title: Autoregulation of thromboinflammation on biomaterial surfaces by a multicomponent therapeutic coating.
abstract: Activation of the thrombotic and complement systems is the main recognition and effector mechanisms in the multiple adverse biological responses triggered when biomaterials or therapeutic cells come into blood contact. We have created a surface which is auto-protective to human innate immunity by combining three fundamentally different strategies, all developed by us previously, which have been shown to induce substantial, but incomplete hemocompatibility when used separately. In summary, we have conjugated a factor H-binding peptide; and an ADP-degrading enzyme; using a PEG linker on both material and cellular surfaces. When exposed to human whole blood, factor H was specifically recruited to the modified surfaces and inhibited complement attack. In addition, activation of platelets and coagulation was efficiently attenuated, by degrading ADP. Thus, by inhibiting thromboinflammation using a multicomponent approach, we have created a hybrid surface with the potential to greatly reduce incompatibility reactions involving biomaterials and transplantation.
authors.affiliation: School of Natural Sciences, Linnaeus University, Sweden.
authors.forename: Per H
authors.initials: PH
authors.lastname: Nilsson
authors.forename: Kristina N
authors.initials: KN
authors.lastname: Ekdahl
authors.forename: Peetra U
authors.initials: PU
authors.lastname: Magnusson
authors.forename: Hongchang
authors.initials: H
authors.lastname: Qu
authors.forename: Hiroo
authors.initials: H
authors.lastname: Iwata
authors.forename: Daniel
authors.initials: D
authors.lastname: Ricklin
authors.forename: Jaan
authors.initials: J
authors.lastname: Hong
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
authors.forename: Bo
authors.initials: B
authors.lastname: Nilsson
authors.forename: Yuji
authors.initials: Y
authors.lastname: Teramura
mesh_terms: D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology*; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology* / Q000528:radiation effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007249:Inflammation / Q000276:immunology* / Q000517:prevention & control; D008422:Materials Testing; D013499:Surface Properties; D013927:Thrombosis / Q000276:immunology* / Q000517:prevention & control
chemical_list: D020099:Coated Materials, Biocompatible