title: A novel murine model of hypertrophic scarring using subcutaneous infusion of bleomycin.
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.
authors.affiliation: 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.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Cameron
authors.forename: Damian H
authors.initials: DH
authors.lastname: Adams
authors.forename: John E
authors.initials: JE
authors.lastname: Greenwood
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Anderson
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Cowin
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity*; D017439:Cicatrix, Hypertrophic / Q000139:chemically induced* / Q000473:pathology*; D020405:Dermis / Q000473:pathology; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D007260:Infusion Pumps; D055104:Infusions, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D015203:Reproducibility of Results
chemical_list: D000903:Antibiotics, Antineoplastic; D001761:Bleomycin