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A Novel Murine Model of Hypertrophic Scarring Using Subcutaneous Infusion of Bleomycin

Cameron, Alexander M. M.B.B.S., B.Med.Sci.; Adams, Damian H. B.Biotech.(Hons.); Greenwood, John E. M.B.Ch.B., M.D.; Anderson, Peter J. M.D., Ph.D.; Cowin, Allison J. Ph.D.

Plastic & Reconstructive Surgery:
doi: 10.1097/01.prs.0000436821.26709.a7
Experimental: Original Articles
Abstract

Background: The development of new therapies for hypertrophic scarring has been hampered by the lack of an appropriate animal model. The authors’ objective was to establish a reproducible murine model of hypertrophic scarring by infusing bleomycin over a prolonged period to stimulate dermal fibroproliferation.

Methods: Osmotic pumps filled with 90 μl of 2.8 mg/ml bleomycin or a control solution (phosphate-buffered saline) were inserted subcutaneously under the dorsal skin of BALB/c mice. The pumps delivered their content at a constant rate of 0.11 μl/hour for 28 days before mice were euthanized or kept alive for a further 28 days and euthanized at day 56. The resulting lesions were analyzed using histological and immunohistochemical techniques.

Results: The lesions displayed histopathological features of hypertrophic scar similar to those observed in humans and had increased cellularity, abnormal collagen I–collagen III ratios, elevated levels of the proscarring cytokine transforming growth factor β1, and increased numbers of myofibroblasts. The 28-day model displayed features analogous to those of a developing human hypertrophic scar, while the 56-day model was analogous to a mature hypertrophic scar.

Conclusions: The bleomycin infusion model stimulates dermal fibroproliferation, creating reproducible murine scars that are comparable to human hypertrophic scars in terms of histological features, collagen content and organization, cellularity, the presence of myofibroblasts, and expression of transforming growth factor β1. The bleomycin model represents a promising technique for studying scar formation and testing new antiscarring therapies.

Author Information

Mawson Lakes, Adelaide, and North Adelaide, South Australia, Australia

From the Center for Regenerative Medicine, Mawson Institute, University of South Australia; the Disciplines of Surgery and Pediatrics, School of Medicine, Faculty of Health Sciences, The University of Adelaide; the Adult Burns Service, Royal Adelaide Hospital; and the Australasian Craniofacial Unit, Women’s and Children’s Hospital.

Received for publication May 7, 2013; accepted June 26, 2013.

Presented in part at the Wound Healing Society 22nd Annual Meeting, in Atlanta, Georgia, April 19 through 22, 2012 (Young Investigator Award finalist and Travel Scholarship recipient); Royal Australasian College of Surgeons 81st Annual Scientific Congress, in Kuala Lumpur, Malaysia, May 6 through 10, 2012; the 36th Annual Scientific Meeting of the Australian and New Zealand Burn Association, in Hobart, Australia, October 9 through 12, 2012 (Best Scientific Presentation runner-up); Conjoint Third Australian Wound and Tissue Repair Society and Ninth Australian Society for Dermatological Research Conference, in Sydney, Australia, May 22 through 24, 2012 (Travel Scholarship recipient).

Disclosure: The authors have no financial interest to declare in relation to the content of this article.

Alexander M. Cameron, M.B.B.S., B.Med.Sci., Center for Regenerative Medicine, Mawson Institute, Building V, University of South Australia, Mawson Lakes Campus, Mawson Lakes Boulevard, Mawson Lakes, South Australia, Australia 5095, alexander.cameron@adelaide.edu.au

©2014American Society of Plastic Surgeons