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These bacteria are growing increasingly recalcitrant to frontline antimicrobial therapeutics like vancomycin due to the prevalence of variant populations such as methicillin\u2010resistant and vancomycin\u2010resistant strains, and there is currently a dearth of novel antibiotics in production. Additionally, <jats:italic>S. aureus<\/jats:italic> has the capacity to hijack the host clotting machinery to generate fibrin\u2010based biofilms that confer protection from host antimicrobial mechanisms and antibiotic\u2010based therapies, enabling immune system evasion and significantly reducing antimicrobial efficacy. Emphasis is being placed on improving the effectiveness of therapeutics that are already commercially available through various means. Fibrin\u2010based nanoparticles (FBNs) were developed and found to interact with <jats:italic>S. aureus<\/jats:italic> through the clumping factor A (ClfA) fibrinogen receptor and directly integrate into the biofilm matrix. FBNs loaded with antimicrobials such as vancomycin enabled a targeted and sustained release of antibiotic that increased drug contact time and reduced the therapeutic dose required for eradicating the bacteria, both in vitro and in vivo. Collectively, these findings suggest that FBN\u2010antibiotic delivery may be a novel and potent therapeutic tool for the treatment of <jats:italic>S. aureus<\/jats:italic> biofilm infections.<\/jats:p>","DOI":"10.1002\/jbm.a.37760","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T12:37:13Z","timestamp":1718368633000},"page":"2071-2085","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Fighting fibrin with fibrin: Vancomycin delivery into coagulase\u2010mediated <i>Staphylococcus aureus<\/i> biofilms via fibrin\u2010based nanoparticle binding"],"prefix":"10.1002","volume":"112","author":[{"given":"Grant","family":"Scull","sequence":"first","affiliation":[{"name":"Joint Department of Biomedical Engineering NC State University and UNC\u2010Chapel Hill  Raleigh North Carolina USA"},{"name":"Comparative Medicine Institute NC State University  Raleigh North Carolina 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