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Controlling the post-implantation inflammatory phase is key to mitigating the foreign body reaction and promoting device integration. This paper compares three coating strategies for including anti-inflammatory agents onto polyether-ether-ketone (PEEK) surfaces, applying two different zwitterions, namely the 2-methacryloyloxyethyl phosphorylcholine (MPC) and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA). Two different PEEK surface types were also compared, namely “rough surface” and “smooth surface” (average roughness: 7 μm ± 4 μm and 1.4 μm ± 0.3 μm, respectively). Focused ion beam-scanning electron microscopy (FIB-SEM) confirmed qualitatively the presence of a thin coating layer with an estimated thickness of 100 nm. X-ray photoelectron spectroscopy and water contact angle measurements showed that both MPC and SBMA coatings were highly stable on the PEEK substrates for up to 8 weeks in simulated physiological conditions, when anchored to the PEEK surfaces by exploiting zwitterionic copolymers with N-[3-(dimethylamino)propyl]acrylamide and using a polydopamine adhesive layer. These coatings were also tested in vitro, evaluating their effects on cell adhesion, and the production of inflammatory markers such as interleukin-1β, interleukin-6, tumor necrosis factor-α and nitric oxide from M1 macrophages. The MPC-based coating on smooth PEEK surfaces showed the most remarkable effects, significantly supporting macrophage viability, reducing the release of pro-inflammatory cytokines, and inhibiting nitric oxide release, suggesting a superior capability to modulate inflammation. These findings pave the way for functional coatings to be used in vivo, with the aim of improving PEEK implants’ safety, integration, and longevity.</jats:p>"],"publicationDate":"2025-11-21","publisher":"Springer Science and Business Media LLC","embargoEndDate":null,"sources":["Crossref","Sci Rep","Scientific Reports"],"formats":["application/pdf"],"contributors":null,"coverages":null,"bestAccessRight":{"code":"c_abf2","label":"OPEN","scheme":"http://vocabularies.coar-repositories.org/documentation/access_rights/"},"container":{"name":"Scientific 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