Successful endothelialization of cardiovascular prostheses
Hemocompatibility of the blood-contacting surface of artificial cardiac prostheses remains a major challenge for their long-term clinical use. We hypothesized that the thrombogenicity of segmented polyurethanes (PUS) used for creating the blood sacs can be reduced by lining the luminal surface with autologous endothelial cells (EC). Over the past years we have optimized our approach by 1. choosing an appropriate (detoxified) biomaterial (Biospan@), 2. generating a controlled, roughened PU surface and 3. precoating the luminal surface with an autologous protein complex (APC) made from plasma cryoprecipitate, 4. using autologous EC isolated from adipose tissue or the jugular vein, 5. designing a seeding device with 3-D rotation, which allows for the effective, uniform endothelialization of fully assembled cardiac prostheses,and 6. developing techniques for non-destructive monitoring of the extent of EC coverage. In vitro studies confirm the importance of exposing the EC lining the blood sacs to hemodynamic forces (flow and cyclic strain) prior to implantation for establishing a nonthrombogenic, shear-resistant EC monolayer. We recently tested fully endothelialized Ventricular Assist Devices (VADs) in vitro in a mock-loop circulation (3.2 l/min flow at 1 Hz) for 6 and 24 hours. At 6 hours, no denudation was observed. After 24 hours the integrity of the EC-monolayer on fibronectin-coated PUS was partially (<300/o) impaired. By contrast, virtually no denudation was observed when the cells were seeded on Biospan@ precoated with bovine cryoprecipitate. Similar results were obtained in our first er vivo tests in which fully endothelialized VADs were connected to an extracorporeal aorta-to aorta bypass in a calf model. Our results provide the first evidence for sucecssful in vitro and w vivo testing of endothelialized VADs and stress the importance of the composition of the extracellular matrix for maintaining a durable EC monolayer.