耳蜗植入学的最新进展通过新颖的功能策略例如双峰电声刺激,其中患者在术前具有完整的低频听力和深刻的高频听力。因此,功能失调的耳蜗毛细胞的协同恢复和保护毛细胞免受耳毒性损伤已成为这种混合系统追求的持久目标。在这项研究中,我们开发了一种复合GelMA/PEDOT:PSS导电水凝胶,适合作为耳蜗植入电极的涂层,用于潜在的局部递送耳再生和耳保护药物。各种材料表征方法(例如,1HNMR光谱,FT-IR,EIS,和SEM),实验模型(例如,鼠耳蜗类器官和氨基糖苷诱导的耳毒性HEI-OC1细胞模型),和生物学分析(例如,共聚焦激光扫描显微镜,实时qPCR,流式细胞术,和生物信息学测序)。结果表明,水凝胶的材料性能良好,如机械(例如,高拉伸应力和杨氏模量),电化学(例如,低阻抗和高电导率),生物相容性(例如,令人满意的耳蜗细胞相互作用和无全身毒性),和生物安全(例如,最小溶血和细胞死亡)特征。此外,由水凝胶可持续释放的CDR药物混合物不仅促进了耳蜗干细胞的扩增,而且促进了从耳蜗支持细胞向毛细胞的转分化。此外,基于水凝胶的药物递送保护毛细胞免受氧化应激和各种形式的程序性细胞死亡(例如,凋亡和铁凋亡)。最后,使用大规模测序,我们丰富了一个复杂的信号通路网络,这些信号通路可能是各种代谢过程和丰富代谢产物的下游.总之,我们提出了一种基于导电水凝胶的双功能药物混合物的局部递送,从而作为双峰听觉康复和超越疾病的耳蜗内治疗的潜在解决方案。
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.