Silk Devices for Tympanic Membrane Repair Show No Ototoxicity in a Rat Model.

Hypothesis: Implantation of ClearDrum ® , a biodegradable silk fibroin device, into the middle ear (ME) cavity in a rat model will not affect hearing thresholds as measured by auditory brainstem response.

Background: Chronic otitis media (COM) is a recurrent middle ear infection often accompanied by tympanic membrane perforation. Our laboratory has developed a biodegradable silk fibroin device (ClearDrum®) designed to treat tympanic membrane perforations in COM. ClearDrum ® acts as a prosthetic eardrum, providing a substrate on which tympanic membrane cells can grow and acts as a long-lasting implant.

Methods: Two formulations were tested based on silk/glycerol and silk/polyurethane blends. Animals were anesthetized, and either a ClearDrum ® formulation or an autologous cartilage graft was surgically implanted into the middle ear. Thresholds of the auditory brainstem response (ABR) were measured at the time of implantation and at 4 and 12 weeks post-implantation to assess hearing after the implantation. After the final measurements at 12 weeks, middle ear and cochlea were harvested for histological assessment.

Results: No significant differences in ABR thresholds between male and female animals were found at any timepoint. Results showed that there were no detrimental effects of either Cleardrum ® formulation on ABR thresholds as compared with implantation of autologous cartilage and no presence of inflammation within the middle ear or cochlea.

Conclusion: Our ABR data suggest no substantial ototoxic effects on outer or inner hair cells and provides some support toward clinical translation of ClearDrum devices.