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

Area of Science:

• Biomaterials Science
• Immunology
• Surface Chemistry

Background:

• Non-specific protein adsorption, or fouling, is a major challenge for biomaterials.
• Antifouling polymer brushes often show unexplained variability in fouling across different plasma donors.

Purpose of the Study:

• To investigate the cause of variable fouling on poly(2-hydroxyethyl methacrylate) (poly(HEMA)) coatings using blood plasma from various donors.
• To elucidate the role of the complement system in accelerated fouling kinetics.

Main Methods:

• Analysis of fouling kinetics on poly(HEMA) using plasma from different donors.
• Identification of proteins deposited on the surface.
• Correlation of fouling with plasma biochemical composition, including complement components.
• Use of heat-inactivated plasma to assess the role of complement activation.

Main Results:

• Complement system activation significantly accelerates fouling kinetics of blood plasma on poly(HEMA).
• The alternative complement pathway, specifically spontaneous C3 activation and subsequent C3b binding, is identified as a key mechanism.
• Fouling deposits contain complement components, and C3a concentrations in plasma correlate with fouling rates.
• Heat-inactivated plasma demonstrated prevention of accelerated fouling, confirming complement's central role.

Conclusions:

• Individual variability in blood plasma significantly impacts biomaterial fouling due to differences in complement system activation.
• The 'tick-over' mechanism of the alternative complement pathway plays a critical role in poly(HEMA) fouling.
• Mechanistic insights into protein interactions, like complement activation, are essential for designing robust antifouling biomaterials.