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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 \u201crough surface\u201d and \u201csmooth surface\u201d (average roughness: 7\u00a0\u03bcm\u2009\u00b1\u20094\u00a0\u03bcm and 1.4\u00a0\u03bcm\u2009\u00b1\u20090.3\u00a0\u03bcm, respectively). Focused ion beam-scanning electron microscopy (FIB-SEM) confirmed qualitatively the presence of a thin coating layer with an estimated thickness of 100\u00a0nm. 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-1\u03b2, interleukin-6, tumor necrosis factor-\u03b1 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\u2019 safety, integration, and longevity.<\/jats:p>","DOI":"10.1038\/s41598-025-25082-5","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T11:28:50Z","timestamp":1763724530000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparison between SBMA and MPC coatings on PEEK surface: stability over time and anti-inflammatory effects in vitr\ufeffo"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2337-1968","authenticated-orcid":false,"given":"Erika","family":"Roventini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3914-1957","authenticated-orcid":false,"given":"Francesco","family":"Iacoponi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3324-6400","authenticated-orcid":false,"given":"Aliria","family":"Poliziani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2205-286X","authenticated-orcid":false,"given":"Paolo","family":"Canepa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3473-2424","authenticated-orcid":false,"given":"Ornella","family":"Cavalleri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5816-9090","authenticated-orcid":false,"given":"Maria A.","family":"Cassa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2163-1296","authenticated-orcid":false,"given":"Paola","family":"Parlanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8976-3711","authenticated-orcid":false,"given":"Carlotta","family":"Pucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9542-3783","authenticated-orcid":false,"given":"Mauro","family":"Gemmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2149-7533","authenticated-orcid":false,"given":"Chiara","family":"Tonda-Turo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8797-3742","authenticated-orcid":false,"given":"Leonardo","family":"Ricotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"25082_CR1","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1038\/s41551-022-00937-8","volume":"6","author":"L Rosalia","year":"2022","unstructured":"Rosalia, L. et al. 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