The Effects of Hyaluronic Acid, Epidermal Growth Factor, and Mitomycin in an Experimental Model of Acute Traumatic Tympanic Membrane Perforation

Hypothesis The goal of this study was to evaluate the effects of hyaluronic acid, epidermal growth factor, and mitomycin C on the healing of acute experimental traumatic perforations of the tympanic membrane. Background Most acute perforations of the tympanic membrane heal spontaneously. However, some form of surgical treatment (i.e., myringoplasty) is needed for nonhealing perforations. Because the closure occurs by squamous epithelial migration, drugs that stimulate this regenerative process may aid in the closure of the perforation, obviating the need for more extensive treatments. Methods Bilateral perforations of the tympanic membrane were created in 30 rats, divided into three groups (A, B, C). The perforations in the right ears were treated with hyaluronic acid, epidermal growth factor, or mitomycin C. Those in the left ears were left untreated for comparison. To examine the healing process in different periods, 5 animals were killed in each group at days 3, 5, 7, 9 and 14. The other 5 animals in each group were observed daily to determine the duration of perforation closures. Thirty surgical specimens (5 right sides from each group and all 15 left sides in all groups) were histopathologically examined for tympanic membrane thickness, fibroblastic reaction, neovascularization, and crust morphology. Results Hyaluronic acid and epidermal growth factor applications significantly shortened the healing in acute experimental traumatic perforations of the tympanic membrane (p = 0.0432); however, the difference between them was not significant (p = 0.3160). On the other side, tympanic membrane perforations treated with topical mitomycin C showed no evidence of closure. There were no significant differences in the histologic parameters between the treated groups and their contralateral control ears. Conclusion Hyaluronic acid and epidermal growth factor accelerated the closure of acute tympanic membrane perforations in rats. This may make them clinically useful in augmenting the efficiency of conservative treatments of acute perforations of the tympanic membrane.