New acrylic microspheres for arterial embolization: Combining radiopacity for precise localization with immobilized thrombin to trigger local blood coagulation

Abstract Particles currently used in arterial embolization therapy have several disadvantages, most importantly their radiolucency. This means the radiologist cannot precisely asses the fate of embolization particles. Microspheres that combine two additional features have been designed. By incorporating an iodine containing monomer, radiopaque microspheres were obtained that display good visibility under standard X-ray conditions. Incorporation of methacrylic acid makes the surface of the spheres suitable for surface functionalization. Here, thrombin was covalently attached to the surface of the radiopaque microspheres. By induction of a thrombus, improved anchoring of the embolization spheres in the blood vessel can be obtained. The immobilized thrombin induced a biphasic response of the blood namely: (1) fast deposition of fibrin on the surface resulting in sphere aggregation and (2) additional thrombin generation in the surrounding blood and a subsequent local thrombus formation. These microspheres with both intrinsic X-ray visibility and a biofunctionalized surface can potentially improve embolization therapies.