Skip to main content
SpringerLink
Log in

Berliner Hautprojekt: Hybride Gewebetechnologie in der Verbrennungsbehandlung und in der Transplantationsmedizin

  • BG-Forschung
  • Published:
Trauma und Berufskrankheit

Zusammenfassung

Schwer Brandverletzte mit großflächigen, operationspflichtigen Läsionen (>70% KOF) benötigen zum Wundverschluss neben weitexpandierten autologen Spalthauttransplantaten (MEEK-Technik) im Labor gezüchtete Keratinozytentransplantate (CEA). Nachteilig sind gerade dabei in Arealen mit komplettem Dermisverlust oft unbefriedigende funktionelle und ästhetische Ergebnisse sowie die lange Herstellungszeit der Kulturhaut von etwa 3 Wochen.

Das Berliner Hautprojekt verbindet das klinische Know-how des Verbrennungszentrums im Unfallkrankenhaus Berlin mit der Zellkulturforschung der Humboldt-Universität und der industriellen Bioreaktorherstellung durch eine Berliner Biotech-Firma. Die Förderung geschieht ausschließlich durch den Wirtschaftssenat der Stadt Berlin.

Ziel ist ein subkonfluenter Zelltransfer mit basalen teilungsaktiven Keratinozyten und Fibroblasten sowie die Entwicklung eines geeigneten Bioreaktors, der die Zellen nach der Transplantation erst noch mit Medium versorgt. So werden Prozesse, die während der Wundheilung ablaufen, im Sinne eines "tissue engineering" in der Wunde ermöglicht.

Dazu werden Keratinozyten und Fibroblasten eines Spenders zeitgleich, getrennt oder als Kokultur auf biologisch abbaubaren Membranen kultiviert und transplantiert. Die Membranen dienen als Carrier und erlauben den Transfer von subkonfluenten Zellen sowie den Zelltransfer direkt auf die Wunde. Mögliche Matrices für Keratinozyten und Fibroblasten sind Gitternetz- und Schwammstrukturen oder Hohlfaserkapillaren.

Abstract

Patients with large areas of deep burns (>70% BSA) need wide, expanded split skin autografts (MEEK-technique) and cultured epithelium autografts (CEA) for wound closure.

In areas with complete loss of dermis, there are often unsatisfactory functional and esthetic results. Additionally, the culture time for CEA-transplants is a disadvantage.

The Berlin Skin Project connects the clinical know how of the largest German burn centre located at the Trauma Centre, Berlin with research in cell culture at the Humboldt University and the industrial production of bioreactors at a Berlin biotechnology company.

The aim of this project is the development of subconfluent cell transfer with basal keratinocytes and fibroblasts capable of division, and the development of an appropriate bioreactor which will continue to provide the cells with medium in the hours immediately after transplantation. This means that the bioreactor will enable "tissue engineering in the wound" by providing (mimicking) processes that take place during natural wound healing.

Support is provided by the Berlin government with the aim of promoting the development of biotechnology in Berlin.

Keratinocytes and fibroblasts, which are taken simultaneously from a donor, are cultured either separately or in coculture on biologically degradable and enzyme-digestible membranes for subsequent transplantation. The use of such membranes has advantages for the developing transplant tissue and its clinical application. Membranes can be used as carriers, as they allow the transfer of subconfluent cells and cell transfer directly onto the wound. Reticule- and sponge-like structures or hollow-fiber capillaries provide possible matrices for keratinocytes and fibroblasts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5
Abb. 6

Literatur

  1. Boyce ST, Hams RG (1983) Calcium regulated differentiation of normal human epidermal keratinocytes in chemically defined clonal culture serum-free serial culture. J Invest Dermatol 81: 31–40

    Google Scholar 

  2. Bruck JC (2002) Begutachtung. In: Bruck JC, Müller JM, Steen (Hrsg) Handbuch der Verbrennungstherapie. Eccomed, Landsberg

  3. Büttemeyer R, Germann G, Henkel-von-Donnersmark G, Steen M (2002) Qualitätssicherung—Basisdaten der Zentren für Brandverletzte 1991–2000 In: Bruck JC, Müller JM, Steen (Hrsg) Handbuch der Verbrennungstherapie. Ecomed, Landsberg

  4. Chen JD, Kim JP, Zhang K et al. (1993) Epidermal growth factor (EGF) promotes human keratinocyte locomotion on collagen by increasing the alpha2 integrin subunit. Exp Cell Res 209: 216–223

    Google Scholar 

  5. Denizot F, Lang R (1986) Rapid colorimetric assay for cell growth and survival. J Immunol Meth 89: 271–277

    Google Scholar 

  6. Eaglstein WH, Falanga V (1998) Tissue engineering and development of Apligraf a human skin equivalent. Cutis 62 [Suppl 1]: 1-8

  7. Germann G, Hartmann B (1996)Thermische und chemische Verletzungen. In: Durst J (Hrsg) Traumatologische Praxis. Schattauer, Stuttgart, S 621–638

  8. Hickerson WL, Compton C, Fletchall S, Smith LR (1994) Cultured epidermal autografts and allodermis combination for permanent burn wound coverage. Burns Suppl 1: 52–55

