Abstract
Objectives:
(1) Test the efficacy of a novel topical growth factor (GF) treatment, delivered by a bioabsorbable polymer, in animal models of chronic tympanic membrane (TM) perforation, Eustachian tube (ET) obstruction, and chronic suppurative otitis media (CSOM). (2) Describe the preclinical work forming the basis for a proposed clinical trial of topical GF treatment.
Methods:
Bilateral chronic TM perforations were created in our novel mouse model (n = 50) and stable at 3 months, using an inhibitor of epidermal growth factor receptor. One ear received topical GF polymer treatment and the other received polymer only. Another mice cohort (n = 42) had chronic perforations created and also surgical obstruction of the ET. A further mice cohort (n = 35) had CSOM created through the above procedure and inoculation of pseudomonas aeruginosa. These perforations and treatments were evaluated microscopically, histologically, and using cytokeratin immunohistochemistry. Toxicity and safety of our polymer and GF were evaluated using auditory brain stem responses (ABR) and otoacoustic emissions (OAE) at 8 weeks following treatment.
Results:
In the chronic TM perforation cohort, 92% (22 of 24) healed compared with 38% (10 of 26) of controls (polymer only) at 4 weeks (P < .01). In the chronic perforation cohort with ET obstruction, 94% (18 of 19) healed compared with 9% (2 of 23) of controls (polymer only) at 6 weeks (P < .01). The ABR and OAE of our cohorts returned to control levels at 8 weeks.
Conclusions:
We demonstrate the efficacy, safety, and nontoxicity of a novel GF treatment in animal models.
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