Nanocellulose, a Versatile Green Platform: From Biosources to Materials and Their Applications

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Nanocellulose, a Versatile Green Platform: From Biosources to Materials and Their Applications Bejoy Thomas, Midhun Raj, Athira B, Rubiyah H, Jithin Joy, Audrey Moores, Glenna Drisko, Clément Sanchez

One of the most distinguishing and useful characteristics of cellulose is the high degree of hydroxylation along the polymer chain; each non-terminal monomer contains three hydroxyl groups. Hydrogen bonding arises between OH groups conveniently positioned within the same cellulose molecule (intramolecular) and between neighboring cellulose chains (intermolecular).
Intermolecular hydrogen bonding creates fibrillar structures and semicrystalline packing, which governs the physical properties of cellulose: namely its high strength and flexibility. Moreover, primary hydroxyl groups (-CH 2 OH) are readily chemically modified, for example through phosphorylation, providing large scope for these materials.
There are three main classes of nanocellulose, cellulose nanocrystals (CNCs), nanofibrillated cellulose (NFC) and bacterial nanocellulose (BNC), classified according to their morphology ( Fig. 2) and source. CNCs and NFCs are obtained via a top-down approach consisting of the disintegration of plant matter via chemical or mechanical treatment 18 . Cellulose is biosynthetized in plants and forms partially crystalline fibers. Mechanical shearing or acid hydrolysis will first weaken and destroy the least crystalline regions to yield the expected nanocellulose. The amorphous sections have different physical properties to crystalline cellulose, forming cellulose nanoparticles by breaking the fibrils at amorphous points. The cellulose fibers can be deconstructed using either mechanical shearing or controlled acid hydrolysis, yielding different structures according to the approach used 4 . Acid hydrolysis results in nanometer-long and highly crystalline rod-like fragments, referred to as CNCs. Mechanical shearing techniques disintegrate cellulose fibers into their sub-structural nanoscale units, resulting in NFCs, which are typically longer, being micrometric in length 5 . BNC is produced via a bottom-up approach using cultures of bacteria to synthesize the material.
Fibrils typically describe higher aspect ratio materials than whiskers or crystals, although there is no strict definition for each of these. No single term is unanimously applied to describe 'nanoscale cellulose'. We will now explain how the three classes of nanocellulose are produced and the unique properties of each.  Marchessault and coworkers discovered in the 1950s that CNC aqueous solutions possess liquid crystal properties 36 , with impressive photonics properties 37 . Above a critical concentration (~4.5 wt%), they will form chiral nematic structures 24,38 , which can be revealed by polarized optical microscopy 38  vol%, the isotropic phase disappeared, giving a fingerprint texture which is characteristic of a cholesteric liquid crystal. Upon moving to even higher concentrations, the fingerprint texture of the liquid crystal phase disappeared as well, and the suspension behaved as a rheological gel.  Interfacing CNCs with other natural or synthetic polymers yields functional composites. A detailed discussion of various methods to prepare CNC composites is found in reviews by R. J.
Moon and A. Dufresne 39 . In addition, surface modification techniques are found to alter the selfassembly behavior of CNCs in suspensions and control the interfacial properties within composites. CNCs bestow composite materials with enhanced mechanical properties, low 20 density and high surface area. The main differences between CNF, CNC and BNC are listed in

Nanofibrillated cellulose (NFC)
NFC is a bundle of stretched cellulose nanofibers 40 [45][46][47] . Chemical treatment includes alkali treatments while biological approaches make use of enzymatic treatments 48,49 . A combination of these techniques is adopted by many researchers to get the desired product.
Analogous to CNCs, the fundamental properties of NFCs also vary in accordance with the raw material source and the specific extraction process employed. With all of these differing treatment methods the resulting NFC can vary dramatically in shape, degree of fibrillation, morphology and properties. Desmaisons, et al. have developed a quality index, based on eight criteria to benchmark the variety of reported NFCs 50 .

Bacterial nanocellulose (BNC)
Bacterial nanocellulose is synthesized and secreted by the Cellulose is the most abundant natural biopolymer, with sources including: (i) agricultural residues (sugarcane bagasse, straw, cornstover, coconut husks, corncobs, wheat and rice husks, palm oil residues, maize straw and fruit skins); (ii) tree trunks and dead forest matter (hardwood and softwood); (iii) energy crops; (iv) food waste; and (v) municipal and industrial biowaste such as used paper, carton and wood from demolition sites 69,70,73 . Acquiring nanocellulose from biomass proceeds in two steps. First, the lignocellulosic material needs to be deconstructed to recover cellulose, alone and as pure as possible. Second, cellulose will be treated to yield nanocellulose. The lignocellulosic structure is such that the strong convalent and H-bonded attractions between layers of lignin, hemicellulose and cellulose prevents an easy access to cellulose itself, thus conferring to wood and plants their ability to resist pest attacks and chemical degradation 75 . A multistep bio-refinery process can be employed to degrade the non-cellulosic content in the lignocellulosic biomass while preserving cellulose.
Lignin covalently cross-links cellulose and hemicelluloses via ester and ether linkages. This cross-linking restricts structural disintegration, referred to as lignocellulosic biomass recalcitrance 76 . In practice, a combination of certain chemicals and mechanical treatments is commonly applied to rupture the biomass structure and obtain nanocellulose. For large scale 35 production, this goal is achieved via Kraft pulping, a method combining mechnical and chemical treatments of biomass to achieve almost pure cellulose 7 . Recenly a new, environmentally friendly method has been reported where poplar wood flour was mixed with different deep eutectic solvents and then subjected to microwave irradiation for 3 min 75 . Eighty% of the lignin content was extracted, leaving behind a cellulosic residue that was 75% crystalline cellulose. The major benefits of this separation technique are the low energy consumption of the microwave treatment and the use of recyclable, bio-sourced deep eutectic solvents. Once pure cellulose is isolated, a further treatment is needed to recover nanocellulose. This typically involves the use of strong acids, as described in details below. Table 3 lists the most recent bio-sources, the isolation method, the type of nanocellulose obtained, the dimensions of the isolated nanocellulose and their applications. To summarize nanocellulose isolation methods and the obtained products:  CNCs range in diameter from 5-35 nm and have a length of a few hundred nanometers.
CNFs on the other hand have larger diameters of between 3-100 nm and are micrometers in length.
 Sulfuric acid hydrolysis is the most frequently used technique to isolate CNC from cellulose.
 Acid hydrolysis is used in combination with a mechanical treatment to produce CNF.
 Both CNCs and CNFs are extensively used as reinforcements in polymer matrices, highlighting their prominence in composite applications.

Nanocellulose isolation
The manner in which the nanocellulose is isolated from the plant matter has a large effect on the morphology and properties of the obtained material. We will now discuss the main isolation methods: mechanical treatment, chemo-mechanical treatment (Kraft pulping), and enzymaticmechanical treatment.

Mechanical treatments
The first two methods to produce microfibrillated cellulose were reported by Herrick, et al. 79 and Turbak, et al. 80 90 . These different treatments have been employed independently and in combination to obtain cellulosic nanomaterials. Fig. 6 shows the morphologies of fibrillated cellulose materials obtained from different sources. Energy consumption and production costs are high when mechanical treatment alone is used to delaminate the fibers [95][96][97] . A significant amount of energy is required to liberate nanosized cellulose from the natural fibers, due to the highly ordered hydrogen bond network of cellulose.  In order to decrease the energy demands of the mechanical isolation process, chemical pretreatments may be applied, such as acid hydrolysis 99 , enzymatic exposure 45,100 , ionic liquid treatment 101 , and carboxymethylation 102 , and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)mediated oxidation to modify the surface 103 . In each of these cases, charged functionalities are introduced to the cellulose backbone, internal repulsions emerge and defects to the hydrogen bond network are created. By combining chemical and mechanical treatments (chemomechanical treatment), individual fibrils (3-5 nm wide) or fibril aggregates (10-20 nm wide) several micrometers in length can be obtained for a reasonable cost when compared to the use of mechanical treatments alone.

Chemo-mechanical treatment (Kraft pulping)
First chemical pretreatments aim to remove non-cellulosic materials like waxes, ashes, lignin, pectin and hemicellulose. Hemicellulose is a random, amorphous material that is dissolved from the lignin structure by breaking the linkages between the carbohydrates and lignin using an acidalkaline pre-treatment 104 . A pretreatment can reduce the energy consumed by mechanical processing from between 20,000-30,000 kWh/ton to 1000 kWh/ton 105 115,116 . With hydrogen peroxide, in ethanol, a nice one step procedure allowed to go dirctely from biomass to oxidized CNCs 117 . With these methods, nanocellulose is recovered in a form of an aqueous suspension, which is then used as is, or further Soxhlet extracted 7 , air, freeze or spray dried 118 , the later being the method of choice for large scale, flow production.

