Nanocellulose, a tiny fiber with huge...

Nanocellulose, a tiny fiber with huge applicationsTiffany Abitbol1,3, Amit Rivkin1,3, Yifeng Cao 1,3, Yuval Nevo1,Eldho Abraham1, Tal Ben-Shalom1, Shaul Lapidot2 andOded Shoseyov1

Available online at www.sciencedirect.com

ScienceDirect

Nanocellulose is of increasing interest for a range of

applications relevant to the fields of material science and

biomedical engineering due to its renewable nature,

anisotropic shape, excellent mechanical properties, good

biocompatibility, tailorable surface chemistry, and interesting

optical properties. We discuss the main areas of nanocellulose

research: photonics, films and foams, surface modifications,

nanocomposites, and medical devices. These tiny

nanocellulose fibers have huge potential in many applications,

from flexible optoelectronics to scaffolds for tissue

regeneration. We hope to impart the readers with some of the

excitement that currently surrounds nanocellulose research,

which arises from the green nature of the particles, their

fascinating physical and chemical properties, and the diversity

of applications that can be impacted by this material.

Addresses1 Robert H. Smith Faculty of Agriculture, Food and Environment, The

Hebrew University of Jerusalem, Rehovot 76100, Israel2 Melodea Ltd, Rehovot 76100, Israel

Corresponding author: Shoseyov, Oded ([email protected])3 These authors contributed equally to this work.

Current Opinion in Biotechnology 2016, 39:76–88

This review comes from a themed issue on Nanobiotechnology

Edited by Michael Nash and Oded Shoseyov

http://dx.doi.org/10.1016/j.copbio.2016.01.002

0958-1669/# 2016 Elsevier Ltd. All rights reserved.

IntroductionIncreased demand for high-performance materials with

tailored mechanical and physical properties, makes

nanocellulose the most attractive renewable material

for advanced applications. Cellulose is the product of

biosynthesis from plants, animals, or bacteria, while the

general term ‘nanocellulose’ refers to cellulosic extracts or

processed materials, having defined nano-scale structural

dimensions. Nanocellulose can be divided to three types

of materials: (I) cellulose nanocrystals (CNCs), also re-

ferred to as nanocrystalline cellulose (NCC) and cellulose

nanowhiskers (CNWs), (II) cellulose nanofibrils (CNFs),

also referred to as nano-fibrillated cellulose (NFC), and

(III) bacterial cellulose (BC). Different approaches are


used to extract nanoparticles from cellulose sources,

resulting in particles with varied crystallinities, surface

chemistries, and mechanical properties [1]. See Figure 1

for electron microscope images of the three types of

nanocellulose.

Currently, CNCs are mainly produced by acid hydrolysis/

heat controlled techniques, with sulfuric acid being

the most utilized acid. Extraction of the crystals from

cellulose fibers involves selective hydrolysis of amor-

phous cellulose regions, resulting in highly crystalline

particles with source-dependent dimensions, for exam-

ple, 5–20 nm � 100–500 nm for plant source CNCs. Sul-

furic acid hydrolysis grafts negatively charged sulfate

half-ester groups onto the surface of the particles, which

act to prevent aggregation in aqueous suspensions due to

electrostatic repulsion between particles. Furthermore,

the rod-like shape of CNCs leads to concentration-

dependent liquid crystalline self-assembly behavior.

CNFs are micrometer-long entangled fibrils that contain

both amorphous and crystalline cellulose domains, unlike

CNCs which have near-perfect crystallinity (ca. 90%).

Entanglement of the long particles gives highly viscous

aqueous suspensions at relatively low concentrations (be-

low 1 wt%). The extraction of CNFs from cellulosic fibers

can be achieved by three types of processes: (I) mechani-

cal treatments (e.g. homogenization, grinding, and mill-

ing), (II) chemical treatments (e.g. TEMPO oxidation),

and (III) combination of chemical and mechanical treat-

ments [2].

