Annals of Biomedical Engineering

, Volume 37, Issue 2, pp 401–409 | Cite as

Novel Organotypic Cultures of Human Skin Explants with an Implant-tissue Biomaterial Interface

  • Antonio Peramo
  • Cynthia L. Marcelo
  • Steven A. Goldstein
  • David C. Martin
Article

Abstract

A novel in vitro culture system of organotypic human skin explants interfacing with external fixator pins is presented. The system was used to observe changes in skin morphology on the skin at the pin interface. To evaluate the performance of this novel system, histological analysis of human skin explants cultured for 5 days at the air–liquid interface was performed. Compared to control explants, specimens interfaced with pins (treated or not with a physiological saline solution) showed a deteriorating basal layer, a disappearing stratum spinosum and increased lost of elastic fibers in the dermis. The model system makes it possible to perform rapid, repeatable studies of living skin response to chronically implanted materials and devices.

Keywords

Organotypic culture Wound healing Skin biomaterial Implant interface External fixation 

Notes

Acknowledgments

We thank Harald Eberhart, College of Engineering, University of Michigan, for help with the glass lid design. We thank Marta Dzaman, Morphology Core, University of Michigan for advice on specimen sectioning and staining. This report is presented as part of the research efforts within the Army Research Office Multidisciplinary University Research Initiative award on Bio-Integrating Structural and Neural Prosthetic Materials and we gratefully acknowledge the funding provided.

