Frontiers in Neuroscience
·
2019
·
IF 3.648
Liang Qiong,Shen Na,Lai Bin,Xu Changjian,Sun Zengjun,Wang Zhengmin,Li Shufeng
Neurostimulation devices use electrical stimulation (ES) to substitute, supplement or modulate neural function. However, the impact of ES on their modulating structures is largely unknown. For example, recipients of cochlear implants using electroacoustic stimulation experienced delayed loss of residual hearing over time after ES, even though ES had no impact on the morphology of hair cells. In this study, using a novel model of cochlear explant culture with charge-balanced biphasic ES, we found that ES did not change the quantity and morphology of hair cells but decreased the number of inner hair cell (IHC) synapses and the density of spiral ganglion neuron (SGN) peripheral fibers. Inhibiting calcium influx with voltage-dependent calcium channel (VDCC) blockers attenuated the loss of SGN peripheral fibers and IHC synapses induced by ES. ES increased ROS/RNS in cochlear explants, but the inhibition of calcium influx abolished this effect. Glutathione peroxidase 1 (GPx1) and GPx2 in cochlear explants decreased under ES and ebselen abolished this effect and attenuated the loss of SGN peripheral fibers. This finding demonstrated that ES induced the degeneration of SGN peripheral fibers and IHC synapses in a current intensity- and duration-dependent manner in vitro. Calcium influx resulting in oxidative stress played an important role in this process. Additionally, ebselen might be a potential protector of ES-induced cochlear synaptic degeneration.
研究领域:
神经科学
·
耳科学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Neurology
·
2025
·
IF 2.8
Renlong Ji,Yanchang Xu,Kang Li,Wen Jiang,Yuan Li,Jianwei Zeng,Wei Li,Caiji Wang,Zeqi Zhao,Yalan Li,Naveena Konduru,Wen Liu,Yuehua Qiao,Xuanyi Li
Objective: To investigate the effects of Zexie decoction on vestibular and auditory function in guinea pigs with endolymphatic hydrolysis induced by desmopressin. Methods: Sixty guinea pigs were randomly and evenly divided into four groups, each group has 15 guinea pigs: normal control group, DDAVP group, DDAVP modeling combined with Zexie Decoction group, and DDAVP combined with Double Zexie group. At 7 and 14 days, bone-conducted cervical vestibular evoked myogenic potential tests, auditory brainstem responses, and distortion-product otoacoustic emissions were conducted on each group of guinea pigs to evaluate their vestibular and auditory function quantitatively. After functional testing, the outer hair cells were observed by scanning electron microscope. On day 14, one guinea pig was randomly selected from both the normal control group and DDAVP group to verify the successful establishment of the model using gadolinium-enhanced magnetic resonance imaging of the inner ear.Results: We conducted BC-cVEMP, ABR, and DPOAE tests on guinea pigs, and the results showed that DDAVP did affect vestibular function and hearing in guinea pigs. Analyses were performed from those results that were statistically significant, Zexie Decoction improved DDAVP-induced vestibular dysfunction and hearing loss dose-dependently, though complete reversal was not achieved. About scanning electron microscopy, outer hair cells of the DDAVP group showed significant loss and cilia lodging, however, treatment with Zexie decoction can alleviate the loss of outer hair cells and the lodging of cilia. When the outer hair cells were exposed to DDAVP for a long time, the improvement effect of Zexie decoction was not as obvious as before.Conclusion: The extent of improvement correlates with the concentration and dosage of Zexie Decoction. Even at double the dosage, Zexie Decoction only partially mitigates the decline in vestibular and auditory function induced by DDAVP, falling short of complete reversal.
