Neutrophil adhesion on polyurethanes preadsorbed with high molecular weight kininogen

Area of Science:

• Biomaterials Science
• Immunology
• Surface Chemistry

Background:

• Biomaterial interactions with blood components, like neutrophils, cause complications in medical procedures (e.g., cardiopulmonary bypass, hemodialysis).
• Inhibiting neutrophil adhesion to biomaterials is a persistent challenge in developing safer medical devices.

Purpose of the Study:

• To investigate the effect of kininogen (HK) adsorption on neutrophil adhesion to various charged polyurethanes.
• To evaluate how HK adsorption influences surface density and the exposure of specific HK domains (D3 and D5H) crucial for neutrophil binding.

Main Methods:

• HK and HKa adsorption onto four polyurethanes: noncharged (PU), cationic (NR(4)), anionic (SO(3)), and zwitterionic (GPC).
• Quantification of adsorbed HK surface density and assessment of D3 and D5H domain exposure.
• Measurement of neutrophil adhesion to modified surfaces, including stimulation with fMLP to increase Mac-1 expression.

Main Results:

• High HK adsorption occurred on PU, NR(4), and SO(3) surfaces at protein concentrations ≥ 100 pmol/mL.
• NR(4) showed the highest HK adsorption and D3/D5H exposure, leading to significant neutrophil adhesion via Mac-1.
• SO(3) surfaces exhibited low D3/D5H exposure, preserving HK's anti-adhesive properties; GPC resisted neutrophil adhesion inherently.

Conclusions:

• Anionic (SO(3)) polyurethanes, when coupled with kininogen, can significantly reduce neutrophil adhesion.
• Zwitterionic (GPC) polyurethanes demonstrate inherent resistance to neutrophil adhesion due to their phosphorylcholine moiety.
• Both SO(3)-kininogen systems and GPC offer potential for developing biomaterial devices with reduced neutrophil adhesion.