Biocompatible Coating for Pediatric Blood Oxygenators

描述（由申请人提供）：项目总结/摘要：临床上可用于成人和小儿体外膜氧合（ECMO）的许多氧合器在微孔中空纤维上采用肝素涂层，以改善生物相容性。尽管应用了这些涂层，但显著的炎症和凝血相关并发症以及血浆渗漏仍与延长的ECMO支持相关。此外，肝素涂层的应用降低了下层中空纤维膜的渗透性，影响其转移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导致用于气体交换的更大的总表面积需求（更大的表面积氧合器），从而加剧了涂层旨在减轻的非常炎症反应的问题。该项目的目标是开发一种改进的血液相容性表面，用于儿科ECMO的初始使用。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问题。据推测，这些生物相容性的具体改善也将导致防止或基本上延迟血浆泄漏的表面。将被评价的肝素基涂层将是非常薄的离子化等离子体（IP）沉积涂层，其不覆盖中空纤维膜壁中的孔。涂层将在膜表面和肝素分子之间引入“间隔分子”，以确保固定的肝素在装置使用期间保持生物活性。预期涂层通过改善整体生物相容性从而减少对循环血液元素的损害以及通过防止或延迟磷脂在纤维表面上的吸附来减少或防止血浆渗漏。使用中空纤维氧合器膜的预阶段I工艺试验已证实肝素与改性膜的共价偶联成功。我们选择儿科ECMO作为我们的初始目标市场有两个关键原因;首先，由于在这样一个小市场中缺乏经济激励，行业对这一患者人群的服务不足。根据申请人的经验，利用SBIR赠款等资金是在该市场推进技术的少数几种方法之一。其次，我们相信这些涂层在非常苛刻的儿科ECMO应用中的成功使用将令人信服地证明我们涂层的有效性。对于没有替代治疗的患者群体，在要求苛刻的应用中的初步使用将使我们能够将该技术的应用扩展到更大的市场，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，并且通常被涂覆以使表面看起来对血液“不可见”。然而，这些涂层不利地影响氧合器的性能，因为它们从未考虑到这种特定应用而设计。本阶段I SBIR建议开发专门为血液氧合器设计的涂层。

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.