title: Studies on a new strategy for surface modification of polymeric biomaterials.
abstract: A new methodology to improve the hemocompatibility of polyurethane (medical grade Pellethane D-55) surfaces is reported. The approach is essentially based on a photochemical immobilization reaction. Two new conjugate molecules, compounds 2 and 3, were prepared. They consist of (i) dipyridamole, a well-known inhibitor of platelet activation, and a vasodilating drug with clinical application, for instance before and during pecutaneous transluminar coronary angioplasty (Dottering); and (ii) an aryl azide, a moiety that exhibits marked photoreactivity. In 2, the dipyridamole unit is directly linked to the aryl azide (via an ester bond), while a short spacer chain separates both units in 3. Upon irradiation of 2 or 3, adsorbed onto the polyurethane foil, the aryl azide is converted into a highly reactive species which reacts with a nucleophilic group on the polymer surface. In this way, the dipyridamole is covalently linked to the polymer. The underlying principle is also used in photoaffinity labeling, a well-known technique in biochemical studies on enzyme structure and function. From UV extinction experiments it could be deduced that the surface-density of immobilized 2 is 4.9 nmol/cm2. The surface density for 3 was 14.6 nmol/cm2. The surfaces were subjected to an in vitro thrombin generation assay. This assay gives a valuable impression about the hemocompatibility of artificial surfaces. These experiments revealed that the clotting times were substantially prolonged as a result of the photoimmobilization of dipyridamole. This was especially the case for immobilized 3. This effect cannot be readily explained. Possibly, the enhanced activity of immobilized 3 is due to the spacer chain. An alternative explanation is that the surface density is larger for 3 than for 2. In addition, the photomodified surfaces were incubated with platelet-rich blood plasma (37 degrees C, 30 min) and subsequently examined by scanning electron microscopy. The morphology of the blood platelets adhered to the surface also showed that hemocompatibility increased in the order untreated polyurethane < polyurethane with immobilized 2 < polyurethane with immobilized 3. Future work will concentrate on evaluation of the role of the spacer (length, hydrophilicity, etc.), as well as on the possible use of this approach with respect to the construction of biomaterials with improved in vivo biocompatibility, in particular hemocompatibility.
authors.affiliation: Biomaterials and Polymer Research Institute Maastricht-Eindhoven (Bioprime), University of Limburg, The Netherlands.
authors.forename: Y B
authors.initials: YB
authors.lastname: Aldenhoff
authors.forename: L H
authors.initials: LH
authors.lastname: Koole
mesh_terms: D000327:Adsorption; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry; D004176:Dipyridamole / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D010777:Photochemistry; D010973:Platelet Adhesiveness / Q000187:drug effects; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D011140:Polyurethanes; D013056:Spectrophotometry, Ultraviolet; D013499:Surface Properties; D013917:Thrombin / Q000096:biosynthesis; D014466:Ultraviolet Rays
chemical_list: D001672:Biocompatible Materials; D011108:Polymers; D011140:Polyurethanes; D004176:Dipyridamole; D013917:Thrombin