Enzymatic-mechanical treatment
Enzymatic pre-treatment can be used to isolate nanocellulose, and has been discussed in detail in a recent review 119 . Enzymatic treatment allows milder hydrolysis conditions than acid hydrolysis. Fig. 8 shows TEM images of CNFs obtained by chemical and enzymatic treatments, where slightly different morphologies can be observed. Enzymatic hydrolysis is considered to be environmentally friendly. As an example of enzymatic hydrolysis, xylanases are hydrolytic enzymes that modify the hemicelluloses present in plant fiber. They can also initiate random hydrolysis of the β-1,4 non-reducing terminal regions located between the glycosidic linkages of the glucose units 120 . Enzymes modify or degrade the lignin and hemicellulose, restricting the degree of hydrolysis or selectively hydrolyzing specified components in the cellulosic fibers.
Henriksson, et al. 100 and Pääkkö, et al. 45 showed that endoglucanase can be used to facilitate the disintegration of wood fiber pulp into MFC nanofibers. Tibolla, et al. 78 compared the chemical and enzymatic pre-treatment of cellulose nanofibers. In general, yields of enzymatically produced nanocellulose are typically much lower than those achieved by mineral acid production methods from cellulosic biomass sources. However, the enzymatic route can be tuned to meet societal demands on clean chemical processes for the production of materials and fine chemicals.
An elegant example of this approach is the coproduction of nanocellulose and biofuels using multifunctional cellulolytic enzymes using Caldicellulosiruptor bescii. This method to produce nanocellulose from lignocellulosic biomass using thermophilic bacteria improved the kinetics, increased the mixing rate, lowered the oxygen solubility, reduced the risk of microbial 47 contamination, and reduced the costs for cooling and heating during the bioconversion process 121,122 . The surface charge of nanocellulose are also affected by the nature of the treatment.
Enzymatical treatment, using xylanaze in order to remove lignin and hemicellulose residues, afforded nanocellulose fibers with a higher zeta potential compared to a classic sulfuric acid treatment. These thus formed more stable suspensions, although authors did not explain the functionality responsible for this property 78 .

Chemical modifications of nanocellulose
The surface chemistry of cellulose can be easily tuned. Surface-modified cellulosic nanomaterials are an excellent platform, designed for targeted applications. The broad applicability of nanocellulose is compromised by its poor dispersibility in non-polar solvents, and its incompatibility and poor interfacial adhesion with hydrophobic matrices. To overcome this issue, researchers have tried a number of modifications-both to the surface and to the 48 nanocellulosic structure. Chemical modification of the surface of cellulose nanoparticles employs pendant surface hydroxyl groups, essentially the primary alcohol group (-CH 2 OH).
Different chemical modification strategies were performed on nanocellulosic materials with the aim to: 1) enhance the efficiency of the isolation process and 2) to change the surface hydrophobicity, which in turn improves the compatibility and the dispersability of nanocelluloses in specific solvents. This topic was reviewed in 2014 by Eyley and Thielemans 123 .

Imparting ionic charges to nanocellulosic surfaces
As explained in 4.2, the synthesis of nanocellulose by sulfuric and phosphoric acid hydrolysis does result in partial functionalization of the surface with sulfate or phosphate half esters. This introduces the charges necessary for aqueous suspendability and isolation process.
Further introduction of ionic charge to the cellulosic surface via phosphorylation, carboxymethylation, oxidation and sulfonation reactions has been studied. Scheme 1 shows the different techniques by which ionic charges can be incorporated onto the nanocellulosic surface.

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Scheme 1: Different surface modification techniques through which ionic charges are imparted to the nanocellulosic surface, giving it a hydrophilic character.

Phosphorylation of cellulose
The incorporation of phosphate ester groups onto a cellulosic backbone significantly alters the original properties. Phosphorylation of cellulose is a well-known surface modification strategy for producing suitable materials for applications in diverse areas including orthopaedics 124  shown to be compatible with calcium phosphate to opening pathways toward hybrid material formation. Therefore this material could be used as an implantable biomaterial in bone and tissue engineering 125 . Phosphorylated cellulose is capable of binding metal ions like Ag + , Fe 3+ , and 50 Cu 2+ , and thus these materials can be used as ion adsorbents to filter water and industrial effluents 133 .
Phosphorylated cellulose (p-cellulose) was also reported as a flame retardant in textiles 134 .
Cellulose is a material of low thermal stability and high flammability (hence extensively used as firewood). Nanocrystalline cellulose is comparably more thermally stable, because the successively with hexanol and ethanol, and then rinse repeatedly with water, to wash away excess H 3 PO 4 . Fig. 9 shows a synthetic scheme of the reaction and SEM images of unmodified cellulose and the obtained triphosphate gels. The filtrate was then centrifuged prior to purification. Purification was carried out by Soxhlet extraction with deionized water and ethanol, 52 for at least 24 h, until tests for inorganic phosphate were negative. The obtained gel was then freeze-dried.

Carboxymethylation
Carboxymethyl groups are introduced to cellulosic surfaces via the carboxymethylation process rendering the surface negatively charged.  146 . In a recent study, Arvidsson, et al. conducted a comparative study of enzymatic and carboxymethylation pretreatments for the production of CNF 147 . They found that even though CNF produced using the carboxymethylation route clearly had a high environmental impact (as the process employed large volumes of organic solvents like ethanol, isopropanol, and methanol and monochloroacetic acid as the carboxymethylating agent), the pretreatment enabled the production of CNF suspensions with lower turbidity. The higher transparency of these suspensions means they could be used in transparent films and composite applications.

Oxidation
2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) mediated oxidation can be used both as a pretreatment to facilitate nanofiber isolation, and as a means to render the nanocellulose surface hydrophobic. De Nooy, et al. 148 first reported this method and showed that TEMPO can only oxidize the primary hydroxymethyl groups of polysaccharides, leaving the secondary hydroxyl groups unaffected. The method selectively converts the exposed C 6 alcohol functions of the glucose unit to a carboxylic acid 149,150 .
Mechanistically, stable nitroxyl radicals from TEMPO enable the conversion of hydroxyl groups to aldehydes, which are subsequently oxidized to carboxylic acids (Fig. 11). When TEMPO/NaOCl/NaOCl 2 , are used to catalytically oxidize cellulose 151

Sulfonation
Sulfonation is another technique to impart anionic charges to the surface of nanocellulosic materials. Concentrated sulfuric acid used for CNC synthesis both catalyzes the hydrolysis of the sources, and enables the formation of sulfate half esters from CNCs 57 hydroxyl groups. Sulfuric acid hydrolysis leads to stable colloidal suspensions of cellulose nanocrystals 106 , which display phase separation into equilibrium ordered chiral nematic phase above a critical concentration 154 . The presence of these sulfate esters at the surface of the CNCs leads to the formation of highly stable colloidal suspensions, which after controlled drying, produces optically active films 155 . The presence of negatively charged sulphate groups on the surface induces the formation of a negative electrostatic layer covering the nanocrystals and improves the dispersion capacity in water. However, it compromises the thermostability of the nanoparticles, especially for a high degree of functionalization with sulfate groups 135 . Perhaps, the thermal stability of H 2 SO 4 -prepared nanocrystals can be increased by neutralization of the nanoparticles with sodium hydroxide.
Hydrolyzing with a combination of sulfuric and hydrochloric acid while sonicating generated spherical CNCs 156 . Due to a lower density of surface sulfate groups, these spherical CNCs demonstrated better thermal stability compared to those obtained by hydrolyzing with pure sulfuric acid. Liimatainen and co-workers used periodate and bisulfite to nanofibrillate hardwood pulp, obtaining sulfonated NFCs with widths between 10-60 nm 157 . To enable nanofibrillation, a density of 0.18 mmol g -1 of sulfonate groups is required, which also yields a highly transparent and viscous gel. Ruiz-Palomero, et al.
reported the use of sulfonated nanocellulose for the efficient dispersive micro solid-phase extraction and determination of silver nanoparticles in food products 158 . This sulfonation process avoids the use of halogenated wastes, and thus is considered green.

