Skip to main content

Advertisement

Log in

An in vitro Model System to Study the Damaging Effects of Prolonged Mechanical Loading of the Epidermis

  • Original Article
  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Pressure ulcers are areas of soft tissue breakdown that result from sustained mechanical loading of the skin and underlying tissues. Today, little is known with respect to the aetiology of these ulcers. This study introduces an in vitro model system to study the effects of clinically relevant loading regimes on damage progression in the epidermis, the uppermost skin layer. Engineered epidermal equivalents (EpiDerm) were subjected to 6.7 and 13.3 kPa for either 2 or 20 h using a custom-built loading device. Tissue damage was assessed by (1) histological examination, (2) tissue viability evaluation, and (3) by the release of a pro-inflammatory mediator, interleukin-1α (IL-1α). Loading the EpiDerm samples for 2 h increased the IL-1α release, although no visible tissue damage was observed. However, in the 20 h loading experiments visible tissue damage and a small decrease in tissue viability were observed. Furthermore, in these experiments the IL-1α release increased with magnitude of loading. It is concluded that this in vitro model system can be applied to improve insight in the epidermal damage process due to prolonged mechanical loading and can serve as a sound basis for effective clinical identification and prevention of pressure ulcers.

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

Access this article

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

Instant access to the full article PDF.

FIGURE 1.
FIGURE 2.
Figure 3.

Similar content being viewed by others

REFERENCES

  1. American Pressure Ulcer Advisory Panel. Pressure ulcers prevalence, cost and risk assessment: consensus development conference statement. Decubitus 2:24–28, 1998.

    Google Scholar 

  2. Augustin, C., and O. Damour. Pharmacotoxicological applications of an equivalent dermis: three measurements of cytotoxicity. Cell. Biol. Toxicol. 11:167–171, 1995.

    Article  PubMed  CAS  Google Scholar 

  3. Bouten, C. V., M. M. Knight, D. A. Lee, and D. L. Bader. Compressive deformation and damage of muscle cell subpopulations in a model system. Ann. Biomed. Eng. 29:153–163, 2001.

    Article  PubMed  CAS  Google Scholar 

  4. Bouten, C. V., C. W. Oomens, F. P. Baaijens, and D. L. Bader. The etiology of pressure ulcers: skin deep or muscle bound?. Arch. Phys. Med. Rehabil. 84:616–619, 2003.

    Article  PubMed  Google Scholar 

  5. Bronneberg, D., and C. V. C. Bouten. New tissue repair strategies. In: Pressure Ulcer Research, edited by D. L. Bader, C. V. C. Bouten, D. Colin, and C. W. J. Oomens. Heidelberg: Springer-Verlag, 2005, pp. 353–374.

    Chapter  Google Scholar 

  6. Cannon, C. L., P. J. Neal, J. A. Southee, J. Kubilus, and M. Klausner. New epidermal model for dermal irritancy testing. Toxicol. In Vitro 8:889–891, 1994.

    Article  Google Scholar 

  7. Chang, W. L., and A. A. Seireg. Prediction of ulcer formation on the skin. Med. Hypotheses 53:141–144, 1999.

    Article  PubMed  CAS  Google Scholar 

  8. Cobb, J. P., R. S. Hotchkiss, I. E. Karl, and T. G. Buchman. Mechanisms of cell injury and death. Br. J. Anaesth. 77:3–10, 1996.

    PubMed  CAS  Google Scholar 

  9. Daniel, R. K., D. L. Priest, and D. C. Wheatley. Etiologic factors in pressure sores: an experimental model. Arch. Phys. Med. Rehabil. 62:492–498, 1981.

    PubMed  CAS  Google Scholar 

  10. Coquette, A., N. Berna, A. Vandenbosch, M. Rosdy, B. De Wever, and Y. Poumay. Analysis of interleukin-1 alpha (IL-1 alpha) and interleukin-8 (IL-8) expression and release in in vitro reconstructed human epidermis for the prediction of in vivo skin irritation and/or sensitization. Toxicol. In Vitro 17:311–321, 2003.