BC is produced extracellularly by microorganisms,

with Gluconacetobacter xylinum being the most efficient

amongst cellulose-producing microorganisms. Different

from plant-source nanocellulose, which may require pre-

treatment to remove lignin and hemicellulosics before

hydrolysis, BC is synthesized as pure cellulose. BC nano-

fibers, characterized by average diameters of 20–100 nm

and micrometer lengths, entangle to form stable network

structures (see Figure 1).

The different types of nanocellulose exhibit distinct

properties which dictate their applicability and function-

ality, that is, certain types of nanocellulose are better

suited for specific applications than others. The unique

properties of nanocellulose include high Young’s modu-

lus/tensile strength (e.g. 150 GPa/10 GPa for CNCs), a

range of aspect ratios that can be accessed depending on

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Nanocellulose, a tiny fiber with huge applications Abitbol et al. 77

Figure 1

CNC CNF BC

100 nm 100 nm 5 µm

Current Opinion in Biotechnology

Representative electron microscope images of the three types of nanocellulose: CNCs, CNFs and BC. Transmission electron microscope images,

CNC and CNF, and scanning electron microscope image, BC, are reproduced with permission from references [3], [4], and [5], respectively.

particle type, and potential compatibility with other

materials, such as polymer, protein, and living cells.

Furthermore, the options for chemical and material pro-

cessing of nanocellulose are extremely versatile, opening

up a wide range of possibilities in terms of structure and

function. The scope of this article encompasses the main

types of nanocellulose outlined above, with a special

focus on cellulose nanocrystals, presenting our opinion

regarding important recent advances in nanocellulose

research and the directions driving current technologies

and future outlooks.

Nanocellulose photonicsNanocellulose is of interest for photonic applications for

reasons inherent to the material; first among these is the

liquid crystalline behavior of CNCs which gives rise to

iridescent films of defined optical character, secondly

both CNCs and CNFs may form optically transparent

stand-alone films. The versatility of these materials lies in

the nature and surface chemistry of cellulose – with

relatively little effort, nanocellulose can be made com-

patible with both hydrophilic and hydrophobic compo-

nents, used as a host for optically active nanoparticles, and

modified to covalently incorporate optically relevant

molecules.

CNCs can form chiral nematic, iridescent, colored films

simply by evaporation of aqueous suspensions [6�,7�,8].

Liquid crystals from cellulose derivatives exhibit either

right-handed or left-handed chirality [9�], whereas the

chiral nematic organization of CNCs is always left-hand-

ed likely a result of the underlying right-handed chirality

of nanocellulose [10��]. Thus, chiral nematic CNC films

selectively reflect left-handed light, and appear colorful

when the helicoidal pitch (P) is on the order of magnitude

of the wavelength of visible light (see Figure 2a). Further,

since P is sensitive to a variety of conditions, it is relatively

straightforward to modulate film color [11�,12]. This

structure-color phenomenon is analogous to the brilliant

photonic colors observed in nature, for example in

butterfly wings and in the seed hull of the Margaritarianobilis fruit.


Over the past five years, CNC-templating had been used

to access a stunningly diverse range of left-handed, chiral

materials, such as mesoporous silica [13�,14], organosilica

[15], cellulose [16], nanocrystalline titania [17], carbon

[18], as well as polymer/CNC nanocomposites [19–21].

The general approach is to create chiral nematic compo-

sites from CNCs and the material of interest, generally

silica or polymer, after which, one component may be

selectively removed, or else the material can be used in

nanocomposite form [22�,23]. The selective removal of

one component of the initial nanocomposite (with or

without modification of the remaining component) gives

a chiral mesoporous material, which can host materials

(e.g. nanoparticles, polymer) or act as a hard-template to

achieve other chiral, mesoporous materials [22�,23]. The

potential applications of these systems include responsive

hydrogels, optical filters, antireflective coatings, chiral

plasmonics [24–29], soft actuators, and flexible electron-

ics; Figure 2b highlights one recent example of a

CNC-templated, mesoporous, fluorescent organosilica

film for chemical sensing [30].

