Long-term mitigation of the foreign-body response with dexamethasone-eluting cochlear implants in mice

Alluri, A.; Hunger, B.; Hossain, m. F.; Fatima, S. M.; Rahman, M. T.; Gay, R.; Mostaert, B. J.; Enke, Y. L.; Hansen, M. R.; Claussen, A. D.

doi:10.64898/2026.08.26.747195

bioRxiv · 10.64898/2026.08.26.747195

Long-term mitigation of the foreign-body response with dexamethasone-eluting cochlear implants in mice

Alluri, A.·Hunger, B.·Hossain, m. F.·Fatima, S. M.·Rahman, M. T.·Gay, R.·Mostaert, B. J.·Enke, Y. L.·Hansen, M. R.·Claussen, A. D.

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Abstract

The inflammatory foreign body response that follows cochlear implantation produces intracochlear fibrosis, neo-ossification, and elevated electrode impedances that can compromise implant performance. Dexamethasone-eluting cochlear implants reduce this response, but the durability of their anti-inflammatory effect over long implantation intervals has not been established. Using a murine model of chronic cochlear implantation in CX3CR1+/eGFP Thy1+/eYFP dual-reporter mice, we compared dexamethasone-eluting and standard mouse cochlear implants at 224 and 336 days post-implantation. Density of CX3CR1+ macrophages, MHCII+CX3CR1+ antigen-presenting macrophages, -SMA+ fibrosis, and neo-ossification were quantified in the scala tympani, Rosenthal canal, and lateral wall of the basal turn. Standard implants produced persistent macrophage and antigen-presenting macrophage infiltration, accompanied by an -SMA+ fibrotic response and neo-ossification. Dexamethasone-eluting implants suppressed macrophage infiltration in all three regions out to 336 days and reduced fibrosis at 224 days. In the subset of cochleae with electrode array translocation, dexamethasone-eluting implants attenuated macrophage infiltration and confined the fibrotic and osseous response to the site of translocation, whereas standard implants produced a widespread response. A reduction in immune cell density was also observed in the contralateral, unimplanted cochleae of animals implanted with dexamethasone-eluting implants, suggesting a wider component to the drug's effect. Dexamethasone-eluting cochlear implants therefore provide sustained, long-term suppression of the cochlear foreign body response in mice, supporting their continued translation toward clinical application. This effect was associated with continued low-level dexamethasone elution out to 336 days post-implantation; further work is needed to assess the durability of this effect at the conclusion of drug elution.

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Alluri, A., Hunger, B., Hossain, m. F., Fatima, S. M., Rahman, M. T., Gay, R., Mostaert, B. J., Enke, Y. L., Hansen, M. R., Claussen, A. D.. 2026-09-01. Long-term mitigation of the foreign-body response with dexamethasone-eluting cochlear implants in mice. https://doi.org/10.64898/2026.08.26.747195

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