In Vivo Interactions with (Tissue Culture Pretreated) Dermal Sheep Collagen


Pretreatment in tissue culture (TC) was previously found to markedly reduce the in vitro cytotoxicity of two types of crosslinked dermal sheep collagens (DSC’s).

This in vivo study confirms our in vitro results, in that TC-pretreatment of crosslinked DSC’s resulted in the marked reduction or elimination of cytotoxic effects, such as increased cell infiltration, a deviant neutrophil-morphology, lipid formation and cell death. TC-pretreatment affected the crosslinked state of both DSC’s in a different way, which could be deduced from the differences in gelatin-formation and presence of giant cells from macrophage- or fibroblast-origin.

The results are explained in view of the differences in crosslinking.

This is a preview of subscription content, access via your institution.


  1. 1.

    Chvapil, M., Kronenthal, R.L., Van Winkle, W., Medical and surgical applications of collagen, Int. Rev. Conn. Tissue Res., 6, 1–61, Eds.: D.A. Hall, D.S. Jackson, Academic Press, London, UK, 1973

    CAS  Article  Google Scholar 

  2. 2.

    Huc, A., Collagen biomaterials: characteristics and applications, J. Am. Leather Chem. Assoc. 80,195–212, 1985

    CAS  Google Scholar 

  3. 3.

    Pharriss, B.B., Collagen as a biomaterial, J. Am. Leather Chem. Assoc., 75, 474–485, 1980

    CAS  Google Scholar 

  4. 4.

    Speer, D.P., Chavpil, M., Eskelson, C.D. and Ulreich, J., Biological effects of residual glutaraldehyde in glutaraldehyde tanned collagen biomaterials, J. of Biomed. Mat. Res., 14, 753–764, 1980.

    CAS  Article  Google Scholar 

  5. 5.

    Ulreich, J.B., Chvapil, M., A quantitative microassay for in-vitro toxicity testing of biomaterials, J. Biomed. Mater. Res., 15, 913–922, 1981

    CAS  Article  Google Scholar 

  6. 6.

    Van Luyn, M.J.A., Van Wachem, P.B., Olde Damink, L., Ten Hoopen, H., Feijen, J., Nieuwenhuis, P., Methylcellulose culture as a new cytotoxicity test system for biomaterials, Mater. in Med. 2, 142–148, 1991

    Article  Google Scholar 

  7. 7.

    Van Luyn, M.J.A., Van Wachem, P.B., Olde Damink, L., Dijkstra, P.J., Feijen, J., Nieuwenhuis, P., Relations between in vitro cytotoxicity and crosslinked dermal sheep collagens, Submitted to J. Biomed. Mater. Res.

  8. 8.

    Van Luyn, M.J.A., Van Wachem, P.B., Jonkman, M.H., Nieuwenhuis, P., Cytotoxicity testing of wound dressings using methylcellulose cell culture, accepted for publication in Biomaterials

  9. 9.

    Van Wachem, P.B., van Luyn, M.J.A., Koerten, H.K., Olde Damink, L., Ten Hoopen, H., Feijen, J., Nieuwenhuis, P., In vivo degradation of processed dermal sheep collagen evaluated with transmission electron microscopy, Biomaterials, 12, 215–223, 1991

    Article  Google Scholar 

  10. 10.

    Van Wachem, P.B., van Luyn, M.J.A., Olde Damink, L., Feijen, J., Nieuwenhuis, P., Tissue interactions with dermal sheep collagen implants: a transmission electron microscopical evaluation, Cells and Materials, 1, 3, 251–263, 1991

    Google Scholar 

  11. 11.

    Van Gulik, T.M., The processing of sheepskin for use as a dermal collagen graft, Neth. J. Surg. 39, 90–94, 1987

    Google Scholar 

  12. 12.

    Van Gulik, T.M., Christiano, R.A., Broekhuizen, A.H., Raaymakers, E.L.F.B., Klopper, P.J., A tanned sheep dermal collagen graft as a dressing for split-skin graft donor sites, Neth. J. Surg., 41, 65–67, 1989

    Google Scholar 

  13. 13.

    Hulstaert, C.E., Kalicharan, D., Hardonk, M.J., Cytochemical demonstration of phosphatases in rat liver by a cerium-based method in combination with osmium tetroxide and potassium ferrocyanide postfixation, Histochemistry 78, 71–79, 1983

    CAS  Article  Google Scholar 

  14. 14.

    Yano, E., Yoshioka, M., Koizumi, A., Relationship between chemical structure and cytotoxicity of aliphatic maines examined by a microtiter system with cultured fibroblasts, Jap. J. Ind. Health, 23, 537–543, 1981

    CAS  Google Scholar 

  15. 15.

    Berode, M., Leuenberger, Ph., Savolainen, H., Phenotype-dependent inhibition of human al-antitrypsin by 1,6 hexanediamine in vitro, Biochem. Int. 17, 141–145, 1988

    CAS  Google Scholar 

  16. 16.

    Johannsen, F.R., Levinskas, G.J., Toxicological profile of orally administered 1,6 hexane diamine in the rat, J. Appl. Toxicol. 7, 259–263, 1987

    CAS  Article  Google Scholar 

  17. 17.

    Cooke, A., Oliver, R.F., Edward, M., An in vitro cytotoxicity study of aldehyde-treated pig dermal collagen, Br. J. Exp. Path. 64, 172–176, 1983

    CAS  Google Scholar 

  18. 18.

    Eybl, E., Griesmacher, A., Grimm, M., Wolner, E., Toxic effects of aldehydes released from fixed pericardium on bovine aortic endothelial cells, J. Bomed. Mater. Res. 23, 1355–1365, 1989

    CAS  Article  Google Scholar 

  19. 19.

    Huang-Lee, L.L., Cheung, D.T., Nimni, M.E., Biochemical changes and cytotoxicity associated with the degradation of polymeric glutaraldehyde derived crosslinks, J. Biomed. Mater. Res. 24, 1185–1201, 1990

    CAS  Article  Google Scholar 

  20. 20.

    Van der Laan, J.S., van Wachem, P.B., Schakenraad, J.M., Nieuwenhuis, P., Dermal sheep collagen for the repair of abdominal wall defects, J. Artif. Organs, 14, 661–666, 1991

    Article  Google Scholar 

Download references


The authors wish to acknowledge Dr.H.K. Koerten from the Laboratory of Electron Microscopy of Leiden University, The Netherlands, for carrying out single-spot X-ray micro analysis [9]. We further wish to acknowledge mr. D. Huizinga, mr. P. van der Sijde and mr. H.R.A. Meiborg from our Laboratory for the photography.

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

van Wachem, P.B., van Luyn, M.J.A., Olde Damink, L.H.H. et al. In Vivo Interactions with (Tissue Culture Pretreated) Dermal Sheep Collagen. MRS Online Proceedings Library 252, 117–124 (1991).

Download citation