Anti-fibrotic drugs reduce the extent of cochlear implant-induced fibrosis in an <em>in vivo </em>guinea pig model of cochlear implantation. — The Association Specialists
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  3. Anti-fibrotic drugs reduce the extent of cochlear implant-induced fibrosis in an in vivo guinea pig model of cochlear implantation.

Anti-fibrotic drugs reduce the extent of cochlear implant-induced fibrosis in an in vivo guinea pig model of cochlear implantation. (21547)

Kady J Braack 1 , Tylah Miles 2 , Kelly Short 3 , Jafri Kuthubutheen 4 5 , Marcus D Atlas 6 7 , Lee Yong Lim 8 , Wilhelmina H.A.M Mulders 1 , Cecilia M Prêle 2 3
  1. School of Human Sciences, University of Western Australia, Crawley 6009, WA, Australia
  2. Institute for Respiratory Health, University of Western Australia, Crawley 6009, WA, Australia
  3. School of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch 6150, WA, Australia
  4. Medical School, University of Western Australia, Crawley 6009, WA, Australia
  5. Department of Otolaryngology Head and Neck Surgery, Sir Charles Gairdner Hospital, Nedlands 6009, WA, Australia
  6. Ear Science Institute, Subiaco 6008, WA, Australia
  7. Centre for Ear Science, Medical School, University of Western Australia, Crawley 6009, WA, Australia
  8. School of Allied Health, Pharmacy, University of Western Australia, Crawley 6009, WA, Australia

Cochlear implants allow restoration of sound perception in individuals with severe to profound hearing loss; however, there is still significant variability in patient outcomes. One potential factor that may account for this unexplained variability is the formation of fibrosis within the cochlea after implantation. The current study investigated the effect of a small molecule inhibitor, with known antifibrotic properties, on the extent of fibrosis after cochlear implantation. The drug was delivered in a novel hydrogel formulation to allow for sustained release of the drug into the cochlea. The therapeutic potential of the drug was assessed using a guinea pig model of cochlear implantation, wherein the drug (n=9) or vehicle (n=13) was applied locally to the round window membrane immediately following insertion of a dummy cochlear implant via a cochleostomy. The extent of intracochlear tissue reaction was quantified using micro–CT before and after contrast staining with osmium tetroxide. Compound action potential thresholds of the auditory nerve were used to assess the effect of drug/implant on hearing thresholds. Drug treatment had a statistically significant effect on the sum of total tissue reaction, with drug treated animals showing a 54% (pre-osmium) and 42% (post-osmium) decrease when compared to controls. This effect was localised to areas close to the round window membrane, where the drug was applied. The drug treated group showed no significant changes in hearing thresholds compared to controls. In summary, we have developed an effective and novel anti-fibrotic drug-hydrogel formulation that reduces the extent of the cochlear implant-induced tissue response.