Enhancing Dermal Matrix Regeneration and Biomechanical Properties of $2^{nd}$ Degree-Burn Wounds by EGF-Impregnated Collagen Sponge Dressing

  • Cho Lee Ae-Ri (College of Pharmacy, Duksung Women's University)
  • Published : 2005.11.01

Abstract

To better define the relationship between dermal regeneration and wound contraction and scar formation, the effects of epidermal growth factor (EGF) loaded in collagen sponge matrix on the fibroblast cell proliferation rate and the dermal mechanical strength were investigated. Collagen sponges with acid-soluble fraction of pig skin were prepared and incorporated with EGF at 0, 4, and 8 $\mu$g/1.7 $cm^{2}$. Dermal fibroblasts were cultured to 80$\%$ confluence using DMEM, treated with the samples submerged, and the cell viability was estimated using MTT assay. A deep, $2^{nd}$ degree- burn of diameter 1 cm was prepared on the rabbit ear and the tested dressings were applied twice during the 15-day, post burn period. The processes of re-epithelialization and dermal regeneration were investigated until the complete wound closure day and histological analysis was performed with H-E staining. EGF increased the fibroblast cell proliferation rate. The histology showed well developed, weave-like collagen bundles and fibroblasts in EGF-treated wounds while open wounds showed irregular collagen bundles and impaired fibroblast growth. The breaking strength (944.1 $\pm$ 35.6 vs. 411.5 $\pm$ 57.0 Fmax, $gmm^{-2}$) and skin resilience (11.3 $\pm$ 1.4 vs. 6.5 $\pm$ 0.6 mJ/$mm^{2}$) were significantly increased with EGF­treated wounds as compared with open wounds, suggesting that EGF enhanced the dermal matrix formation and improved the wound mechanical strength. In conclusion, EGF-improved dermal matrix formation is related with a lower wound contraction rate. The impaired dermal regeneration observed in the open wounds could contribute to the formation of wound contraction and scar tissue development. An extraneous supply of EGF in the collagen dressing on deep, $2^{nd}$ degree-burns enhanced the dermal matrix formation.

