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，其特征是脑组织中 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。 通常使用长期植入的分流系统进行治疗，这在 维持脑积水患者的正常状态。不幸的是，这些重要的医疗 设备的高故障率在后两年内高达40%- 植入率在10年内达到98%。虽然脑积水可能是在生活中获得的， 大约每1000名新生儿中就有一人被诊断为先天性脑积水。这个 每年治疗儿童脑积水患者的医院护理费用估计为 在美国超过20亿美元。很大一部分分流故障可以归因于 因炎症反应、血栓或脉络膜导致的脑室导管阻塞 神经丛组织向内生长。尽管已经尝试使用原位清理方法 使用激光、超声波或电灼术来清除导管阻塞，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。对于患有以下疾病的患者 脑积水，一种自我清除的脑室导管，可以延缓生物污垢闭塞，可能导致 减少昂贵的分流替代手术，因此总体上减少了 发病率/死亡率。为了非侵入性地解决原位导管阻塞问题，我们开发了 基于薄膜的磁性微驱动器，并将其集成到可植入的导管中 努力创造自动清除的智能导管。与其他传感器相比，微细加工 静磁执行器由于其简单和强大，是对抗生物污垢的理想选择 驱动力。由于磁性微致动器由外部施加的磁力驱动 在现场，生物污垢的清除可以非侵入性地进行，而不需要额外的手术程序。 以前，我们已经演示了在静态和非静态情况下消除细胞阻塞的能力 然而，使用磁性微执行器的动态流体环境没有活体评估 已经完成了测量我们体内自我清除导管的功能能力。 在这项建议中，我们试图通过使用脑室内出血诱导的 动物模型。通过比较有无脑室导管的封堵过程 集成磁性微执行器，我们将能够确定生物污垢的去除能力 我们体内的自我清除导管。拟议中的研究结果将显著 提高我们对自清除导管对抗生物污垢能力的认识 在可植入设备上，这可能对脑积水以外的其他应用有利。

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.