Covalent Engineering of a Durable Zwitterionic Sulfobetaine Interface on Titanium via Phosphonate Bridging and Anhydride Activation for Biofouling Resistance

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.