References

  1. 1.
    Aro H. T., D. M. Markel, E. Y. S. Chao. Cortical bone reaction at the interface of external fixation half-pins under different looking conditions. J. Trauma 1993;35:776–785PubMedCrossRefGoogle Scholar
  2. 2.
    Bedoni M., C. Sforza, C. Dolci, E. Donetti. Proliferation and differentiation biomarkers in normal human breast skin organotypic cultures. J. Dermatol. Sci. 2007;46:139–142PubMedCrossRefGoogle Scholar
  3. 3.
    Branemark R., P. I. Branemark, B. Rydevik, R. R. Myers. Osseointegration in skeletal reconstruction and rehabilitation: a review. J. Rehabil. Res. Dev. 2001;38:175–181PubMedGoogle Scholar
  4. 4.
    Campbell A. A., L. Song, X. S. Li, B. J. Nelson, C. Bottoni, D. E. Brooks, E. S. DeJong. Development, characterization, and anti-microbial efficacy of hydroxyapatite-chlorhexidine coatings produced by surface-induced mineralization. J. Biomed. Mater. Res. (Appl. Biomater.) 2000;53:400–407CrossRefGoogle Scholar
  5. 5.
    Green S. A., M. J. Ripley. Chronic osteomyelitis in pin tracks. J. Bone Joint Surg. Am. 1984;66:1092–1098PubMedGoogle Scholar
  6. 6.
    Gupta D., C. H. Tator, M. S. Shoichet. Fast-gelling injectable blend of hyaluronan and methylcellulose for intrathecal, localized delivery to the injured spinal cord. Biomaterials 2006;27:2370–2379PubMedCrossRefGoogle Scholar
  7. 7.
    Le Poole I. C., R. M. Van der Wijngaard, W. Westeerhof, J. A. Dormans, F. M. Van der Berg, R. P. Verkruisen, K. P. Dingemans, P. K. Das. Organotypic culture of human skin to study melanocyte migration. Pigment Cell Res. 1994;7:33–43PubMedCrossRefGoogle Scholar
  8. 8.
    Mahan J., D. Seligson, S. L. Henry, P. Hynes, J. Dobbins. Factors in pin tract infections. Orthopedics 1991;14:305–308PubMedGoogle Scholar
  9. 9.
    Masse A., A. Bruno, M. Bosetti, A. Biasibetti, M. Cannas, P. Gallinaro. Prevention of pin track infection in external fixation with silver coated pins: clinical and microbiological results. J. Biomed. Mater. Res. (Appl. Biomater.) 2000;53:600–604CrossRefGoogle Scholar
  10. 10.
    Mooney V., S. A. Schwartz, A. M. Roth, M. J. Gorniowsky. Percutaneous implant devices. Ann. Biomed. Eng. 1977;5:34–46PubMedCrossRefGoogle Scholar
  11. 11.
    Moroni A., V. L. Caja, C. Maltarello. Enhancement of the bone fixation external pin interface: a biomechanical and morphological in vivo experimental study. Bioceram 1994;7:229–234Google Scholar
  12. 12.
    NNIS System. National Nosocomial Infections Surveillance (NNIS) system report, data summary from January 1992 through June 2003, issued August 2003. Am. J. Infect. Control 2003;31:481–498CrossRefGoogle Scholar
  13. 13.
    Pendergrass C. J., A. E. Goodship, G. W. Blunn. Development of a soft tissue seal around bone-anchored transcutaneous amputation prostheses. Biomaterials 2006;27:4183–4191CrossRefGoogle Scholar
  14. 14.
    Peramo, A., C. Marcelo, S. Goldstein, and D. C. Martin. Novel In Vitro Tissue Culture System for Interfacing Biological Tissues to Implanted Devices. Invention Disclosure, University of Michigan Technology Transfer Office, 2007Google Scholar
  15. 15.
    Pickup J. C., F. Hussain, N. D. Evans, N. Sachedina. In vivo glucose monitoring: the clinical reality and the promise. Biosens. Bioelectron. 2005;20:1897–1902PubMedCrossRefGoogle Scholar
  16. 16.
    Rammelt S., T. Illert, S. Bierbaum, D. Scharnweber, H. Zwipp, W. Schneiders. Coating of titanium implants with collagen, RGD-peptide and chondroitin sulfate. Biomaterials 2006;27:5561–5571PubMedCrossRefGoogle Scholar
  17. 17.
    Resau J. H., K. Sakamoto, J. R. Cottrell, E. A. Hudson, S. J. Meltzer. Explant organ culture: a review. Cytotechnology 1991;7:137–149PubMedCrossRefGoogle Scholar
  18. 18.
    Schalamon J., T. Petnehazy, H. Ainoedhofer, E. B. Zwick, G. Singer, M. E. Hoellwarth. Pin tract infection with external fixation of pediatric fractures. J. Pediatr. Surg. 2007;42(9):1584–1587PubMedCrossRefGoogle Scholar
  19. 19.
    Stoscheck C. M., L. B. Nanney, L. E. King Jr. Quantitative determination of EGF-R during epidermal wound healing. J. Invest. Dermatol. 1992;99:645–649PubMedCrossRefGoogle Scholar
  20. 20.
    Supp D. M., S. T. Boyce. Engineered skin substitutes: practices and potentials. Clin. Dermatol. 2005;23:403–412PubMedCrossRefGoogle Scholar
  21. 21.
    Svensjo T., B. Pomahac, F. Yao, J. Slama, E. Eriksson. Accelerated healing of full-thickness skin wounds in a wet environment. Plast. Reconstr. Surg. 2000;106:602–612PubMedCrossRefGoogle Scholar
  22. 22.
    Tammi R., C. T. Jansen, R. Santti. Histometric analysis of human skin in organ culture. J. Invest. Dermatol. 1979;73:138–140PubMedCrossRefGoogle Scholar
  23. 23.
    Tavakkol A., J. Varani, J. T. Elder, C. C. Zouboulis. Maintenance of human skin in organ culture: role for insulin-like growth factor-1 receptor and epidermal growth factor receptor. Arch. Dermatol. Res. 1999;291:643–651PubMedCrossRefGoogle Scholar
  24. 24.
    Tebbs S. E., A. Sawyer, T. S. Elliott. Influence of surface morphology on in vitro bacterial adherence to central nervous catheters. Br. J. Anaesth. 1994;72:587–591PubMedCrossRefGoogle Scholar
  25. 25.
    Varani J., S. E. G. Fligiel, L. Schuger, P. Perone, D. R. Inman, C. E. M. Griffiths, J. J. Voorhees. Effects of all-trans retinoic acid and Ca2+ on human skin in organ culture. Am. J. Pathol. 1993;142:189–198PubMedGoogle Scholar
  26. 26.
    Von Eiff C., W. Kohnen, K. Becker, B. Jansen. Modern strategies in the prevention of implant-associated infections. Int. J. Artif. Organs 2005;28:1146–1156Google Scholar
  27. 27.
    Von Recum A. F. Applications and failure modes of percutaneous devices: a review. J. Biomed. Mater. Res. 1984;18:323–336CrossRefGoogle Scholar
  28. 28.
    Winter G. D. Transcutaneous implants: reactions of the skin-implant interface. J. Biomed. Mater. Res. Symp. No. 5 (Part I) 1974;13:99–101CrossRefGoogle Scholar
  29. 29.
    Xu W., D. H. Xu, D. A. Crocombe. Three-dimensional finite element stress and strain analysis of a transfemoral osseointegration implant. Proc. Inst. Mech. Eng. [H] 2006;220:661–670Google Scholar

Copyright information

© Biomedical Engineering Society 2008

Authors and Affiliations

  • Antonio Peramo
    • 1
  • Cynthia L. Marcelo
    • 2
  • Steven A. Goldstein
    • 3
    • 4
  • David C. Martin
    • 1
    • 4
    • 5
  1. 1.Department of Materials Science and EngineeringUniversity of MichiganAnn ArborUSA
  2. 2.Department of SurgeryUniversity of MichiganAnn ArborUSA
  3. 3.Department of Orthopedic SurgeryUniversity of MichiganAnn ArborUSA
  4. 4.Department of Biomedical EngineeringUniversity of MichiganAnn ArborUSA
  5. 5.Macromolecular Science and Engineering CenterUniversity of MichiganAnn ArborUSA

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