Biomaterial-triggered complement activation pathways. Complement activation occurs via the CP, LP, or AP. All pathways converge to form C3 convertases and then C5 convertases, with release of the potent anaphylatoxins C3a and C5a. Generation of C5b triggers assembly of the C5b-9 MAC which induces lysis, damage, or cell activation. Regulation is achieved at multiple levels by soluble and membrane-associated factors (C1-INH, FH, FI, CD55, CD46, polyphosphate, CD59, clusterin, vitronectin, and thrombomodulin). C1-INH, C1 esterase inhibitor; CRP, C-reactive protein; TAFIa, activated thrombin activatable fibrinolysis inhibitor; TM, thrombomodulin. Readers are referred to 2 reviews for full descriptions of the pathways.^16,17