Improving the Host Response to Implantable Glucose Sensors via Nitric Oxide Release

 描述(申请人提供)：糖尿病是一种代谢性疾病，困扰着2900多万美国人。这种疾病表现为血糖水平异常，导致其他重要的健康状况，包括肾衰竭、神经损伤、失明、心脏病发作和中风。对于300多万使用胰岛素控制高血糖的糖尿病患者来说，通过指刺试验频繁监测血糖浓度是疾病管理的协议。由于对血糖浓度的了解有限，手指点刺试验提供的间歇采样是不够的。无论是学术上的还是商业上的，许多工作都集中在开发一种植入式葡萄糖生物传感器，这种传感器可以实现连续的血糖监测。然而，即使是今天FDA批准的生物传感器也容易由于异物反应而导致分析性能差和使用寿命有限。为了纠正这一点，我们正在开发生物传感器，这种传感器可以缓慢释放低水平的一氧化氮(NO)，这是异物反应的媒介。在这项第二阶段的生物安全研究计划中，我们将使用不释放膜对现有的FDA批准的传感器进行改装，在糖尿病猪模型中验证传感器的性能，根据ISO-10993标准对我们的葡萄糖传感器膜进行生物兼容性测试，并准备并向美国食品和药物管理局提交指定申请和预提交申请。

 DESCRIPTION (provided by applicant): Diabetes mellitus is a metabolic disorder afflicting more than 29 million Americans. This disease manifests itself with abnormal blood glucose levels that lead to other significant health conditions including kidney failure, nerve damage, blindness, heart attack, and stroke. For more than 3 million diabetics using insulin to control hyperglycemia, frequent monitoring of blood glucose concentrations via finger prick testing is protocol for disease management. Intermittent sampling afforded by finger prick testing is inadequate due to the narrow glimpse of blood glucose concentrations provides. Much work, both academic and commercial, has focused on developing an implantable glucose biosensor that would allow for continuous blood glucose monitoring. However, even today's FDA-approved biosensors are prone to poor analytical performance and limited-use lifetimes due to the foreign body response. To remedy this, we are developing biosensors that slowly release low levels of nitric oxide (NO), a mediator of the foreign body response. In this Phase II SBIR Program, we will modify existing FDA-approved sensors with NO-release membranes, validate sensor performance in a diabetic pig model, subject our glucose sensor membranes to biocompatibility testing according to ISO-10993 standards; and, prepare for and file a request for designation (RFD) and a pre-submission with the U.S. Food and Drug Administration.