In vivo evaluation of implantable self-clearing catheter for hydrocephalus

项目摘要 脑积水是一种神经系统疾病，其特征是脑积水异常积聚， 脑室内的脑脊液。这种使人衰弱的疾病没有已知的治疗方法 并且通常使用长期植入的分流系统进行治疗， 维持脑积水患者的正常状态。不幸的是，这些重要的医疗 设备的故障率很高，在安装后的头两年内高达40%， 10年内植入率高达98%。虽然脑积水可以在生活中获得， 大约每1000个新生儿中就有一个被诊断为先天性脑积水。的 据估计，治疗小儿脑积水患者的年度医院护理费用 在美国超过20亿美元。大部分分流失败可归因于 由于炎症反应、血凝块或脉络膜导致脑室导管闭塞 神经丛组织长入。尽管已经尝试使用原地清除方法， 使用激光、超声波或电烙术去除导管阻塞物，这些外科手术 干预措施由于其侵入性而没有得到广泛接受。患者 脑积水，自清洁脑室导管，延缓生物污染闭塞可能导致 减少昂贵的分流置换手术，因此总体减少 发病率/死亡率。为了在原位非侵入性地解决导管阻塞，我们开发了 基于薄膜的磁性微致动器，并将其集成到可植入导管中， 努力创造自我清洁的智能导管。与其他传感器相比， 静磁致动器由于其简单性和强大的抗生物污染能力， 驱动力由于磁性微致动器是由外部施加的磁场驱动的， 在该领域，生物污垢去除可以非侵入性地进行，而无需额外的外科手术。 以前，我们已经证明了在静态和静态环境中去除细胞闭塞的能力。 使用磁性微致动器的动态流体环境，然而，没有体内评估 已经完成了测量我们的自清洁导管在体内的功能能力。 在这项提议中，我们试图通过使用脑室内血管内诱导的 动物模型通过比较有无脑室导管的闭塞过程， 集成磁性微执行器，我们将能够确定生物污垢去除能力 我们体内的自清洁导管。拟议研究的结果将大大 提高我们对自清洁导管抗生物污染能力的认识 这可能有利于脑积水以外的其他应用。

Project Summary Hydrocephalus is a neurological disorder characterized by an abnormal accumulation of cerebrospinal fluid in the ventricles of the brain. This debilitating disease has no known cure and is typically treated using a chronically implanted shunt system, which is critical in maintaining normalcy in hydrocephalus patients. Unfortunately, these important medical devices are plagued with a high rate of failure of up to 40% within the first two years post- implantation and up to 98% within 10 years. Although hydrocephalus may be acquired in life, approximately one in every 1000 newborns is diagnosed with congenital hydrocephalus. The annual cost of hospital care for treating pediatric hydrocephalus patients is estimated to exceed $2 billion in the United States. A large portion of shunt failures can be attributed to occlusions at the ventricular catheter due to inflammatory reaction, blood clots, or choroid plexus tissue ingrowth. Although there have been attempts to use in situ clearing methods using laser, ultrasound, or electrocautery to remove catheter obstructions, these surgical interventions did not attain wide acceptance due to their invasiveness. For patients with hydrocephalus, a self-clearing ventricular catheter that retards biofouling occlusion could lead to a reduction in costly shunt replacement surgeries and therefore an overall reduction in morbidity/mortality. To address catheter obstruction non-invasively in situ, we have developed thin-film-based magnetic microactuators and integrated them into implantable catheters in an effort to create self-clearing smart catheters. Compare to other transducers, microfabricated magnetostatic actuators are ideal for combatting biofouling due to their simplicity and strong actuation force. Since magnetic microactuators are powered by an externally applied magnetic field, the biofouling-removal can be done non-invasively without additional surgical procedures. Previously, we have demonstrated capability to remove cellular occlusions in both a static and a dynamic fluid environment using magnetic microactuators, however, no in vivo evaluation has been done to measure the functional capability of our self-clearing catheters in the body. In this proposal, we seek to fill this gap by using an intraventricular hemorrhage-induced animal model. By comparing the occlusion process of ventricular catheters with and without integrated magnetic microactuators, we will be able to determine biofouling-removal capability of our self-clearing catheters in the body. The results from proposed studies will significantly improve our knowledge on the capability of our self-clearing catheters in combatting biofouling on implantable devices, which may be beneficial for other applications beyond hydrocephalus.