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Due to biofilm impenetrability, traditional antimicrobial agents are often ineffective in combating biofilms. Herein, a biphasic scaffold is reported as an antimicrobial delivery system by integrating nanofiber mats with dissolvable microneedle arrays for the effective treatment of bacterial biofilms. Different combinations of antimicrobial agents, including AgNO<jats:sub>3<\/jats:sub>, Ga(NO<jats:sub>3<\/jats:sub>)<jats:sub>3<\/jats:sub>, and vancomycin, are incorporated into nanofiber mats by coaxial electrospinning, which enables sustained delivery of these drugs. The antimicrobial agents\u2010incorporated dissolvable microneedle arrays allow direct penetration of drugs into biofilms. By optimizing the administration strategies, drug combinations, and microneedle densities, biphasic scaffolds are able to eradicate both methicillin\u2010resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA) and MRSA\/<jats:italic>Pseudomonas aeruginosa<\/jats:italic> blend biofilms in an ex vivo human skin wound infection model without necessitating surgical debridement. Taken together, the combinatorial system comprises of nanofiber mats and microneedle arrays can provide an efficacious delivery of multiple antimicrobial agents for the treatment of bacterial biofilms in wounds.<\/jats:p>","DOI":"10.1002\/adhm.202100135","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T18:55:54Z","timestamp":1619117754000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Simultaneous Delivery of Multiple Antimicrobial Agents by Biphasic Scaffolds for Effective Treatment of Wound Biofilms"],"prefix":"10.1002","volume":"10","author":[{"given":"Yajuan","family":"Su","sequence":"first","affiliation":[{"name":"Department of Surgery\u2010Transplant and Mary and Dick Holland Regenerative Medicine Program University of Nebraska Medical Center  Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alec","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Department of Surgery\u2010Transplant and Mary and Dick Holland Regenerative Medicine Program University of Nebraska Medical Center  Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon L.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Surgery\u2010Plastic Surgery University of Nebraska Medical Center  Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald R.","family":"Hollins","sequence":"additional","affiliation":[{"name":"Department of Surgery\u2010Plastic Surgery University of Nebraska Medical Center  Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangshun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology University of Nebraska Medical Center  Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8126-1397","authenticated-orcid":false,"given":"Jingwei","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Surgery\u2010Transplant and Mary and Dick Holland Regenerative Medicine Program University of Nebraska Medical Center  Omaha NE 68198 USA"},{"name":"Department of Mechanical and Materials Engineering College of Engineering University of Nebraska\u2010Lincoln  Lincoln NE 68588 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10201-4"},{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2016.94"},{"key":"e_1_2_7_1_3","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2017.99"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2018.10.011"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2011.0333"},{"key":"e_1_2_7_2_3","doi-asserted-by":"publisher","DOI":"10.12968\/jowc.2016.25.Sup9.S11"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ma11122468"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(00)01913-2"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-020-0420-1"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-017-0478-y"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ijos.2014.65"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2018.03.007"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/1751-7915.13471"},{"key":"e_1_2_7_6_3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168595"},{"key":"e_1_2_7_6_4","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201900599"},{"key":"e_1_2_7_6_5","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-07321-6"},{"key":"e_1_2_7_6_6","doi-asserted-by":"publisher","DOI":"10.1039\/C8NR09802F"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics11070322"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2016.02.006"},{"key":"e_1_2_7_7_3","doi-asserted-by":"publisher","DOI":"10.1039\/C8NR05784B"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-020-02884-3"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02001-07"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.3109\/17435390.2013.870243"},{"key":"e_1_2_7_10_1","first-page":"7520","volume":"10","author":"Gross C. 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