Miniature Device to Promote Lung Development

描述（由申请方提供）：先天性腹股沟疝（CDH）影响1/2000的新生儿。CDH是一种疾病，其中部分隔膜无法形成，允许腹部器官迁移到胸部，导致受影响婴儿的肺发育不全（发育不全）。虽然在防治这一疾病方面取得了很大进展，但发病率和死亡率仍然很高。来自全球50多个中心的汇总结果表明，标准产后治疗的总生存率为68%。幸存者的特定发病率包括神经发育、营养、感觉神经性听力和肺功能缺陷。这种疾病对公共卫生的影响也很大，因为在最近的一项研究中，CDH已被确定为第三大成本最高的出生缺陷。这种先天性异常的严重后果导致其他人寻求在出生前纠正CDH或其主要后果肺发育不全的方法，从而允许更正常的出生后功能。迄今为止，最有希望的子宫内治疗包括完全闭塞胎儿气管，这已被证明可以促进肺生长。然而，该过程损害了已知严格调节适当肺发育的阶段性机械力。为了克服这一点，我们建议使用微型阀来提供动态气管闭塞（dTO），以促进肺生长。在初步实验中，在胎羊CDH模型中，使用定制设计的改良脑室腹膜分流阀来维持6-8 mmHg的气管压力，但允许肺液流出。与完全闭塞相比，dTO导致肺形态测量学和功能改善（接近正常）。在这里，我们建议进一步定义最佳肺生长的压力特性，并创建一个微型设备，将允许微创部署。为了创建该设备，将使用MEMS（微机电系统）微制造技术制造微型阀，该技术允许精确控制设备几何形状和性能规格。第I阶段的具体目标是：（1）建立微阀设计，开启压力在2-10 mmHg范围内;（2）确定最佳肺发育的阀压设置。 公共卫生相关性：大约每2000名新生儿中就有1名患有先天性腹股沟疝（CDH）。与囊性纤维化和脊柱裂一样常见，CDH由于胎儿肺发育不良而引起显著的长期发病率、死亡率和社会经济成本。建议的STTR项目的最终目标是应用新技术开发治疗CDH的微型设备。

DESCRIPTION (provided by applicant): Congenital diaphragmatic hernia (CDH) affects 1 in 2000 newborns. CDH is a disorder in which part of the diaphragm fails to form, allowing abdominal organs to migrate into the chest, resulting in lung hypoplasia (underdevelopment) in affected infants. Although great strides have been made in the management of this disease, significant morbidity and mortality persist. Pooled results from over 50 centers worldwide indicate overall survival to be 68% with standard, postnatal therapy. Specific morbidities in survivors include neurodevelopmental, nutritional, sensorineural hearing, and pulmonary function deficiencies. The public health impact of this disease is also significant, in that CDH has been identified as the third-most-costly of birth defects in a recent study. The severe consequences of this congenital anomaly have led others to pursue methods of correcting CDH or its main consequence, lung hypoplasia, prior to birth, allowing for more normal postnatal function. The most promising in utero therapy developed thus far consists of complete occlusion of the fetal trachea, which has been shown to encourage lung growth. However, this procedure impairs the phasic mechanical forces that are known to critically regulate proper lung development. To overcome this, we propose the use of a miniature valve to provide dynamic tracheal occlusion (dTO) to promote lung growth. In preliminary experiments, a custom-designed, modified ventriculoperitoneal shunt valve was used to maintain a tracheal pressure of 6-8 mmHg, yet allow for efflux of lung fluid, in a fetal lamb CDH model. Compared to complete occlusion, dTO resulted in improved (near-normal) lung morphometrics and function. Here, we propose to further define the pressure characteristics for optimal lung growth and to create a miniature device that will allow for minimally invasive deployment. To create the device, a microvalve will be made using MEMS (micro electro mechanical systems) microfabrication techniques that allow for precise control of device geometry and performance specifications. The Phase I Specific Aims are to: (1) Establish microvalve designs with opening pressures in the range of 2-10 mmHg and (2) Determine valve pressure setting for optimal lung development. PUBLIC HEALTH RELEVANCE: Congenital diaphragmatic hernia (CDH) afflicts approximately 1 in 2000 newborns. As common as cystic fibrosis and spina bifida, CDH incurs significant long-term morbidity, mortality, and socioeconomic costs due to poor fetal lung development. The ultimate goal of the proposed STTR project is to apply novel technologies to develop a miniature device for treatment of CDH.