title: Effect of P144® (Anti-TGF-β) in an "In Vivo" Human Hypertrophic Scar Model in Nude Mice.
abstract: BACKGROUND
  Hypertrophic scars are one of the most important complications in surgery due to their cosmetic and functional impairments. Previous studies in tissue fibrotic disorders have shown promising results by inhibiting the biological activity effect of Transforming Growth Factor-beta 1 (TGF-β1). The aim of the current study was to determine the clinical effect of the inhibition of TGF-β1 signaling in human hypertrophic scars implanted in nude mice by topical application of an inhibitor of TGF-β1 (P144®).
  
  
  METHODS
  A total of 30 human hypertrophic scars were implanted in 60 nude mice. The animals were divided in two groups, group A (placebo) and group B (treatment). Group C (basal) was considered as the preimplanted scar samples and they were not implanted in the nude mice. After the shedding period, topical application of a lipogel containing placebo (group A) or P144 (group B) was daily administered during two weeks. The animals were sacrificed upon completion of the study. Total area, thickness and collagen fibers area were measure and compared across all groups. Immunohistochemistry was also performed in order to quantify collagen type I and type III and elastic fiber expressions present in the dermis.
  
  
  RESULTS
  Successful shedding was achieved in 83,3% of the xenografts. The mean time for shedding was 35±5.4 days. Statistically significant differences were found in the total area, collagen fibers area and thickness between the groups. Increased elastic fibers and decreased collagen I were found in the P144-treated group compared to the basal group.
  
  
  CONCLUSIONS
  Topical application of an inhibitor of TGF-β1 may promote scar maturation and clinical improvement of hypertrophic scar morphology features in an "in vivo" model in nude mice after two weeks of treatment.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Shan Shan
authors.initials: SS
authors.lastname: Qiu
authors.affiliation: Digna Biotech S.L., Pamplona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Dotor
authors.affiliation: Department of Plastic and Reconstructive Surgery, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Hontanilla
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D000071837:Fibrillins; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D000071837:Fibrillins; D008840:Microfilament Proteins; D016212:Transforming Growth Factor beta; D003094:Collagen