Generation of nanocellulosic materials with hydrophobic surfaces
As cellulose is hydrophilic, it absorbs water upon exposure. The sensitivity of nanocellulosic materials towards moisture can be tuned by using various chemical modification techniques such 58 as esterification, silylation, amidation, urethanization and etherification making the cellulosic surface hydrophobic. In accordance with the commonly accepted definition, a surface is defined to be hydrophilic when its contact angle with water is smaller than 90° and hydrophobic otherwise 159

Acetylation
Acetylation of cellulosic fibers is commonly performed to increase hydrophobicity. The lignocellulosic fibers are plasticized upon the acetylation of cellulosic alcohols 160 . Acetylation of nanocellulose usually involves the gradual addition of acetic anhydride and dry acetic acid with either sulfuric or perchloric acid to catalyze the reaction. Sassi and Chanzy were the first to propose the two main mechanisms of acetylation 161 . These two mechanisms, respectively named the fibrous process and the homogeneous process, rely on the presence or absence of a swelling diluent. For instance, in the fibrous process, a diluent such as toluene is added to the reaction medium where acetylated cellulose remains insoluble. A high degree of acetylation is obtained and the original morphology is preserved. In the diluent-free homogeneous process, acetylated chains are soluble in the reaction medium consisting of acetic acid and a catalytic amount of sulfuric acid. Consequently, the cellulosic substrates are found to undergo substantial morphological changes upon extensive acetylation. Cetin, et al. 162 164 . The group used aqueous alkenyl succinic anhydride emulsions as a template.
The obtained derivative was found to possess a highly hydrophobic character. In a recent work by Missoum, et al. the feasibility of using ionic liquids as a reaction media to carry out the esterification of NFCs was reported 165 . Co-solvents 1-butyl-3-methyl-imidazoliumhexafluorophosphate and acetic anhydride were successfully employed, allowing the original NFC morphology and crystallinity to be preserved.
These chemical acetylation methods use expensive and/or corrosive chemicals, which raise concerns over the sustainability of the whole process. Recently, acetylation of nanofibrillated cellulose using acetic anhydride as an acyl doner has reported using enzyme lipase from Aspergillus niger 166 . Enzymatic acetylation on NFC yielded much higher hydophobicity (contact angle of 84±9°) compared to chemical acetylation (contact angle of 33±3°) 166 . Transesterification of cellulose using acylating agents such as vinyl propionate and vinyl acrylate can make the surfaces of nanocellulose hydrophobic as demonstrated by increased contact angles [167][168][169][170] . Acyl modification of hydroxyethylcellulose has been reported in the presence of -galactosidase from Aspergillus oryzae. Surface modification has also been performed using succinic anhydride, vinyl stearate, vinyl acetate, and vinyl acrylate through transesterification in N,Ndimethylacetamide (DMAc) using lipase from Pseudomonas cepacia.

Etherification
Etherification forms a widely used chemical pretreatment method that facilitates cellulose defibrillation to prepare nanosized NFC. The process involves the carboxymethylation of cellulose fibers, which proceeds by first activating the fibers with an aqueous alkali hydroxide, such as NaOH, and then converting the hydroxyl groups to carboxymethyl moieties with monochloroacetic acid or its sodium salt 171 . Drawbacks include the use of toxic halocarbons and sometimes increasing the hydrophilicity of the resulting NFCs. Etherification has been used to graft cationically charged species onto a CNC surface, such as epoxypropyltrimethyl ammonium chloride (EPTMAC) 172 . Alkali-activated hydroxyl moieties along the cellulose backbone reacted via a nucleophilic addition to the epoxide of EPTMAC. Stable aqueous suspensions with thixotropic gelling properties were obtained.

Silylation
Silane surface modification is a simple way to increase the hydrophobicity of a hydrophilic cellulose surface. Alkyldimethylchlorosilanes are generally used for the purpose of silylation 9 .
Gousse and co-workers studied the rheological properties of NFC after a mild silylation proceduring using isopropyl dimethylchlorosilane 173  Silylation is a multi-purpose functionalization method.

Urethanization
Reaction between isocyanate and the surface hydroxyl groups of nanocellulosic materials entails the formation of covalent bonds, i.e. a urethane linkage between the two, thus urethanization can serve as an alternative to esterification. Urethanization, carbanylation and carbamation 123 are a few synonyms reported in the literature for the process. In a study conducted by Siqueira and co-workers, the surface modification of CNC and NFC by noctadecyl isocyanate was studied and found to enhance hydrophobicity 176  CNCs were incorporated into ureidopyrimidone functionalized telechelic poly(ethylene-cobutylene), yielding light-healing capabilities with superior mechanical properties.

Amidation
A carbodiimide-mediated reaction is the most common way to amidate cellulosic surfaces.
The reaction usually targets the carboxylic groups of pre-oxidized nanocellulose substrates. The

Polymer grafting on cellulose
Grafting polymers onto cellulose is an excellent way to modify the chemical and physical properties of the material 179 . Polymer-cellulose composites have been synthesized to stabilize nanocellulose, for abrasion and wear resistance, for shape-retaining materials, to change the hydrophilicity/hydrophobicity of the surface and the sorbancy, and to obtain elasticity, stimuliresponsive materials, ion exchangers, electrolytes, thermal resistance, and self-cleaning surfaces ( Fig. 12). Polymer-grafted cellulose combines good mechanical properties with good biocompatibility and low degradability, thus such materials have been used in surgical repair 180 .
Polymer grafting has been performed using different methods that can be divided into three categories ( Fig. 13): grafting-to, grafting-from and grafting-through. In the grafting-to approach, purified and well-characterized polymers or peptides are attached to the cellulose, typically by coupling the reactive end group of the polymer to the hydroxyl groups of the cellulose backbone.
A wide variety of polymers, (e.g. polypropylene, polystyrene, poly(lactic acid), and poly(caprolactone) to mention a few) can be grown and attached to the cellulose, as long as there is a linkable functionality. In the grafting-from method the cellulose is first functionalized with an initiator and then monomers are polymerized directly from the surface. This method can achieve higher polymer densities than when grafting-to, but it is difficult to characterize the resulting polymers, and the polydispersity of the polymers can be higher than in the grafting-to approach. When applying grafting-through, the cellulose is first functionalized with polymerizable species, such as with vinyl-bearing molecules. The functionalized cellulose is then mixed with a co-monomer and the polymerization is initiated. Among these methods, graftingfrom is the most popular method to date 4,181 , with focused reviews on ring-opening polymerization 182 , controlled radical polymerization grafting methods 183    Functionalizing nanocellulose with polymers may also proceed via electrostatic interaction or macromolecular physisorption toproduce the desired effect. As an example, modified spruce Oacetyl galactoglucomannans with a low-degree of oxidation was readily and irreversibly physisorbed to nanofibrillated cellulose in water 191 . Galactoglucomannan-functionalized cellulose can improve the tensile strength of paper and can be more readily modified with bioactive molecules than non-modified cellulose.
When a covalent attachment is desired, grafting-to using atom transfer radical polymerization (ATRP), free radical, reversible addition-fragmentation chain transfer (RAFT) and ring-opening polymerization are often applied. The desired end product determines which polymerization method should be used. ATRP is a free-living radical polymerization applied to styrenes, (meth) acrylates, (meth)acrylamides and acrylonitriles. RAFT is another free-living radical polymerization used for the same set of monomers and also for vinyl esters and vinyl amides.
RAFT has an additional advantage in that its end group can be easily reduced to a thiol 192 , providing a functionality that can be further modified. Ring-opening polymerization is used for cyclic monomers (epoxides, lactones, lactames) and can be achieved using radical, anionic or cationic initiators. Thus ring-opening polymerization is preferred for the production of mechanically reinforced biocompatible polymers 193 .
In grafting-to, it is possible to use classical methods to attach the polymer or peptide to the cellulose surface. For example, cellulose was modified at the C 6 position with thiocarbonylthio species, which were then used as a substrate for a hetero Diels-Alder reaction with dienecontaining fluorinated polymers and peptide sequences via both thermal and photochemical activation (Fig. 12E) 190 . The photochemical conjugation was used in combination with a mask to spatially control the regions of functionalization.

Atom transfer radical polymerization (ATRP) grafting-to synthesis
A variety of polymers have been grown from cellulose surfaces using ATRP and the lower copper consumption variant, activators regenerated by electron transfer (ARGET) ATRP 194 . The first ATRP report, appearing in 2002, described the reaction of surface hydroxyl groups with 2bromoisobutyryl bromide, which was used to initiate the ATRP polymerization of methyl acrylate 179 . The resulting cellulosic materials were extremely hydrophobic, having a contact angle of 133°.
CNC has been grafted with poly(methyl acrylate) to produce materials dispersible in tetrahydrofuran, chloroform, dimethylformamide, and dimethyl sulfoxide, in contrast to nonmodified CNCs 195 . A 1,10-carbonyldiimidazole-mediated esterification reaction with the cellulose generated a macroinitiator, which was then used to polymerize methyl acrylate. The polymerization was initiated by Cu(0) coming from copper wire, decreasing copper consumption.
Superhydrophobic cellulose substrates (contact angle >170°) were prepared by growing poly(glycidyl methacrylate) from a cellulose surface functionalized with an ATRP initiator 188 ( Fig. 12C). Pendant hydroxyl groups along the acrylate backbone were post-functionalized with pentadecafluorooctanoyl chloride to highly fluorinate the polymer. These materials combined hydrophobicity with surface roughness to achieve the lotus-leaf affect. The hydrophobic/hydrophilic character of functionalized cellulose was used to demonstrate the livingness of a grafted polymer on the cellulose surface 196 . First poly(methyl acrylate) was grafted-from the cellulose using ATRP, a second block of 2-hydroxyethyl methacrylate was then grown. The first block rendered the cellulose very hydrophobic, but the second block returned water absorbency to the material.
Hydroxypropyl cellulose was grafted with methyl methacrylate and hexadecyl methacrylate using the grafting-from approach 197  ATRP grafting-to cellulosic surfaces has been so well developed that research in this area is now turning towards commercialization. Hydrophobic poly(methylmethacrylate) has been grafted-from a variety of different cellulose surfaces using industrially friendly conditions 199 .
That is, the solvent-free solution was not deoxygenated before the ARGET ATRP polymerization, minimal washing was required to remove physisorbed polymer, the solution could be recycled for a second cycle and no sacrificial initiator was needed. The reaction required 3 h and was performed between 40 and 80 °C.

