Ex vivo evaluation of blood coagulation on endothelial glycocalyx-inspired surfaces using thromboelastography

Zang, Yanyi; Vlcek, Jessi; Cuchiaro, Jamie; Popat, Ketul C.; Olver, Christine S.; Kipper, Matt J.; Reynolds, Melissa M.

doi:10.1007/s44164-021-00001-w

Cited by 2 publications

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References 69 publications

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“…We have previously reported on PEM surfaces that mimic features of the endothelial glycocalyx and that thereby reduce platelet adhesion and activation, reduce protein adsorption and polymerization, suppress pro-inflammatory responses from leukocytes and macrophages, and reduce bacterial attachment. ,,,,, These biomimetic surfaces designed to mimic the topography and chemistry of the glycocalyx are composed of (polycationic) chitosan and (polyanionic) hyaluronan PEMs, with heparin- or chondroitin sulfate-containing proteoglycan-like nanoparticles and graft copolymers adsorbed onto their surfaces. ,, These materials have shown promise as blood-contacting materials, and their interactions with bacteria, platelets, blood proteins, and leukocytes have been evaluated. , We have also recently reported studies of the stability of these surfaces with respect to enzymatic degradation . However, their interactions with whole human blood and their mechanical durability under flowing fluid have not yet been characterized.…”

Section: Introductionmentioning

confidence: 99%

Modifications to Polysaccharide Polyelectrolyte Multilayers: Improved Mechanical Stability and Hemocompatibility

Vlcek

Reynolds

Kipper

2022

ACS Appl. Polym. Mater.

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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.

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