title: Animal models of chronic tympanic membrane perforation: a 'time-out' to review evidence and standardize design.
abstract: OBJECTIVE
  To review the literature on techniques for creation of chronic tympanic membrane perforations (TMP) in animal models. Establishing such models in a laboratory setting will have value if they replicate many of the properties of the human clinical condition and can thus be used for investigation of novel grafting materials or other interventions.
  
  
  METHODS
  A literature search of the PubMed database (1950-August 2014) was performed. The search included all English-language literature published attempts on chronic or delayed TMP in animal models. Studies of non English-language or acute TMP were excluded.
  
  
  RESULTS
  Thirty-seven studies were identified. Various methods to create TMP in animals have been used including infolding technique, thermal injury, re-myringotomy, and topical agents including chemicals and growth factor receptor inhibitors. The most common type of animal utilized was chinchilla, followed by rat and guinea pig. Twenty three of the 37 studies reported success in achieving chronic TMP animal model while 14 studies solely delayed the healing of TMP. Numerous experimental limitations were identified including TMP patency duration of <8 weeks, lack of documentation of total number of animals attempted and absence of proof for chronicity with otoscopic and histologic evidence.
  
  
  CONCLUSIONS
  The existing literature demonstrates the need for an ideal chronic TMP animal model to allow the development of new treatments and evaluate the risk of their clinical application. Various identified techniques seem promising, however, a need was identified for standardization of experimental design and evidence to address multiple limitations.
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: allenwang_@hotmail.com.
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.
authors.forename: Jeffrey T
authors.initials: JT
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, Skull Base Surgery, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Friedland
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: D000818:Animals; D035843:Biomedical Research / Q000592:standards*; D002682:Chinchilla; D002908:Chronic Disease; D004195:Disease Models, Animal; D006168:Guinea Pigs; D051381:Rats; D012107:Research Design / Q000592:standards*; D018058:Tympanic Membrane Perforation / Q000209:etiology*; D014945:Wound Healing
keywords: Animal model; Chronic; Otology; Surgery; Tympanic membrane; Tympanic membrane perforation