Free radical grafting-to synthesis
Cellulose nanocrystals were incorporated into thermoresponsive poly(Nisopropylacrylamide) cryogels (Fig. 12D) 189 . Both cellulose that was physically adsorbed and covalently bound, by modifying the surface with polymerizable species, was studied. The physically adsorbed nanocrystals were more hydrophilic and thus it was possible to homogeneously incorporate larger loadings. However, the covalently bound nanocrystals generated gels demonstrating faster diffusion, due to the pore structure, and a higher degree of swelling. When heated above the LCST of the polymer (above 32 °C), the gel reversibly shrunk.
The addition of cellulose nanocrystals to the gel allowed the gel to recover its form after compression, in contrast to the pure polyacrylamide gels.

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Soluble cellulose was synthesized using RAFT to polymerize acrylic monomers 200 . A macro chain transfer agent was created by attaching dithioesters to the primary alcohol at the C 6 position of the cellulose backbone, followed by polymerization of either ethyl acrylate or Nisopropylacrylamide.
Poly(2-(dimethylamino)ethyl methacrylate) was grafted from a cellulose surface using RAFT 201 . The polymer chains could be cleaved from the cellulose using acidic conditions, allowing the polymer to be characterized and compared to polymer grown freely in solution. The same procedure and characterization had been applied to polystyrene grafted onto cellulose, showing that the molecular weight of the polystyrene is narrow, but the grafting density and coverage can be improved 202 .
RAFT has also been used to grow antimicrobial polymers from cellulose surfaces. Alkyl bromides with 8, 12 or 16 carbon atoms were used to quaternize poly(2-(dimethylamino)ethyl methacrylate) chains on the cellulose surface in order to add cationic charges 203 . These materials were then tested for antibacterial activity against Escherichia coli by incubating bacterial solutions in the presence of the hybrid cellulose materials. It was found that the non-modified and 1-bromooctane quaternized polymer-grafted cellulose displayed the highest antibacterial activity. The longer alkyl chains increased the hydrophobicity of the cellulose, and thus decreased the interaction between the material and bacteria in solution.

Ring-opening polymerization grafting-to synthesis
In an effort to make nanocomposites for tissue engineering repair, biomedical implants, and

Post-polymerization grafting-from
Poly(styrene) and poly(t-butyl acrylate) were grafted-from oxidized cellulose microcrystals using an amidation reaction that coupled terminal amines on the polymers with the carboxylic acid groups of the cellulose substrate 185 . A grafting density of 60-64 wt% was achieved, which was sufficient to allow the nanocomposite to be soluble in toluene and acetone. The cellulose microcrystals were not degraded by the functionalization method. This method could be applied to a large variety of polymers.

Nanocellulose-based materials
The need for sustainable alternatives to conventional petroleum-based materials triggers a growing demand for bio-based materials for applications in all areas of the industry.
Nanocellulose has been incorporated into many types of materials, both in pure and composite forms.

Nanocellulose as a templating agent
The use of nanocellulose as a templating agent has been reviewed recently [206][207][208] . As explained above, CNCs exhibit chiral nematic properties 24,38 . Self-assembly can be preserved and translated upon drying or spin coating of such solutions, forming iridescent and birefringent films 209 . An in depth study of the drying effects has been published by the Vignoli group 210 . The chiral nematic phases, also called cholesteric phases, observed in the CNC solutions can be described as the superimposition of planes in which all CNC rods are directionally parallel, while the overall direction of the rods from one plane to the next is tilted 24 . This results in helicoidal structures, acting as a 1D photonic structure able to reflect polarized light with a wavelength correspoing to the pitch of the CNC structures. These phases were shown to be tunable using a magnetic field 211 . These phases have been used as templates in several schemes in order to afford ordered nano-and mesostructured materials 207 . The MacLachlan group developed a method to use this pattern to template silica morphology by evaporation-induced self-assembly of CNCs with silica precursors to obtain composite films with chiral nematic structures. The removal of CNC afforded chiral nematic mesoporous silica 212 , featuring iridescence (Fig. 14). Interestingly, the reflected color of the obtained films could be tuned between the UV and the IR region, by varying the concentration of the alkoxysilane precursor. Organosilica, in the form of ethylene-bridged mesoporous silica were also synthesized using this method to afford flexible and iridescent films 213 . In another scheme, the chiral nematic CNC/silica composites were pyrolized before silica was removed by alkaline treatment 214 . This resulted in glassy black films composed of freestanding mesoporous carbon. Graphitic C 3 N 4 was also produced in a similar fashion for application in H 2 evolution 215 . CNC has also been used as a hard template to form porous hematite by casting a sol containing CNC and an iron salt, which then gelled upon drying 216 .
Mesoporous titania can not be produced by the same method, yet CNC structured silica was used as a template in itself to cast TiO 2 with chiral nematic ordering 214 . The chiral nematic structure of CNCs was also applied to the development of soft films. By crosslinking latex nanoparticles with CNC upon synthesis, the Kumacheva group produced a soft film while preserving the CNC photonic properties 217 . Chiral plasmonic films were also made using CNCs as templates. In this case, gold nanorods were incorporated into a CNC chiral nematic phase. The resulting materials obtained by slow drying still featured chiral order, resulting in chiral photonic crystal properties with circular dichroism 218 . Self-assembled CNCs have also been incorporated into polymer matrices, where tactoid formation and dynamics were observed by scanning electron and confocal optical microscopy 219,220 .
Mesoporous metal oxides prepared via CNC templating offer an excellent entry into highly catalytic materials. TiO 2 -coated nanocellulose materials with high porosity possess photocatalytic activity, demonstrating potential in water purification 221,222 . Chemical Society.

Hydro-and aerogels of nanocellulose
The field of hydro-and aerogels of nanocellulose has been extensively reviewed by Cranston and coworkers in 2017 223 . The preparation, physicochemistry, properties, morphologies and applications of nanocellulose-reinforced foams and aerogels have been recently reviewed 224 .
These types of materials are being intensely ivestigated because nanocellulose is a particularly suitable building block to form gels, because of its combined lightweight and toughness. The hydrophilic surface of these nanocelluloses allows them to serve as building blocks in hydrogels, where they can be cross-linked via hydrogen bonding, covalent bonding or ionic interactions into three-dimensional networks with a large array of different metals, organic species and polymers.
Hydrogels are highly hydrated chemically or physically cross-linked networks that can be produced from nanocellulose alone, or in hybrid structures with additional polymers. Surface functionalization and self-assembly processes can be used to fine-tune the properties of the hydrogel. CNCs gel in water above a concentration of 10 wt% 225 . Controlling the ionic content of water changes CNC gelation behavior, as CNC is itself a charged species 226 . Gelation could even be switched, through the addition of imidazoles to the CNC aqueous suspension 227 . The CNC suspension turned from a gel (produced from bubbling the solution with CO 2 ) to a liquid after N 2 gas exposure. CNCs physically or chemically modified with polymers improved the hydrogel properties. For instance, CNCs were used to reinforce polyvinyl alcohol hydrogels 228,229 . Such systems were prepared with a CNC content up to 7 wt% and showed excellent resistance against microorganisms 230   The mechanical properties of nanocellulose aerogels can be improved either chemically or through processing, e.g. through freezing-solvent exchange-ambient drying 240 . For example, TEMPO-modified CNFs were processed into an aerosol and post-synthetically cross-linked with methylene diphenyl diisocyanate 241 . The cross-linking improved the thermal stability and the 79 strength of the aerogel. It also changed the hydrophobicity, rendering the material suitable for chloroform separation from water. TEMPO-oxidized CNFs have been shaped into aerogel microspheres using polyamide-epichlorohydrin resin as a crosslinker 242 . These aerogels were capable of adsorbing 120 g/g H 2 O and could be used to extract phenol and copper. They were easily recovered and regenerated by simply squeezing and rinsing the microspheres.
Graphene oxide-nanocellulose composites have been formed into aerogels 8,243 and membranes 244 . The pore structure of the composite allows for a good flux while maintaining excellent strength and flexibility.