In addition to chiral nematic materials, other CNC-based

systems have been prepared with varied optical func-

tionalities, including fluorescence [31–33], surface plas-

mons (Figure 2c) [34–36], low refractive index [37], and

UV-blocking [38]. Proposed applications include green-

house plastics, anticounterfeiting technologies, particle

tracking, and sensing. One recent study by our group

described optically tunable CNC-based coatings for

greenhouse covers. Coating polyethylene with a mixture

of CNCs, ZnO and SiO2 nanoparticles, not only rein-

forced the plastic but also blocked harmful UV rays due

to the absorption of UV-light by ZnO. Additionally,

infrared blocking was achieved by the SiO2 nanoparti-

cles, contributing to energy conservation at night

(Figure 2d) [38].

Finally, the optical transparency and good mechanical

properties of CNF films make them highly relevant

as substrates for optoelectronics, and also in applications

such as coatings and packaging [39]. Similar to


78 Nanobiotechnology

Figure 2

1 2 3

CNC Suspension CNC/OrganosilicaComposite

MesoporousOrganosilica

PPV coatedOrganosilica

Natural light views UV light view

10 mm

PPV/OrganosilicaPPV/OrganosilicaMesoporous Organosilica

P/2

50 μm

100

90

80

70

60

50

40

30

20

10

0

% T

rans

mitt

ance

500 nm

(a) (b)

(c) (d)

2% CNC/0.2% ZnO

2% CNC/2% ZnO

5% CNC/2.5% ZnO

6% CNC/2.5% ZnO

5% CNC/3% ZnO

5% CNC/5% ZnO

8.75% CNC/5% ZnO (100 μm)

2% CNC/0.4% ZnO

5% CNC/0.5% ZnO

5% CNC/1% ZnO

5% CNC/1% ZnO (100 μm)

200 250 300 350 400 450 500 550 600

Wavelength (nm)

Current Opinion in Biotechnology

(a) The wavelength of the reflected light is given by l = nPsign u, where n is the average refractive index, P is the pitch of the helicoidal CNC

organization, and sign u describes the change in reflected wavelength with incident angle. It is possible to measure P by polarized optical

microscopy (POM image shown in foreground), where P/2 is the distance between dark lines (POM image reproduced with permission from

Figure 1 of reference [7�], http://pubs.acs.org/doi/pdf/10.1021/la501741r. (b) Polymerization of poly( p-phenylenevinylene (PPV) within the pores of

CNC-templated mesoporous organosilica produced films that were iridescent, fluorescent, and able to detect 2,4,6-trinitrotoluene (TNT) by

fluorescence quenching (adapted with permission from reference [30]). (c) Cellulose nanocrystals decorated with silver nanoparticles in the

presence of surfactant (adapted with permission from reference [35]). (d) Transmission spectra of CNC/ZnO nanoparticle films, at different

nanoparticle ratios, showing reduction of UV transmission at wavelengths below 400 nm. Film thicknesses are either 50 mm or 100 mm (figure

provided by Valentis Nanotech as an extension of data presented in reference [38]).

CNC-based systems, CNF films may incorporate addi-

tives such as other nanomaterials [40–42], polymer

[43,44], or surface modifications to impart desired prop-

erties such as hydrophobicity [45]. The drawback of

CNFs vs. CNCs is the relatively high viscosity of CNFs

even at low concentrations, which limits their use in high-

speed coating.

Nanocellulose films and foamsCNC films have been widely researched, mainly for their

chiral nematic organization and optical properties (see

Nanocellulose Photonics), and also for their gas barrier

[38,46,47], water sorption [47], and mechanical properties.

Recently, the thermal conductivity of CNCs was studied

by Diaz et al., from a single crystal to films with different

degrees of alignment [48].


