Thermoresponsive and Photocrosslinkable Poly(2-alkyl-2-oxazoline) Toolbox - Customizable Ultralow-Fouling Hydrogel Coatings for Blood Plasma Environments.

This study focuses on developing surface coatings with excellent antifouling properties, crucial for applications in the medical, biological, and technical fields, for materials and devices in direct contact with living tissues and bodily fluids such as blood. Our approach combines thermoresponsive poly(2-alkyl-2-oxazoline)s, known for their inherent protein-repellent characteristics, with established antifouling motifs based on betaines. The polymer framework was constructed from various monomer types, including a novel benzophenone-modified 2-oxazoline for photocrosslinking and an azide-functionalized 2-oxazoline, allowing subsequent modification with alkyne-substituted antifouling motifs through copper(I)-catalyzed azide-alkyne cycloaddition. From these polymers surface-attached networks were created on benzophenone-modified gold substrates via photocrosslinking, resulting in hydrogel coatings with several micrometers thickness when swollen with aqueous media. Given that poly(2-alkyl-2-oxazoline)s can exhibit a lower critical solution temperature in water, we compared their temperature-dependent solubility to the swelling behavior of the surface-attached hydrogels upon thermal stimulation. The antifouling performance of these hydrogel coatings in contact with human blood plasma was further evaluated by surface plasmon resonance and optical waveguide spectroscopy. All surfaces demonstrated extremely low retention of blood plasma components, even with undiluted plasma. Notably, hydrogel layers with sulfobetaine moieties allowed efficient penetration by plasma components, which could then be easily removed by rinsing with buffer. This article is protected by copyright. All rights reserved.