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: 7687382
• 负责人: Patrick Thomas Cahalan
• 金额: $ 88.59万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7687382
• 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; Pump; 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; cost effective; design; feeding; improved; in vivo; meetings; pressure; prevent; public health relevance; 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）：许多在临床上可用于儿科（和成人）体外膜氧合（ECMO）使用肝素涂层，例如在设备表面上的CARMEDA生物活性表面，包括微孔空心纤维，以提高生物相容性。尽管采用了这些涂层，但与ECMO的扩展支持仍然相关。此外，当前肝素涂层的应用减少了基础空心纤维膜的渗透性，影响了它们传递氧气和二氧化碳的能力。这些涂层引起的气体交换效率的降低会导致更大的总生物材料表面积需求（较大的微孔空心纤维表面积氧化剂）加剧了炎症反应问题，涂层旨在减轻涂层，并导致启动量增加。在这项工作的第一阶段中，对旨在克服这些局限性并提供增强的生物活性和稳定性的五个离子化等离子体（IP）沉积涂层进行了原型型和评估。两期I涂料超过了我们第I期提议中概述可行性的标准。每个人都表现出足够水平的活性肝素和血浆耐药性，可缓解与长期使用膜氧合有关的并发症，而不会过度降低纤维的气体渗透率。这种可行性的证明值得一项正式的II阶段研究和开发工作，其总体目标是将涂料技术从概念验证验证到涂料组成和沉积过程的水平，并且足够一致，可以追求一件或两种涂料的商业化。拟议的开发计划将解决：1）优化涂料组成，2）优化涂料过程，3）全面的体外绩效评估，4）人类血液中的体外生物相容性评估和5）动物体内长期测试。在完成此II期项目后，我们将生产并验证了基于肝素的，生物相容性的涂层，该涂层在使用前进行了灭菌和储存后，可渗透，高度生物活性，并保留其生物活性，并预防或延迟血浆泄漏。这样的涂层具有减少与现有血氧和其他接触血液接触的医疗装置相关的炎症反应和随后的发病率的巨大潜力。 Ension将儿科血氧作为第一个用于改进的生物相容性涂层来解决的市场领域，尽管它仅代表了该产品的整体市场中的一小部分，因为它将允许快速开发并用作访问其他市场细分其他应用的垫脚石。体外膜氧合（ECMO）与严重的并发症和儿科患者的可能性较差有关，这是由于血液材料相互作用引起的血液而变化。公共卫生相关性：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发工作，该涂层具有高度生物活性，具有成本效益，并在使用前进行了灭菌和存储后保持其生物活性。这种涂层具有减少炎症反应和随后使用现有血氧和其他接触血液连接医疗设备而导致的发病率的巨大潜力。

项目成果

Effects of surface-bound and intravenously administered heparin on cell-surface interactions: inflammation and coagulation.

表面结合肝素和静脉注射肝素对细胞表面相互作用的影响：炎症和凝血。

• DOI: 10.1177/0267659113475834
• 发表时间: 2013
• 期刊: Perfusion
• 作者: Johnson,G;Curry,B;Cahalan,L;Prater,R;Biggerstaff,J;Hussain,A;Gartner,M;Cahalan,P
• 通讯作者: Cahalan,P