Another widely researched area is the alignment of CNC

films by the application of external forces, such as

magnetic, electric, and shear. CNCs align with their

long axes perpendicular to the direction of the magnetic

field, due to the negative magnetic susceptibility of

cellulose [49]. CNCs can also be aligned in an electric

field, in this case with their long axes parallel to the field,

enabling the preparation of uniaxially aligned films from

suspensions in non-polar solvent [50], as well as from

aqueous suspensions [51]. Shear alignment can also be

used to induce directionality in CNC suspensions,

which is retained in the films upon drying. Techniques

that produce shear-aligned films, include spin-coating

[52,53], Langmuir-Blodgett [54], Langmuir-Schaeffer

[55], rotational shear [56], and convective shear

[57,58]. Interestingly, the alignment of the long-axes


http://pubs.acs.org/doi/pdf/10.1021/la501741r


of the CNCs does not always coincide with the direction

of the shear [58].

CNC films have been proposed for diverse applications,

ranging from food packaging [59] to cellular orientation

[53] and electronics. It was recently shown that ultrathin,

aligned CNC films exhibit a large piezoelectric response

and thus have potential in flexible electronic devices

[60�]. The combination of CNCs and conducting poly-

mers is another approach to produce flexible, conductive

films in which the CNC component enhances the me-

chanical properties of the conductive polymers, which are

typically poor. Moreover, chiral nematic order can be

preserved in such films. The topic of conductive CNC

films, as well as chiral mesoporous carbon films, which can

be used as supercapacitor electrodes with near-ideal

capacitor behavior, is discussed in depth in a recent

review [22�].

CNC foams and aerogels have not been investigated as

intensively as films. Unlike cellulose fibers and nanofi-

bers, it is difficult to form stable 3D structures from

CNCs due to limited entanglement. In recent years,

several different methods based upon physical interac-

tions between CNCs have been utilized to prepare foams

and aerogels, including freeze drying and solvent-

exchange/critical point drying (CPD). CNC properties,

such as charge, size and concentration, play a major role in

the self-organization of the particles and thus in the

architecture of the resulting foams [61–65,66�]. Recently,

chemical-crosslinking/CPD was used to produce all-

CNC aerogels, which exhibited good mechanical and

shape recovery properties, especially in water [67�].Further, the incorporation of capacitive nanoparticles

within the aerogels resulted in supercapacitors with

excellent capacitance retention at high charge-discharge

rates [68��].

Nanocellulose functionalizationThe surface hydroxyl groups and relatively large specific

surface area provide abundant active sites for nanocellu-

lose modification. Covalent modifications, such as oxida-

tion [69], esterification [70,71], etherification [72],

polymer grafting [73,74], and silylation [75,76], as well

as noncovalent binding [77], are proposed to introduce

functional groups onto nanocellulose surfaces or as pre-

cursors for further modification [75]. Compared to CNFs

and BC, CNC functionalization is gathering more interest

mainly due to its impressive mechanical properties and

interesting optical properties. Therefore, the surface

modifications discussed herein focus on CNCs. Table 1

presents a summary of some of the main CNC surface

functionalizations mentioned in this review.

The hydrophilic nature of the hydroxyl groups causes

poor dispersion of CNCs in nonpolar solvents and poly-

mer matrices, thus hydrophobization is often employed to


improve compatibility. Aside from commonly used alkyl

groups, a number of hydrophobic groups with different

functional groups, such as fluorine [70], alkenyl [76,78],

alkynyl [71], thiol groups [75,79��], pyridine moieties

[80], etc., have been attached. These functionalizations

not only enhance the dispersion of modified CNCs in

organic solvents, but also support specific interactions at

the interface between CNCs and the matrix, thereby

improving mechanical properties.

Different fluorophores have been covalently attached on

the surface of CNCs, including FITC [81], RBITC [82],

DTAF [33], poly(amidoamine) dendrimers [83], etc. The

fluorescent particles are expected to have potential in

biomiaging, biodetection, and biosensing areas.

