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Despite substantial advances in material design, most antibacterial wound dressings remain passive, empirically developed, and poorly adapted to the dynamic biological microenvironment of infection. Nanocellulose (NC), offers exceptional mechanical strength, high surface area, and excellent biocompatibility, positioning it as a versatile matrix for advanced therapeutic applications. Recent innovations focus on engineering NC composites through functionalization with bioactive moieties that enable the activation or localized release of antimicrobial agents selectively within pathological microenvironments. These advanced NC systems are specifically designed to overcome biofilm penetration barriers while minimizing systemic toxicity through site\u2010specific intervention. This review delineates the evolution from fundamental material design principles, such as NC morphology control and surface chemistry modulation, to the development of NC\u2010based platforms capable of disrupting mature biofilms and eliminating pathogenic bacteria. We highlight the breadth, versatility, and long\u2010term potential of NC derivatives and composites as adaptable platforms for antibacterial and antibiofilm applications across multiple infected tissues, including skin, bone, diabetic foot ulcers, and dental infections. Furthermore, we emphasize the translational significance of NC\u2010based hydrogels and scaffolds in future healthcare, positioning them as next\u2010generation, clinically relevant platforms.<\/jats:p>","DOI":"10.1002\/smll.74933","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T15:36:57Z","timestamp":1786030617000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nanocellulose as an Active Biointerface: Design Principles for Infection\u2010Adaptive and Regenerative Biomaterials"],"prefix":"10.1002","volume":"22","author":[{"given":"Tejal V.","family":"Patil","sequence":"first","affiliation":[{"name":"Department of Biosystems Engineering Kangwon National University  Chuncheon Republic of Korea"},{"name":"Interdisciplinary Program in Smart Agriculture Kangwon National University  Chuncheon Republic of Korea"},{"name":"Institute of Forest Science Kangwon National University  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