Establishment And Identification An Animal Model With Chronic Tympanic Membrane Perforation In Rats

Objectives: Chronic tympanic membrane perforation（TMP）is a common disease in otolaryngology.At present,surgical repair（e.g.myringoplasty）with autologous grafts is the main treatment for the chronic TMPs.Currently,the use of novel biomaterials provides new options for the repair of chronic TMPs.A reliable animal model of chronic TMP is essential to evaluate the efficacy and safety of these therapeutic approaches prior to the clinical trials.Hence,the purpose of this study is to investigate two types of animal models with chronic TMPs. Methods: Sixty male Sprague-Dawley rats were randomly divided into three experimental groups following traumatic perforation of the eardrums:（1）VTMD group（n=20）: Implant of ventilation tube in conjunction with topical application of mitomycin C and dexamethasone;（2）MMPID group（n=20）: Topical application of MMPI and dexamethasone;（3）control group（n=20）: No treatment after TMP.Another group of ten rats were involved as normal controls to examine the hearing thresholds.The animals were evaluated by otoscopy,histology,and auditory brainstem response（ABR）at 8 weeks postoperatively. Results: In this study,the VTMD group demonstrated nineteen out of twenty rats（95%）with chronic TMPs whereas the MMPID group only presented two out of twenty rats（10%）with chronic perforations at 8 weeks post-surgery.By contrast,all perforations were completely closed in the control group.ABR testing revealed that there were no significant differences in hearing thresholds among three groups prior-and post-perforation of the eardrums（P > 0.05）.On week 8postoperatively,hearing threshold in the VTMD group was significantly higher compared against the other three groups（P<0.001）,suggesting the presence of chronic TMPs resulting in hearing loss.Histologically,the outer squamous epithelium at the perforation edge merged with the inner mucosal epithelium forming a joint-like structure in the VTMD group.However,the TMPs in the MMPID group completely healed while the squamous epithelium at the perforation site was still thickened infiltration with a few inflammatory cells. Conclusion: In this study,the use of ventilation tube implantation in conjunction with topical application of mitomycin C and dexamethasone successfully established an animal model with chronic TMPs in rats.However,the usage of topical application of MMPI and dexamethasone failed to create such animal model.