| Background: Tympanic membrane (TM) perforation is a common condition that afflicts ~1% of the world population.Management of chronic TM perforations has traditionally required tympanoplasty, a surgical intervention. Tympanoplasty is successful in > 90% of patients, but concerns with this procedure include operative risks, cost, and the lack of technical resources in developing countries. These issues warrant investigation into non-surgical alternatives to tympanoplasty. Recent studies have suggested that growth factors may be an effective non surgical alternative for treating chronic TM perforations. Epidermal growth factor is an important modulator of cell growth, and its role in normal wound healing is well documented. Epidermal growth factor receptors have been identified in tympanic membranes of different animals. The ability of epidermal growth factor to promote healing of tympanic membrane perforations has recently been shown in experimental animals. Objective: To develop.an animal model of chronic TM perforation in the guinea pig and to assess the efficacy of EGF in the treatment of chronic nonhealing perforations in the animal model. Method: ①35 guinea pigs (1–2 years old, 400 to 600 g) were used,and 5 guinea pigs served as normal contral. All animals were anesthetized with ketamine (100 mg/kg), then bilateral central perforations were created in 30 guinea pigs by excising 80% of the tympanic membrane with a thermal needle. The animals were observed for 10-week to ensure chronicity of the TM perforations. After 4 weeks, the perforation sizes were assessed. Perforations constituting < 50% of the TM surface area were enlarged to ~80% by using the thermal needle. After another 6 weeks of observation, the size of the perforations was evaluated by otomicroscopy and photographically documented. Ten weeks after we created the TM perforations, guinea pigs with TM perforations >50% of total surface area are a persisted for 10 weeks in 44 ears. ②All TM perforations were treated by removing their epithelial free margins and packing the middle ears and external ear canals with a large Gelfoam pledget which was placed over the TM perforation in contact with both the TM remnant and medial ear canal wall.Left ears served as experimental ears and right ears served as their controls. In left ears, 150 μL of rhEGF was applied topically via a graduated micropipette. In right ears, 150 μL of NS was applied to the Gelfoam pledget Repeat doses of 150 mL of either the EGF solution or NS alone were administered every other day for a total of five doses for each ear. To discourage infection, intramuscular injections of ampicillin sodium (150 mg/kg) were given on treatment days.The Gelfoam in the external ear canal was removed from the external ear canal after ten days All guinea pigs were killed after 3-month ,then the temporal bones of every animals were fixed in 10% formalin, decalcified, sectioned at 3 μm; every eighth section was stained with hematoxylin-eosin and examined histologically Frequency data (TM perforations healed vs. nonhealed) were analyzed with McNemar's [chi]~2 analysis. Tympanic Membrane Thickness were analyzed with One-way ANOVA Results: 1 . 10 weeks after the initial excision, 44 of 60(73.3%) TM perforations remained at >= 50% of TM area . Forty-four ears were enteredinto the protocol, and one animal was lost because of anesthetization.16 ears were included in the analysis.because of otitis media and other reasons . 2.Statistical difference between treated and control ears in the incidence of perforation closure was evident (p <0.05) .Closure of TM perforations was achieved in 76.2 percent (16/21) of EGF-treated ears versus 21.7 percent (5/23) of control ears. 3.The normal guinea pig TM is very similar to the human TM, consisting of a trilaminar structure composed of stratified keratinizing squamous epithelium on the lateral surface; a lamina propria, containing dense fibrous connective tissue with an outer radiate and inner circular fiber arrangement; and a medial mucosal layer contiguous w...
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