title: Rat model of chronic tympanic membrane perforation: Ventilation tube with mitomycin C and dexamethasone.
abstract: OBJECTIVE
  Chronic tympanic membrane perforation (TMP) in a clinical setting may attract surgical intervention. With the advent of modern biomaterials, new options are available for myringoplasty but safety and efficacy need evaluation in a chronic TMP animal model. The aim of this study was to evaluate the efficacy of ventilation tube (VT) insertion in conjunction with topical application of mitomycin C/dexamethasone (M/D) for the creation of chronic TMP in rats.
  
  
  METHODS
  Thirty male Sprague-Dawley rats underwent myringotomy of the right tympanic membrane (TM) and were divided into three experimental groups: spontaneous healing (myringotomy control), VT insertion for 2 weeks and VT insertion for 2 weeks in conjunction with topical application of M/D (VT-M/D). All TMs were regularly assessed by otoscopy for 10 weeks and then animals were sacrificed for histological evaluation.
  
  
  RESULTS
  In the VT-M/D group, seven out of ten (70%) perforations were patent at 10 weeks (mean patency, 57.9 days; P<0.01). The VT group had two out of ten (20%) perforations patent at 10 weeks (mean patency, 26.5 days; P<0.01), while all TMPs from the myringotomy control group were closed by day 9 (mean patency, 7.2 days). Histologically, the TMPs patent at week 10 had a stratified squamous epithelialized rim, keratinocyte layer thickening around the perforation edge as well as increased collagen deposition and macrophage infiltration.
  
  
  CONCLUSIONS
  Chronic TMP in a rat model was successfully created by VT insertion and the efficacy was increased in combination with topical application of M/D.
authors.affiliation: Ear Sciences Centre, School of Surgery, The University of Western Australia, Perth, Western Australia, Australia; Ear Science Institute Australia, Perth, Western Australia, Australia; Department of Otolaryngology, Head and Neck, Skull Base Surgery, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia. Electronic address: allen.wang@earscience.org.au.
authors.forename: Allen Y
authors.initials: AY
authors.lastname: Wang
authors.affiliation: Ear Sciences Centre, School of Surgery, The University of Western Australia, Perth, Western Australia, Australia; Ear Science Institute Australia, Perth, Western Australia, Australia; Department of Otolaryngology, Head and Neck Surgery, Ningbo Lihuili Hospital (Ningbo Medical Centre), Ningbo, Zhejiang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Ear Sciences Centre, School of Surgery, The University of Western Australia, Perth, Western Australia, Australia; Ear Science Institute Australia, Perth, Western Australia, Australia.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Liew
authors.affiliation: Ear Sciences Centre, School of Surgery, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Wang
authors.affiliation: Akershus University Hospital and University of Oslo, Norway; Center for Clinical Research Västerås, University of Uppsala, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: von Unge
authors.affiliation: Ear Sciences Centre, School of Surgery, The University of Western Australia, Perth, Western Australia, Australia; Ear Science Institute Australia, Perth, Western Australia, Australia; Department of Otolaryngology, Head and Neck, Skull Base Surgery, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Atlas
authors.affiliation: Ear Sciences Centre, School of Surgery, The University of Western Australia, Perth, Western Australia, Australia; Ear Science Institute Australia, Perth, Western Australia, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Dilley
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002908:Chronic Disease; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D008297:Male; D008876:Middle Ear Ventilation; D016685:Mitomycin / Q000494:pharmacology; D009225:Myringoplasty; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D038781:Otoscopy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014432:Tympanic Membrane / Q000187:drug effects* / Q000601:surgery*; D018058:Tympanic Membrane Perforation / Q000473:pathology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D019384:Nucleic Acid Synthesis Inhibitors; D016685:Mitomycin; D003907:Dexamethasone
keywords: Animal model; Chronic; Dexamethasone; Mitomycin C; Tympanic membrane perforation; Ventilation tube