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Instead of designing implants to produce the desired immune responses, this might more easily be achieved with the use of surface modification technology, which can alter the biological profile of the implant without compromising function or performance. In the present study, we generated two polyelectrolyte (PE) multilayer (PEM) coatings from polystyrenesulfonate (PSS) and poly(allylamine hydrochloride) (PAH). These two coatings had identical chemical compositions, but the wettability and surface charge were adjusted by altering the deposition conditions. Testing the immune response to these coatings in vitro showed that the differing surface properties of the two coatings impacted morphology (circularity) and actin-cytoskeleton formation (podosomal structures) of THP-1-derived macrophages. We furthermore observed a substantial pro-inflammatory response toward the coating with the medium hydrophilic properties and moderate surface charge density (PEM_MH), while the highly hydrophilic and strongly negatively charged coating (PEM_HH) resulted in a much milder inflammatory response. Application of the latter coating to implant materials that elicited pronounced inflammatory responses resulted in a substantial reduction in the inflammatory response observed. This was validated by using blood-derived primary human immune cells. The dampened pro-inflammatory effect could be observed with two different materials: polymer membranes and titanium. Our results highlight the promise of pure PEM coatings without any additional substances as a tool to tune the immune response toward established medical implants.<\/jats:p>","DOI":"10.1021\/acsabm.5c01021","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T07:27:38Z","timestamp":1761636458000},"page":"9766-9779","source":"Crossref","is-referenced-by-count":1,"title":["Polyelectrolyte Multilayer\nCoatings As a Tunable Tool\nto Control Inflammatory Response to Biomaterials in Vitro"],"prefix":"10.1021","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3874-9012","authenticated-orcid":true,"given":"Florian","family":"Rosahl","sequence":"first","affiliation":[{"name":"NMI Natural and Medical Sciences Institute at the University of Tu\u0308bingen , ,","place":["Reutlingen, Germany, 72770"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So\u0308ren","family":"Segan","sequence":"additional","affiliation":[{"name":"NMI 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72770"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Strano","sequence":"additional","affiliation":[{"name":"NMI Natural and Medical Sciences Institute at the University of Tu\u0308bingen , ,","place":["Reutlingen, Germany, 72770"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Gerlach","sequence":"additional","affiliation":[{"name":"NMI Natural and Medical Sciences Institute at the University of Tu\u0308bingen , ,","place":["Reutlingen, Germany, 72770"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumen","family":"Krastev","sequence":"additional","affiliation":[{"name":"NMI Natural and Medical Sciences Institute at the University of Tu\u0308bingen , ,","place":["Reutlingen, Germany, 72770"]},{"name":"Reutlingen University, Faculty Life Sciences , ,","place":["Reutlingen, Germany, 72762"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4062-6043","authenticated-orcid":true,"given":"Tonya","family":"Andreeva","sequence":"additional","affiliation":[{"name":"Reutlingen University, Faculty Life Sciences , ,","place":["Reutlingen, Germany, 72762"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Schneiderhan-Marra","sequence":"additional","affiliation":[{"name":"NMI Natural and Medical Sciences Institute at the University of Tu\u0308bingen , ,","place":["Reutlingen, Germany, 72770"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Martin","sequence":"additional","affiliation":[{"name":"NMI Natural and Medical Sciences Institute at the University of Tu\u0308bingen , ,","place":["Reutlingen, Germany, 72770"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Burkhardt","sequence":"additional","affiliation":[{"name":"NMI Natural 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