Biocompatible Coating for Pediatric Blood Oxygenators - Phase II

用于儿科血液氧合器的生物相容性涂层 - II 期

• 批准号: 7536166
• 负责人: Patrick Thomas Cahalan
• 金额: $ 69.15万
• 依托单位: ENSION, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7536166
• 关键词: Address; Adhesions; Adult; Affect; Animals; Area; Biocompatible; Biocompatible Materials; Blood; Blood Platelets; Calculi; Carbon Dioxide; Childhood; Coagulation Process; Deposition; Development; Devices; Embolism; Engineering; Equilibrium; Evaluation; Extracorporeal Membrane Oxygenation; Extravasation; Fiber; Fibrin; Gases; Generations; Heparin; Human; In Vitro; Inflammatory; Inflammatory Response; Leukocytes; Marketing; Measures; Mechanics; Medical Device; Membrane; Membrane Oxygenators; Methods; Morbidity - disease rate; Organ; Outcome; Oxygen; Oxygenators; Patients; Pediatrics; Penetration; Performance; Phase; Plasma; Platelet Activation; Platelet Count measurement; Process; Program Development; Public Health; Pump; Range; Research Design; Resistance; Sepsis Syndrome; Spectroscopy, Fourier Transform Infrared; Staging; Surface; System; Technology; Testing; Thick; Thrombin; Time; Visual; Work; adjudicate; aqueous; base; biomaterial compatibility; blood oxygenator; commercialization; concept; cost effective; day; design; feeding; improved; in vivo; pressure; prevent; research and development; research study; scale up; success; surfactant

DESCRIPTION (provided by applicant): Many oxygenators clinically available for pediatric (and adult) extracorporeal membrane oxygenation (ECMO) utilize heparin coatings such as Carmeda BioActive Surface on device surfaces, including the microporous hollow fibers, to improve biocompatibility. Despite application of these coatings, significant inflammatory and coagulation-related complications, as well as plasma leakage, remain associated with extended ECMO support. Furthermore, application of current heparin coatings reduces permeance of the underlying hollow fiber membranes affecting their capacity to transfer oxygen and carbon dioxide. Reductions in gas exchange efficiency caused by these coatings result in greater total biomaterial surface area requirements (a larger microporous hollow fiber surface area oxygenator) thus exacerbating the inflammatory response problem the coating is intended to mitigate, as well as leading to increased priming volumes. During Phase I of this work five ionized plasma (IP) deposited coatings designed to overcome these limitations and to provide enhanced bioactivity and stability were prototyped and evaluated. Two Phase I coatings exceeded the criteria outlined in our Phase I proposal to adjudicate feasibility. Each demonstrated sufficient levels of active heparin and plasma resistance to mitigate complications associated with long-term use of membrane oxygenation, without unduly decreasing the gas permeance of the fibers. This demonstration of feasibility warrants a formal Phase II research and development effort with the overall objective of advancing the coating technology from proof-of-concept to a level where coating composition and deposition processes are robust and sufficiently consistent to pursue commercialization of one or both coatings. The proposed development program will address: 1) optimization of coating composition, 2) optimization of coating processes, 3) comprehensive in vitro performance assessments, 4) in vitro biocompatibility evaluations in human blood, and 5) prolonged in vivo testing in animals. Upon completion of this Phase II project we will have produced and validated a heparin-based, biocompatible coating that is gas permeable, highly bioactive, maintains its bioactivity after being sterilized and stored prior to use, and prevents or delays plasma leakage. Such a coating has significant potential to reduce inflammatory response and subsequent morbidity associated with existing blood oxygenators and other blood-contacting medical devices. Ension has targeted pediatric blood oxygenators as the first market segment to be addressed with this improved biocompatible coating, even though it represents only a small portion of the overall market for this product, because it will permit rapid development and serve as a stepping stone for access to other applications in other market segments. Extracorporeal membrane oxygenation (ECMO) is associated with serious complications and potentially poor outcomes in pediatric patients due to changes to the blood resulting from blood- biomaterial interaction. PUBLIC HEALTH RELEVANCE: This Phase II project represents the main research and development effort for realization of a heparin-based biocompatible coating that is highly bioactive, cost- effective, and maintains its bioactivity after being sterilized and stored prior to use. Such a coating has significant potential to reduce inflammatory response and subsequent morbidity resulting from use of existing blood oxygenators and other blood-contacting medical devices.

描述（由申请人提供）：临床上可用于儿科（和成人）体外膜肺氧合（ECMO）的许多氧合器在设备表面（包括微孔中空纤维）上使用肝素涂层，例如 Carmeda BioActive Surface，以提高生物相容性。尽管应用了这些涂层，但严重的炎症和凝血相关并发症以及血浆渗漏仍然与延长 ECMO 支持有关。此外，当前肝素涂层的应用降低了下面的中空纤维膜的渗透性，影响了它们传输氧气和二氧化碳的能力。这些涂层引起的气体交换效率降低导致需要更大的总生物材料表面积（更大的微孔中空纤维表面积氧合器），从而加剧了涂层旨在缓解的炎症反应问题，并导致启动量增加。在这项工作的第一阶段，对五种电离等离子体 (IP) 沉积涂层进行了原型设计和评估，这些涂层旨在克服这些限制并提供增强的生物活性和稳定性。两个第一阶段涂层超出了我们第一阶段提案中概述的可行性判断标准。每一种都表现出足够水平的活性肝素和血浆抵抗力，以减轻与长期使用膜氧合相关的并发症，而不会过度降低纤维的气体渗透性。这种可行性论证保证了正式的第二阶段研究和开发工作，总体目标是将涂层技术从概念验证推进到涂层成分和沉积过程稳健且足够一致的水平，以实现一种或两种涂层的商业化。拟议的开发计划将解决：1）涂层成分的优化，2）涂层工艺的优化，3）全面的体外性能评估，4）人体血液的体外生物相容性评估，以及5）长时间的动物体内测试。该二期项目完成后，我们将生产并验证一种基于肝素的生物相容性涂层，该涂层具有透气性、高生物活性，在使用前灭菌和储存后仍能保持其生物活性，并防止或延迟血浆泄漏。这种涂层具有显着的潜力，可以减少与现有血液氧合器和其他血液接触医疗设备相关的炎症反应和随后的发病率。 Ension 将儿科血液氧合器作为这种改进的生物相容性涂层解决的第一个细分市场，尽管它只占该产品整个市场的一小部分，因为它将允许快速发展并作为进入市场的垫脚石其他细分市场的其他应用程序。由于血液-生物材料相互作用导致血液变化，体外膜肺氧合 (ECMO) 与儿科患者的严重并发症和潜在不良预后相关。公共健康相关性：该第二阶段项目代表了实现基于肝素的生物相容性涂层的主要研究和开发工作，该涂层具有高生物活性、成本效益，并在使用前灭菌和储存后保持其生物活性。这种涂层具有显着的潜力，可以减少由于使用现有的血液氧合器和其他血液接触医疗设备而导致的炎症反应和随后的发病率。