IMMOBILIZATION OF THEOPHYLLINE ON MEDICAL-GRADE POLYURETHANE INHIBITSSURFACE-INDUCED ACTIVATION OF BLOOD-PLATELETS

Conjugate molecule 2, in which theophylline and a 4-azidobenzoyl group are separated by a short spacer chain, was adsorbed onto polyurethane sheets and subsequently irradiated with ultraviolet light. The result ing photoreaction at the polymer surface led to immobilization of theo phylline. The modified polymer surface thus obtained was subjected to different physico-chemical experiments, i.e., X-ray photoelectron spec troscopy, attenuated total reflection infrared spectroscopy, and water contact-angle measurements. These experiments clearly pointed out tha t theophylline is linked to and exposed at the surface of the modified polymer. In addition, the modified surface was subjected to various i n vitro biochemical tests, i.e. (i) a thrombogenicity assay in which t he surface was contacted with either platelet-rich blood plasma (PRP) or platelet-free blood plasma (PFP), and formation of thrombin was mon itored as a function of time and (ii) studies focussed on adhesion of blood platelets to the surface, both in a static system, and under flo w conditions, The latter experiments were conducted with a parallel-pl ate flow chamber. The biochemical rests revealed that the modification leads to a marked increase of the lag-time for surface-induced thromb in formation provided that PRP was used in the test (experimental lag- times for the modified surface and the untreated control: ca. 1270 and 576 s, respectively). Using PFP, the fag-times of the modified and un treated surfaces do not differ substantially (698 and 549 s, respectiv ely), Studying adhesion of blood platelets in a static set-up, the mod ified surface showed adhesion of only few platelets with nearly unchan ged morphology, whereas extensive adsorption of activated platelets (e vident from spreading and formation of pseudopods) was found for the u ntreated control surface. These observations were made with scanning e lectron microscopy. The experiments with the parallel-plate flow chamb er showed adhesion of approximately 30.000 platelets per square cm of the modified surface, for shear rates in the range 12.5-300 s(-1). The density of adhered platelets for the untreated surface was found to b e higher by one order of magnitude.