Nanocellulose-nanocarbon composites
Nanocellulose has been combined with nanocarbons, i.e., carbon quantum dots, carbon nanotubes and graphene-related materials, to add functionality to cellulose-based materials (Fig.   16). In doing so, nanocellulose possesses attractive properties previously mentioned: biocompatibility, biodegradability, non-toxicity, and excellent mechanical properties particularly for use in cloths: durability, flexibility, soft texture, breathability and deformability. Thus, nanocellulose is typically used as a support for nanocarbons, which are otherwise difficult to process into either a material or a free-standing substrate due to difficulties with aggregation and processing. Nanocellulose/nanocarbon composites have much higher mechanical strength than polymer/nanocarbon materials 245 . Nanocellulose is inexpensive compared to carbon nanotubes and graphene-related materials. By doping cellulose with nanocarbons, a percolation threshold can be reached, rendering the entire fabric electrically conductive for a fraction of the price of the pure nanocarbon material. The chemistry previously developed, such as surface modification techniques to increase cellulose solubility 246 , have been applied to the fabrication of the 80 cellulose-nanocarbon composites, but it has also been possible to create stable dispersions without such pre-treatments thanks to favorable interactions between the nanocarbon and the cellulose which interrupt the tendency for both cellulose and nanocarbons to auto-aggregate 247 .
Cellulose nanocrystals can also be used to stabilize the surface of polymer latexes 248,249 , for example through a Pickering emulsion 250 . Most applications envisaged for nanocarbonnanocellulose materials require mechanically robust materials with electrical conductivity, with biocompatibility being often a desirable quality. The composite materials will now be presented, separating nanocarbons into carbon quantum dots, carbon nanotubes and graphene-related materials.

Nanocellulose-carbon quantum dot composites
Carbon quantum dot research began in 2004 and has been an intense area of research ever since because carbon quantum dots are fluorescent, non-toxic and readily water-dispersible 255 .
Moreover, carbon quantum dots can be obtained from a host of different sources, from food, to standard petro-chemicals to cellulose. The optical properties of carbon quantum dots are intriguing because different studies often produce contradictory results. For instance, carbon quantum dots have been synthesized from microcrystalline cellulose using an ionic liquid, 1buty-3-methylimidazolium chloride, as a catalyst 256 . These carbon quantum dots exhibited excitation-dependent fluorescence emission behavior. Carbon quantum dots with excitationindependent fluorescent properties have been synthesized from the same precursor, microcrystalline cellulose, but using harsher conditions, that is a concentrated solution of sulfuric acid and higher temperature (200 °C instead of 100 °C) 257 . Perhaps the excitation-independent behavior is a sign of a more homogeneous batch of carbon quantum dots. The quantum yield of the excitation-independent carbon quantum dots was higher (32%) than that of the excitationdependent materials (4.7%). Much work to understand the phenomena behind the optical properties of carbon quantum dots remains, but in the meantime a couple of efforts have been made to incorporate carbon quantum dots into materials.
A cellulose fabric was pyrolysed under argon at 1000 °C to produce a conducting carbon cloth 258 . This cloth could be used to produce hydrogen and oxygen through water electrolysis.
Because of the highly disordered structure and the high conductivity of the cellulose cloth, hydrogen generation could be performed using low voltages (0.2 V). At low voltage only hydrogen was produced, where above a threshold voltage both hydrogen and oxygen were liberated. During electrolysis carbon quantum dots of 5-7 nm were produced within the cloth which exhibited excitation-dependent fluorescence. In contrast to the cellulose cloth, the graphite anode did not form carbon quantum dots, even at higher applied voltages.
Self-standing cellulose/carbon quantum dot composite films were prepared which demonstrated transparency and photoluminescence 254 . A regenerated film of microcrystalline cellulose was prepared and then dipped into a solution of pre-prepared carbon quantum dots. The maximum photoluminescent intensity occurred at 419 nm with long-afterglow luminescence that lasted for over 10 minutes. By adding carbon quantum dots to the regenerated cellulose film, the film became softer, but still demonstrated excellent mechanical properties.

Nanocellulose-carbon nanotube composites
Carbon nanotubes have excellent mechanical strength, high electrical and thermal conductivities, high stability and high aspect ratios. They increase the mechanical strength of the cellulose composite and the composite becomes conductive as long as there are a sufficient number of junctions between the dispersed carbon nanotubes. Carbon nanotubes and cellulose have a high affinity for one another, making them natural partners in composite materials. IR spectroscopy has shown that the interaction between carbon nanotubes and cellulose is noncovalent and nondestructive 259 . Carbon nanotubes are notoriously difficult to disperse in water and organic solvents; however, their mixture with cellulose nanocrystals allows them to be readily dispersed in water 260 . Similarly, Raman spectroscopy shows that carbon nanotubes disrupt the intra-and intermolecular hydrogen bonding between native cellulose strains that are responsible for its typical insolubility in water 247 . Cellulose-carbon nanotube mixtures remained as stable aqueous suspensions for months at pH 6 to 10. A more recent investigation has shown that a fluctuation in the counterion species on the nanocellulose surface induces polarization in the sp 2 network of the nanocarbon 261 . The higher the surface charge on the nanocellulose, the better the interaction with the nanocarbon and the better the dispersive qualities.
Carbon nanotube-cellulose composites have been predominately investigated as conductive papers 252,262,263 and conductive fibers for wearable electronics 254 , with one report of an aerogel 264 .
Individual carbon nanotubes are prone to wrap around the cellulose fibers, forming a pulp that can be cast into a paper with uniform electrical conductivity using standard papermaking technology 254 . The composite paper had electromagnetic interference shielding efficiencies superior to metal-printed circuit-boards. Moreover, by adding carbon nanotubes to cellulose, the tensile strength and the stiffness of the paper increased, producing a strong, flexible material.
The increase in ductility is thought to be due to having both short and long entangled objects: the cellulose nanocrystals prevent the carbon nanotubes from aggregating, thus preserving junctions in the extensive nanotube network 246 .
Cellulose-carbon nanotube composites have been used as foldable, lightweight, self-standing scaffolds for both titania 265 and polyaniline 266 for use as supercapacitor electrodes and as biomimetic actuators and biosensor. Polyaniline and carbon nanotubes are excellent materials for conducting electrodes, but their combination yields poor films due to problems with carbon nanotube aggregation 267 . Cellulose is an excellent support, where the cellulose and carbon nanotubes are premixed and then aniline is polymerized from the surface of these two materials to form a porous composite. By adding polyaniline, the electrode gains a larger integrated cyclovoltammetric area and a larger specific capacitance 268 . If this polymer-carbon composite is further doped with ClO 4 and Clions, the surface conductivity is increased by an order of magnitude, creating a low power consumption actuator 269 . Low power consumption actuators could be used in microwave-driven biological devices.

Nanocellulose-graphene-related material composites
Graphene has extraordinary electronic transport properties and high electrocatalytic activities. Cellulose-graphene composites are highly porous, with excellent shape retention. Biosensors and scaffolds using electrical stimulation have been envisioned using graphenerelated materials. However the hydrophobicity of this class of carbon material is problematic. By designing a cellulose-graphene composite not only is the hydrophobicity addressed, but the mechanical properties are also improved. Graphene oxide films were functionalized with bacterial cellulose fibers, reducing the contact angle from 93 to 14°2 75 . These hydrophilic films 86 were then used as supports for cell adhesion, growth and proliferation. The composite had much better cellular response than the graphene film alone.
In another scheme, CNCs were used as a additive to help improve dispersion of carbon fibers with graphite in ordet o achieve ha conductivity 276 .
Through these examples, it is clear that nanocarbons and nanocellulose are highly compatible, increasing the mechanical properties over the individual components and yielding excellent properties in domains ranging from electrical conductivity, to ion permeability, to chemical sensing. The role of the cellulose is always the same: to provide a strong, flexible scaffold for the nanocarbon, allowing the desirable properties of the nanocarbon to be integrated into a non-toxic, environmentally friendly device.

Nanocellulose-organic polymer matrices
Nanocellulose has been widely applied as a filler to reinforce polymer composites. The role of the interfacial layer on the mechanical reinforcement has been explored in depth. The assembly occurs via hydrogen-bonding of parallel chains between the native cellulose and crystalline domains. Due to this structure and the high surface area of the composites, if load is effectively transferred to the hard reinforcing phase, then the modulus of the composite is similar to that of randomly orientated rigid CNC with high strength and modulus 277 .
Nanocellulose and organic polymeric materials form composites with a complex network of inter-and intramolecular hydrogen bonds, excellent mechanical properties and the ability to assemble themselves into a tight, high-strength and high-stiffness structure. Nanocellulose has been used to reinforce a wide range of polymer matrices, such as poly(styrene-co-butyl acrylate) 278 , poly(vinyl acetate) 279 , poly(ethylene oxide-co-epichlorohydrin) 280 , poly(styrene-co-butadiene) 281 , polyurethane 282 , and epoxy resins 283 . A number of methods such as compression molding 284 , freeze drying, hot pressing 285 , and solution impregnation 286 are employed for the preparation of these organic composites, however, casting is the most common technique used [287][288][289] . Fig. 17  This method does not use any template or surfactant molecules, while the BC serves as a support.
The stiffness and brittleness of polyaniline is compensated by the more ductile cellulose 304 .

