggia; Clemens Schiestl; Claudia Meuli-Simmen; Ernst Reichmann; Martin Meuli Journal: Pediatr Surg Int Date: 2013-01 Impact factor: 1.827
Authors: Sophie Böttcher-Haberzeth; Thomas Biedermann; Luca Pontiggia; Erik Braziulis; Clemens Schiestl; Bart Hendriks; Ossia M Eichhoff; Daniel S Widmer; Claudia Meuli-Simmen; Martin Meuli; Ernst Reichmann Journal: J Invest Dermatol Date: 2012-09-13 Impact factor: 8.551
Authors: Thomas Biedermann; Luca Pontiggia; Sophie Böttcher-Haberzeth; Sasha Tharakan; Erik Braziulis; Clemens Schiestl; Martin Meuli; Ernst Reichmann Journal: J Invest Dermatol Date: 2010-04-08 Impact factor: 8.551
Authors: Suradip Das; Wisberty J Gordián-Vélez; Harry C Ledebur; Foteini Mourkioti; Panteleimon Rompolas; H Isaac Chen; Mijail D Serruya; D Kacy Cullen Journal: NPJ Regen Med Date: 2020-06-05
Authors: Agnes S Klar; Thomas Biedermann; Claudia Simmen-Meuli; Ernst Reichmann; Martin Meuli Journal: Pediatr Surg Int Date: 2016-12-20 Impact factor: 1.827
Authors: Suradip Das; Wisberty J Gordián-Vélez; Harry C Ledebur; Foteini Mourkioti; Panteleimon Rompolas; H Isaac Chen; Mijail D Serruya; D Kacy Cullen Journal: NPJ Regen Med Date: 2020-06-05