Skip to main content

Development of salmon milt DNA/salmon collagen composite for wound dressing


This study aims to develop a novel wound dressing comprising salmon milt DNA (sDNA) and salmon collagen (SC). The sDNA/SC composites were prepared by incubating a mixture of an acidic SC solution, an sDNA solution, and a collagen fibrillogenesis inducing buffer (pH 6.8) containing a crosslinking agent (water-soluble carbodiimide) for gelation, and a subsequent ventilation-drying process to give sDNA/SC films. The conjugation between sDNA and SC were confirmed by sDNA-elution assay and fluorescence microscopy. The sDNA/SC films with various doses of sDNA (sDNA/SC weight ratios of 1:5, 1:10, and 1:20) were used for in vitro cell cultures to evaluate their growth potentials of normal human dermal fibroblasts (NHDF) and normal human epidermal keratinocytes (NHEK). It was found that NHDF proliferation was increased by sDNA conjugation, whereas NHEK proliferation was dose-dependently inhibited. In light of the in vitro results, the appropriate dose of sDNA for in vivo study was determined to be the ratio of 1:10. For the implantation in full-thickness skin defects in rat dorsal region, the sDNA/SC films were reinforced by incorporating them on a porous SC sponge, because the sDNA/SC films exhibited early contraction and inadequate morphologic stability when implanted in vivo. The regenerated tissue in the sDNA/SC sponge group showed similar morphology to native dermis, while the SC sponge group without sDNA showed epithelial overgrowth, indicating that additional sDNA could reduce epidermal overgrowth. Furthermore, blood capillary formation was significantly enhanced in the sDNA/SC sponge group when compared to the SC sponge group. In conclusion, the results suggest that the sDNA/SC composite could be a potential wound dressing for clinical applications.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6


  1. 1.

    S.K. Purna, M. Babu, Burns 26, 54 (2000). doi:10.1016/S0305-4179(99)00103-5

    Article  CAS  Google Scholar 

  2. 2.

    D. Queen, H. Orsted, H. Sanada, G. Sussman, Int. Wound J. 1, 59 (2004). doi:10.1111/j.1742-4801.2004.0009.x

    Article  Google Scholar 

  3. 3.

    A.F. Falabella, Dermatol. Ther. 19, 317 (2006). doi:10.1111/j.1529-8019.2006.00090.x

    Article  Google Scholar 

  4. 4.

    J.A. Ramshaw, J.A. Werkmeister, V. Glattauer, Biotechnol. Genet. Eng. Rev. 13, 335 (1996)

    CAS  Google Scholar 

  5. 5.

    C.J. Doillon, F.H. Silver, Biomaterials 7, 3 (1986). doi:10.1016/0142-9612(86)90080-3

    Article  CAS  Google Scholar 

  6. 6.

    M. Ishihara, K. Nakanishi, K. Ono, M. Sato, M. Kikuchi, Y. Saito et al., Biomaterials 23, 833 (2002). doi:10.1016/S0142-9612(01)00189-2

    Article  CAS  Google Scholar 

  7. 7.

    C.H. Lee, A. Singla, Y. Lee, Int. J. Pharm. 221, 1 (2001). doi:10.1016/S0378-5173(01)00691-3

    Article  CAS  Google Scholar 

  8. 8.

    M. Mian, F. Beghe, E. Mian, Int. J. Tissue React. 14(Suppl), 1 (1992)

    CAS  Google Scholar 

  9. 9.

    E. Song, S. Yeon Kim, T. Chun, H.J. Byun, Y.M. Lee, Biomaterials 27, 2951 (2006). doi:10.1016/j.biomaterials.2006.01.015

    Article  CAS  Google Scholar 

  10. 10.

    M.M. Giraud-Guille, L. Besseau, C. Chopin, P. Durand, D. Herbage, Biomaterials 21, 899 (2000). doi:10.1016/S0142-9612(99)00244-6

    Article  CAS  Google Scholar 

  11. 11.

    S. Yunoki, N. Nagai, T. Suzuki, M. Munekata, J. Biosci. Bioeng. 98, 40 (2004)

    CAS  Google Scholar 

  12. 12.