Polymer grafting has been investigated to modify CNCs

by ‘grafting-onto’ and ‘grafting-from’ techniques. The

grafted chains improve the association between polymer

matrix and CNC filler, and facilitate stress-transfer to

enhance the strength of nanocomposite materials. More-

over, polymer grafting may be used to impart unique

properties to the modified CNCs. For example, CNCs

have been grafted with thermo-responsive PNIPAM

brushes [74], cationic polymers (PAEM [73], PAEMA

[73], and PQDMAEMA [84]), as well as antimicrobial

polyrhodanine [85].

Cationic CNCs have been prepared using different surface

functionalization methods. Recently, CO2-switchable ag-

gregation and redispersion was reported for cationic CNC-

APIm (1-(3-aminopropyl)imidazole) [86] and for CNCs

grafted with 4-(1-bromo-methyl)benzoic acid (producing

ImBnOO-g-CNCs) [87�]. The ionic liquid 1-methyl-3-

propargylimidazolium bromide ([MPIM]Br) was grafted

to azido-CNCs using copper (II) sulfate as catalyst, pre-

senting the opportunity to prepare CNC-supported ion-

exchange or catalytic materials [88]. Also, cationic poly[2-

(dimethylamino)ethyl methacrylate] (PDMAEMA)-

grafted CNCs exhibited pH-responsive properties and

were used for dual-responsive Pickering emulsion stabili-

zation [89], drug delivery [90] and viral delivery [84].

The high specific surface area makes CNCs attractive

supports for nanoparticles (NPs). Catalytically active

‘NPs@CNC’ hybrids have been produced, where CNCs

act as the support material and/or reducing agent. The

following highly efficient catalysts, Ru(0)NPs@CNCs [91]

and Pd(0)NPs@CNCs [92], were reported for arene hydro-

genation and carbon-carbon bond formation in the Mizor-

oki-Heck cross-coupling reaction, respectively. Enhanced

catalytic properties were observed for AuNPs@CNCs in

the reduction of 4-nitrophenol [93�].

Nanocellulose in thermoplastic materialsNanocellulose, including CNCs and CNFs, is extensively

used as a filler in thermoplastic polymeric matrices to



Table 1

Direct CNC surface functionalizations mentioned in this review

Reaction Functional groups (CNC-OR) Characteristics Ref.

Esterification Hydrophobic and oleophobic materials [70]

Poly(butadiene) rubber reinforcement via cross-linking by thiol-ene click reaction [78]

Reinforcement in GAP/PTPB polymer matrix [71]

Improved hydrophobicity and dispersibility in organic solvents, for natural rubber

reinforcement

[79��]

pH-responsive [80]

Silylation Carbon–carbon double bond for free radical polymerization [76]

Allows facile functionalization of cellulose under mild conditions [75]

Cationization pH sensitive, CO2 controlled flocculation [86]

R1=H, Me

pH sensitive, CO2 controlled flocculation [87�]

produce cost-effective, highly durable nanocomposite

materials, with a ‘greener’ footprint. The native crystal-

linity, high strength, and moderate to high aspect ratio

(ca. 10–1000 length/diameter; type dependent) of nano-

cellulose are relevant for stress-transfer and load-bearing

in thermoplastics, such as starch, polyvinyl alcohol (PVA)

[94], poly lactic acid (PLA) [95–97], polycarbonate (PC)

[98], polyurethane (PU) [99], and polymethyl methacry-

late (PMMA) [100]. In order to improve compatibility

with hydrophobic matrices, it may be necessary to modify

nanocellulose surfaces (see section on Nanocellulose

Functionalization).

Many in-depth scientific papers covering nanocellulosic

materials with thermoplastic components have been pub-

lished over the past two decades; Table 2 summarizes and

highlights some of the most recent, industrially and

scientifically important reports, with reference to type

of nanocellulose used, manufacturing technique, and

proposed applications.