    PubMed  CAS  Google Scholar 

  11. Corsini, E., A. Bruccoleri, M. Marinovich, and C. L. Galli. Endogenous interleukin-1 alpha associated with skin irritation induced by tributyltin. Toxicol. Appl. Pharmacol. 138:268–274, 1996.

    Article  PubMed  CAS  Google Scholar 

  12. Corsini, E., and C. L. Galli. Cytokines and irritant contact dermatitis. Toxicol. Lett. 28:102–103, 277–282, 1998.

    Google Scholar 

  13. Diegelmann, R. E. and M. C. Evans. Wound healing: an overview of acute, fibrotic and delayed healing. Front. Biosci. 9:283–289, 2004.

    Article  PubMed  CAS  Google Scholar 

  14. Dinarello, C. A. Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist. Int. Rev. Immunol. 16:457–499, 1998.

    Article  PubMed  CAS  Google Scholar 

  15. Dinsdale, S. M. Decubitus ulcers in swine: light and electron microscopy study of pathogenesis. Arch. Phys. Med. Rehabil. 54:51–56, 1973.

    PubMed  CAS  Google Scholar 

  16. Dinsdale, S. M. Decubitus ulcers: role of pressure and friction in causation. Arch. Phys. Med. Rehabil. 55:147–152, 1974.

    PubMed  CAS  Google Scholar 

  17. Elias, P. M., and D. S. Friend. The permeability barrier in mammalian epidermis. J. Cell Biol. 65:180–191, 1975.

    Article  PubMed  CAS  Google Scholar 

  18. Faller, C., and M. Bracher. Reconstructed skin kits: reproducibility of cutaneous irritancy testing. Skin Pharmacol. Appl. Skin Physiol. 15:74–91, 2002.

    Article  PubMed  CAS  Google Scholar 

  19. Faller, C., M. Bracher, N. Dami, and R. Roguet. Predictive ability of reconstructed human epidermis equivalents for the assessment of skin irritation of cosmetics. Toxicol. In Vitro 16:557–572, 2002.

    Article  PubMed  CAS  Google Scholar 

  20. Gibbs, S., H. Vietsch, U. Meier, and M. Ponec. Effect of skin barrier competence on SLS and water-induced IL-1 alpha expression. Exp. Dermatol. 11:217–223, 2002.

    Article  PubMed  CAS  Google Scholar 

  21. Goldstein, B. and J. Sanders. Skin response to repetitive mechanical stress: a new experimental model in pig. Arch. Phys. Med. Rehabil. 79:265–272, 1998.

    Article  PubMed  CAS  Google Scholar 

  22. Herrman, E. C., C. F. Knapp, J. C. Donofrio, and R. Salcido. Skin perfusion responses to surface pressure-induced ischemia: Implication for the developing pressure ulcer. J. Rehabil. Res. Dev. 36:109–120, 1999.

    PubMed  CAS  Google Scholar 

  23. Jacobs, J. J. L., C. Lehe, K. D. A. Cammans, P. K. Das, and G. R. Elliott. Methyl Green-Pyronine Staining of Porcine Organotypic Skin Explant Cultures: An Alternative Model for Screening for Skin Irritants. ATLA 28:279–292, 2000.

    Google Scholar 

  24. Jacobs, J. J. L., C. Lehe, K. D. A. Cammans, P. K. Das, and G. R. Elliott. An in vitro model for detecting skin irritants: methyl green-pyronine staining of human skin explant cultures. Toxicol. In Vitro 16:581–588, 2002.

    Article  PubMed  CAS  Google Scholar 

  25. Junqueira, L. C., J. Carneiro, and R. O. Kelley. De Huid. In: Functionele Histologie, edited by P. N. Wisse and L. Ginsel. Maarssen: Elsevier Gezondheidszorg, 2000, pp. 419–437.

    Google Scholar 

  26. Kupper, T. S. Immune and inflammatory processes in cutaneous tissues. Mechanisms and speculations. J. Clin. Invest. 86:1783–1789, 1990.

    Article  PubMed  CAS  Google Scholar 

  27. Leveque, J. L., P. Hallegot, J. Doucet, and G. Pierard. Structure and function of human stratum corneum under deformation. Dermatology 205:353–357, 2002.

