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 美国有超过 1500 万患者患有慢性肺部疾病，这些患者的病情是逐渐恶化的。 呼吸功能下降，并伴有急性加重，导致短暂但危险的， 每年，这会导致 690 万人次去急诊室、70 万人次住院， 不幸的是，每年的肺移植手术数量不足 2,400 例。 如果不进行移植，患者就会死于疾病，因此非常需要一种安全、永久的方法 为了满足这一需求，我们正在开发一种能够永久呼吸的人工肺。 支持，肺辅助装置 (PAD) PAD 是一种紧凑、高度生物相容性的气体交换器， 当与心室辅助装置结合使用时，可以提供永久、移动、静脉或静脉动脉 可以为患有慢性肺病的患者提供持续数月至数年的体外呼吸支持。 在护理机构或家里，每 2-3 个月或更长时间返回医院进行定期 PAD 为了实现这一目标，PAD 必须具有比现有氧合器更好的生物相容性， 这会导致严重的出血并发症，同时还会因几周内形成凝块而失败。 通过采用新颖的专利 PAD 设计来实现这一目标，该设计专注于减缓凝块形成并对其进行涂覆 具有聚羧基甜菜碱 (DOPA-PCB) 表面涂层 DOPA-PCB 涂层可有效减少蛋白质。 人工肺的吸附、血小板结合和体内凝块形成。 涂层的开发是为了检查在长达 3 的储存期内是否仍能保持其抗凝功能 因此，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) 包含微型人工肺的 DOPA-PCB 涂层电路是否保持其 能够在体内测试期间减缓凝块形成和设备功能退化长达 3 个月 我们的第一阶段成功标准是 DOPA-PCB 涂层继续 (1) 减少。 纤维蛋白原吸附超过 80%，并且 (2) 最多 3 个月后血凝块重量减少超过 50% 如果成功，第二阶段研究将扩展所描述的测试。 长达六个月的储存，并在两个月的绵羊 ECMO 研究中检查涂层的有效性 全尺寸 PAD 涂有 DOPA-PCB 或商用肝素涂层，保存时间长达 6 经过几个月的研究，该涂层将准备好在传统 ECMO 期间进行商业应用。 重症监护病房外的支持或长期目标治疗。