Nanocellulose-protein compositesThe combination of nanocellulose and protein in nano-

composite materials aims to combine attractive qualities

from each component in a synergistic fashion. In terms of


material science applications, this strategy often falls

under the umbrella of ‘biomimicry’, where nature inspires

the fabrication of functional materials; in this case the

approach may aspire to recreate the hard/soft composite

mechanical motif that is prevalent in many natural organ-

isms [130], casting nanocellulose in the role of ‘hard’ and

protein as the ‘soft’ player.

A promising and versatile approach to achieve nanocel-

lulose-protein composites is via a carbohydrate binding

module (CBM) linker. Recombinant proteins that incor-

porate a CBM can be bound to nanocellulose surfaces;

recently our group has prepared hard/soft nanocomposite

films based on CNCs and a recombinant elastic protein

motif from resilin (exon 1 from Drosophila Melanogaster)

engineered to include a CBM [131]. Additionally, the

resilin-CBM-CNCs were used to mechanically reinforce a

hydrophobic epoxy resin [132]. In fact, the mechanical

behavior of protein-CBM-CNC nanocomposites is com-

plex and dependent on various factors including hydra-

tion, interactions among constituents, and crosslinking

[131,133].

In addition, CBMs and CBM-proteins/bioactive moie-

ties (e.g. biotin) have been bound to nanocellulose for



Table 2

Summary of recent advances in nanocellulose-thermoplastic composites

Nanocellulose

type

Polymer component Manufacturing technique Applications

CNCs Methylcellulose Hydrogel by aqueous

dispersion

Thermoreversible and tunable nanocellulose-based

hydrogels [101]

Plasticized starch Solution casting Transparent materials [102]

Starch Blending [103], solution

casting [104]

Air permeable, resistant, surface-sized paper [103],

food packaging [104]

PVA Solution casting Stretchable photonic devices [105], Wound diagnosis/

biosensor scaffolds [31], conductive materials [106]

Plasticized PLA Twin-screw extruder Film blowing, packaging [107]

Maleic-anhydride grafted PLA Electrospinning Bone tissue engineering [108�]

Cellulose esterified with

lauroyl chloride

Solution casting and

thermorpressing

Interface melting [109]

PC Matsterbatch melt extrusion

process

Optical devices [110]

PC based polyurethane blend Solution casting Smart actuators and sensors [80]

Ethylene-co-vinyl acetate

rubber

Solution mixing and

vulcanization

Transparent, rubbery materials [111]

PU Solution casting High temperature biomedical devices [112]

CNFs Polyethylene glycol PEG-g-CNF ribbons by

stretching hydrogel

Ultra-high tensile strength and modulus for

optoelectronic and medical devices [113]

Amorphous dialcohol

cellulose

Oxidation + reduction of CNF

surface

Barrier films [114]

Polyethylene Extrusion [115–117] High performance cellulosics [115], environmentally

friendly HDPE [116], Evaluation of cotton filler in LDPE

[117]

Thermoplastic starch Solution casting Decreased water sensitivity [118], thermally stable

starch [119]

Maize amylopectin Solution casting Continuous papermaking [120]

Polyvinyl amine Layer by layer Self-healing polymer films [121]

Polyacrylamide Solution casting Films with good mechanical, optical thermal and

oxygen barrier properties [122]

PVA Solution casting Flexible displays, optical devices, packaging and

automobile windows [123], Food packaging [124] [125]

Carboxymethyl cellulose Solution casting Edible coatings and packaging materials [126]

Poly(butylene adipate-co-

terephthalate)

Injection molding Light-weight and high performance materials for

defense, infrastructure and energy [127]

BC Poly(ethylene oxide) based

block copolymer

Solution casting Transparent biocomposites [128]

CNFs, CNCs, BC PMMA Solution casting Packaging, flexible screens, optically transparent films

and light-weight materials for ballistic protection [129]

detection/bioimaging [134], and also to study the inter-

action of CBMs with crystalline cellulose, that is, under-

standing the interaction of CBMs with recalcitrant

cellulose is critical to biofuel developments.

