Tanfloc and carboxymethyl-kappa-carrageenan polyelectrolyte multilayers impart antithrombotic activity, enhanced re-endothelialization and antimicrobial activity on blood-contacting materials.

Blood-contacting medical devices are susceptible to thrombosis, infection, and impaired endothelialization, complications that are often managed pharmacologically, despite the risk of systemic side effects. As an alternative, surface modification provides a localized strategy to improve hemocompatibility and reduce complications at the blood-material interface. Heparinized surfaces have been used for several decades in blood-contacting applications because heparinization mimics the lining of blood vessels and imparts multiple biochemical functions that improve blood compatibility. However, animal-derived heparin products have multiple challenges that motivate the search for alternatives. In this study, we developed multifunctional polyelectrolyte multilayer surfaces (PEMs) utilizing the polycation Tanfloc (TAN) combined with heparin and candidate plant-derived and animal-derived alternatives: carboxymethyl-kappa-carrageenan (CMKC), kappa-carrageenan (KC), or hyaluronic acid (HA), deposited on titania nanotube (TiNT) surfaces. We extensively characterized CMKC, a chemically modified polysaccharide that integrates both sulfate and carboxyl functional groups, aiming to replicate and potentially surpass the anticoagulant and antimicrobial performance of heparin-based coatings. TAN-CMKC coatings demonstrated exceptional biological outcomes, including significantly reduced fibrinogen adsorption, minimized platelet and leukocyte adhesion, and superior resistance against bacterial colonization by clinically relevant strains, Staphylococcus aureus and Pseudomonas aeruginosa. Furthermore, these multilayers markedly accelerated endothelial cell adhesion, proliferation, and migration, simultaneously suppressing smooth muscle cell (SMC) proliferation and phenotypic modulation. Comparative analyses revealed that CMKC's combined sulfate and carboxyl functionalities substantially enhanced hemocompatibility, endothelialization, and antimicrobial efficacy relative to coatings containing exclusively sulfate (KC), carboxyl (HA), or animal-derived heparin. This work substantiates TAN-CMKC PEMs as a potent, sustainable biomaterial strategy for advanced cardiovascular device coatings.