Bridging nanocellulose and biological responses through protein corona complexes

Nanocellulose (NC) has emerged as a promising sustainable biomaterial for diverse biomedical applications, including drug delivery, tissue engineering, and regenerative medicine. Upon exposure to biological fluids, NC surfaces are immediately coated with proteins, forming a protein corona (PC) that fundamentally redefines the material's biological identity and governs its biocompatibility, cellular interactions, and therapeutic efficacy. This review systematically examines how NC's physicochemical properties, including surface charge, functional groups, crystallinity, dimensions, and morphology, dictate PC formation and composition, subsequently influencing cellular uptake, immune responses, and intracellular signaling pathways. We further discuss strategic surface engineering approaches to modulate PC formation for optimized biomedical performance, alongside current challenges and future perspectives in personalized medicine applications. By elucidating the NC-PC interface dynamics, this review provides critical insights for rational design and high-value utilization of NC-based biomaterials in advanced biomedical applications.