The Relation Between Protein Adsorption and Hemocompatibility of Antifouling Polymer Brushes.

Whenever an artificial surface comes into contact with blood, proteins are rapidly adsorbed onto its surface. This phenomenon, termed fouling, is then followed by a series of undesired reactions involving activation of complement or the coagulation cascade and adhesion of leukocytes and platelets leading to thrombus formation. Thus, considerable efforts are directed towards the preparation of fouling-resistant surfaces with the best possible hemocompatibility. Herein, a comprehensive hemocompatibility study after heparinized blood contact with seven polymer brushes prepared by surface-initiated atom transfer radical polymerization is reported. The resistance to fouling is quantified and thrombus formation and deposition of blood cellular components on the coatings are analyzed. Moreover, identification of the remaining adsorbed proteins is performed via mass spectroscopy to elucidate their influence on the surface hemocompatibility. Compared with an unmodified glass surface, the grafting of polymer brushes minimizes the adhesion of platelets and leukocytes and prevents the thrombus formation. The fouling from undiluted blood plasma is reduced by up to 99%. Most of the identified proteins are connected with the initial events of foreign body reaction towards biomaterial (coagulation cascade proteins, complement component, and inflammatory proteins). In addition, several proteins that are not previously linked with blood-biomaterial interaction are presented and discussed.

Complement Activation Dramatically Accelerates Blood Plasma Fouling On Antifouling Poly(2-hydroxyethyl methacrylate) Brush Surfaces.

Non-specific protein adsorption (fouling) triggers a number of deleterious events in the application of biomaterials. Antifouling polymer brushes successfully suppress fouling, however for some coatings an extremely high variability of fouling for different donors remains unexplained. The authors report that in the case of poly(2-hydroxyethyl methacrylate) (poly(HEMA)) this variability is due to the complement system activation that causes massive acceleration in the fouling kinetics of blood plasma. Using plasma from various donors, the fouling kinetics on poly(HEMA) is analyzed and correlated with proteins identified in the deposits on the surface and with the biochemical compositions of the plasma. The presence of complement components in fouling deposits and concentrations of C3a in different plasmas indicate that the alternative complement pathway plays a significant role in the fouling on poly(HEMA) through the "tick-over" mechanism of spontaneous C3 activation. The generated C3b binds to the poly(HEMA) surface and amplifies complement activation locally. Heat-inactivated plasma prevents accelerated fouling kinetics, confirming the central role of complement activation. The results highlight the need to take into account the variability between individuals when assessing interactions between biomaterials and blood plasma, as well as the importance of the mechanistic insight that can be gained from protein identification.