Andersson Jonas, Bexborn Fredrik, Klinth Jeanna, Nilsson Bo, Ekdahl Kristina Nilsson
Division of Clinical Immunology, Uppsala University, Uppsala, Sweden.
J Biomed Mater Res A. 2006 Jan;76(1):25-34. doi: 10.1002/jbm.a.30377.
In the present work we have bound Pluronic, a class of triblock copolymers consisting of a block of polypropylene oxide (PPO) surrounded on each side by polyethylene oxide (PEO) blocks, to polystyrene surfaces and investigated the thrombogenicity and complement activation of this construct upon exposure to whole blood. The surface was highly inert towards coagulation, unfortunately at the expense of increased complement activation. We, therefore, as an alternative approach, used End-Group Activated Pluronic to conjugate factor H, a regulator of complement activation (RCA), to the surface. The bound factor H did not detach from the surface upon incubation with human serum. Furthermore, factor H bound in a physiological conformation could to a significant degree attenuate complement activation at the Pluronic surface. Thus, we have created a hybrid surface in which the coagulation-inert properties of the original Pluronic are supplemented with a specific complement-inhibitory effect. Medical device technology includes numerous potential applications for crosslinkers that are capable of specifically binding biomolecules to surfaces with retained activity. These applications include coupling of functional biomolecules to biomedical devices such as stents and grafts. The biomolecule may be an RCA, antibody, or other beneficial ligand.
在本研究中,我们将普朗尼克(一类三嵌段共聚物,由聚环氧丙烷(PPO)嵌段和两侧的聚环氧乙烷(PEO)嵌段组成)连接到聚苯乙烯表面,并研究了该构建体在接触全血时的血栓形成性和补体激活情况。该表面对凝血具有高度惰性,但遗憾的是,这是以补体激活增加为代价的。因此,作为一种替代方法,我们使用端基活化的普朗尼克将补体激活调节剂(RCA)因子H偶联到表面。与人血清孵育后,结合的因子H未从表面脱离。此外,以生理构象结合的因子H在很大程度上可以减弱普朗尼克表面的补体激活。因此,我们创建了一种混合表面,其中原始普朗尼克的凝血惰性特性辅以特定的补体抑制作用。医疗设备技术包括交联剂的众多潜在应用,这些交联剂能够将生物分子特异性结合到具有保留活性的表面。这些应用包括将功能性生物分子偶联到生物医学设备,如支架和移植物。生物分子可以是RCA、抗体或其他有益配体。