研究领域:
药理学
·
听力学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·Vol. 12
·期 21
·2412158
·
IF 14.1
Lei Ren,Yangnan Hu,Xiaoqiong Ding,Menghui Liao,Tian Shen,Sixing Cao,Hui Zhang,Hong Cheng,Yanru Qi,Pan Feng,Xinyi Pang,Ling Lu,Huan Wang,Wenwen Liu,Renjie Chai,Lin Cheng
Severe to profound sensorineural hearing loss seriously affects the communication and cognitive ability of the patients. Cochlear implantation (CI) is currently the most effective treatment, while it may damage the remaining inner ear function due to its poor biocompatibility and the resultant fibrosis. Herein, a porous methacrylated poly(dimethylsiloxane) (MA-PDMS)-coated cochlear electrode is presented for CI and hearing protection. The porous MA-PDMS is filled with a hybrid hydrogel system made of dexamethasone sodium phosphate (Dex), Ti 3 C 2 T x MXene (MXene), and methacrylate gelatin (GelMA). The coating shows good biocompatibility and drug loading and release capacity in vitro, protective effects on hair cells (HCs) and spiral ganglion neurons (SGNs) of the inner ear, as well as the residual hearing protection and the effective fibrosis reduction in vivo. It is anticipated that this porous electrode drug-loading coating may provide a valuable reference strategy for the future cochlear electrode transplantation system.
研究领域:
生物医学工程
·
耳鼻喉科学
·
材料科学
·
纳米技术
·
药物递送系统
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2025
·Vol. 113
·期 3
·e37892
·
IF 3.9
Yingjie Wang,Haobo Li,Junming Zhang,Mengyu Chen,Yiyin Pan,Xiangxin Lou
Hearing loss is often regarded as “invisible disability” which seriously affects the quality of life. The majority of hearing loss cases are caused by the damage to inner ear hair cells or connected spiral ganglion cells, and there is a lack of effective treatment measures. In recent years, significant progress has been made in the use of two-dimensional (2D) culture systems to induce the regeneration of auditory cells. However, the regenerated hair cells cannot form effective functional ciliary bundles under the 2D system, let alone establish synaptic contact with spiral ganglion cells, so they cannot truly achieve physiological repair of hearing. In this study, our aim is to construct a three-dimensional (3D) organ of Corti organoid through 3D bioprinting, which combines “3D culture scaffold + multiple induction signals + inner ear stem cells.” Then we evaluate the effects of the organoids on the differentiation of inner ear stem cells into auditory cells. We found that the organoids promoted adhesion and growth of inner ear stem cells, as well as the production of hair cells and nerve cells. The research may develop a novel approach for studying auditory cell regeneration and hearing loss repair.
研究领域:
再生医学
·
听力科学
·
组织工程学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2018
·
IF 2.441
Mian Zu,Jinan Jiang,Hui Zhao,Shili Zhang,Yan Yan,Shiwei Qiu,Shuolong Yuan,Jiawei Han,Yue Zhang,Weiwei Guo,Shiming Yang
Irreversible hearing loss induced by aminoglycoside in human through local or systemic administration route negatively impacts quality of life. The aim of this work was to develop and validate an analytical method suitable for the detection and quantification of neomycin in cochlear perilymph of guinea pig after local application. The SupelMIP SPE column was used for the pre-treatment of matrix. Chromatographic separation was conducted by a reversed phase ODS column (100 × 2.1 mm, 3 μm) at 40 °C in gradient mode with 0.2‰ (v/v) HFBA in water and 0.2‰ (v/v) HFBA in acetonitrile as mobile phase , at a flow rate of 0.30 mL/min, with retention time of 3.50 and 3.62 min for internal standard tobramycin and analyte neomycin , respectively. The MS was performed with positive ionization mode, with data acquisition in Multi Reaction Monitor (MRM) mode. This method was proved to be specific, accurate (97.1–115% of nominal values) and precise (CV% < 15%). Calibration curves for matrix matched standard of neomycin ranged from 1.25 to 200 μg/mL, with LOD and LLOQ of 0.625 and 1.25 μg/mL in blank matrix. The matrix effect was corrected to (−0.1) - 1.33 by adding internal standard. The relative SPE recovery values were ≥98.9% in low, medium and high QC samples. Neomycin in matrix proved to be stable under room temperature - and −20 °C, or under three freeze-thawing cycles, or under processing as well. Finally, the proposed method was successfully applied to a toxicokinetics study of neomycin in perilymph after round window membrane (RWM) administration, which was in accordance with threshold shift of auditory brainstem response (ABR) test related to hearing loss.
