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ACS Nano · 2021 · IF 15.881

Acoustic Core–Shell Resonance Harvester for Application of Artificial Cochlea Based on the Piezo-Triboelectric Effect

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
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Biomolecules · 2024 ·Vol. 14 ·期 1 ·95 · IF 4.8

GelMA/PEDOT:PSS Composite Conductive Hydrogel-Based Generation and Protection of Cochlear Hair Cells through Multiple Signaling Pathways

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

CAS / MDL: 155090-83-8
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
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Frontiers in Cell and Developmental Biology · 2021 · IF 6.684

Long-Term Release of Dexamethasone With a Polycaprolactone-Coated Electrode Alleviates Fibrosis in Cochlear Implantation

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.

CAS / MDL: 75-09-2
研究领域: 耳鼻喉科 · 生物材料 · 神经科学 · 药理学
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Advanced Healthcare Materials · 2022 ·Vol. 12 ·期 1 ·2200807 · IF 11.092

Zwitterionic Polymer/Polydopamine Coating of Electrode Arrays Reduces Fibrosis and Residual Hearing Loss after Cochlear Implantation

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
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Biomaterials Advances · 2023 · IF 0

Preparation, characterization, and in vitro/vivo evaluation of a multifunctional electrode coating for cochlear implants

Muqing Xu,Anning Chen,Dongxiu Chen,Shengquan Wu,Zhipeng Deng,Hang Wen,Huiling Zhong,Kejin Lu,Jie Tang,Dong Ma,Hongzheng Zhang

Cochlear implantation (CI) is the primary intervention for patients with sensorineural hearing loss to restore their hearing. However, approximately 90 % of CI recipients experience unexpected fibrosis around the inserted electrode arrays due to acute and chronic inflammation. This fibrosis leads to progressive residual hearing loss. Addressing this complication is crucial for enhancing CI outcomes, yet an effective treatment has not yet been found. In this study, we developed a multifunctional dexamethasone (DXM)-loaded polytrimethylene carbonate (PTMC) electrode coating to mitigate inflammatory reactions and fibrosis after CI. This thin and flexible coating could preserve the mechanical performance of the electrode and reduce the implantation resistance for CI. The in vitro release studies demonstrated the DXM-PTMC coating's efficient drug loading and sustained release capability over 90 days. DXM-PTMC also showed long-term stability, high biocompatibility, and effective anti-inflammatory effects in vitro and in vivo . Compared with the uncoated group, DXM-PTMC coating significantly inhibited the expression of inflammatory factors, such as NO, TNF-α, IL-1β, and IL-6. DXM-PTMC coating suppressed fibrosis in rat implantation models for 3 weeks by reducing both acute and chronic inflammation. Our findings suggest that DXM-PTMC coating is a novel strategy to improve the outcomes of CI.

CAS / MDL: 50-02-2
研究领域: 生物医学工程 · 药学 · 组织工程 · 神经科学
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Biomaterials Advances · 2024 · IF 5.5

Preparation and characterization of neural stem cell-loaded conductive hydrogel cochlear implant electrode coatings

Zhiyi Wang,Yu Yan,Wenxin Chen,Zhiping Tan,Qingfeng Yan,Qingqing Chen,Xue Ding,Jiahua Shen,Min Gao,Yang Yang,Lulu Yu,Fuzhi Lin,Yong Fu,Xiaoqiang Jin,Xiaohua Yu

Sensorineural deafness is a hearing impairment resulting from damage to the auditory nerve or inner ear hair cells. Currently, cochlear implants (CIs) are widely used as hearing aids for sensorineural deafness patients. A fundamental limitation of cochlear implants (CIs) is that spiral ganglion neurons (SGNs) cannot be replenished. This greatly restricts the rehabilitation of sensorineural deafness. Additionally, the insertion of CIs can cause secondary cochlear damage, worsening the condition of the patients' cochlear. Therefore, a new type of neural stem cells (NSCs) loaded graphene oxide-polyaniline/GelMA (GO-PAni/GelMA) conductive hydrogel electrode for cochlear implant was fabricated via in-situ radical polymerization and cyclic UV curing technique. On the one hand, the hydrogel electrode, as a direct contact layer, helps to avoid the physical hurt for cochlear. On the other hand, NSCs were supplemented via the hydrogel carrier and neuronal differentiation was induced by electrical stimulation, which was validated by the experimental results of immunofluorescence, Phalloidin Staining and RT-qPCR. Furthermore, based on RNA sequencing and transcriptome analysis, we hypothesized that the neuronal differentiation of NSCs was adjusted by the calcium signaling pathway and GABAergic synapse. Overall, our cell loading conductive hydrogel electrode may be an effective solution to sensorineural deafness. The revelation of the mechanism of neuronal differentiation promoted by electrical stimulation provides a basis for further sensorineural deafness treatment using conductive hydrogel CI electrode.

CAS / MDL: 7782-42-5
研究领域: 生物医学工程 · 神经科学 · 材料科学 · 组织工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY · 2018 · IF 2.297

A cochlear implant loaded with dexamethasone and coated with hyaluronic acid to inhibit fibroblast adhesion and proliferation

Kunhong Yu,Jingwen Hou,Zhu Jin,Keqin Wu,Shaohui Xu,Ning Yang,Yuanyuan Shen,Tingting Tang,Shengrong Guo

Inflammation and fibrosis caused by inserting cochlear implants into the inner ear are of great concern in clinical treatment. To address these issues, we studied new cochlear implant electrode analogs, polydimethylsiloxane (PDMS) filaments loaded with anti-inflammation/fibrosis dexamethasone (Dex) and coated with hyaluronic acid (HA) as a surface modifier. The PDMS filaments were prepared by incorporating Dex into PDMS that contained different amounts of poloxamer 188 (P188) as a drug release enhancer. HA coatings were performed to prevent protein adsorption by treating the surfaces of the PDMS filaments with O 2 plasma, 3-aminopropyltriethoxysilane and HA in sequence. The prepared PDMS filaments were investigated by attenuated total reflection Fourier transform infrared spectroscopy , contact angle measurement and atomic force microscopy . Their protein adsorption and drug release behaviors were examined as well. L929 mouse fibroblast cells were used to evaluate the anti-cell adhesion/proliferation effects of the PDMS filaments. The results showed that the prepared PDMS filaments had the expected structure, good surface properties and excellent anti-fibroblast cell proliferation effects. The HA coatings provided filament surfaces that were more hydrophilic, smoother and more protein-repelling. Dex release was significantly facilitated by adding P188 and slightly slowed down by the HA coatings. The PDMS filaments that contained 5% Dex and 5% P188 and that were coated with HA showed a significant decrease in the fibroblast cell number by approximately 51%, with obviously reduced cell adhesion on the surfaces.

研究领域: 生物医学工程 · 药剂学 · 材料科学 · 细胞生物学
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