In the search for an effective animal model of hypertrophic burn scarring

Mitchell Nash1, Prof. Andrew Holland2, Prof. John Harvey3

1 Burn Fellow Westmead Children’s Hospital Sydney, Westmead, NSW, 2145, mitchellnash@gmail.com
2 Prof. of Paediatric Surgery, Children’s Hospital Sydney, Westmead, NSW, 2145, Andrew.Holland@health.nsw.gov.au
3 Head of Burns Unit, Children’s Hospital Sydney, Westmead, NSW, 2145, John.Harvey@health.nsw.gov.au

Hypertrophic scarring (HTS) is characterised by the development of a thick red raised itchy scar. HTS is particularly common in children following a burn injury with an incidence of 20% in burns that heal under 21 days and over 90% when healing is delayed beyond 40 days. Recent laser therapy has shown some promise as an effective therapy (3), however, there are no randomised controlled trials and very little experimental evidence to support its use(4). In order to help develop and evaluate effective alternative treatments the search for an effective reproducible animal model for hypertrophic burns scars has been ongoing for more that 35 years (5).

The porcine model is well supported in the literature as the best available animal model for investigating human skin burns in terms of histological match, immunohistochemistry, scar formation, cost effectiveness and housing/experimental practicality (5-8). The Red Duroc pig strain was selected as the strain has been well validated by the Harborview Medical Centre group (9-12). We report a novel technique of using a skin expander underneath a contact thermal burn to create constant tension on the burn wound to develop reproducible HTS. This concept was extrapolated from a paper by Aarabi et al which concluded that “mechanical loading early in the proliferative phase of wound healing produces hypertrophic scars by inhibiting cellular apoptosis through an Akt-dependent mechanism”13. This was identified using an external frame to expand the wound

We will report the histological and immunochemistry findings of these expanded burn wound as compared to a control (non-expanded) burn. These experiments were conducted with ethical approval from Westmead Children’s Hospital.

References

  1. Cubison TC, Pape SA, Parkhouse N. Evidence for the link between healing time and the development of hypertrophic scars (HTS) in paediatric burns due to scald injury. Burns. 2006;32(8):992-9.
  2. Berman B, Viera MH, Amini S, Huo R, Jones IS. Prevention and management of hypertrophic scars and keloids after burns in children. J Craniofac Surg. 2008;19(4):989-1006.
  3. Anderson RR, Donelan MB, Hivnor C, Greeson E, Ross EV, Shumaker PR, et al. Laser treatment of traumatic scars with an emphasis on ablative fractional laser resurfacing: consensus report. JAMA Dermatol. 2014;150(2):187-93.
  4. Kaufmann R, Hibst R. Pulsed 2.94-microns erbium-YAG laser skin ablation–experimental results and first clinical application. Clin Exp Dermatol. 1990;15(5):389-93.
  5. Meyer W, Schwarz R, Neurand K. The skin of domestic mammals as a model for the human skin, with special reference to the domestic pig. Curr Probl Dermatol. 1978;7:39-52.
  6. Ramos ML, Gragnani A, Ferreira LM. Is there an ideal animal model to study hypertrophic scarring? J Burn Care Res. 2008;29(2):363-8.
  7. Kempf M, Cuttle L, Liu PY, Wang XQ, Kimble RM. Important improvements to porcine skin burn models, in search of the perfect burn. Burns. 2009;35(3):454-5.
  8. Rapp SJ, Rumberg A, Visscher M, Billmire DA, Schwentker AS, Pan BS. Establishing a Reproducible Hypertrophic Scar following Thermal Injury: A Porcine Model. Plast Reconstr Surg Glob Open. 2015;3(2):e309.
  9. Engrav LH, Tuggle CK, Kerr KF, Zhu KQ, Numhom S, Couture OP, et al. Functional genomics unique to week 20 post wounding in the deep cone/fat dome of the Duroc/Yorkshire porcine model of fibroproliferative scarring. PLoS One. 2011;6(4):e19024.
  10. Harunari N, Zhu KQ, Armendariz RT, Deubner H, Muangman P, Carrougher GJ, et al. Histology of the thick scar on the female, red Duroc pig: final similarities to human hypertrophic scar. Burns. 2006;32(6):669-77.
  11. Zhu KQ, Engrav LH, Gibran NS, Cole JK, Matsumura H, Piepkorn M, et al. The female, red Duroc pig as an animal model of hypertrophic scarring and the potential role of the cones of skin. Burns. 2003;29(7):649-64.
  12. Zhu KQ, Carrougher GJ, Gibran NS, Isik FF, Engrav LH. Review of the female Duroc/Yorkshire pig model of human fibroproliferative scarring. Wound Repair Regen. 2007;15 Suppl 1:S32-9.
  13. Aarabi S, Bhatt KA, Shi Y, Paterno J, Chang EI, Loh SA, Gurtner GC et al. Mechanical load initiates hypertrophic scar formation through decreased cellular apoptosis. FASEB J. 2007;21(12):3250-61.

Key Words

Hypertrophic Scar, Porcine, Laser

Biography

Burns Registrar at Royal North Shore Hospital Sydney. Previous experience at Concord Burns Unit and Westmead Children’s Burns Unit.

About ANZBA

ANZBA is a not for profit organisation and the peak body for health professionals responsible for the care of the burn injured in Australia and New Zealand. ANZBA encourages higher standards of care through education, performance monitoring and research.

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