Biocompatible Coating for Pediatric Blood Oxygenators

DESCRIPTION (provided by applicant): 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 two 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 one 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). Children requiring extracorporeal membrane oxygenation (ECMO) have their blood exposed to larges 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.