Long-term mitigation of the foreign-body response with dexamethasone-eluting cochlear implants in mice
- 1University of Iowa
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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BibTeX
@misc{alluri2026longterm,
title = {{Long-term mitigation of the foreign-body response with dexamethasone-eluting cochlear implants in mice}},
author = {A. Alluri and B. Hunger and m. F. Hossain and S. M. Fatima and M. T. Rahman and R. Gay and B. J. Mostaert and Y. L. Enke and M. R. Hansen and A. D. Claussen},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.26.747195},
url = {https://www.biorxiv.org/content/10.64898/2026.08.26.747195v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Long-term mitigation of the foreign-body response with dexamethasone-eluting cochlear implants in mice
AU - A. Alluri
AU - B. Hunger
AU - m. F. Hossain
AU - S. M. Fatima
AU - M. T. Rahman
AU - R. Gay
AU - B. J. Mostaert
AU - Y. L. Enke
AU - M. R. Hansen
AU - A. D. Claussen
PY - 2026
DA - 2026/08/26
PB - bioRxiv
DO - 10.64898/2026.08.26.747195
UR - https://www.biorxiv.org/content/10.64898/2026.08.26.747195v1
AB - 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.
ER -