Functionalized Coatings for Enhanced Neural Interfaces

描述（由申请人提供）：拟开发一种生物活性聚合物涂层，该涂层可促进中枢神经系统中使用的记录和刺激电极形成功能增强且长期稳定的神经电极界面。该聚合物将含有细胞粘附和蛋白水解可降解的肽，其中加入神经生长因子（NGF）作为缓慢释放的神经营养因子，以促进神经过程延伸到电极表面。在接近电极的神经突的生长锥处产生的纤溶酶将通过靶肽的水解来降解聚合物基质。这种降解将增强NGF的释放，并在电极的活性位点打开聚合物，以保持电极表面的低阻抗特性，并确保电极功能不受聚合物的损害。电极表面与可行的神经过程的紧密接近应该增强神经记录的稳定性和灵敏度，并且可以降低用于神经兴奋的电荷注入阈值。该聚合物涂层旨在与低阻抗电极材料如氧化铱和氮化钛以及常规贵金属电极一起使用。阶段I的目的是开发用于聚合物合成的方法，量化NGF洗脱速率，评估聚合物对电极的相关电化学性质的影响，评估纤溶酶对聚合物降解的影响，以及通过量化PC12细胞在含有聚合物的NGF洗脱团块的培养物中的响应来评估NGF洗脱的影响。第二阶段计划将在适当的动物模型中测试聚合物的益处。该聚合物的预期应用是在神经假体中开发，作为神经退行性疾病（如ALS和闭锁综合征）患者的辅助装置，用于脊髓损伤和中风的康复，以及治疗与疾病相关的感觉缺陷。用于治疗震颤、帕金森病和癫痫的基于电刺激的疗法也代表了潜在的应用。

DESCRIPTION (provided by applicant): The development of a biologically active polymer coating that promotes the formation of a functionally enhanced and chronically stable nerve-electrode interface for recording and stimulation electrodes used in the central nervous system is proposed. The polymer will contain both cell adhesion and proteolytically degradable peptides with nerve growth factor (NGF) added as a slowly releasable neurotrophin to promote extension of neural processes to the electrode surface. Plasmin produced at the growth cones of neurites approaching the electrode will degrade the polymer matrix by hydrolysis of the target peptides. This degradation will enhance release of NGF and open the polymer at the active site of the electrode to preserve the low-impedance properties of the electrode surface and ensure that electrode function is not impaired by the polymer. The close proximity of the electrode surface to viable neural processes should enhance the stability and sensitivity of neural recording and may reduce charge-injection thresholds for neural excitation. The polymer coatings are intended for use with low impedance electrode materials such as iridium oxide and titanium nitride, as well as conventional noble metal electrodes. The Phase I aims are to develop methods for polymer synthesis, quantify NGF elution rates, assess the effects of the polymer on the relevant electrochemical properties of electrodes, evaluate the effects of plasmin on polymer degradation, and assess the effects of NGF elution by quantifying the response of PC12 ceils in a culture containing a NGF-eluting bolus of the polymer. A Phase II program would test the benefits of the polymer in an appropriate animal model. Intended applications of the polymer are in neural prostheses being developed as assistive devices for patients with neurodegenerative disorders such as ALS and locked-in syndrome, for rehabilitation in spinal cord injury and stroke, and for treatment of diseaserelated sensory deficits. Electrical stimulation-based therapies for the treatment of tremor, Parkinsons disease, and epilepsy also represent potential applications.