title: Complement inhibition in biomaterial- and biosurface-induced thromboinflammation.
abstract: Therapeutic medicine today includes a vast number of procedures involving the use of biomaterials, transplantation of therapeutic cells or cell clusters, as well as of solid organs. These treatment modalities are obviously of great benefit to the patient, but also present a great challenge to the innate immune system, since they involve direct exposure of non-biological materials, cells of non-hematological origin as well as endothelial cells, damaged by ischemia-perfusion in solid organs to proteins and cells in the blood. The result of such an exposure may be an inappropriate activation of the complement and contact/kallikrein systems, which produce mediators capable of triggering the platelets and PMNs and monocytes, which can ultimately result in thrombotic and inflammatory (i.e., a thrombo-inflammatory) response to the treatment modality. In this concept review, we give an overview of the mechanisms of recognition within the innate immunity system, with the aim to identify suitable points for intervention. Finally, we discuss emerging and promising techniques for surface modification of biomaterials and cells with specific inhibitors in order to diminish thromboinflammation and improve clinical outcome.
authors.affiliation: Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, SE-751 85 Uppsala, Sweden; Linnæus Center of Biomaterials Chemistry, Linnæus University, SE-391 82 Kalmar, Sweden.
authors.forename: Kristina N
authors.initials: KN
authors.lastname: Ekdahl
authors.affiliation: Linnæus Center of Biomaterials Chemistry, Linnæus University, SE-391 82 Kalmar, Sweden.
authors.forename: Shan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, SE-751 85 Uppsala, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Nilsson
authors.affiliation: Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, SE-751 85 Uppsala, Sweden; Department of Bioengineering, The University of Tokyo, 7-3-1Hongo, Bunkyo-Ku, Tokyo, 113-8656, Japan. Electronic address: teramura@bioeng.t.u-tokyo.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Teramura
mesh_terms: D001672:Biocompatible Materials / Q000009:adverse effects / Q000627:therapeutic use*; D001792:Blood Platelets / Q000276:immunology*; D003167:Complement Activation; D003165:Complement System Proteins / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation / Q000276:immunology / Q000628:therapy*; D058990:Molecular Targeted Therapy; D013922:Thrombocytosis / Q000276:immunology / Q000628:therapy*
chemical_list: D001672:Biocompatible Materials; D003165:Complement System Proteins
keywords: Biomaterials; Coagulation; Complement; Inflammation; Platelets; Therapeutic medicine