Enhancing anti-thrombogenicity of biodegradable polyurethanes through drug molecule incorporation

Abstract

Sufficient and sustained anti-thrombogenicity is essential for blood-contacting materials, because blood coagulation and thrombosis caused by platelet adhesion and activation on material surfaces may lead to functional failure and even fatal outcomes. Covalently conjugating antithrombogenic moieties into polymer, instead of surface modifying or blending, can maintain the anti-thrombogenicity of polymer at a high level over a time range. In this study, series of randomly crosslinked, elastic, biodegradable polyurethanes (PU-DPA) were synthesized through a one-pot and one-step method from polycaprolactone (PCL) diol, hexamethylene diisocyanate (HDI) and anti-thrombogenic drug, dipyridamole (DPA). The mechanical properties, hydrophilicity, in vitro degradation, and anti-thrombogenicity of the resultant PU-DPA polymers can be tuned by altering the incorporated DPA amount. The surface and bulk hydrophilicity of the polyurethanes decreased with increasing hydrophobic DPA amount. All PU-DPA polymers exhibited strong mechanical properties and good elasticity. The degradation rates of the PU-DPAs decreased with increasing DPA content in both PBS and lipase/PBS solutions. Covalently incorporating DPA into the polyurethane significantly reduced the platelet adhesion and activation compared to the polyurethane without DPA, and also can achieve sustained anti-thrombogenicity. The PU-DPA films also supported the growth of human umbilical vein endothelial cells. The attractive mechanical properties, blood compatibility, and cell compatibility of this anti-thrombogenic biodegradable polyurethane indicate that it has a great potential to be utilized for blood-contacting devices, and cardiovascular tissue repair and regeneration.

Rational design of biodegradable thermoplastic polyurethanes for tissue repair

“…The cross-linked PUs are also easily integrated with desired biofunctions using appropriate functional components. Our group developed a nonthrombogenic biodegradable PUs from HDI, PCL, and dipyridamole (DPA, an antithrombogenic drug with four hydroxyl groups) via a one-pot/one-step synthesis [ 308 ]. A series of crosslinked conductive PUs from PGS and aniline pentamer are also interesting and have been used for neural cell culture [ 82 , 85 ].…”

Inhibition of Inflammation‐Associated Thrombosis with ROS‐Responsive Heparin‐DOCA/PVAX Nanoparticles

“…The larger of the BCI, the higher anticoagulant potential of the material has. Heparin sodium and Tirofiban are two commercial drugs to prevent thrombus on clinic medicine, which are used in this work for comparison. Heparin consists predominantly of 1–4 linked uronic acid and glucosamine subunits, and a specific pentasaccharide sequence of heparin is required for efficient binding of AT‐III.…”

Biobased polyurethanes for biomedical applications

“…This section is focused on the incorporation of active compounds directly into the PU backbone. With this approach, not only PUs access intrinsic antibacterial, anti-inflammatory [ 77 ] and/or antiplatelet adhesion properties [ 78 ], but in the case of implants, the bioactive compound can also be released during PU biodegradation, allowing a stable compound release over time [ 79 ]. In order to increase PU antimicrobial activity, known bactericide with initial active hydrogen functionalities might be used, such as chloramphenicol [ 80 ] or metal derivatives such as cobalt (II) hydroxide Co(OH)2 [ 81 ].…”