# Cellulose Nanofibers and Other Biopolymers for Biomedical Applications. A Review
## 2 Nanocellulose and Other Cellulose Derivatives  
Cellulose is the most abundant polymer on the planet--40% of all organic matter is cellulose with 75-100 billion [1] tonnes produced each year through photosynthesis (wood and cotton being the primary industrial sources) [29]. Cellulose was first discovered in 1838 and is the principle constituent of plant cell walls. Structurally, cellulose is a carbohydrate with similar chemical composition to starch (C\({}_{6}\)H\({}_{10}\)O\({}_{5}\))\({}_{\rm{n}}\). Although the chemical composition is similar, and both are formed by glucose as a monomer with (1,4) glycosidic bonds, there is a difference in the type of bond, since the cellulose monomers are \(\beta\)-1,4 bonds, and the starch bonds are \(\alpha\)-1,4. However, unlike starch, cellulose is insoluble in water solvents. Starch (formed by amylose and amylopectin) dissolves in water because of the \(\alpha\)-1,4 glycosidic causes the formation of a helical structure that does not form inter-strand hydrogen bonds, producing easily-disruptable non-polar interactions between glucopyranose rings. In the case of the cellulose, this presents a structure that is tightly bound in a set of hydrogen bonds between individual chains, resulting in an inter-strand hydrogen bond (Figure 1A) that can easily expand and flex to allow the penetration of water, which together with its higher degree of polymerisation, mean that it is insoluble. Currently, nanomaterials derived from cellulose have garnered significant interest, due to their excellent inherent and physical properties, such as high tensile strength and elastic modulus (130-150 GPa), high specific surface area (up to several hundreds of m\({}^{2}\)/g), low density (1.6 g/cm\({}^{3}\)), reactive surfaces combined with biodegradability and renewability [9]. Figure 1B-E shows different examples of the structure of nanocellulose obtained using transmission electron microscopy. Nanocellulose has been widely used for biomedical applications, due to its attractive properties of biocompatibility, mechanical strength, chemical and morphological controllability [1; 32]. CNC and CNF have been used in hydrogel preparation for several applications, such as wound dressing [1], drug delivery [33] and tissue engineering scaffolding [34]. Also, BNC is believed to be a promising and cost-efficient natural nanomaterial for biomedical applications, due to the high mechanical properties and its high purity and non-toxic properties. In this case, there are two major limitations to the use of BNC in biomedical uses. One of them is its limited production because of the high capital investments, production cost and lack of well-organised scale-up processes. Another problem is that the pore size of the BNC matrix is not sufficiently big to house the cells, limiting the cell penetration and hindering their proliferation and differentiation. In order to reduce the production costs of the BNC, several lines of action are being carried out, such as the study of the influence of static and agitated modes to optimise the production process [35], the discovery of new and more effective strains to produce BNC [36], and the use of novel substrates rich in sugars, such as agri-food industry wastewater, wood extracts, etc. [37; 38]. Its rheology and shear thinning behaviour make nanocellulose suitable for use in the formulation of bioinks for 3D bioprinting. This technology can be used for several applications, including wound dressings, drug delivery and as the basis for scaffolds for regenerative medicine. The formulation of  
Figure 1: Cellulose structure and intra/intermolecular hydrogen bonding pattern (**A**). Morphological and structural characteristics of the unmodified and oxidised nanocellulose samples: Transmission electron micrographs of cellulose nanocrystals (**B**), oxidised cellulose nanocrystals (**C**), cellulose nanofibers (**D**) and oxidised cellulose nanofibers (**E**). Reprinted with permission from [PERSON] et al. [30] and [PERSON] et al. [31].