    N. Nagai, K. Mori, Y. Satoh, N. Takahashi, S. Yunoki, K. Tajima et al., J. Biomed. Mater. Res. A 82, 395 (2007). doi:10.1002/jbm.a.31110

    Google Scholar 

  13. 13.

    N. Nagai, S. Yunoki, Y. Satoh, K. Tajima, M. Munekata, J. Biosci. Bioeng. 98, 493 (2004)

    CAS  Google Scholar 

  14. 14.

    M. Yamada, K. Kato, K. Shindo, M. Nomizu, M. Haruki, N. Sakairi et al., Biomaterials 22, 3121 (2001). doi:10.1016/S0142-9612(01)00061-8

    Article  CAS  Google Scholar 

  15. 15.

    J.J.J.P. Van Den Beucken, M.R.J. Vos, P.C. Thune, T. Hayakawa, T. Fukushima, Y. Okahata et al., Biomaterials 27, 691 (2006). doi:10.1016/j.biomaterials.2005.06.015

    Article  Google Scholar 

  16. 16.

    W. Liu, S. Sun, Z. Cao, X. Zhang, K. Yao, W.W. Lu et al., Biomaterials 26, 2705 (2005). doi:10.1016/j.biomaterials.2004.07.038

    Article  CAS  Google Scholar 

  17. 17.

    E. Holen, O.A. Bjørge, R. Jonsson, Nutrition 22, 90 (2006). doi:10.1016/j.nut.2006.01.001

    Article  CAS  Google Scholar 

  18. 18.

    T. Fukushima, T. Hayakawa, Y. Inoue, K. Miyazaki, Y. Okahata, Biomaterials 25, 5491 (2004). doi:10.1016/j.biomaterials.2004.01.006

    Article  CAS  Google Scholar 

  19. 19.

    M. Yamada, K. Kato, M. Nomizu, N. Sakairi, K. Ohkawa, H. Yamamoto et al., Chemistry (Easton) 8, 1407 (2002)

    CAS  Google Scholar 

  20. 20.

    N. Nagai, S. Yunoki, T. Suzuki, M. Sakata, K. Tajima, M. Munekata, J. Biosci. Bioeng. 97, 389 (2004)

    CAS  Google Scholar 

  21. 21.

    L.H. Olde Damink, P.J. Dijkstra, M.J. Van Luyn, P.B. Van Wachem, P. Nieuwenhuis, J. Feijen, Biomaterials 17, 765 (1996). doi:10.1016/0142-9612(96)81413-X

    Article  CAS  Google Scholar 

  22. 22.

    K.E. Kaldler, D.F. Holmes, J.A. Trotter, J.A. Chapman, Biochem. J. 316(Pt 1), 1 (1996)

    Google Scholar 

  23. 23.

    S. Thellung, T. Florio, A. Maragliano, G. Cattarini, G. Schettini, Life Sci. 64, 1661 (1999). doi:10.1016/S0024-3205(99)00104-6

    Article  CAS  Google Scholar 

  24. 24.

    P.W. Cook, N.M. Ashton, M.R. Pittelkow, J. Invest. Dermatol. 104, 976 (1995). doi:10.1111/1523-1747.ep12606228

    Article  CAS  Google Scholar 

  25. 25.

    M.C. Montesinos, A. Desai, J.F. Chen, H. Yee, M.A. Schwarzschild, J.S. Fink et al., Am. J. Pathol. 160, 2009 (2002)

    CAS  Google Scholar 

Download references


Shen thanks the Japan Society for the Promotion of Science (JSPS) for a post-doctoral fellowship for foreign researchers.

Author information



Corresponding author

Correspondence to XuanRi Shen.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Shen, X., Nagai, N., Murata, M. et al. Development of salmon milt DNA/salmon collagen composite for wound dressing. J Mater Sci: Mater Med 19, 3473–3479 (2008).

Download citation


  • Sponge
  • Bovine Spongiform Encephalopathy
  • Chum Salmon
  • Skin Regeneration
  • Normal Human Dermal Fibroblast