Richardson Rachael T, Wise Andrew K, Thompson Brianna C, Flynn Brianna O, Atkinson Patrick J, Fretwell Nicole J, Fallon James B, Wallace Gordon G, Shepherd Rob K, Clark Graeme M, O'Leary Stephen J
The Bionic Ear Institute, East Melbourne, Victoria 3002, Australia.
Biomaterials. 2009 May;30(13):2614-24. doi: 10.1016/j.biomaterials.2009.01.015. Epub 2009 Jan 29.
Sensorineural hearing loss is associated with gradual degeneration of spiral ganglion neurons (SGNs), compromising hearing outcomes with cochlear implant use. Combination of neurotrophin delivery to the cochlea and electrical stimulation from a cochlear implant protects SGNs, prompting research into neurotrophin-eluting polymer electrode coatings. The electrically conducting polypyrrole/para-toluene sulfonate containing neurotrophin-3 (Ppy/pTS/NT3) was applied to 1.7 mm2 cochlear implant electrodes. Ppy/pTS/NT3-coated electrode arrays stored 2 ng NT3 and released 0.1 ng/day with electrical stimulation. Guinea pigs were implanted with Ppy/pTS or Ppy/pTS/NT3 electrode arrays two weeks after deafening via aminoglycosides. The electrodes of a subgroup of these guinea pigs were electrically stimulated for 8 h/day for 2 weeks. There was a loss of SGNs in the implanted cochleae of guinea pigs with Ppy/pTS-coated electrodes indicative of electrode insertion damage. However, guinea pigs implanted with electrically stimulated Ppy/pTS/NT3-coated electrodes had lower electrically-evoked auditory brainstem response thresholds and greater SGN densities in implanted cochleae compared to non-implanted cochleae and compared to animals implanted with Ppy/pTS-coated electrodes (p<0.05). Ppy/pTS/NT3 did not exacerbate fibrous tissue formation and did not affect electrode impedance. Drug-eluting conducting polymer coatings on cochlear implant electrodes present a clinically viable method to promote preservation of SGNs without adversely affecting the function of the cochlear implant.
感音神经性听力损失与螺旋神经节神经元(SGNs)的逐渐退化有关,这会影响人工耳蜗植入的听力效果。将神经营养因子递送至耳蜗并结合人工耳蜗的电刺激可保护SGNs,这促使人们对可释放神经营养因子的聚合物电极涂层展开研究。将含有神经营养因子-3(Ppy/pTS/NT3)的导电聚吡咯/对甲苯磺酸盐应用于面积为1.7平方毫米的人工耳蜗电极。涂有Ppy/pTS/NT3的电极阵列可储存2纳克NT3,并在电刺激下以每天0.1纳克的速度释放。通过氨基糖苷类药物致聋两周后,将涂有Ppy/pTS或Ppy/pTS/NT3的电极阵列植入豚鼠体内。对这些豚鼠亚组的电极进行每天8小时、持续2周的电刺激。植入涂有Ppy/pTS电极的豚鼠植入耳蜗中出现了SGNs损失,这表明电极插入造成了损伤。然而,与未植入耳蜗相比,以及与植入涂有Ppy/pTS电极的动物相比,植入经电刺激的涂有Ppy/pTS/NT3电极的豚鼠,其电诱发听觉脑干反应阈值更低,植入耳蜗中的SGN密度更高(p<0.05)。Ppy/pTS/NT3不会加剧纤维组织形成,也不会影响电极阻抗。人工耳蜗电极上的药物洗脱导电聚合物涂层是一种临床上可行的方法,可促进SGNs的保存,且不会对人工耳蜗的功能产生不利影响。