    Google Scholar 

  9. Hitt AI, Luna EJ (1994) Membrane interactions with the actin cytoskeleton. Curr Opin Cell Biol 6: 120–130

    Google Scholar 

  10. Howling GI, Dettmar PW, Gadard PA et al. (2001) The effect of chitin and chitosan on the proliferation of human skin fibroblasts and keratinocytes in vitro. Biomaterials 22: 2959–2966

    Google Scholar 

  11. Johnen C, Kage A, Oechel A, Neuhaus P, Gerlach JC (2001) Investigation on reconstruction of skin for autologous transplantation. Transplant Proc 33: 618–619

    Google Scholar 

  12. Jones JC, Kurpakus MA, Cooper HM, Quaranta V (1991) A function for the integrin alpha 6 beta 4 in the hemidesmosome. Cell Regul 2: 427–438

    Google Scholar 

  13. Kaiser HW, Stark GB, Kopp J et al. (1994) Cultured autologous keratinocytes in fibrin glue suspension. Exclusively and combined with STS- allograft—preliminary clinical and histological report of a new technique. Burns 20: 23–29

    Google Scholar 

  14. Luna EJ, Hitt AI (1992) Cytoskeleton-plasma membrane interactions. Science 258: 955–964

    Google Scholar 

  15. Luger TA, Schwarz T (1994) Epidermal growth factors and cytokines. Marcel Dekker, New York

  16. Maas-Szabowski N, Shimotoyodome A, Fusenig NE (1999) Keratinocyte growth regulation in fibroblast co-cultures via a double paracrine mechanism. J Cell Sci 112: 1843–1853

    Google Scholar 

  17. Phillips TJ, Gilchrest BA (1992) Clinical application of cultured epithelium. Epith Cell Biol 1: 39–46

    Google Scholar 

  18. Purdue GF et al. (1997) A multicenter clinical trial of a biosynthetic skin replacement, Dermagraft-TC, compared with cryopreserved human cadaver skin for temporary coverage of excised burn wounds. J Burn Care Rehabil 18: 52–57

    Google Scholar 

  19. Raff T, Hartmann B, Wagner H, Germann G (1996) Experience with the modified Meek technique. Acta Chir Plast 38: 142–146

    Google Scholar 

  20. Rheinwald JG, Green H (1975) Formation of keratinizing ephithelium in culture by a cloned cell line derived from a teratoma. Cell 6: 317–330

    Google Scholar 

  21. Rheinwald JG, Green H (1975) Serial cultivation of strains of human epidermal keratinocytes. The formation of keratinizing colonies from single cells. Cell 6: 331–343

    Google Scholar 

  22. Rheinwald JG, Green H (1977) Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes. Nature 265: 421–424

    Google Scholar 

  23. Rodeck U, Jost M, Kari C et al. (1997) EGF-R dependent regulation of keratinocyte survival. J Cell Sci 110: 113–121

    Google Scholar 

  24. Sonnenberg A, Calfat J, Janssen H et al. (1991) Integrin alpha 6/beta4 complex is located in hemidesmosomes, suggesting a major role in epidermal cell-basement membrane adhesion. J Cell Biol 113: 907–917

    Google Scholar 

  25. Smola H, Stark HJ, Thiekötter G et al. (1998) Dynamics of basement membrane formation by keratinocyte-fibroblast interaction in organotypic skin culture. Exp Cell Res 239: 399–410

    Google Scholar 

  26. Trent JF, Kirsner RS (1998) Tissue engineering skin: Apligraf, a bi-layered living skin equivalent. Int J Pract 52: 408–413

    Google Scholar 

  27. Wang HJ, Wan HL, Yang TS et al. (1996) Acceleration of skin graft healing by growth factors. Burns 22: 10–14

    Google Scholar 

  28. Wainwright DJ (1995) Use of an acellular allograft dermal matrix (AlloDerm) in the management of full-thickness burns. Burns 21: 243–248

    Google Scholar 

  29. Zacchi V, Soranzo C, Cortivo R et al. (1998) In vitro engineering of human tissue. J Biomed Mater Res 40: 187–194

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. AG: Experimentelle Chirurgie, Charité—Campus Virchow-Klinikum, Berlin

    C. Johnen & J. C. Gerlach

  2. Zentrum für Schwerbrandverletzte mit Plastischer Chirurgie, Unfallkrankenhaus Berlin, Berlin

    B. Hartmann

  3. AG: Experimentelle Chirurgie, Charité—Campus Virchow-Klinikum, Forschungshaus R.2.0105, Augustenburger Platz 1, 13353 , Berlin

    C. Johnen

Authors
  1. C. Johnen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. C. Gerlach
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Hartmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Johnen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Johnen, C., Gerlach, J.C. & Hartmann, B. Berliner Hautprojekt: Hybride Gewebetechnologie in der Verbrennungsbehandlung und in der Transplantationsmedizin. Trauma Berufskrankh 5, 347–352 (2003). https://doi.org/10.1007/s10039-003-0757-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10039-003-0757-5

Schlüsselwörter

Keywords

Search

Navigation