Complement activation by substituted polyacrylamide hydrogels for embolisation and implantation.

Abstract

An inflammatory reaction has always been observed in vivo around particles used for therapeutic embolisation. Hydrogel microspheres based on Trisacryl, prepared by polymerisation of N-acryloyl-2-amino-2-(hydroxymethyl)-1,3-propanediol in the presence of a crosslinking agent, are amongst the best materials for such a purpose. The aim of this work was to evaluate in vitro the complement-activating capacity of the OH-bearing Trisacryl particles either microporous, or macroporous, or partially substituted with carboxylate, or diethylaminoethyl, or sulphonate groups, in order to be able to decrease the inflammatory reaction in vivo. Complement was activated in the presence of Trisacryl, but about seven times less than in the presence of Sephadex, despite a quasi-similar density in OH groups, and more than two times less than in the presence of hydroxymethylated polystyrene despite a higher OH density. This demonstrates that not only OH density, but also other features linked to the type of polymeric backbone, are involved in complement activation by OH-bearing polymeric surfaces. The microporous and macroporous particles activated complement at a similar level when crushed and a slight increase was observed on the rough surface of the macroporous microspheres, but the presence of the macropores did not increase complement activation. Concerning the effects of substituting groups on Trisacryl, a clear decrease in the complement activation has been found only in the presence of sulphonate groups.