Surface-attached PEO in the form of activated Pluronic with immobilized factor H reduces both coagulation and complement activation in a whole-blood model.
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.
Andersson
Jonas
J
Division of Clinical Immunology, Uppsala University, Uppsala, Sweden.
Bexborn
Fredrik
F
Klinth
Jeanna
J
Nilsson
Bo
B
Ekdahl
Kristina Nilsson
KN
D001672:Biocompatible Materials; D001777:Blood Coagulation / Q000187:drug effects*; D003167:Complement Activation / Q000187:drug effects*; D017242:Complement Factor H / Q000008:administration & dosage* / Q000302:isolation & purification; D003432:Cross-Linking Reagents; D004355:Drug Stability; D006801:Humans; D066298:In Vitro Techniques; D008422:Materials Testing; D020442:Poloxamer; D011092:Polyethylene Glycols; D013388:Succinimides; D013499:Surface Properties; D013501:Surface-Active Agents
D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D013388:Succinimides; D013501:Surface-Active Agents; D020442:Poloxamer; C018151:N-succinimidyl 3-(2-pyridyldithio)propionate; D011092:Polyethylene Glycols; D017242:Complement Factor H