Biocompatible Coating for Pediatric Blood Oxygenators - Phase II

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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.