Modifications to Polysaccharide Polyelectrolyte Multilayers: Improved Mechanical Stability and Hemocompatibility

Abstract

Cardiovascular implant surfaces and blood-contacting components of extracorporeal blood circuits induce blood clot formation (thrombosis) and red blood cell lysis (hemolysis) when in contact with flowing whole blood. These complications are prevented by systemic drugs, such as anticoagulant and antiplatelet therapies, which may cause additional complications. Therefore, stable surfaces that locally inhibit blood coagulation and hemolysis at the blood−material interface are an important research goal. Biopolymer-based polyelectrolyte multilayer surface coatings (PEMs) can modulate blood−material interactions. Ultrathin PEMs have been proposed as blood-compatible surfaces, but the mechanical stability of these nanoscale surfaces against shear forces has yet to be evaluated. Herein, we evaluated the mechanical durability of biomimetic PEM surfaces against shear flow and further modified these surfaces with polydopamine (PDA) and carbodiimide cross-linking to improve stability. The PDA-modified and cross-linked PEMs were more stable than unmodified PEMs. PDA-containing and cross-linked surfaces were compared to PEMs modified with proteoglycan mimetic nanoparticles and graft copolymers, which we have previously used to improve blood−material interactions. To evaluate hemocompatibility, we also performed whole blood clotting, thromboelastography, and hemolysis studies. All of the tested surfaces reduce clot formation when in contact with whole human blood. Modifying PEMs with PDA and amide cross-links improves their stability but does not significantly influence blood−material interactions. All of the surfaces prevent blood clotting when in direct contact with blood, indicating localized anticlotting activity. Only surfaces containing heparin nanoparticles and graft copolymers also reduce blood clotting or inhibit clot formation altogether in blood previously exposed to the surfaces, indicating potential systemic anticoagulant activity. PEMs are a versatile platform for developing blood-contacting materials, which are amenable to modifications that both increase mechanical stability and improve hemocompatibility.