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Myelinated and unmyelinated nerve fibers reinnervate tissue-engineered dermo-epidermal human skin analogs in an in vivo model


Biedermann, T; Klar, A S; Böttcher-Haberzeth, S; Reichmann, E; Meuli, M (2016). Myelinated and unmyelinated nerve fibers reinnervate tissue-engineered dermo-epidermal human skin analogs in an in vivo model. Pediatric Surgery International, 32(12):1183-1191.

Abstract

PURPOSE: The clinical application of autologous tissue-engineered skin analogs is an important strategy to cover large skin defects. Investigating biological dynamics, such as reinnervation after transplantation, is essential to improve the quality of such skin analogs. Previously, we have examined that our skin substitutes are reinnervated by host peripheral nerve fibers as early as 8 weeks after transplantation. Here, we wanted to investigate the presence and possible differences regarding myelinated and unmyelinated host nerve fibers 15 weeks after the transplantation of light and dark human tissue-engineered skin analogs.
METHODS: Human epidermal keratinocytes, melanocytes, and dermal fibroblasts were isolated from human light and dark skin biopsies. Keratinocytes and melanocytes were seeded on fibroblast-containing collagen type I hydrogels after expansion in culture. After additional culturing, the tissue-engineered dermo-epidermal skin analogs were transplanted onto full-thickness skin wounds created on the back of immuno-incompetent rats. Skin substitutes were excised and analyzed 15 weeks after transplantation. Histological sections were examined with regard to the ingrowth pattern of myelinated and unmyelinated nerve fibers into the skin analogs using markers, such as Substance P, NF200, and S100-Beta.
RESULTS: We found myelinated and unmyelinated peripheral host nerve fibers 15 weeks after transplantation in the dermal part of our human skin substitutes. In particular, we identified large-diameter-myelinated Aβ- and Aδ-fibers, and small-diameter C-fibers. Furthermore, we observed myelinated nerves in close proximity to CD31-positive blood capillaries. In the long run, both types of ingrown host fibers showed an identical pattern in both light and dark skin analogs.
CONCLUSION: Our data suggest that myelinated and unmyelinated peripheral nerves reinnervate human skin substitutes in a long-term in vivo transplantation assay. Our tissue-engineered skin analogs attract A- and C-fibers to supply both light and dark skin analogs. Potentially, this process restores skin sensitivity and has, therefore, a significant relevance with regard to future application of autologous pigmented dermo-epidermal skin substitutes onto patients.

Abstract

PURPOSE: The clinical application of autologous tissue-engineered skin analogs is an important strategy to cover large skin defects. Investigating biological dynamics, such as reinnervation after transplantation, is essential to improve the quality of such skin analogs. Previously, we have examined that our skin substitutes are reinnervated by host peripheral nerve fibers as early as 8 weeks after transplantation. Here, we wanted to investigate the presence and possible differences regarding myelinated and unmyelinated host nerve fibers 15 weeks after the transplantation of light and dark human tissue-engineered skin analogs.
METHODS: Human epidermal keratinocytes, melanocytes, and dermal fibroblasts were isolated from human light and dark skin biopsies. Keratinocytes and melanocytes were seeded on fibroblast-containing collagen type I hydrogels after expansion in culture. After additional culturing, the tissue-engineered dermo-epidermal skin analogs were transplanted onto full-thickness skin wounds created on the back of immuno-incompetent rats. Skin substitutes were excised and analyzed 15 weeks after transplantation. Histological sections were examined with regard to the ingrowth pattern of myelinated and unmyelinated nerve fibers into the skin analogs using markers, such as Substance P, NF200, and S100-Beta.
RESULTS: We found myelinated and unmyelinated peripheral host nerve fibers 15 weeks after transplantation in the dermal part of our human skin substitutes. In particular, we identified large-diameter-myelinated Aβ- and Aδ-fibers, and small-diameter C-fibers. Furthermore, we observed myelinated nerves in close proximity to CD31-positive blood capillaries. In the long run, both types of ingrown host fibers showed an identical pattern in both light and dark skin analogs.
CONCLUSION: Our data suggest that myelinated and unmyelinated peripheral nerves reinnervate human skin substitutes in a long-term in vivo transplantation assay. Our tissue-engineered skin analogs attract A- and C-fibers to supply both light and dark skin analogs. Potentially, this process restores skin sensitivity and has, therefore, a significant relevance with regard to future application of autologous pigmented dermo-epidermal skin substitutes onto patients.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Clinic for Surgery
Dewey Decimal Classification:610 Medicine & health
Language:German
Date:December 2016
Deposited On:12 Jan 2017 15:31
Last Modified:15 Jan 2017 06:22
Publisher:Springer
ISSN:0179-0358
Publisher DOI:https://doi.org/10.1007/s00383-016-3978-y
PubMed ID:27651370

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