Biocompatible Coating for Pediatric Blood Oxygenators

用于儿科血液氧合器的生物相容性涂层

• 批准号: 7154287
• 负责人: Patrick Thomas Cahalan
• 金额: $ 15.3万
• 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 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7154287
• 关键词: animal tissue; artificial membranes; biomaterial compatibility; biomaterial development /preparation; biomaterial evaluation; biomaterial interface interaction; blood; blood oxygenator; chemical property; heparin; medically underserved population; pediatrics; phospholipids; physical property; plasma; respiratory gas; surface coating; surface property

DESCRIPTION (provided by applicant): Project Summary/Abstract: Many oxygenators clinically available for adult and pediatric extracorporeal membrane oxygenation (ECMO) employ heparin coatings on microporous hollow fibers to improve biocompatibility. Despite application of these coatings, significant inflammatory and coagulation-related complications, as well as blood plasma leakage, remain associated with extended ECMO support. In addition, application of heparin coatings reduces permeance of the underlying hollow fiber membranes affecting their capacity to transfer oxygen and carbon dioxide. The reduction in gas exchange efficiency caused by the coating can, in some applications, result in greater total surface area requirements (a larger surface area oxygenator) for gas exchange, thus exacerbating the very inflammatory response problem the coating is intended to mitigate. The goal of this project is to develop an improved blood-compatible surface for initial use in pediatric ECMO. The proposed development program will simultaneously address optimization of blood compatibility and gas permeance characteristics of coated hollow fiber membranes. It is hypothesized that these specific improvements in biocompatibility will also result in a surface that prevents or substantially delays blood plasma leakage. The heparin-based coatings that will be evaluated will be very thin ionized plasma (IP)-deposited coatings that do not cover the pores in the wall of the hollow fiber membrane. The coatings will incorporate "spacer molecules" between the membrane surface and the heparin molecules to ensure that the immobilized heparin remains bioactive during use of the device. The coatings are expected to reduce or prevent blood plasma leakage by improving overall biocompatibility-thereby reducing damage to circulating blood elements-as well as by preventing or delaying adsorption of phospholipids on the fiber surfaces. Pre-Phase I process trials using hollow fiber oxygenator membranes have confirmed successful covalent coupling of heparin to the modified membranes. We have chosen pediatric ECMO as our initial target market for 2 key reasons; first, this patient population is underserved by industry due to lack of financial incentive in such a small market. From the applicant's experience, leveraging funding such as SBIR grants is 1 of the few ways to advance technology within this market. Secondly, we believe that successful use of these coatings in the very demanding pediatric ECMO application will convincingly demonstrate the effectiveness of our coating. Initial use in a demanding application, for a patient population without alternative treatments, will allow us to expand applications of this technology to larger markets such as acute respiratory distress syndrome (ARDS). Project Narrative: Children requiring extracorporeal membrane oxygenation (ECMO) have their blood exposed to large amounts of foreign material. The blood oxygenator used in ECMO is the largest source of this foreign material and is often coated to make the surface appear, "invisible" to the blood. However, these coatings deleteriously affect the performance of the oxygenator since they were never designed with this specific application in mind. This Phase I SBIR proposes development of a coating specifically designed for the blood oxygenator.

描述（由申请人提供）： 项目摘要/摘要：临床上可用于成人和儿童体外膜肺氧合（ECMO）的许多氧合器在微孔中空纤维上采用肝素涂层以提高生物相容性。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，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。在某些应用中，由涂层引起的气体交换效率的降低可能导致气体交换需要更大的总表面积（更大表面积的氧合器），从而加剧涂层旨在缓解的炎症反应问题。该项目的目标是开发一种改进的血液相容性表面，初步用于儿科 ECMO。拟议的开发计划将同时解决涂层中空纤维膜的血液相容性和气体渗透特性的优化。据推测，生物相容性的这些具体改进也将导致表面防止或显着延迟血浆渗漏。将要评估的肝素涂层将是非常薄的电离等离子体 (IP) 沉积涂层，不会覆盖中空纤维膜壁上的孔。涂层将在膜表面和肝素分子之间结合“间隔分子”，以确保固定的肝素在装置使用过程中保持生物活性。该涂层有望通过改善整体生物相容性（从而减少对循环血液成分的损害）以及防止或延迟纤维表面上磷脂的吸附来减少或防止血浆渗漏。使用中空纤维氧合器膜的第一阶段前工艺试验已证实肝素与改性膜成功共价偶联。我们选择儿科 ECMO 作为我们的初始目标市场有两个主要原因：首先，由于市场规模如此之小，缺乏财政激励，工业界对这一患者群体的服务不足。根据申请人的经验，利用 SBIR 拨款等资金是该市场内推进技术发展的少数方法之一。其次，我们相信，在要求非常严格的儿科 ECMO 应用中成功使用这些涂层将令人信服地证明我们涂层的有效性。最初在要求苛刻的应用中使用，对于没有替代治疗的患者群体，将使我们能够将该技术的应用扩展到更大的市场，例如急性呼吸窘迫综合征（ARDS）。项目叙述：需要体外膜肺氧合 (ECMO) 的儿童的血液暴露于大量异物。 ECMO 中使用的血液氧合器是这种异物的最大来源，通常会进行涂层处理，使表面看起来对血液“不可见”。然而，这些涂层会对充氧器的性能产生有害影响，因为它们在设计时从未考虑到这种特定应用。该第一期 SBIR 建议开发专为血液氧合器设计的涂层。