Animal Model of Chronic Tympanic Membrane Perforation

Chronic tympanic membrane perforations (TMP) can be a source of significant morbidity from hearing loss, recurrent middle ear infections, changes in lifestyle, and risk of cholesteatoma formation. Laboratory experiments of TMP have been fraught by the rapid and high rate of spontaneous healing observed in animal models. There is controversy on the minimal time that perforations in animal models must have in order to be considered chronic TMP and thus have clinical relevance, with authors suggesting time periods of perforation patency of 8-12 weeks. In this article, we sought to create a clinically significant experimental model that could yield a high rate of perforation patency for at least 8 weeks. Animals undergoing acute TMP were exposed to three different experimental situations to delay the healing of the perforation: fractionated radiation, topical lipopolysaccharide application, and a combined dexamethasone and mitomycin C (DXM/MC) solution. In our study, the use of DXM/MC reliably produced TMP lasting at least 8 weeks in 86.48% of the cases without the need to reopen the perforation, infolding the edges of the membrane, or using physical barriers to prevent TMP closure. Histologically, the resulting perforated tympanum showed hyaline changes of the remnant tympanum and hyperkeratosis of the squamous epithelia of the external auditory canal. We believe that this model is reproducible and has potential use in experiments of delayed healing of TMP. Anat Rec, 303:619-625, 2020. © 2019 American Association for Anatomy.