Complement activation on poly(ethylene oxide)-like radiofrequency glow discharge-deposited surfaces

Nonspecific protein adsorption, particularly fibrinogen (Fg), is thought to be an initiating step in the foreign body response (FBR) to biomaterials by promoting phagocyte attachment. In previous studies, we therefore prepared radiofrequency glow discharge (ethylene oxide)-like tetraglyme (CH(3)O(CH(2)CH(2)O)(4)CH(3)) coatings adsorbing <10 ng/cm(2) Fg and showed that they had the expected low monocyte adhesion in vitro. However, when these were implanted in vivo, many adherent inflammatory cells and a fibrous capsule were found, suggesting the role of alternative proteins, such as activated complement proteins, in the FBR to these materials. We therefore investigated complement interactions with the tetraglyme surfaces. First, because of its well-known role in complement C3 activation, we measured the hydroxyl group (-OH) content of tetraglyme, but found it to be low. Second, we measured C3 adsorption to tetraglyme from plasma. Low amounts of C3 adsorbed on tetraglyme, although it displayed higher binding strength than the control surfaces. Finally, complement activation was determined by measuring C3a and SC5b-9 levels in serum after incubating with tetraglyme, as well as other surfaces that served as positive and negative controls, namely poly(vinyl alcohol) (PVA) hydrogels, Silastic sheeting, and poly(ethylene glycol) self-assembled monolayers with different end groups. Despite displaying low hydroxyl group concentration, relatively high C3a and SC5b-9 levels were found in serum exposed to tetraglyme, similar to the values in our positive control, PVA. Our results support the conclusion that complement activation by tetraglyme is a possible mechanism involved in the FBR to these biomaterials.