90
The nature of the interation between CNCs and polymeric materials has been further studied by the group of Ikkala using cryo transmission electron microscopy 305 . Dendronized glycopolymers featured multivalent interactions with CNCs and polymer wrapping.

Nanocellulose-inorganic nanoparticle composites
Organic-inorganic hybrid nanomaterials often have improved physicochemical properties including thermal, mechanical and optical properties, and conductivity, due to the synergetic effect of the combined physical and chemical interactions between the organic and inorganic components 277,306 Fig. 18. The CNC surface hydroxyl groups are oxidized to carbon-oxygen double bonds while reducing the silver on the surface. Ruthenium nanoparticles, which are notoriously difficult to produce using common RuCl 3 as a precursor, were formed through a combination of CNC surface and chemical oxidation 325 .

Properties and applications of nanocellulosic materials
Many factors influence the properties of nanocellulosic materials: the maturity of the fibers, the origin of the plant matter, their chemical composition, the separation process employed, defects in the fibers (e.g. pits and nods), and the environmental conditions in which the plant was grown. The mechanical, optical and gas barrier properties of nanocellulosic materials have been well studied, bringing them to a mature stage in terms of their applications (Fig. 19).

Mechanical reinforcement
Compared to glass fibers, low density nanocellulose fibers have high tensile modulus strength, with a Young's modulus around 70 GPa 333 at a density around 2.6 g/cm 3 Table 4 lists a literature survey of the CNCs, CNFs and BCs used to reinforce composites.
Nanocellulose fibers are added to cement to decrease shrinkage during drying, to increase sound absorption and to produce a more environmentally friendly, less hazardous material. Such composites are an alternative to asbestos. However, nanocellulose-cement matrices are less durable due to the hydrophilicity of the cellulose component and its lower chemical stability.
Moreover, the cement and the cellulose components can lose adhesion with time, leading to crack formation. Two composites preparation methods were used: 1. cellulose fibers were coated with bacterial nanocellulose and 2. bacterial nanocellulose was injected into the cement composite as a gel 339 . Depending on the way in which the bacterial nanocellulose was incorporated, the surface basicity, degree of hydration, surface roughness and fiber mineralization were favorably impacted.  Foams, hydrogels and aeorgels are lightweight materials with a particular need for mechanical reinforcement. CNCs and CNFs have formed a focal point as mechanical stabilizers for these materials (See Section 6.2). Foams can be mechanically stabilized with nanocellulose filler, however their morphology is altered 340 . Typically, the pore sizes within the foam become smaller and more polydisperse as the nanocellulose acts to nucleate wall formation. By changing the surface chemistry of the nanocellulose filler, it can be a highly desireable foam stabilizer 341 .

Barrier properties and packaging
Most conventional materials used to package food are non-degradable petrochemical-based polymers, creating considerable environmental impact. The low permeability of cellulose, which is enhanced further by the nanoscale demensions and highly crystalline nature of cellulosic nanoparticles, and their ability to form a dense percolating network due to hydrogen bonds are desirable properties for filtration and packaging, especially food packaging 342  showed that a densely packed film of MFC is optically transparent, because a tight fiber packing with small interstitial spacing poorly scatter lights 353 . However, the degree of transparency was related to the processing conditions. Nogi's group prepared optically transparent cellulose based nanopapers with a range of transmittance [354][355][356] .
Cellulose nanofibers form biodegradable coatings and films alone or in combination with inorganic fillers, such as clay or calcium carbonate. These films can replace the non-degradable plastic coatings used in packaging 357 . The use of nanocellulosic materials for packaging has arisen due to an intensive search for bio-based food packing materials, taking into consideration efficiency, food safety and environmental consciousness.
Food packaging requires gas impermeability, particularly oxygen. Cellulose is hydrophilic in nature and thus absorbs water when immersed or exposed to moisture. The oxygen barrier properties of nanocellulosic materials have been studied, revealing that NFC films were sufficiently impermeable 358 . Hydrophilicity clearly compromises the use of nanocellulosic materials in applications requiring materials with water and gas barriers, thus for packaging the surface is modified to increase the hydrophobicity of the material. Polymer grafting onto nanocellulosic surfaces is typically used for packaging.
Researchers have demonstrated packaging strategies in which cellulosic materials are employed in a layered system (sandwiched or the so called multilayer packaging films). In this case, the cellulosic materials are isolated from the humid environment and hence protect the materials inside from the effects of moisture [359][360][361][362][363]   Typically humidity disrupts the intermolecular hydrogen bonding between cellulose chains, but the crosslinking effectively maintained the film structure.
In another study, the nanocellulose acted itself as the cross-linker, being used as reinforcing filler in chitosan films 369 . The surface of the nanocellulose was decorated with aldehyde groups, which readily reacted with the chitosan to cross-link the film. This improved the film stability in water and its tensile strength, but at the expense of the elongation at break point. Yao, et al.
recently reported the preparation of CNF-montmorillonite composites using dopamine as a 109 linker 370 . Interfacial adhesion between the matrix and the reinforcing materials is important for mechanical and barrier performance, especially under high humidity conditions. Dopamine is conjugated to cellulose nanofibrils and hence it acts as an effective linker between CNF and montmorillonite. Such nanocomposites showed excellent gas barrier properties at high relative humidity (95%).
Nanocellulosic materials are widely used to prepare nanopapers exhibiting high strength, large surface area, transparency, foldablity and low thermal expansion coefficients.
Nanocellulosic materials have been extensively reported for the production of transparent films, and aerogels, exhibiting extraordinary mechanical, thermal, and optical properties.
Nanocellulose-ZnO-carbon dots composite films were synthesized and have proven to act as excellent UV-blocking protective shields, thanks to excellent transparency of CNCs 371 . Starchbased coating formulations have been filled with CNF and zinc oxide in order to create antibacterial coatings on paper. The coated papers showed bactericidal activity against grampositive and gram-negative bacteria 372 . Bacterial adhesion to CNF films and TEMPO-oxidized CNF films is low 373 . Bacterial adhesive ability was largely increased by treating TEMPOoxidized CNF films with polyelectrolytes, showing the importance of surface chemistry in either augmenting or diminishing material interactions with bacteria. The excellent air-barrier and antimicrobial activity of nanocellulose coatings has been reconfirmed by El-Samahy, et al. 374 .

Medical applications
Nanocellulose is interesting for biomedical materials because of its mechanical properties, nanofibrous network and its natural source, which is increasingly important for consumers with 110 regards to health care products. Thus, applications for nanocellulose in hydrogels, threads and scaffolds have been developed (Fig. 21).
Despite extensive research in the area of biomaterial synthesis for bone engineering applications, researchers are looking for a material with osteoconductive and osteoinductive properties and a surface structure closer to the natural extracellular matrix for improved cell/material interactions. Bacterial cellulose has emerged as an effective biopolymer and extensively used as a matrix for the synthesis of biomaterials for tissue engineering and regenerative medicine applications due to its high mechanical properties, bio and cyto compatibilities, and low cytotoxicity 62,67,375 . Recentely, Saska and co-workers showed that a nanocellulose-collagen-apatite composite associated with osteogenic growth peptide can be effectively used for bone regeneration 376 .
Nanocellulose has been found to be non-cytotoxic and thus has been proposed as a tissue culture medium to support cell proliferation 377 . In a recent work reported by Petreus, et al. 124 , hydrosoluble phosphorous acid-functionalized cellulose was evaluated for cytotoxicity and for use as a tissue scaffold material. Phosphorous acid-derivatized cellulose was obtained by reacting microcrystalline cellulose with a molten mixture of phosphorous acid and urea. The obtained water-soluble films were subjected to cell compatibility studies and found to exhibit good cytocompatibility due to their non-toxic nature. However, a more recent report has found that cellulose nanocrystals induced an inflammatory response and were capable of entering cells, where nanofibrillated cellulose were relatively toxic 378 . Thus the size and shape seem to have a large influence on the cytotoxicity and inflammatory response to nanocellulose. The surface chemistry has also been shown to have a large effect on inflammatory response 379 .
Modified nanocellulosic materials are particularly pertinent to bone and tissue engineering thanks to nanocellulose's biocompatibility, mechanical properties and compatibility with other biological materials such as collagen and apatite. Phosphorylated nanocellulose has been studied as a biocompatible material as scaffolds for bone regeneration. Once implanted, phosphorylated cellulose promotes calcium phosphate precipitation, upon which the material closely resembles bone. The products obtained by Granja, et al. were crystalline monoesters, which swelled in water, and which could be sterilized with gamma irradiation without being significantly damaged. In another study, a hybrid composite for bone regeneration was constructed through the covalent attachment of collagen to a bacterial cellulose matrix 376 . Carbonate apatite and osteogenic growth peptide were incorporated into this composite in order to form a bone-like material capable of encouraging supported cell growth.
Wounds present a risk of infection and thus promoting healing can avoid more serious health problems. Nanocellulose threads have been decorated with human stem-cells in order to accelerate healing 380 . These threads could be prepared with the patient's own cells a week before surgery to avoid an immune reaction. To keep the threads moist, they were treated with glutaraldehyde. Nanofibrillated cellulose has been crosslinked with calcium ions to form a hydrogel for wound-healing dressings 381 . The hydrogel is nontoxic and noninflammatory. It Poly(vinyl alcohol)-based hydrogels containing nanocellulose have been proposed for ophthalmic applications as these composite materials are soft and flexible, yet mechanically strong (see Fig. 21a). They can also be transparent and can have a water content of up to 90% 383 .
When films of the poly(vinyl alcohol)-nanocellulose composites were subjected to strain, they underwent a reorganization of the nanocellulose alignment, visualized via birefringence measurements.
A double membrane hydrogel composed of alginate and CNC shows great promise for the targeted released of antibiotic drugs via controlled sewlling mechanisms. 384 CNF films have also been used for the loading and controlled release of active substances 385 . Dong,et al. proposed modified CNCs for targeted drug delivery of chemotherapeutics 386 . CNC-chitosan hydrogels produced via a solvent-free process have also been proposed for stomach specific drug delivery due to their mechanical properties and pH sensitive drug delivery characteristics 387 . A transdermal drug delivery system has been proposed by constructing a membrane via the radical polymerization of N-methacryloyl glycine within the entangled strands of bacterial cellulose. 388 The resulting transparent membranes (see Fig. 21c 394 . In addition to drug delivery applications, CNC-based biosensors for human neutrophil elastase detection have been reported 395 .
Nanocellulose-based 3D bioprinting may revolutionize the field of tissue engineering and regenerative medicine as the 3D bioprinter is able to dispense materials while moving in X, Y, and Z directions, enabling the bottom-up engineering of complex structures 396 . Porous hydrogels have been printed by forming a printable paste out of fibrillated nanocellulose, alginate and glycerin 397 . Although further research is required to improve the mechanical properties, these printed hydrogels show a glimpse of an exciting future.

