DOI QR코드

DOI QR Code

Preparation of Reproducible and Responsive Scar Model and Histology Analysis

  • Published : 2010.02.20

Abstract

Unlike human, with some exceptions, animals do not heal with excessive scar. The lack of suitable animal model has hindered the development of effective scar therapy. We previously reported that partial thickness rabbit ear wound model resembles human wound heal process. This study was designed to prepare a hypertropic scar wound model which can be employed for testing anti-scar therapy. Four wounds were created down to the bare cartilage on the anterior side of each rabbit ear using 8-mm dermal biopsy punch and histology analysis at post operation day (POD) 5, 28 and 48 were performed. As the outcome of scar formation is largely determined by the early inflammatory response to the wounding and the degree and the duration of occlusion, cephalodin(50 mg/kg) was injected daily and medical occlusive dressings were applied. Five micro wound and scar sections were stained with hematoxylin and eosin for quantification of epidermal regeneration and scar hypertrophy. Sections were also stained using Masson's trichrome and Sirius red to evaluate collagen organization and rete ridge formation. Wound closure process was assessed to 7wks post wounding. Complete removal of the epidermis, dermis and perichondrial layer caused delayed epithelialization, which results in hypertropic scarring. The inability of the wounds to contract and the delay in epithelialization in rabbit ear was likely due to cartilage and it created scar elevation. The results suggest that full thickness surgical punch wound model in rabbit ear could be employed as a reliable and reproducible scar wound model for testing anti-scar therapy.

Keywords

References

  1. M. Hardy, The biology of scar formation, Physical Therapy, 69, 1014-1024 (1989).
  2. R.R. Reid, N. Roy, J.E. Mogford, H. Zimmerman, C. Lee and T.A. Mustoe, Reduction of hypertropic scar via retroviral delivery of a dominant negative $TGF-{\beta}$ receptor II, J. Plast. Recon. Anes. Surg, 60, 64-72 (2007). https://doi.org/10.1016/j.bjps.2005.12.026
  3. I. Kim, J.E. Mogford, C. Witschi, M. Nafassi and T.A. Mustoe, Inhibition of prolyl 4-hydroxylase reduces scar hypetrophy in a rabbit model of cutaneous scarring, Wound Rep. Reg. 11, 368-372 (2003) https://doi.org/10.1046/j.1524-475X.2003.11509.x
  4. K. Richey, L. Engrav, E. Pavlin, M. Murray, J. Gottlieb and M. Walkinshaw, Topical growth factors and wound contraction in the rat: literature review and definition of the rat model, Annals of plastic surgery, 23, 159-165 (1989). https://doi.org/10.1097/00000637-198908000-00011
  5. D.L. Gu, D.W. Kang, D. Manavel and M.A. Zepada, Rabbit ear excessive scarring model using growth factor stimulators, Wound Rep. Reg. 12, A9 (2008) https://doi.org/10.1111/j.1067-1927.2004.0abstractac.x
  6. S.A. Eming, S. Wemer, P. Bugnon, C. Wickenhauser, L. Siewe, O. Utermohlen, J.M. Davidson, T. Krieg and A. Roers, Accelerated wound closure in mice deficient for interleukin-10, Am. J. Pathol., 170, 188-201 (2007). https://doi.org/10.2353/ajpath.2007.060370
  7. T.A. Wilgus, A.M.Ferreira, T.M. Oberyszyn, V.K. Bergdall, and L.A. Dipietro, Regulation of scar formation by vascular endothelial growth factor, Lab. Invest., 88, 579-590 (2008). https://doi.org/10.1038/labinvest.2008.36
  8. O. Kloeters, A. Tandara and T.A. Mustoe, Hypertropic scar model in the rabbit ear: a reproducible model for studying scar tissue behavior with new observation on silicone gel sheeting for scar reduction, Wound Rep. Reg., 18, S40-S45 (2007). https://doi.org/10.1111/j.1524-475X.2007.00224.x
  9. R.G. Reish, B.Zuhaili, J. Bergmann, P. Aflaki, T. Koyama, F.Hacki, E. Waisbren, J.A. Canseco, K.D. Verma, E.Eriksson and F.Yao, Modulation of scarring in a liquid environment in the Yorkshire pig, Wound Rep.Reg. 17, 806-816 (2009). https://doi.org/10.1111/j.1524-475X.2009.00546.x
  10. A. Cho Lee and H.K. Moon, Controlled partial skin thickness burns: rabbit ear as a 2nd degree burn wound model for studies of topical therapy, J Kor. Pharm. Sci., 36, 339-342 (2006).
  11. B.M. Stramer, R Mori and P. Martin, The inflammation-fibrosis link? A Jekyll and Hyde role for blood cells during wound repair, J. Invest. Dermatol., 127, 1009-1017 (2007). https://doi.org/10.1038/sj.jid.5700811

Cited by

  1. Local Silencing of Connective Tissue Growth Factor by siRNA/Peptide Improves Dermal Collagen Arrangements vol.15, pp.6, 2018, https://doi.org/10.1007/s13770-018-0166-2