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地塞米松洗脱型人工耳蜗可减轻人和小鼠耳蜗的炎症及异物反应。

Dexamethasone-eluting cochlear implants reduce inflammation and foreign body response in human and murine cochleae.

作者信息

Rahman Muhammad Taifur, Mostaert Brian J, Eckard Peter, Fatima Shakila Mahmuda, Scheperle Rachel, Razu Ibrahim, Hunger Bryce, Olszewski Rafal T, Gu Shoujun, Garcia Cristina L, Khan Nashwaan Ali, Bennion Douglas M, Oleson Jacob, Kirk Jonathon R, Enke Ya Lang, Gay Robert D, Morell Robert J, Hirose Keiko, Hoa Michael, Claussen Alexander D, Hansen Marlan R

机构信息

Department of Otolaryngology-Head and Neck Surgery, The University of Iowa, Iowa City, IA, 52242, USA.

Auditory Development and Restoration Program, Neurotology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.

出版信息

Sci Rep. 2025 Aug 20;15(1):30615. doi: 10.1038/s41598-025-10739-y.

Abstract

The inflammatory foreign body response (FBR) following cochlear implantation (CI) can negatively impact CI outcomes, including increased electrode impedances. This study aims to investigate the long-term efficacy of dexamethasone-eluting cochlear implant and locally delivered dexamethasone, a potent anti-inflammatory glucocorticoid, on the intracochlear FBR and electrical impedance post-implantation in a murine model. Preliminary impedance data in humans are also provided as a complement to the murine data to illustrate generalizability and reinforce implications related to clinical application. The left ears of CX3CR1 Thy1 (macrophage-neuron dual reporter) mice were implanted with dexamethasone-eluting cochlear implants (Dex-CI) or standard implant (Standard-CI) while the right ear served as unoperated control. Another group of dual reporter mice was implanted with a standard CI electrode array followed by injection of dexamethasone in the middle ear to mimic current clinical practice (Dex-local). Mouse implants were electrically stimulated with serial measurements of electrical impedance. Human subjects were implanted with either standard or Dex-CI followed by serial impedance measurements. Dex-CI reduced electrical impedance in the murine model and human subjects and inflammatory FBR in the murine model for an extended period. Dex-local in the murine model is ineffective for long-term reduction of FBR and electrode impedance. Our data suggests that dexamethasone-eluting arrays are more effective than the current clinical practice of locally applied dexamethasone in reducing FBR and electrical impedance.

摘要

人工耳蜗植入(CI)后的炎性异物反应(FBR)会对CI结果产生负面影响,包括电极阻抗增加。本研究旨在探讨地塞米松洗脱人工耳蜗及局部递送地塞米松(一种强效抗炎糖皮质激素)对小鼠模型人工耳蜗植入后耳蜗内FBR和电阻抗的长期疗效。还提供了人类的初步阻抗数据作为小鼠数据的补充,以说明普遍性并强化与临床应用相关的意义。将CX3CR1 Thy1(巨噬细胞-神经元双报告基因)小鼠的左耳植入地塞米松洗脱人工耳蜗(Dex-CI)或标准人工耳蜗(Standard-CI),而右耳作为未手术对照。另一组双报告基因小鼠植入标准CI电极阵列,随后在中耳注射地塞米松以模拟当前临床实践(Dex-local)。对小鼠人工耳蜗进行电刺激并连续测量电阻抗。人类受试者植入标准人工耳蜗或Dex-CI,随后进行连续阻抗测量。Dex-CI降低了小鼠模型和人类受试者的电阻抗,并在较长时间内降低了小鼠模型中的炎性FBR。小鼠模型中的Dex-local对长期降低FBR和电极阻抗无效。我们的数据表明,地塞米松洗脱阵列在降低FBR和电阻抗方面比当前局部应用地塞米松的临床实践更有效。

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