Sensing and biosensing
Protecting human health and ensuring well-being requires the detection of various molecules in the environment, including small molecules, macromolecules and biomolecules 398 . The world sensor market is projected to grow at an annual rate of more than 10%, reaching $20 billion by 2020, which is driven by intensified global manufacturing competition and advances in pollution prevention, health care and biomedical applications. Sensors for health care and biomedical applications are of increasing importance. Key areas in the biomedical field include chemical sensors for consumer health monitoring (e.g., for glucose and cholesterol), for home use, biocompatible materials for use with implants and prostheses 399 . Sensors also play a role in preventing accidental fire explosions, atmospheric environmental testing, and the industrial production of poisonous and harmful gases.
Nanocellulose-based materials possess photonic, colloidal and surface properties making them very attractive sensors, as discussed in a recent review 400  properties for applications in sensing. 404 The porous and hydrophilic nanocellulose substrate is highly permeable to liquids and gases and it also allows efficient vertical fluid delivery (wicking) of analytes entering the bottom surface to the sensing electronics above, thereby reducing the analyte delivery time (Fig. 22). The use of an organic electrochemical transistor decal simplifies the fabrication and operation, while the nanocellulose provides the required mechanical properties and permeability. Multiple devices have been fabricated on one substrate and can easily peeled from the backing substrate by simply moistening the nanocellulose sheet, and reattached to any surface, as shown in Fig. 22. A cellulose nanocrystal/polyvinylpyrrolidone composite film was designed, featuring iridescent properties to allow distinguishing between similar organic solvents. 405 Nanocellulose-based organic/inorganic hybrid nanocomposites are of interest for (bio)sensing of different analytes including gases, biomarkers, drugs, proteins, DNA, pathogens, toxic and hazardous compounds; even in real samples, including environmental, biological or clinical samples. Functionalized nanocellulose colloidal properties can be used to interact with biomolecules, as shown recently by the Thielemans group using albumin 406 . Silver nanoparticles were coated on nanofibrilated cellulose in order to obtain a surface enhanced resonance spectroscopy (SERS) platform for the detection of pesticides 407 . In SERS, the presence of a coinage metal enhances the typically weak Raman signal via the surface plasmon resonance anteanna effect. These CNC/silver hybrids formed a 3D fiber network able to increase surface roughness, an established mechanism for SERS effect optimization 408,409 .
TEMPO-oxidized nanocellulose has been used to form a hydrogel to support fluorescent carbon quantum dots 410 . This hybrid material was used to monitor the fluorescent quenching upon detection laccase enzymes. The nanocellulose hydrogel matrix increased the intensity of the fluorescent signal without shifting the excitation or emission wavelengths. This was attributed to the better dispersion of the carbon quantum dots in the hydrogel than in the absence of nanocellulose thanks to a favorable interaction between the support and fluorophore surfaces.
TEMPO-oxidized nanofibrillated cellulose was also used as a platform for imobilizing a sensing biomolecule, C-phycocyanin, which acted as an effective biosensor for copper ion detection 411 .

Electronic and engineering applications
The most significant future optoelectronic application for nanocellulosic materials is that of lightweight, flexible supercapacitors. Nanocellose provides the needed mechanical support for freestanding and flexible materials, and is combined with a conductive material-typically a polymer-to provide high volumetric capacitance. The most common conductive polymers used are polypyrrole, polyaniline and poly(ethylenedioxythiphene). Nyström, et al. prepared CNFbased electro-active composites by coating cellulose fibrils with polypyrrole 91 . In addition to being electro-active, this composite was also conductive and could store energy. An optimization of the polypyrrole/nanocellulose system yielded a material with a nearly ideal pseudocapacitive response 412 .
Recently CNF was used as a precursor for carbon nanofibers, producing an anode for sodium-ion batteries 413 . CNF has been also used in organic light emitting diodes by coating the cellulose with an indium tin oxide film 414  Unfortunately the electrical properties of the hybrid film were not reported. 119 Nanopapers have been used as templates to produce electronic materials 418 . Nanocellulose films exhibit improved conductivity 419 , taking advantage of a dense nanocellulose packing and minimal porosity compared to traditional papers treated with conductive material. Nanocellulose substrates have been used as the host matrix for metals (Au, Ag, Pd, and Ni), minerals (Ca x (PO4) y , CaCO 3 and montmorillonite), and carbon (carbon nanotubes and graphene) nanomaterials 420,421 .
The electroluminescent properties exhibited by cellulose-based systems are promising for achieving transparent and flexible light-emitting papers 422 . Nanofibrillated cellulose with luminescent phosphorous on a silver nanowire coated polyvinylidene difluoride membrane showed electroluminescent properties and can be used as the active component in optoelectronic devices 423 . This provides the foundation for the commercialization of viable, flexible and transparent light-emitting papers.

Energy conservation and production
The field of nanocellulose-based materials for electrochemical energy storage has been recently reviewed 424 . Nanocellulose is incorporated into composite materials both to conserve and to generate energy. For instance, paraffin@CNF core-shell materials have been prepared for thermal regulation, absorbing solar heat during hot periods for release when the temperature lowers 425 . The nanocellulose provided a high strength matrix, where paraffin would not have formed an easily manipulable paper on its own. However, by far the main application of nanocellulose in energy applications is its use as a (super)capacitor due to its high permanent electric dipole moment, lightweight, good mechanical properties, good optical transparency, and its minimal porosity, thermal expansion coefficient, and air permeability 426 . The reader interested in supercapacitors based on cellose is directed to a complete and specialized review of the topic 427 . In charge storage devices, nanocellulose is typically combined with a nanocarbon and a conductive polymer to produce a high specific capacitance that well exceeds that of nanocarbonbased materials without nanocellulose 428 . Metal-free, all organic supercapacitors using nanocellulose cost less than 10% of commercial units, while maintaining half of the specific capacitance 429 .
In pursuit of supercapacitors, polypyrrole was polymerized from the surface of cellulose, and then graphene oxide sheets were incorporated into the material 430 . There was excellent contact between the polypyrrole and the graphene, yielding good conductance and high capacitance.
Because the ion diffusion pathways were short, the active-sites were highly accessible and thus the composite paper did not require a current collector, a binder or other additives. Previously cellulose and graphene oxide were combined before polymerizing pyrrole within the pores of the A LiCoO 2 /multiwall carbon nanotube/NCF paper was produced with a higher energy density than other currently reported freestanding electrodes, thus such a composite is enticing as a flexible battery 435 . The lightweight, low volume composite was fabricated by mixing the LiCoO 2 , carbon nanotubes and NCF in solution and casting a membrane. This paper had a capacity of 216 mAh/g at 4.7 V, and a volumetric energy densityof 720 mAh/cm 3 .
One final exciting prospect for nanocellulose-based materials is the capture of minute quantities of energy that were previously too small to harvest. This is the concept behind many wearable and bioelectronics nanodevices. The first nanocellulose triboelectric nanogenerator has been developed where a power density of 8.1 μC/m 2 can be generated from a light mechanical force of 16.8 N (Fig. 23) 436 . To build the nanogenerator, a BNC film was sandwiched between two copper films that acted as current collectors. The lower copper layer also acted as a friction source when pressed in contact with the BNC film. An electrical potential is created upon the release of the two pressed surfaces in friction. When the BNC film and copper film are pressed together, they develop oppositely charged surfaces in order to compensate for differing surface energy and other physical properties. Upon release, current flows through an external circuit to reestablish the resting equilibrium state of the BNC and lower copper film.

