Fine-Tuned Functionalizable Terpolymer Brush Nanocoating Resists Protein Adsorption and Bacterial Adhesion while Promoting Macrophage Activity and Osteoblast Proliferation

Developing multifunctional biomaterial surfaces that resist biofouling while supporting cellular activity remains a significant challenge in biomedical engineering. We present a finely tuned functionalizable terpolymer brush nanocoating composed of zwitterionic carboxybetaine methacrylamide (CBMAA), sulfobetaine methacrylamide (SBMAA) and nonionic <i>N</i>-(2-hydroxypropyl) methacrylamide (HPMAA) with balanced antifouling cytocompatible characteristics through optimized surface hydration and charge. We analyzed chemical composition, thickness, <i>ζ</i>-potential, and wettability using X-ray photoelectron spectroscopy, infrared spectroscopy, spectroscopic ellipsometry, electrokinetic analysis, and water contact angle measurements. Systematic monomer ratio tuning identified poly(CBMAA 20 mol %-<i>co</i>-HPMAA 77 mol %-<i>co</i>-SBMAA 3 mol %) as the optimal composition, reducing protein adsorption by 98% in serum-rich media and suppressing <i>Staphylococcus epidermidis</i> and <i>Pseudomonas aeruginosa</i> adhesion by 99%, effectively preventing biofilm formation under both static and flow conditions. Furthermore, macrophages exhibit enhanced mobility on terpolymer coatings due to their high hydration and low protein adsorption, underpinning reduced adverse immune response. Postfunctionalization with Gly-Arg-Asp (RGD) peptides enabled the adhesion of osteoblast-like SaOS-2 cells while maintaining antifouling efficacy. The tunable multifunctionality of terpolymer brushes in resisting fouling, promoting macrophage phagocytic activity, and supporting SaOS-2 cell adhesion makes them suitable for both antifouling applications and medical implants requiring host tissue integration.