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This study reports the development of sulfonium\u2010cross\u2010linked hyaluronic acid (HA)\u2010based polymer (HA\u2010SS\u2010HA) as an inherent antimicrobial agent and antibiotic carrier. The HA\u2010SS\u2010HA polymer offers the potential for encapsulating various classes of antibiotics and accomplishing a stimuli\u2010responsive release profile in the presence of hyaluronidase produced by bacterial cells within their extracellular environment. Systematic antibacterial studies reveal that the HA\u2010SS\u2010HA\u2010encapsulated antibiotics (vancomycin, amoxicillin, and tetracycline) restore its activity against the antibiotic\u2010resistant bacterial cells methicillin\u2010resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA) and vancomycin\u2010resistant <jats:italic>Enterococci<\/jats:italic> (VRE), and <jats:italic>Pseudomonas aeruginosa<\/jats:italic>. The HA\u2010SS\u2010HA gel shows robust efficacy in eradicating the mature biofilm of <jats:italic>Staphylococcus aureus<\/jats:italic> (<jats:italic>S. aureus<\/jats:italic>). The membrane\u2010disrupting activity reveals that HA\u2010SS\u2010HA can also counteract the antibiotic resistance mechanism of the bacterial cells. The in vivo studies reveal excellent wound\u2010healing activity of HA\u2010SS\u2010HA in albino laboratory\u2010bred (BALB\/c) mice. The outcome of additional antibacterial studies reveals that antibiotics\u2010encapsulated HA\u2010SS\u2010HA hydrogel can effectively combat Gram\u2010negative, Gram\u2010positive, and antibiotic\u2010resistant bacterial strains. Therefore, revitalizing the activity of commercial antibiotics by HA\u2010SS\u2010HA can be considered a valuable and economically effective strategy to fight against antibiotic\u2010resistant bacteria.<\/jats:p>","DOI":"10.1002\/adhm.202302790","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T03:59:36Z","timestamp":1698811176000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Sulfonium\u2010Cross\u2010Linked Hyaluronic Acid\u2010Based Self\u2010Healing Hydrogel: Stimuli\u2010Responsive Drug Carrier with Inherent Antibacterial Activity to Counteract Antibiotic\u2010Resistant Bacteria"],"prefix":"10.1002","volume":"13","author":[{"given":"Anjali","family":"Patel","sequence":"first","affiliation":[{"name":"Centre for Environment Indian Institute of Technology Guwahati  Guwahati Assam 781039 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