Adsorption, separation, decontamination and filtration
Nanocellulose composites may find application in water 437,438 and air purification 439  Nanocellulose as an adsorbent for environmental remediation has been recently reviewed 446 .
Typically nanocellulose is valued in adsorption and separation due to its high hydrophilicity as well as its morphology and mechanical properties to form supports and membranes.  Nanocellulose membranes and aerogels have been used to purify air. MFC films were found to be excellent CO 2 barriers, allowing CO 2 to be efficiently separated from N 2 and CH 4 , even under high humidity 454 . TEMPO-oxidized cellulose nanofibrils were dispersed in tert-butyl alcohol and then freeze-dried to form an aerogel 439 . This aerogel had a high surface area (300 m 2 /g) and an interconnected, but tortuous macroporosity. These aerogels proved to be efficient air filters with insignificant pressure drops. These simple cellulose nanofibril-based materials can be used for air filtration as they performed better than conventional filters.
Nanocellulose can be used as a coating in self-cleaning surfaces. To this effect, solid surfaces have been coated with a CNF monolayer through a simple physical deposition 443 . The excellent hydration of surface polar groups strongly inhibits hydrophobes from adsorbing on the surface and also effectively removes hydrophobes, if they adsorb, upon action with water. The surface is then free from oils, ranging from viscous engine oil to polar n-butanol 443 . The self-cleaning function is correlated to the unique molecular structure of the CNF, in which abundant surface polar carboxyl and hydroxyl groups are uniformly, densely, and symmetrically arranged to form a polar corona on a crystalline nanocellulose strand.
AgNPs-BC nanocomposites have been widely used to remove bacterial contamination. For instance, due to the high water holding capacity and high biocompatibility, they have been used in wound dressing materials with improved antimicrobial activity, the development of 126 antibacterial food-packaging materials 455,456 , bactericidal paper for water remediation 457 and nanocomposites for laundering 458,459 . They are efficient substrates for substrate enhanced Raman scattering (SERS) and used in water-treatment 460,461 .

Catalysis
Interest towards green methods has advanced steadily in the field of catalysis. Metal and metal oxide nanoparticles have been used as catalysts for waste water purification, esterification of long chain fatty acids in biofuel production, decontamination and chemical production 462,463 .

Fire retardants and thermal stability
Phosphorylated cellulose provides a rare combination of good thermal stability and low flammability. Native cellulose and most of its derivatives can be characterized by low thermal stability and high flammability, burning without charring 470  Imparting flame retardancy to cellulose fibrils will make these materials safer commercial products.
Sirviö, et al. studied the thermal properties of phosphonated nanocellulose 474 . In this work, phosphonate functional groups were introduced to nanocellulose using bisphosphonate compounds via a periodate oxidation followed by reductive amination. Depending on the oxidation degree, either bisphosphonate nanofibrils or nanocrystals were obtained. Compared to mechanically produced NFC, bisphosphonate nanocellulose possessed good thermal stability and char-forming abilities, even with a low degree of substitution (0.22-0.32 mmol g −1 ).
Bisphosphonate nanocellulose can potentially be used as a composite reinforcement and a char-  Surprisingly the formation of a graphene-nanocellulose composite also has flame resistance, due to the fact that the peak of heat release rate is 25% lower for the composite than for CNFs alone 8 . This composite material was more resistant to combustion than polymeric foams with halogenated fire retardants.
Although phosphorylation is the current best surface modification technique to increase thermal stability, several other functional groups perform the same role. Esterification with benzoyl and pivaloyl esters, esters without α-hydrogens, increases the thermal stability from decomposition of nanocellulose at 230 °C to above 300 °C by preventing depolymerization 475 .
Functionalization with thermally stable, long chain amides was able to increase the onset temperature of thermal decomposition by 90 °C 476 . The key is to use thermally stable functional groups.

Future perspectives
Phosphorylation of nanocellulose is expected to open new areas of research, particularly in catalysis. Traditionally, liquid acids like H 2 SO 4 , HF or Lewis acids such as ZnCl 2 and AlCl 3 have been used as catalysts in homogeneous catalysis. However, these are highly corrosive and highly hygroscopic, making them difficult to handle. Under the reaction conditions, these reagents are converted to toxic materials. The standard workup procedure for these reagents involves neutralization followed by water quenching, which prevents them from being used again and leads to substantial quantities of aqueous waste. Since the reagents are irreversibly lost during the workup process the overall atom efficiency of the process becomes very low, which means that the use of homogeneous catalysts is not an environmentally acceptable process [477][478][479] .
Moreover, their thermal stability is also poor. Heterogeneous catalysis can overcome the drawbacks of homogeneous catalysis. But a significant problem associated with heterogeneous catalyst is the poor reactivity as a function of surface area 480  In this era of increasing environmental concern, sustainability and renewability are taken into account in the early stages of scientific research. Thus nanocellulosic materials stand to potentially replace conventional packaging materials, fire retardants, catalysts, adsorbents, and mechanical reinforcement materials. We expect that gelation methods for phosphorylated nanocellulose and their applications in various domains of life will be a topic of intense study in the coming years.

Conclusions
The word cellulose brings the image of a tree to mind, so it is natural to conjure images of carpentry and wood-based composites when thinking of cellulose-based materials.
Nanocellulose, that is cellulose broken into nanometric objects, is interesting for two main reasons: 1. It can be sourced from a wide range of natural materials, including biomass.
Managing biomass could transform waste into a valuable product. Moreover, plant waste is often burned, thus processing it avoids air pollution. Thus environmental management encourages its use. 2. It has a number of excellent properties and thus can be incorporated into a variety of materials. Nanocellulose has been studied not only for applications in packaging, films and 132 paper, but also for much more surprising domains: biomedicine, microelectronics, optics, catalysts and even flame retardants. The broader and more versatile properties originate from the size and chemistry introduced by scaling down to the nanometer. The nanostructure, and thus the properties, depends on many factors, the cellulose source (i.e. cellulose nanocrystals, nanofibrillated cellulose or bacterial nanocellulose), the degradation treatment applied (i.e. mechanical, chemical, enzymatic or a combination of these), and the surface chemistry.
Nanocellulose is abundant, renewable, non-toxic and biodegradable. Although nanoscale cellulose has many new properties, it does not lose the excellent mechanical properties exhibited by bulk cellulosic materials, such as high strength and high elasticity modulus. Thus, nanocellulose has been put to use as nanoscale reinforcement materials for polymers.
Nanocellulose-enriched polymer nanocomposites were found to be more efficient and have better mechanical properties than those produced using conventional micro-or macrocomposite materials. The hydrophilic nature, which poses a limit to some applications of nanocellulose, can be overcome using surface modification techniques. Carboxymethylation, amidation, esterification, etherylation, silylation, sulfonation and phosphorylation are surface modifications performed on nanocellulose, with the aim of altering the properties and extending their applications. Nanocellulose can also be functionalized with polymers using the grafting-to, grafting-from or grafting-through methods.
Nanocellulose has been used in a diverse range of composites, combined with nanocarbons (graphene-related materials, carbon nanotubes and carbon quantum dots), polymers, and inorganic materials (oxides, ceramics, metals and alloys). It is rather difficult to create homogenous inorganic-nanocellulose composites due to compatibility issues. Nanocellulose markedly improves organic materials, thus the most promising composites are nanocarbon or 133 polymer based composites. Nanocellulose and nanocarbons are highly compatible. Though both types of materials are notoriously difficult to disperse, their combination creates dispersions that are stable for months. The thermal and mechanical properties and the transparency of nanocellulose-polymer composites are well above that of the polymer alone. Nanocellulose is added to composites as a support material, as it retains its flexibility and excellent mechanical properties upon their integration into a composite.
Phosphorylation of nanocellulose received particular emphasis in this review, because it marks an area rich with potential and needing further research. Different methods for phosphorylating cellulose have been discussed. Phosphorylated nanocellulosic materials are produced using more environmentally friendly methods than other popular functionalization techniques. But the real interest in exploring these materials lies in their unique properties.
Nanocellulose-phosphate supports will be explored to heterogenize homogeneous catalysts as a means to create recyclable, sustainable catalysts with high activity and selectivity. Furthermore, gelation methods for phosphorylated nanocellulose and their applications in various domains of life will be intensively studied to produce the next generation of biological implants, adsorbents and flame retardants.

Biographies
Bejoy Thomas studied chemistry at the University of Bangalore (India) and received his doctoral