Evaluation of the Effect of Commercial Processing on Artificial Lung Zwitterionic Coatings

商业加工对人工肺两性离子涂层效果的评估

• 批准号: 9909574
• 负责人: David Skoog
• 金额: $ 29.81万
• 依托单位: ADVANCED RESPIRATORY TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-15 至 2021-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9909574
• 关键词: Acute; Address; Adsorption; Air Movements; Anticoagulants; Anticoagulation; Area; Beds; Binding; Blood; Blood Platelets; Blood flow; Cessation of life; Chronic lung disease; Clinical; Coagulation Process; Control Groups; Coupled; Dangerousness; Destinations; Development; Device Designs; Devices; Discipline of Nursing; Disease; Effectiveness; Electrons; Emergency department visit; Ensure; Evaluation; Fiber; Fibrinogen; Fibrinopeptide A; Floor; Frequencies; Gases; Goals; Hemorrhage; Heparin; Home environment; Hospitalization; Hospitals; Hour; Housing; Hydrogen Peroxide; Hydrophobicity; Intensive Care Units; Lead; Left; Legal patent; Lung; Lung Transplantation; Measures; Medical Device; Methods; Modeling; Monitor; Oryctolagus cuniculus; Oxygenators; P-Selectin; Patients; Phase; Platelet Count measurement; Polymers; Polypropylenes; Process; Proteins; Quality of life; Resistance; Respiratory physiology; Sampling; Scanning; Schedule; Self-Help Devices; Severity of illness; Sheep; Sterilization; Surface; Technology; Testing; Time; Transplantation; Weight; air filter; artificial lung; biomaterial compatibility; commercial application; design; experience; experimental study; in vivo; in vivo evaluation; novel; phase 2 study; respiratory; success; surface coating; thrombogenesis; ventricular assist device

Abstract Over 15 million patients in the U.S. suffer from chronic lung diseases. These patients experience a gradual decline in respiratory function that is coupled with acute exacerbations that lead to a transient, but dangerous, worsening of their disease. Yearly, this results in 6.9 million emergency room visits, 700,000 hospitalizations, and 180,000 deaths. Unfortunately, there are less than 2,400 lung transplants every year. Thus, most of these patients will succumb to their disease without a transplant, and there is a great need for a safe, permanent means of respiratory support. To address this need, we are developing an artificial lung capable of permanent respiratory support, the pulmonary assist device (PAD). The PAD is a compact, highly biocompatible gas exchanger that, when coupled with a ventricular assist device, can provide permanent, mobile, venovenous or venoarterial extracorporeal respiratory support lasting months to years. Patients with chronic lung disease could be supported within a nursing facility or at home and return to the hospital every 2-3 or more months for scheduled PAD replacement. To accomplish this goal, the PAD must have far greater biocompatibility than current oxygenators, which cause serious bleeding complications while also failing due to clot formation within a few weeks. This is accomplished by starting with a novel, patented PAD design focused on slowing clot formation and coating it with a polycarboxybetaine (DOPA-PCB) surface coating. The DOPA-PCB coating is effective at reducing protein adsorption, platelet binding, and in vivo clot formation in artificial lungs. The next commercial phase of the coating’s development is to examine if maintains its anticoagulation function over a storage period of up to 3 months. Thus, we will determine if (1) small, DOPA-PCB coated fiber samples maintain their ability to inhibit fibrinogen adsorption and (2) if DOPA-PCB coated circuits containing miniature artificial lungs maintain their ability to slow clot formation and device functional degradation during in vivo testing for up to 3 months after coating and sterilization. Our Phase I Success Criteria are that the DOPA-PCB coating continues to (1) reduce fibrinogen adsorption by greater than 80% and (2) reduces clot weight by greater than 50% after up to 3 months of storage when compared to the uncoated control. If successful, Phase II studies will extend the described tests out to six months of storage and examine coating effectiveness during two-month sheep ECMO studies using full-scale PADs coated with either DOPA-PCB or commercial heparin coatings and stored for periods of up to 6 months. Following these studies, the coating will be ready for commercial application during traditional ECMO support or longer-term, destination therapy outside of the intensive care unit.

抽象的 美国超过1500万患者患有慢性肺部疾病。这些患者经历了成绩 呼吸功能下降，加上急性加重，导致短暂但危险， 他们的疾病恶化。每年，这会导致690万急诊室就诊，70万住院治疗， 和180,000人死亡。不幸的是，每年不到2400个肺移植。那，大多数 患者将屈服于没有移植的疾病，并且非常需要安全，永久的手段 呼吸支持。为了满足这一需求，我们正在开发一种能够永久呼吸系统的人造肺 支持，肺辅助装置（PAD）。垫子是一种紧凑的，高度生物相容性的气体交换器， 当与心室辅助装置结合时，可以提供永久性，移动，人脉或静脉 体外呼吸支持持续数月到几年。可以支持患有慢性肺部疾病的患者 在护士设施或家里，每2-3或更长时间返回医院以进行预定的垫子 替代品。为了实现这一目标，垫必须比当前的充充的生物相容性要大得多， 这会导致严重的出血并发症，同时由于几周内凝块形成而失败。这是 通过从小说，专利的垫设计开始，以减慢凝块形成并涂覆它来完成 带有聚碳纤维（DOPA-PCB）表面涂层。 DOPA-PCB涂层可有效减少蛋白质 人造肺中的吸附，血小板结合和体内凝块形成。下一个商业阶段 涂料的发展是检查是否在最多3个存储期间保持其抗凝功能 月份。这是，我们将确定（1）小的DOPA-PCB涂层纤维样品是否保持其抑制能力 纤维蛋白原吸附和（2）如果含有微型人造肺的DOPA-PCB涂层电路 在体内测试期间最多3个月的体内测试期间慢慢凝块形成和设备功能降解的能力 涂层和灭菌。我们的I阶段成功标准是DOPA-PCB涂层继续（1）减少 纤维蛋白原的吸附大于80％，（2）将凝块的重量降低了3个月后的50％以上 与未涂层的对照相比，存储的存储空间。如果成功，第二阶段研究将扩展所述测试 在两个月的绵羊ECMO研究期间进行六个月的存储和检查有效性 涂有DOPA-PCB或商业肝素涂层的全尺寸垫，存储长达6个 月份。遵循这些研究，涂层将准备好在传统ECMO期间进行商业应用 重症监护室以外的支持或长期，目的地治疗。