Biology subjects

Claussen, A. D.

Publications and source records attributed to Claussen, A. D..

4 recordsLinked to original sources

bioRxiv2026

Establishment of a cochlear lymphatic vascular network and immune surveillance system following cochlear implantation

Hearing loss is a highly prevalent sensory abnormality often addressed with cochlear implants (CI) that provide auditory rehabilitation for deaf patients. However, a universal inflammatory foreign body response (FBR) to the implanted materials negatively impacts CI outcomes. The mechanistic basis for immune cell infiltration and propagation of the FBR directed against CIs is not defined. Using mouse CI models and quantitative, highly tractable reporters for lymphatics, blood vessels, and immune cells, we identify inner ear lymphatic vessels and changes to the immune surveillance system following cochlear implantation. Histopathological analysis of implanted temporal bones from human subjects shows that both blood vessels and lymphatics are evident within the scala tympani of the implanted cochlea. Our data reveal a rich lymphatic vascular network in the inner ear, closely associated with the perilymphatic and endolymphatic spaces. Lymphatics proliferate within the perilymphatic space of the implanted cochleae and appear to traffic immune cells. Together, our data provide direct evidence that concurrent proliferation of blood vessels and recruitment of blood-borne immune cells comprise an 'immune surveillance system' in the implanted cochleae that promotes the FBR. Our findings also highlight potential opportunities to limit adverse FBR outcomes following cochlear implantation.

systems biology↗

bioRxiv2026

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

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.

neuroscience↗

bioRxiv2022

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

ObjectivesThe objectives of this study were to assess the effects of cochlear implant (CI) biomaterials on the function of macrophages and fibroblasts, two key mediators of the foreign body response (FBR) and to determine how these materials influence fibrous tissue growth and new bone formation within the cochlea. MethodsMacrophages and fibroblasts were cultured on polydimethylsiloxane (PDMS) and platinum substrates and human CI electrodes in vitro. Cell count, cell proliferation, cytokine production, and cell adhesion were measured. CI electrodes were implanted into murine cochleae for one week without electrical stimulation. Implanted cochleae were harvested for 3D X-ray microscopy with the CI left in-situ. The location of new bone growth within the scala tympani (ST) with reference to different portions of the implant (PDMS vs platinum) was quantified. ResultsCell counts of macrophages and fibroblasts were significantly higher on platinum substrates and platinum contacts of CI electrodes. Fibroblast proliferation was greater on platinum relative to PDMS, and cells grown on platinum formed more/larger focal adhesions. 3D x-ray microscopy showed neo-ossification in the peri-implant areas of the ST. Volumetric quantification of neo-ossification showed a trend toward greater bone formation adjacent to the platinum electrodes compared to areas opposite or away from the platinum electrode bearing surfaces. ConclusionsFibrotic reactions are biomaterial specific, as demonstrated by the differences in cell adhesion, proliferation, and fibrosis on platinum and PDMS. The inflammatory reaction to platinum contacts on CI electrodes likely contributes to fibrosis to a greater degree than PDMS, and platinum contacts may influence the deposition of new bone, as demonstrated in the in vivo data. This information can potentially be used to influence the design of future generations of neural prostheses.

bioengineering↗

bioRxiv2021

Chronic Cochlear Implantation with and without Electric Stimulation in a Mouse Model Induces Robust Cochlear Influx of CX3CR1+/GFP Macrophages.

BackgroundCochlear implantation is an effective auditory rehabilitation strategy for those with profound hearing loss, including those with residual low frequency hearing through use of hybrid cochlear implantation techniques. Post-mortem studies demonstrate the nearly ubiquitous presence of intracochlear fibrosis and neo-ossification following cochlear implantation. Current evidence suggests post-implantation intracochlear fibrosis is associated with delayed loss of residual acoustic hearing in hybrid cochlear implant (CI) recipients and may also negatively influence outcomes in traditional CI recipients. This study examined the contributions of surgical trauma, foreign body response and electric stimulation to intracochlear fibrosis and the innate immune response to cochlear implantation and the hierarchy of these contributions. MethodsNormal hearing CX3CR1+/GFP mice underwent either round window opening (sham), acute CI insertion or chronic CI insertion with no, low- or high-level electric stimulation. Electric stimulation levels were based on neural response telemetry (NRT), beginning post-operative day 7 for 4 hours per day. Subjects (n=3 per timepoint) were sacrificed at 4 hours, 1,4,7,8,11,14 and 21 days. An unimplanted group (n=3) served as controls. Cochleae were harvested at each time-point and prepared for immunohistochemistry with confocal imaging. The images were analyzed to obtain CX3CR1+ macrophage cell number and density in the lateral wall (LW), scala tympani (ST) and Rosenthals canal (RC). ResultsA ST peri-implant cellular infiltrate and fibrosis occurred exclusively in the chronically implanted groups starting on day 7 with a concurrent infiltration of CX3CR1+ macrophages not seen in the other groups. CX3CR1+ macrophage infiltration was seen in the LW and RC in all experimental groups within the first week, being most prominent in the 3 chronically implanted groups during the second and third week. There were no significant differences in macrophage infiltration related to levels of electric stimulation. ConclusionsThe cochlear immune response was most prominent in the presence of chronic cochlear implantation, regardless of electric stimulation level. Further, the development of intracochlear ST fibrosis was dependent on the presence of the indwelling CI foreign body. An innate immune response was evoked by surgical trauma alone (sham and acute CI groups) to a lesser degree. These data suggest that cochlear inflammation and intrascalar fibrosis after cochlear implantation are largely dependent on the presence of a chronic indwelling foreign body and are not critically dependent on electrical stimulation. Also, these data support a role for surgical trauma in inciting the initial innate immune response.

neuroscience↗