Cochlear implant material effects on inflammatory cell function and foreign body response

Foggia, Megan J.; Claussen, Alexander D.; Higgins, Timon; Vielman-Quevedo, Rene; Mostaert, Brian; Xu, Honghui; Kirk, Jonathon; Hansen, Marlan R.

doi:10.1016/j.heares.2022.108597

Cited by 10 publications

(3 citation statements)

References 33 publications

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“…( Kane et al, 2012 ) Importantly, the C57/B6 background mimics hearing loss patterns seen in many human CI candidates with post-lingual onset of high-frequency hearing loss. ( Jensen et al, 2022 ) One plausible explanation for our results is that macrophages play a protective role for SGNs in C57/B6 mice and in the absence of macrophages, early onset SGN degeneration is accelerated. Experiments inhibiting CSF1R with PLX5622 in mice with CBA/J background can provide additional insights into this issue.…”

Section: Discussionmentioning

confidence: 73%

Contribution of macrophages to intracochlear tissue remodeling responses following cochlear implantation and neural survival

Rahman,

Mostaert,

Hunger

et al. 2023

Preprint

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Introduction: Cochlear implants (CIs) restore hearing to deafened patients. The foreign body response (FBR) following cochlear implantation (post-CI) comprises an infiltration of macrophages, other immune and non-immune cells, and fibrosis into the scala tympani; a space that is normally devoid of cells. This FBR is associated with negative effects on CI outcomes including increased electrode impedances and loss of residual acoustic hearing. This study investigates the extent to which macrophage depletion by an orally administered CSF-1R specific kinase (c-FMS) inhibitor, PLX-5622, modulates the tissue response to CI and neural health. Materials and methods: 10-12-week-old CX3CR1+/GFP Thy1+/YFP mice on C57Bl6 background with normal hearing were fed chow containing 1200 mg/kg PLX5622 or control chow for the duration of the study. 7-days after starting the diet, 3-channel cochlear implants were implanted ear via the round window. Serial impedance and neural response telemetry (NRT) measurements were acquired throughout the study. Electric stimulation began 7 days post-CI until 28- days post-CI for 5 hrs/day, 5 days/week, with programming guided by NRT and behavioral responses. Cochleae harvested at 10-, 28- or 56-days post-CI were cryosectioned and labeled with antibody against α-smooth muscle actin (α-SMA) to identify myofibroblasts and quantify the fibrotic response. Using IMARIS image analysis software, the outlines of scala tympani, Rosenthal canal, modiolus and lateral wall for each turn were traced manually to measure region volume. Density of nuclei, CX3CR1+ macrophages, Thy1+ spiral ganglion neuron (SGN) numbers and ratio of volume of α-SMA+ space/volume of scala tympani were calculated. Results: Cochlear implantation in control diet subjects caused infiltration of cells, including macrophages, into the cochlea: this response was initially diffuse throughout the cochlea and later localized to the scala tympani of the basal turn by 56-days post-CI. Fibrosis was evident in the scala tympani adjacent to the electrode array. Mice fed PLX5622 chow showed reduced macrophage infiltration throughout the implanted cochleae across all timepoints. However, scala tympani fibrosis was not reduced relative to control diet subjects. Further, mice treated with PLX5622 showed increased electrode impedances compared to controls. Finally, treatment with PLX5622 decreased SGN survival in implanted and contralateral cochleae. Discussion: The data suggest that macrophages play an important role in modulating the intracochlear tissue response following CI and neural survival.

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Section: Discussionmentioning

confidence: 73%

Contribution of macrophages to intracochlear tissue remodeling responses following cochlear implantation and neural survival

Rahman,

Mostaert,

Hunger

et al. 2023

Preprint

Self Cite

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“…However, as a common complication, postoperative fibrosis in the cochlea impairs the long‐term outcome of CI 3 . Fibrous tissue grows up over time, forming a dense fibrous sheath around the CI electrode 4 .…”

Section: Introductionmentioning

confidence: 99%

“…However, as a common complication, postoperative fibrosis in the cochlea impairs the long‐term outcome of CI. 3 Fibrous tissue grows up over time, forming a dense fibrous sheath around the CI electrode. 4 It increases the impedance of CI circles, leading to a decreased dynamic range of stimulation 5 and decreased CI battery life.…”

Section: Introductionmentioning

confidence: 99%

Electrical stimulation of cochlear implant promotes activation of macrophages and fibroblasts under inflammation

Zhang,

Chen,

Wang

et al. 2023

Laryngoscope Investig Oto

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ObjectivesThe implanted electrodes deliver electric signals to spiral ganglion neurons, conferring restored hearing of cochlear implantation (CI) recipients. Postimplantation intracochlear fibrosis, which is observed in most CI recipients, disturbs the electrical signals and impairs the long‐term outcome of CI. The macrophages and fibroblasts activation is critical for the development of intracochlear fibrosis. However, the effect of electric stimulation of cochlear implant (ESCI) on the activity of macrophages and fibroblasts was unclear. In the present study, a human cochlear implant was modified to stimulate cultured macrophages and fibroblasts.MethodsBy measuring cellular marker and the expression level of cytokine production, the polarization and activity of macrophages and fibroblasts were examined with or without ESCI.ResultsOur data showed that ESCI had little effects on the morphology, density, and distribution of culturing macrophages and fibroblasts. Furthermore, ESCI alone did not affect the polarization of macrophages or the function of fibroblasts without the treatment of inflammatory factors. However, in the presence of LPS or IL‐4, ESCI further promoted the polarization of macrophages, and increased the expression of pro‐inflammatory or anti‐inflammatory factors, respectively. For fibroblasts, ESCI further increased the collagen I synthesis induced by TGF‐β1 treatment. Nifedipine inhibited ESCI induced calcium influx, and hereby abolished the promoted polarization and activation of macrophages and fibroblasts.ConclusionOur results suggest that acute inflammation should be well inhibited before the activation of cochlear implants to control the postoperative intracochlear fibrosis. The voltage‐gated calcium channels could be considered as the targets for reducing postimplantation inflammation and fibrosis.Level of EvidenceNA.

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Reducing the foreign body response on human cochlear implants and their materials in vivo with photografted zwitterionic hydrogel coatings

et al. 2023

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Cochlear implant material effects on inflammatory cell function and foreign body response

Cited by 10 publications

References 33 publications

Contribution of macrophages to intracochlear tissue remodeling responses following cochlear implantation and neural survival

Contribution of macrophages to intracochlear tissue remodeling responses following cochlear implantation and neural survival

Electrical stimulation of cochlear implant promotes activation of macrophages and fibroblasts under inflammation

Reducing the foreign body response on human cochlear implants and their materials in vivo with photografted zwitterionic hydrogel coatings

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