van der Heiden A P, Goebbels D, Pijpers A P, Koole L H
Center for Biomaterials Research, Maastricht University, The Netherlands.
J Biomed Mater Res. 1997 Nov;37(2):282-90. doi: 10.1002/(sici)1097-4636(199711)37:2<282::aid-jbm19>3.0.co;2-g.
Phosphorylcholine groups attached to polymer surfaces are known to improve hemocompatibility. A photochemical method is presented to couple phosphorylcholine-containing aryl azides to poly(etherurethane) surfaces (PEUs). Two aryl azides that consist of a photoactivatable 4-azidobenzoyl group, a short spacer chain, and a phosphorylcholine endgroup were synthesized. The two compounds differ only in the type of spacer used: triethylene glycol for compound 1 and hexanediol for compound 2. These compounds were physically adsorbed to PEU surfaces. Upon UV irradiation, reactive intermediates are formed that react with nucleophilic groups on the polymer surface. The modified surfaces showed decreased underwater contact angles, indicating that hydrophilic phosphorylcholine groups are present at the surface. ESCA measurements showed the presence of phosphorus and positively charged nitrogen atoms in the outermost polymer layers (analyzed depth about 50 A), which is a strong indication of the presence of phosphorylcholine groups. Hemocompatibility in vitro was tested with thrombin generation assays and platelet adhesion tests. In thrombin generation assays the clotting time of platelet-rich plasma in contact with the polymer surface is determined. Clotting times were clearly prolonged for the modified surfaces. Surfaces modified with compound 2 showed slightly higher clotting times than those modified with compound 1. Repeated surface modification with compound 2 further increased the clotting time. For the tested surfaces an increase in the clotting time corresponds to an increase in the concentration of phosphorylcholine groups at the surface (as measured by ESCA and contact angle). Platelet adhesion studies with scanning electron microscopy demonstrated that fewer platelets (showing less activation) adhered to the modified surfaces than to the unmodified polyurethane.
已知附着在聚合物表面的磷酰胆碱基团可改善血液相容性。本文提出了一种光化学方法，将含磷酰胆碱的芳基叠氮化物偶联到聚（醚聚氨酯）表面（PEUs）。合成了两种由可光活化的4-叠氮苯甲酰基、短间隔链和磷酰胆碱端基组成的芳基叠氮化物。这两种化合物仅在所用间隔链的类型上有所不同：化合物1用三甘醇，化合物2用己二醇。这些化合物物理吸附在PEU表面。经紫外线照射后，会形成与聚合物表面亲核基团反应的活性中间体。改性表面的水下接触角减小，表明表面存在亲水性磷酰胆碱基团。ESCA测量表明，在聚合物最外层（分析深度约50埃）存在磷和带正电荷的氮原子，这有力地表明存在磷酰胆碱基团。通过凝血酶生成试验和血小板黏附试验对体外血液相容性进行了测试。在凝血酶生成试验中，测定富含血小板血浆与聚合物表面接触时的凝血时间。改性表面的凝血时间明显延长。用化合物2改性的表面比用化合物1改性的表面凝血时间略高。用化合物2反复进行表面改性进一步延长了凝血时间。对于测试表面，凝血时间的增加对应于表面磷酰胆碱基团浓度的增加（通过ESCA和接触角测量）。用扫描电子显微镜进行的血小板黏附研究表明，与未改性的聚氨酯相比，附着在改性表面的血小板（活化程度较低）较少。
