Nanocellulose as an Active Biointerface: Design Principles for Infection-Adaptive and Regenerative Biomaterials

Antibiotic resistance and biofilm-associated infections represent persistent barriers to effective tissue healing, particularly in chronic and implant-associated wounds. 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-specific 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-based platforms capable of disrupting mature biofilms and eliminating pathogenic bacteria. We highlight the breadth, versatility, and long-term 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-based hydrogels and scaffolds in future healthcare, positioning them as next-generation, clinically relevant platforms.