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Quaternized polysaccharides are cationic antimicrobial candidates; however, the limitation of homogeneous synthesis solvents that affect the molecular structure and biological activities, as well as their drug resistance remains unclear. Therefore, the authors homogeneously synthesize a series of quaternized chitin (QC) and quaternized chitosan (QCS) derivatives via a green and effective KOH\/urea system and investigate their structure\u2013activity relationship and biological activity in vivo and in vitro. Their study reveals that a proper match of degree of quaternization (<jats:italic>DQ<\/jats:italic>) and degree of deacetylation (<jats:italic>DD\u2032<\/jats:italic>) of QC or QCS is key to balance antimicrobial property and cytotoxicity. They identify QCS\u20102 as the optimized antimicrobial agent with a <jats:italic>DQ<\/jats:italic> of 0.46 and <jats:italic>DD\u2032<\/jats:italic> of 82%, which exhibits effective broad\u2010spectrum antimicrobial properties, good hemocompatibility, excellent cytocompatibility, and effective inhibition of bacterial biofilm formation and eradication of mature bacterial biofilms. Moreover, QCS\u20102 exhibits a low propensity for development of drug resistance and significant anti\u2010infective effects on MRSA in vivo comparable to that of vancomycin, avoiding excessive inflammation and promoting the formation of new blood vessels, hair follicles, and collagen deposition to thus expedite wound healing.<\/jats:p>","DOI":"10.1002\/smll.202104885","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T10:57:36Z","timestamp":1644231456000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Quaternized Polysaccharide\u2010Based Cationic Micelles as a Macromolecular Approach to Eradicate Multidrug\u2010Resistant Bacterial Infections while Mitigating Antimicrobial Resistance"],"prefix":"10.1002","volume":"18","author":[{"given":"Fang","family":"Xie","sequence":"first","affiliation":[{"name":"Hubei Engineering Center of Natural Polymers\u2010based Medical Materials College of Chemistry &amp; Molecular Sciences Wuhan University  Wuhan 430072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biological Repositories Frontier Science Center for Immunology and Metabolism Medical Research Institute Zhongnan Hospital of Wuhan University Wuhan University  Wuhan 430071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximian","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering School of Materials Science and Engineering East China University of Science and Technology  Shanghai 200237 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Lu","sequence":"additional","affiliation":[{"name":"Hubei Engineering Center of Natural Polymers\u2010based Medical Materials College of Chemistry &amp; Molecular Sciences Wuhan University  Wuhan 430072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runhui","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering School of Materials Science and Engineering East China University of Science and Technology  Shanghai 200237 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biological Repositories Frontier Science Center for Immunology and Metabolism Medical Research Institute Zhongnan Hospital of Wuhan University Wuhan University  Wuhan 430071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0660-4740","authenticated-orcid":false,"given":"Jie","family":"Cai","sequence":"additional","affiliation":[{"name":"Hubei Engineering Center of Natural Polymers\u2010based Medical Materials College of Chemistry &amp; Molecular Sciences Wuhan University  Wuhan 430072 China"},{"name":"Research Institute of Shenzhen Wuhan University  Shenzhen 518057 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,7]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17042"},{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-1990-9"},{"key":"e_1_2_7_1_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1791-1"},{"key":"e_1_2_7_1_4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1708556114"},{"key":"e_1_2_7_1_5","doi-asserted-by":"publisher","DOI":"10.1038\/nature06536"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2007.24"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1145"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2005.04.017"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-0691.2003.00679.x"},{"key":"e_1_2_7_4_1","unstructured":"a) World Health Organization Antimicrobial resistance global report on surveillance WHO Geneva2014 257;"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature.2017.21550"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7CS00748E"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201506306"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2015.10.090"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2016.162"},{"key":"e_1_2_7_6_3","first-page":"1904106","volume":"24","author":"Wang Y.","year":"2019","journal-title":"Adv. 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