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However, its role in regulating the interactions of peptide\u2010 and saccharide\u2010based materials with pathogens and immune cells remains to be fully elucidated. In this study, we selectively designed a pair of glycopeptide isomers, L\u2010FFK\u2010\u03b2\u2010D\u2010Gal and D\u2010FFK\u2010\u03b2\u2010D\u2010Gal, as biomimetic antibiotics to study how molecular chirality affects antibacterial and immunomodulatory activity. Although the nanofibers formed by the two isomers have similar morphology, in vitro experiments show that the L\u2010FFK\u2010\u03b2\u2010D\u2010Gal assemblies showed stronger bactericidal activity to both Gram\u2010positive bacteria and Gram\u2010negative bacteria than their D\u2010enantiomer counterparts. This enhanced antibacterial effect is mainly related to increased bacterial membrane permeability, impaired energy metabolism, signal transduction destruction, and L\u2010enantiomer\u2010induced amino acid biosynthesis inhibition. In vivo studies further show that these glycopeptide assemblies effectively reduce bone infections by directly eliminating bacteria and triggering chirality\u2010dependent antibacterial immune responses. This chiral glycopeptide\u2010based antibacterial immunotherapy pronouncedly enhances the antibacterial efficacy of biological materials, highlighting its potential for treating infectious osteomyelitis.<\/jats:p>","DOI":"10.1002\/adhm.71194","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T07:22:36Z","timestamp":1777274556000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chirality\u2010Modulated Glycopeptide Antibacterial Immunotherapy Against Osteomyelitis"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0867-0178","authenticated-orcid":false,"given":"Yingying","family":"Huang","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Science Zhejiang Chinese Medical University  Hangzhou China"},{"name":"Zhejiang Engineering Research Center For Tissue Repair Materials &amp; Wenzhou Key Laboratory of Biomaterials and Engineering Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Cheng","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science Zhejiang Chinese Medical University  Hangzhou China"},{"name":"Zhejiang Engineering Research Center For Tissue Repair Materials &amp; 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