研究领域:
药理学
·
分析化学
·
耳科学
✓ 已验证
DOI
高影响因子
ARCHIVES OF TOXICOLOGY
·
2025
·
IF 6.9
Tang Wei,Zong Shimin,Du Peiyu,Yu Xuan,Li Ting,Liu Bo,Zhong Yu,Lei Wenyang,Yu Wenting,Xiao Hongjun
Cochlear hair cell death is the primary cause of cisplatin-induced ototoxicity, currently lacking widely applicable clinical methods for effective prevention and treatment. In this study, an in vivo cisplatin-induced ototoxicity model was established by intraperitoneal injection of 12 mg/kg cisplatin. We found that ablation of SIRT3 exacerbates cisplatin-induced hearing loss and cochlear hair cell damage. An in vitro cisplatin-induced ototoxicity model was established using 5 µM cisplatin in cochlear explants and OC-1 cells. We found that the absence of SIRT3 impairs cochlear hair cell glycolytic metabolism, leading to excessive accumulation of ROS and significant reduction in MMP levels, thereby promoting apoptosis. In contrast, overexpression of SIRT3 in OC-1 cells promotes cochlear hair cell survival and reduces cochlear hair cell apoptosis. Inhibition of PFKFB3 reduces glycolytic metabolism in OC-1 cells, and the protective effect conferred by SIRT3 overexpression is lost. In summary, the protective effect of SIRT3 may be mediated by the regulation of PFKFB3-dependent glycolysis and the mitigation of cisplatin-induced excessive ROS accumulation.
研究领域:
耳鼻喉科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2021
·
IF 15.881
Jiaqi Zheng,Zhaohan Yu,Yunming Wang,Yue Fu,Dan Chen,Huamin Zhou
The demand for flexible, efficient, and self-powered cochlear implants applied to remedy sensorineural hearing loss caused by dysfunctional hair cells remains urgent. Herein, we report an acoustic core–shell resonance harvester for the application of artificial cochleae based on the piezo-triboelectric effect. Integrating dispersed BaTiO3 particles as cores and porous PVDF-TrFE as shells, the acoustic harvest devices with ingenious core–shell structures exhibit outstanding piezo-triboelectric properties (Voc = 15.24 V, DAsc = 9.22 mA/m2). The acoustic harvest principle reveals that BaTiO3 nanocores resonate with sound waves and bounce against porous PVDF-TrFE microshells, thereby generating piezo-triboelectric signals. By experimental measurement and numerical modeling, the vibration process and resonance regulation of acoustic harvest devices were intensively investigated to regulate the influential parameters. Furthermore, the acoustic harvesters exhibit admirable feasibility and sensitivity for sound recording and show potential application for artificial cochlea.
研究领域:
生物医学工程
·
材料科学
·
听力学
✓ 已验证
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2018
·
IF 5.08
Muqing Xu,Dong Ma,Dongxiu Chen,Jieqing Cai,Qiaofang He,Fan Shu,Jie Tang,Hongzheng Zhang
Cochlear inflammatory response after cochlear implantation (CI) is an important mechanism for implantation trauma and hearing loss. The hearing loss was also caused by damage to auditory hair cells (HCs), whereas ion homeostasis within the cochlea can ensure survival of HCs. In our study, pure hyaluronic acid (HA) was crosslinked with 1, 4-butanediol diglycidyl ether (BDDE) and the successful preparation of the cross-linked hydrogel (CHA) was confirmed by rheological characteristics and FTIR spectra. Artificial perilymph (APL) was prepared to simulate the ion homeostasis microenvironment within scala tympani of human cochlear, and served as the major component of artificial perilymph soaked CHA (APL-CHA). The conductivity experiment indicated that APL-CHA is more suitable to the requirements of the electrical conductivity in scala tympani. The electrode coating process found that the extrusion coating method have advantages of controllable adhesive capacity of APL-CHA, uniform coating thickness and smooth surface as compared to common method. Due to CI surgery application requirement, optimization of coating process was selected as follows: extrusion coating method, degree of 3.6 vol%, pinhole diameter of 32G (110 μm), pressure of 200 ± 15.81 Psi. Controlled dexamethasone 21-phosphate sodium salt (DSP) release of 20 days could be demonstrated using the hydrogel filled reservoir via a validated HPLC method. The morphological structure of CHA showed different sizes of porous structure among APL-CHA provided structural basis for drug delivery. L929 fibroblasts culture and Spiral Ganglion Neuron Explants culture results revealed that APL-CHA possesses fine biological compatibility. APL-CHA shows a promising application in CI surgery and has great potential in preventing hearing loss with well simulation of ion homeostasis within the cochlear, local DSP delivery for target anti-inflammatory, approximate conductivity within the scala tympani and optimization of electrode coating process.