    Article  PubMed  CAS  Google Scholar 

  28. Luger, T. A. Epidermal cytokines. Acta. Derm. Venereol. Suppl. (Stockh) 151:61–76, 1989.

    CAS  Google Scholar 

  29. Mansbridge, J. Tissue-engineered skin substitutes. Expert Opin. Biol. Ther. 2:25–34, 2002.

    Article  PubMed  Google Scholar 

  30. Mast, B. A. and G. S. Schultz. Interactions of cytokines, growthfactors, and proteases in acute and chronic wounds. Wound Repair Regen. 4:411–420, 1996.

    Article  PubMed  CAS  Google Scholar 

  31. McCord, J. M. Oxygen-derived free radicals in postischemic tissue injury. N. Engl. J. Med. 312:159–163, 1985.

    PubMed  CAS  Google Scholar 

  32. McCord, J. M. Oxygen-derived radicals: A link between reperfusion injury and inflammation. Fed. Proc. 46:2402–2406, 1987.

    PubMed  CAS  Google Scholar 

  33. Mosmann, A. S. Rapid colorimetric assay for cellular growth and survivalapplication to proliferation and cytotoxicity assays. J. Immunol. Methods 65:55–63, 1983.

    Article  PubMed  CAS  Google Scholar 

  34. Peirce, S. M., T. C. Skalak, and G. T. Rodeheaver. Ischemia-reperfusion injury in chronic pressure ulcer formation: a skin model in the rat. Wound Repair Regen. 8:68–76, 2000.

    Article  PubMed  CAS  Google Scholar 

  35. Ponec, M., E. Boelsma, S. Gibbs, and M. Mommaas. Characterization of reconstructed skin models. Skin Pharmacol. Appl. Skin Physiol. 15:4–17, 2002.

    Article  PubMed  CAS  Google Scholar 

  36. Ronquist, G., A. Andersson, N. Bendsoe, and B. Falck. Human epidermal energy metabolism is functionally anaerobic. Exp. Dermatol. 12:572–579, 2003.

    Article  PubMed  CAS  Google Scholar 

  37. Rosdy, M., and L. C. Clauss. Terminal epidermal differentiation of human keratinocytes grown in chemically defined medium on inert filter substrates at the air–liquid interface. J. Invest. Dermatol. 95:409–414, 1990.

    Article  PubMed  CAS  Google Scholar 

  38. Vande Berg, J. S., and R. Rudolph. Pressure (decubitus) ulcer: variation in histopathology—a light and electron microscope study. Hum. Pathol. 26:195–200, 1995.

    Article  PubMed  CAS  Google Scholar 

  39. Wang, Y. N., and J. E. Sanders. Skin model studies. In: Pressure Ulcer Research, edited by D. L. Bader, C. V. C. Bouten, D. Colin, and C. W. J. Oomens. Heidelberg: Springer-Verlag, 2005, pp. 263–285.

    Chapter  Google Scholar 

  40. Welss, T., D. A. Basketter, and K. R. Schroder. In vitro skin irritation: facts and future. State of the art review of mechanisms and models. Toxicol. In Vitro 18:231–243, 2004.

    Article  PubMed  CAS  Google Scholar 

  41. Whittemore, R. Pressure-reduction support surfaces: a review of the literature. J. Wound Ostomy Continence Nurs. 25:6–25, 1998.

    PubMed  CAS  Google Scholar 

Download references

ACKNOWLEDGMENTS

The authors wish to thank Dr. S. Gibbs and her co-workers at the Department of Dermatology, VU University Medical Centre in Amsterdam, for their support with the tissue staining and the histological examination. We further thank Dr. J. Engel at the Center for Quantitative Methods in Eindhoven for his help with the statistical analyses. This work was financially supported by SenterNovem, an agency from the Ministry of Economic Affairs in the Netherlands.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Debbie Bronneberg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bronneberg, D., Bouten, C.V.C., Oomens, C.W.J. et al. An in vitro Model System to Study the Damaging Effects of Prolonged Mechanical Loading of the Epidermis. Ann Biomed Eng 34, 506–514 (2006). https://doi.org/10.1007/s10439-005-9062-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-005-9062-8

Keywords

Navigation