Antiplatelet Co-drug Delivery System Surface Coating for Improved Hemocompatibility on a Nitric Oxide-Releasing Medical-Grade Polymer

Abstract Polycaprolactone (PCL) is a biodegradable polymer widely used in biomedical applications; however, its hydrophobic surface promotes protein adsorption, platelet activation, bacterial adhesion, and thrombosis, limiting its use in blood-contacting devices. In this work, we report a multifunctional co-drug delivery coating approach that modifies native PCL to enhance hemocompatibility. A nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP), is incorporated within the PCL substrate to provide sustained antiplatelet, antithrombotic, and antibacterial activity, while a hydrophilic HydroMed D4 polyurethane coating loaded with the antiplatelet drug ticagrelor (TIC) forms an antibiofouling interface and enables controlled drug elution. The performance of this integrated system was evaluated as a function of TIC loading and compared with relative controls to assess its antifoulant and thromboresistant properties under plasma protein and whole-blood exposure. The layered coating significantly reduced protein adsorption, platelet adhesion/activation, and bacterial attachment compared with single-component surfaces, demonstrating complementary effects that enhance hemocompatibility. This platform establishes a scalable approach to engineer biodegradable polymers into multifunctional coatings suitable for blood-contacting medical devices, such as catheters and vascular interfaces.