研究领域:
生物医学工程
·
药剂学
·
听力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomolecules
·
2024
·Vol. 14
·期 1
·95
·
IF 4.8
Fei Tan,Xuran Li,Xiao Li,Maoxiang Xu,Khawar Ali Shahzad,Lei Hou
Recent advances in cochlear implantology are exemplified by novel functional strategies such as bimodal electroacoustic stimulation, in which the patient has intact low-frequency hearing and profound high-frequency hearing pre-operatively. Therefore, the synergistic restoration of dysfunctional cochlear hair cells and the protection of hair cells from ototoxic insults have become a persistent target pursued for this hybrid system. In this study, we developed a composite GelMA/PEDOT:PSS conductive hydrogel that is suitable as a coating for the cochlear implant electrode for the potential local delivery of otoregenerative and otoprotective drugs. Various material characterization methods (e.g.,1H NMR spectroscopy, FT-IR, EIS, and SEM), experimental models (e.g., murine cochlear organoid and aminoglycoside-induced ototoxic HEI-OC1 cellular model), and biological analyses (e.g., confocal laser scanning microscopy, real time qPCR, flow cytometry, and bioinformatic sequencing) were used. The results demonstrated decent material properties of the hydrogel, such as mechanical (e.g., high tensile stress and Young’s modulus), electrochemical (e.g., low impedance and high conductivity), biocompatibility (e.g., satisfactory cochlear cell interaction and free of systemic toxicity), and biosafety (e.g., minimal hemolysis and cell death) features. In addition, the CDR medicinal cocktail sustainably released by the hydrogel not only promoted the expansion of the cochlear stem cells but also boosted the trans-differentiation from cochlear supporting cells into hair cells. Furthermore, hydrogel-based drug delivery protected the hair cells from oxidative stress and various forms of programmed cell death (e.g., apoptosis and ferroptosis). Finally, using large-scale sequencing, we enriched a complex network of signaling pathways that are potentially downstream to various metabolic processes and abundant metabolites. In conclusion, we present a conductive hydrogel-based local delivery of bifunctional drug cocktails, thereby serving as a potential solution to intracochlear therapy of bimodal auditory rehabilitation and diseases beyond.Keywords:conductive hydrogel;hair cell;hair cell regeneration;apoptosis;ferroptosis;cochlear implant;electroacoustic stimulation;GelMA;PEDOT:PSS
研究领域:
生物材料
·
生物医学工程
·
人工耳蜗学
·
再生医学
·
耳科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Jie Tang,Bairu Chen,Fang Yu,Long Xu,Muxin Yu,Chunji Wang,Fang Zhang,Li Zhang,Yujia Yang,Jiani Hou,Xingfei Li,Weihao Xu,Nenghua Zhang
Increasing evidence links hearing loss to environmental pollutant exposure, with cochlear hair cell being a key target. Bisphenol A (BPA) has been suggested to cause ototoxicity, but its mechanism is not fully understood. In this study, cell viability was assessed by varying concentrations of BPA (0–150 μM) exposed to mouse cochlear hair cells (HEI-OC1), followed by RNA transcriptome sequencing to identify the possible molecular mechanisms. Results showed that BPA above 50 μM reduced cell viability in a dose-dependent manner. RNA sequencing identified 1764 differentially-expressed genes, comprised of 1152 up-regulated and 612 down-regulated genes. Notably, estrogen receptor-related genes were enriched, with a marked up-regulation of estrogen receptor α (ER-α) at both mRNA and protein levels. GO and KEGG analyses revealed the main pathway involvement for oxidative damage, lipid metabolism, protein phosphorylation, and DNA damage. STRING analyses constructed gene networks to identify functionally interacting genes correlated with pyroptotic pathways. BPA exposure induced pyroptosis-like morphological changes characterized by cell swelling, rounding, and membrane blebbing. Increased intracellular ROS and mitochondrial superoxide (MitoSOX) levels, reduced mitochondrial membrane potential ( ΔΨm ), and elevated intracellular calcium (Ca²⁺) levels were observed. Flow cytometry showed an increased proportion of apoptotic and necrotic cells. Pyroptosis-related genes, including caspase-3, caspase-8, caspase-9, and GSDME, were down-regulated, while IL-1β and IL-18 were up-regulated. Protein expressions of caspase-3, caspase-8, caspase-9, and GSDME were decreased, while cleaved caspase-3 and N-terminal GSDME (GSDME-NT) were increased. Furthermore, ROS inhibitor N-acetylcysteine (NAC) and the ER-α antagonist fulvestrant alleviated BPA-induced cell death, and suppressed the protein expressions of the pyroptotic pathway. These results demonstrate that BPA exposure induces ototoxicity possibly through activating ER-α and triggering mitochondrial ROS that contributes to pyroptosis.
