as enzymes and sensing molecules for diverse applications in biosensors, bioseparation, and biocatalysis. [1] Compared to solid support materials such as synthetic polymer resins, inorganic particles, and polymer/inorganic composites, cellulose nanomaterials or nanocelluloses offer unique properties including versatile surface chemistry, biocompatibility, biodegradability, optical and mechanical performance. Nanocellulose-based materials including nanopaper and aerogel from nanofibrillated cellulose, [2] membranes/felts from electrospun cellulose nanofibers, [3] and cellulose nanocrystals (CNCs) [4] have been previously functionalized for point-of-care diagnosis, antibacterial medical textiles and filters, labeling and bioimaging applications. In addition, regenerated nanocellulose hydrogel, [5] bleached kraft wood pulp fibers, [6] filter paper, [7] and regenerated amorphous cellulose [8] have also been utilized for immobilization of functional enzymes, or for purification of cellulose-binding moduletagged protein. Furthermore, in order to obtain designed flow channels and pore structures instead of randomly packed columns for separation applications, regenerated cellulose columns have been prepared by using 3D printing and functionalized with ion exchange ligands for chromatographic purification of viral particles. [9] To avoid energyand resource-intensive production methods for the bottom-up fabrication of cellulose structures with hierarchical order over different length scales using nanocellulose or regenerated cellulose, top-down structural engineering and novel chemical modification methods are more favorable in redesigning wood for different functional applications. [10] Benefitting from the high amount of large, open-ended vessels in hardwood species (>30% of wood), enzymes have been immobilized on poplar wood by nanoparticle-mediated adsorption and used as a flow-through heterogeneous biocatalyst. [11] Hardwoods have two primary types of cells with very different geometries and functions: open-ended water-conducting vessels with a diameter of 50-800 µm, and load-bearing fibers of 1-2 mm length and 15 µm width. [12] On the other hand, tracheids with a width of ≈30 µm and a length of 2-4 mm are the predominant wood cells in softwood species. [12a] Tracheids are close-ended and joined top-to-bottom via pits to allow the conduction of water upward. Compared to hardwoods, softwoods have a rather homogenous cellular structure with uniform-sized wood cells (Figure S1, Supporting Information). Such cellular Protein immobilization on a stationary phase, such as nanocelluloses, is widely used in biodiagnostic, biocatalytic, and bioseparation applications. With the top-down approach which utilizes the native hardwood honeycomb structure, mesoporous cellulose scaffolds can be fabricated without the need for energy-consuming production and bottom-up assembly of nanocelluloses. However, this approach is difficult for preparing softwood-based cellulose scaffolds due to the disintegration of wood cells after complete ...