Skip to main content
Log in

Investigation into the tensile properties of collagen/chondroitin-6-sulphate gels: the effect of crosslinking agents and diamines

  • Cellular Engineering
  • Published:
Medical and Biological Engineering and Computing Aims and scope Submit manuscript

Abstract

Artificial skin substitutes based on autologous keratinocytes are being developed for grafting onto burns patients. In order to be used successfully in the clinic, these skin substitutes need to have sufficient strength to allow ease of handling. This may be achieved by crosslinking the collagen substratum on which the cells are cultured. The influence of potential crosslinking agents on the tensile properties of acellular collagen gels has been investigated, including the glycosaminoglycan, chondroitin-6-sulphate (Ch6SO4), the water-soluble carbodiimide crosslinking agents 1-ethyl-3-(3-diaminopropyl) carbodiimide (EDAC), and 1,1-carbonyldiimidazole (CDI), and the polyamines, putrescine and diaminohexane. Values for Young's modulus, maximum load, stress, displacement and percentage strain at maximum load were generated by subjecting the samples to a tear propagation test. Incorporation of 20% Ch6SO4 into collagen gels caused a significant increase in the Young's modulus, maximum load and stress at maximum load. Crosslinking treatment with EDAC, CDI or polyamines had little further benefit, and in many cases resulted in a decrease in particular parameters. In terms of mechanical strength, the best crosslinking combination proved to be the combination of CDI and diaminohexane, with results either improved or maintained when compared with the control no treatment variants. However, previous experience suggests that the use of CDI as a crosslinking reagent may inhibit infiltration and proliferation of fibroblasts in the substratum and it may be necessary to reach a compromise to obtain the best combination of biological and mechanical properties for artificial skin substitutes.

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.

Institutional subscriptions

Similar content being viewed by others

References

  • Agache, P. G., Monneur, C., Leveque, J. L. andDeRigal, J. (1980): ‘Mechanical properties and Young's modulus of human skinin vivo,’Arch. Dermatol. Res.,269, pp. 221–232

    Article  Google Scholar 

  • Chapuis, J. F. andAgache, P. (1992): ‘A new technique to study the mechanical properties of collagen lattices,’J. Biomech.,25, pp. 115–120

    Article  Google Scholar 

  • Elsdale, T. andBard, J. (1972): ‘Collagen substrata for studies on cell behavior,’J. Cell. Biol.,54, pp. 626–637

    Article  Google Scholar 

  • Gunner, G. W., Hutton, W. C. andBurlin, T. E. (1979): ‘The mechanical properties of the skinin vivo—a portable handheld extensometer,’Brit. J. Dermatol.,100, pp. 161–163

    Article  Google Scholar 

  • Hanthamrongwit, M., Wilkinson, R., Osborne, C. S., Reid, W. H. andGrant, M. H. (1996): ‘Confocal laser scanning microscopy for determining the structure of and keratinocyte infiltration through collagen sponges,’J. Biomed. Mater. Res.,30, pp 331–339

    Article  Google Scholar 

  • Lafrance, H., Yahia, L., Germain, L., Guillot, M. andAuger, F. A. (1995): ‘Study of the tensile properties of living skin equivalents,’Biomed. Mater. Eng.,5, (4), pp 195–208

    Google Scholar 

  • Marchand, R., Woerly, S., Bertrand, L. andValdes, N. (1993): ‘Evaluation of two cross-linked collagen gels implanted in the transected spinal cord,’Brain Res. Bull.,30, pp. 415–422

    Article  Google Scholar 

  • Matsuda, K., Suzuki, S., Isshiki, N. andYoshioka, K. (1990): ‘Influence of glycosaminoglycans on the collagen sponge component of a bilayer artificial skin,’Biomater.,11, 351–355

    Article  Google Scholar 

  • Matsuda, K., Suzuki, S., Isshiki, N. andIkada, Y. (1993): ‘Refreeze dried bilayer artificial skin,’ ——ibid.,14 (13), pp. 1030–1035

    Article  Google Scholar 

  • Miyata, T., Tiara, T., Noishiki, M. (1992): ‘Collagen engineering for biomaterial use,’Clin. Mater.,9, pp. 139–148

    Article  Google Scholar 

  • Olde Damink, L. H. H., Dijkstra, P. J., van Luyn, M. J. A., van Wachem, P. B., Nieuwenhuis, P. andFeijen, J. (1994): ‘Gluteraldehyde as a crosslinking agent for collagen-based biomaterials,’J. Mater. Sci. Mater. Med.,6, pp. 460–472

    Article  Google Scholar 

  • Olde Damink, L. H. H., Dijkstra, P. J., van Luyn, M. J. A., van Wachem, P. B., Nieuwenhuis, P. andFeijen, J. (1996): ‘Crosslinking of dermal sheep collagen using a water-soluble carbodiimide,’Biomater.,17, pp. 765–773

    Article  Google Scholar 

  • Osborne, C. S., Reid, W. H. andGrant, M. H. (1997): ‘Investigation into cell growth on collagen/chrondroitin-6-sulphate gels: the effect of crosslinking agents and diamines,’J. Mater. Sci. Mater. Med.,8, pp. 179–184

    Article  Google Scholar 

  • Pierard, G. E. (1980): ‘Investigating rheological properties of skin by applying a vertical pull,’Bioeng. Skin.,2, pp. 31–36

    Google Scholar 

  • Suzuki, S., Matsuda, K., Isshiki, N., Tamada, Y. andIkada, Y. (1990a): ‘Experimental study of a newly developed bilayer artificial skin,’Biomater.,11, pp. 356–360

    Article  Google Scholar 

  • Suzuki, S., Matsuda, K., Isshiki, N., Tamada, Y., Yoshioka, K. andIkada, Y. (1990b): ‘Clinical evaluation of a new bilayer artificial skin, composed of collagen sponge and a silicone layer,’Brit. J. Surg.,43, pp. 47–54

    Article  Google Scholar 

  • Weadock, K., Olson, R. M. andSilver, F. H. (1984): ‘Evaluation of collagen crosslinking techniques,’Biomat. Med. Dev. Art. Org.,11, (4), pp. 293–318

    Google Scholar 

  • Yannas, I. V. andBurke, J. F. (1980): ‘Design of an artificial skin. I Basic design principles,’J. Biomed. Mater. Res.,14, pp. 65–81

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Osborne, C.S., Barbenel, J.C., Smith, D. et al. Investigation into the tensile properties of collagen/chondroitin-6-sulphate gels: the effect of crosslinking agents and diamines. Med. Biol. Eng. Comput. 36, 129–134 (1998). https://doi.org/10.1007/BF02522870

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02522870

Keywords

Navigation