研究领域:
毒理学
·
耳科学
·
分子生物学
·
环境健康
·
细胞死亡机制
·
内分泌干扰物
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2021
·
IF 6.684
Chen Dongxiu,Luo Yanjing,Pan Jing,Chen Anning,Ma Dong,Xu Muqing,Tang Jie,Zhang Hongzheng
Cochlear implantation (CI) is the major treatment for severe sensorineural hearing loss. However, the fibrotic tissue forming around the electrodes reduces the treatment effectiveness of CI. Dexamethasone (DEX) is usually applied routinely in perioperative treatment of cochlear implantation (CI), but its diffusion in the inner ear after systemic administration is limited. In the present study, an electrode coated with polycaprolactone (PCL) loaded with dexamethasone was developed with a simple preparation process to maintain the stability of the electrode itself. The DEX-loaded PCL coating has good biocompatibility and does not change the smoothness, flexibility, or compliance of the implant electrode. Stable and effective DEX concentrations were maintained for more than 9 months. Compared with the pristine electrode, decreasing intracochlear fibrosis, protection of hair cells and spiral ganglion cells, and better residual hearing were observed 5 weeks after PCL-DEX electrode implantation. The PCL-DEX electrode has great potential in preventing hearing loss and fibrosis by regulating macrophages and inhibiting the expression of the fibrosis-related factors IL-1β, TNF-α, IL-4, and TGF-β1. In conclusion, the PCL-DEX electrode coating shows promising application in CI surgery.
研究领域:
耳鼻喉科
·
生物材料
·
神经科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2022
·Vol. 12
·期 1
·2200807
·
IF 11.092
Anning Chen,Dongxiu Chen,Kai Lv,Guowei Li,Jing Pan,Dong Ma,Jie Tang,Hongzheng Zhang
Since the first surgery 50 years ago, cochlear implantation (CI) is the major treatment for patients with severe sensorineural hearing loss. However, unexpected foreign body reactions (FBRs) after surgery are reported in 90% of CI recipients, resulting in the formation of fibrosis in the cochlea and progressive residual hearing loss. Zwitterion modification is universally used to reduce bio-fouling and suppress FBRs but never for CI. In the present study, a zwitterionic coating is developed, which is composed of poly sulfobetaine methacrylate (PSB) and polydopamine (PDA) for cochlear implants. The PSB-PDA coating shows a series of characters for an ideal anti-FBRs material, including super-hydrophilicity, low protein and cell adsorption, long-term stability, and high biocompatibility. Compared to the uncoated controls, PSB-PDA coating inhibits the activation of macrophages and reduces the release of inflammatory factors (TNF- α , IL-1 β , NO) and fibrosis-related factors (TGF- β 1, α -SMA, collagen I). PSB-PDA coated electrode arrays suppress fibrosis completely and preserve residual hearing significantly in rat CI models. These results suggest that PSB-PDA coating is a novel strategy for anti-fibrosis to improve the outcomes of CI.
研究领域:
生物医学工程
·
材料科学
·
听力研究
·
生物材料
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）