Assessing protein antifouling performance and hemocompatibility of poly(2-isopropenyl-2-oxazoline) based hydrogels

• PiPOx hydrogels demonstrate excellent antifouling properties against serum proteins. • PiPOx hydrogels show excellent hemocompatibility outperforming PEG • Water exists predominantly in the non-freezing state in PiPOx hydrogels. Poly(2-isopropenyl-2-oxazoline) (PiPOx) is a versatile functional polymer used for the synthesis of biomaterials due to its biocompatibility, water solubility and possibility of polymer analogous modification. The 2-oxazoline pendent group allow facile modification with (di)carboxylic acids enabling access to a wide range of biomaterials including polymer conjugates, hydrogels and nanofibers. Despite its use in hydrogel synthesis for biomedical applications, its interactions with body fluids, particularly proteins were not investigated. In the present study, we report for the first time the potential of PiPOx hydrogels systems crosslinked with biofriendly hydroxy/amino acids to be used in blood contacting biomedical applications by evaluating their interaction with serum proteins at physiological relevant concentrations, and with human platelet-rich plasma. Differential scanning calorimetry (DSC) of swollen hydrogels was used to evaluate the water forms in the hydrogels and provide preliminary information on their blood compatibility. DSC shows that water predominantly exists in the non-freezing state, with its content strongly dependent on the crosslinker type. PiPOx hydrogels crosslinked with amino acids containing cationic groups display a higher amount of non-freezing water due to ion-dipole interactions, while hydroxyl-rich crosslinkers such as malic acid exhibit higher fractions of free water. The protein adsorption studies demonstrate superior anti-fouling properties even under high protein concentrations, particularly for the hydrogels crosslinked with amino acids. Furthermore, platelet adhesion assays confirm the excellent hemocompatibility of PiPOx hydrogels, outperforming the polyethylene glycol gold standard, due to the combined effects of network chemistry and hydrophilicity of 2-oxazoline groups.