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Antimicrobial polymers, with their ability to rapidly kill bacteria by disrupting or crossing membranes and\/or targeting multiple microbial functions without inducing resistance, offer a promising solution. This perspective explores recent innovations in the design and synthesis of antimicrobial polymers, focusing on their chemical motifs, structural derivatives, and their applications in combating systemic and topical infections. We also highlight key challenges in translating these materials from laboratory research to clinical practice, including issues related to the high dose required, bioavailability and stability in systemic infection treatment, and ability to disperse and kill biofilms in localized infection management. By addressing these challenges, antimicrobial polymers could play a crucial role in the development of next-generation therapeutics to combat multidrug-resistant pathogens. This perspective attempts to summarize significant insights for the design and development of advanced antimicrobial polymers to overcome AMR, offering potential pathways to improve clinical outcomes in treating systemic and local infections.<\/jats:p>","DOI":"10.1021\/acsbiomaterials.4c02147","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:04:51Z","timestamp":1744848291000},"page":"2470-2480","source":"Crossref","is-referenced-by-count":16,"title":["Chemical\nInnovations of Antimicrobial Polymers for\nCombating Antimicrobial Resistance"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6576-6838","authenticated-orcid":true,"given":"Zhangyong","family":"Si","sequence":"first","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Ningbo, China, 315300"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3761-7517","authenticated-orcid":true,"given":"Mary B.","family":"Chan-Park","sequence":"additional","affiliation":[{"name":"Nanyang Technological University , ,","place":["Singapore, 637459"]},{"name":"Nanyang Technological University , ,","place":["Singapore, 636921"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"2026090710065403700_cit1","volume-title":"The coming\nmicrobial crisis: Our antibiotic bubble is about to burst","author":"Ba\u0308umler","year":"2024"},{"issue":"8030","key":"2026090710065403700_cit2","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1038\/d41586-024-02971-9","article-title":"Tackling antimicrobial\nresistance needs a tailored approach\u2500four specialists weigh\nin","volume":"633","author":"Saha","year":"2024","journal-title":"Nature"},{"issue":"10459","key":"2026090710065403700_cit3","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1016\/S0140-6736(24)01867-1","article-title":"Global\nburden of bacterial\nantimicrobial resistance 1990\u20132021: a systematic analysis with\nforecasts to 2050","volume":"404","author":"Naghavi","year":"2024","journal-title":"Lancet"},{"issue":"5","key":"2026090710065403700_cit4","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1038\/s41579-022-00820-y","article-title":"Molecular\nmechanisms of antibiotic\nresistance revisited","volume":"21","author":"Darby","year":"2023","journal-title":"Nat. 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