Covalent Engineering of a Durable Zwitterionic Sulfobetaine Interface on Titanium via Phosphonate Bridging and...

Biofouling of titanium implants, initiated by nonspecific protein adsorption and followed by bacterial and cellular adhesion, remains a critical challenge that compromises long-term implant performance. Herein, we report a covalent interfacial engineering strategy to construct a robust zwitterionic sulfobetaine interface on titanium via a stepwise grafting approach. This method integrates phosphonate anchoring, maleic anhydride activation, and subsequent ring-opening immobilization of sulfonated amines, enabling the formation of a chemically stable and high-density zwitterionic layer directly on the titanium surface. X-ray photoelectron spectroscopy confirms the successful progression of each functionalization step and the formation of well-defined interfacial chemistry. The optimized surface exhibits superhydrophilicity with a water contact angle of 14.75° and demonstrates ultralow fouling characteristics. Specifically, the modified interface significantly suppresses adhesion of Escherichia coli, human fibroblasts, and blood components by 87, 89, and 96%, respectively, compared to pristine titanium. Mechanistically, the densely grafted zwitterionic sulfobetaine moieties generate a strongly hydrated interfacial network that effectively inhibits protein adsorption and subsequent biofouling cascades. Importantly, the covalent Ti-O-P anchoring and stable amide linkages impart excellent resistance to hydrolytic degradation, maintaining antifouling performance after prolonged immersion in aqueous and physiological environments for up to three weeks. This work establishes a simple yet highly effective platform for covalent immobilization of zwitterionic functionalities on inert metal surfaces, offering a scalable and durable solution for next-generation antifouling and bioinert titanium-based medical implants.