Keywords

References

  1. Beaubien, J., Boisjoly, H. M., Gagnon, P., and Guidoin, R., Mechanical properties of the rabbit cornea during wound healing after treatment with epidermal growth. Can. J. Ophthalmol., 29, 61-65 (1994)
  2. Beausang, E., Floyd, H., Dunn, K. W., Orton, C. I., and Ferguson, M. W. J., A new quantitative scale for clinical scar assessment. Plast. Reconstr. Surg., 102, 1954-1961 (1998) https://doi.org/10.1097/00006534-199811000-00022
  3. Berthod, F., Germain, L., Li, H., Xu, W., Damour, O., and Auger, F. A., Collagen fibril network and elastic system remodeling in a reconstructed skin transplanted on nude mice. Matrix Biol., 20, 463-473 (2001) https://doi.org/10.1016/S0945-053X(01)00162-7
  4. Brown, G. L., Curtsinger, L. J., White, M., Mitchell, R. O., Pietsch, J., Nordquist, R, Fraunhofer, A., and Schultz, G. S., Acceleration of tensile strength of incisions treated with EGF and TGF-beta. Ann. Surg., 208, 788-794 (1988) https://doi.org/10.1097/00000658-198812000-00019
  5. Buckley, A., Davidson, J. M. Kamerath, C. D., Wolt, T. B., and Woodward, S. C., Sustained release of epidermal growth factor accelerates wound repair. Proc. Natl. Acad. Sci. U.S.A., 82, 7340-7344 (1985) https://doi.org/10.1073/pnas.82.21.7340
  6. Celebi, N., G$\"{o}$n$\"{u}$l, B., and Koz, M., Effect of epidermal growth factor dosage forms on dermal wound strength in mice. J. Pharm. Pharmacol., 46, 386-387 (1994) https://doi.org/10.1111/j.2042-7158.1994.tb03820.x
  7. Cho Lee, A. R. and Moon, H. K., Effect of Topically Applied Silver Sulfadiazine on Fibroblast Cell Proliferation and Biomechanical Properties of the Wound, Arch. Pharm. Res., 26, 855-860 (2003) https://doi.org/10.1007/BF02980032
  8. Cho Lee, A. R., Moon, H. K., and Lee, J., The roles of epidermal growth factor in enhancing dermal matrix regeneration and its implication in wound contraction and scar formation. Wound Rep. Reg., 11, A34 (2003)
  9. Cho Lee, A. R., Suzuki, Y., Shigematsu, A., and Jung. K., Wound healing effect of epidermal growth factor after topical application. Proceed. Int'l. Symp. Control. Rel. Bioact. Mater., 23, 325-326 (1996)
  10. Cho Lee, A. R., Leem, H., Lee, J., and Park, K. C., Reversal of silver sulfadiazine-impaired wound healing by epidermal growth factor. Biomaterials, 26, 4670-4676 (2005) https://doi.org/10.1016/j.biomaterials.2004.11.041
  11. Cho Lee, A. R., Yoon, J. J., Lim, H., Park, Y., Jung, K. H., and Lee, J., Preparation of alginate microsphere and collagen sponge for controlled release and its application to wound dressing. Proceed. Int'l. Symp. Control. Rel. Bioact. Mater., 26, 471-472 (1999)
  12. Cross, S. E. and Roberts, M. S., Defining a model to predict the distribution of topically applied growth factors and other solutes in excisional full-thickness wounds. J. Invest. Dermatol., 112, 36-41 (1999) https://doi.org/10.1046/j.1523-1747.1999.00473.x
  13. Curtsinger, L. J., Pietsch, J. D., Brown, G. L., Ackerman, D., Polk, H. C., and Schultz, G. S., Reversal of adriamycinimpaired wound healing by transforming growth factor-beta. Sur. Gynecol. Obst., 168, 517-522 (1989)
  14. Davis, P. A. and Westell, C., A Comparison of Biomechanical Properties of Excised Mature Scars from HIV Patients and Non-HIV Controls. Am. J. Surg., 180, 217-222 (2000) https://doi.org/10.1016/S0002-9610(00)00468-2
  15. Eisinger. M, Sadan. S, Silver. I. A., and Flick, R. B., Growth regulation of skin cells by epidermal cell-derived factors: Implications for wound healing. Proc. Natl. Acad. Sci. U.S.A., 85, 1937-1941 (1988) https://doi.org/10.1073/pnas.85.6.1937
  16. Franklin, J. D. and Lynch, J. B., Effects of topical applications of epidermal growth factor on wound healing. Plast. Reconstr. Surg., 64,766-770 (1979) https://doi.org/10.1097/00006534-197912000-00003
  17. Inoue, M., Li-Jun Zhon, L. J., Gunji, H., Ono, I., and Kaneko, F., Effects of cytokines in burn blister fluids on fibroblast proliferation and their inhibition with the use of neutralizing antibodies. Wound Rep. Reg., 4, 426-432 (1996) https://doi.org/10.1046/j.1524-475X.1996.40406.x
  18. Kingsnorth, A. N., Vowles, R., and Nash, J. R. G., Epidermal growth factor increases tensile strength in intestinal wounds in pigs. Br. J. Surg., 77, 409-412 (1990) https://doi.org/10.1002/bjs.1800770417
  19. Leibowitz, H. M., Morello, S. Jr., Stern, M., and Kupferman, A., Effect of topically administered epidermal growth factor on corneal wound strength, Arch. Ophthalmol., 108,734-737 (1990) https://doi.org/10.1001/archopht.1990.01070070120048
  20. Laato, M., Niinikoski, J., Gerdin, B., and Lebel, L., Stimulation of wound healing by epidermal growth factor. A dosedependent effect. Ann. Surg., 203, 379-381 (1986) https://doi.org/10.1097/00000658-198604000-00007
  21. Morine, G., Rand, M., Burgess, L. P., Voussoughi, J., and Graeber, G. M., Wound healing: relationship of wound closing tension to tensile strength in rats. Laryngoscope, 99, 783-788 (1989)
  22. Mukhopadhyay, A., Tan, E. K. J., Khoo, Y. T. A., Chan, S. Y., Lim, I. J., and Phan, T. T., Conditioned medium from keloid keratinocytes/keloid fibroblast coculture induces contraction of fibroblast-populated collagen lattices. Br. J. Dermatol., 152, 639-645 (2005) https://doi.org/10.1111/j.1365-2133.2005.06545.x
  23. Mustoe. T. A., Pierce, G. F., and Thomasen, A., Accelerated healing of incisional wound in rats induced by transforming growth factor type-b. Science, 237, 1333-1336 (1987) https://doi.org/10.1126/science.2442813
  24. Piscatelli, S. J., Michaels, B. M., Gregory, P., Jennings, R. W. Longaker, M. T., Harrison, M. R., and Siebert, J. W., Fetal fibroblast contraction of collagen matrices in vitro: the effects of epidermal growth factor and transforming growth factor-b. Ann. Plast. Surg., 33, 38-45 (1994) https://doi.org/10.1097/00000637-199407000-00008
  25. Yao, F., Visovatti, S., Chen, M., Slama, J., Wenger, A., and Eriksson, E., Age and growth factors in porcine full-thickness wound healing. Wound Rep. Reg., 9, 371-377 (2001) https://doi.org/10.1046/j.1524-475x.2001.00371.x