The modification of biomedical scaffolds, including BC

membranes, with proteins to improve cell adhesion is

vital. A recent example from the literature uses the RGD

(Arg-Gly-Asp) cell adhesion sequence in concert with

antimicrobial gentamicin to produce BC membranes that

exhibited antimicrobial properties and also promoted the

growth of human fibroblasts [135]. Similarly, the immo-

bilization and cross-linking of collagen on the surface of

BC membranes improved bioactivity [136], and silk-fi-

broin/BC membranes showed improved cell attachment

and growth [137].


Finally, CNCs are also attractive for the mechanical

reinforcement of protein-based materials, including col-

lagen [138], gluten [139], and prolamin [140]. The role of

nanocellulose as a filler in protein-based materials is two-

fold: (1) viewed as an inexpensive nanofiller material,

nanocelluose may permit reduction of protein component

without sacrifice to mechanical properties, and (2) it may

actually improve mechanical properties due to inherent

reinforcing capabilities related to aspect ratio and crystal-

linity.

Nanocellulose in medical applicationsNanocellulose is a promising biomaterial for medical appli-

cations owing to its good biocompatibility [141–143] and

relatively low toxicity [144�], as well as distinct geometry,

surface chemistry, rheology, crystallinity and self-assembly



behavior [1,145,146]. While it is generally accepted that BC

is non-toxic [141], the issue of biotoxicity is less resolved for

other nanoparticles of cellulose, such as CNCs and CNFs.

The toxicity of these materials depends on particle size,

surface chemistry, and process purity. Preliminary results

indicate low dermal and oral toxicity, but are conflicting

with regards to inhalation and cytotoxicity [144�].

The assembly and surface chemistry properties of nano-

cellulose are useful in scaffold design — to enhance me-

chanical properties [147–150], cell adhesion, proliferation

and differentiation [149–155], and cellular patterning

[53,148,156,157]. With the possibility of diverse fabrica-

tion shapes, such as membrane-like structures having

tailorable porosities and surface chemistries, BC and

CNCs are inherently suitable for tissue engineering scaf-

folds [145], such as coatings [158], membranes and hydro-

gels [150,159–161], electrospun nanofibers [149,162], and

all-cellulose nanocomposites [148].

Another hot topic is nanocellulose-based materials

for drug delivery [163], in the form of membranes

[164–166], tablet coatings [167], and in composite-bio-

polymer delivery systems [168,169]. These materials can

be loaded with the drug of choice, and provide good drug

stability as well as a controlled release profile [170,171]. In

addition, CNC surface modification has been used to

design novel carriers [172–174]; a particularly versatile

modification of CNCs uses an aromatic linker to facilitate

both binding and controlled release of amine-containing

drugs [174]. Furthermore, nanocellulose is a promising

candidate for protein immobilization, preserving the

structural integrity of the protein, and enhancing activity

and long-term storage stability [175��].

Nanocellulose per se does not possess properties for tissue

regeneration and healing. However, it does provide a

versatile platform when used in combination with other

biomaterials, such as collagen, to support and promote

cellular activities for tissue regeneration and repair. Exam-

ples are found for both hard and soft tissue regeneration

[143,176,177], with skin repair being the most explored and

clinically advanced in the field [146,175��,178]. Moreover,

the ability of BC/BC-biocomposites to absorb exudate and

be easily removed, coupled with their hydrophilic nature,

make these materials superior compared to conventional

dressings [178]. In fact, several BC-based products are

already available on the market (e.g. XCell1 and BioFill).

Nanocellulose BC wound dressings can also play a role in

antimicrobial treatment, since the porous network pro-

vides a physical barrier against external infections while

allowing release of pre-loaded antimicrobial agents. Both

inorganic [179–185] and organic [135,186–191] antimicro-

bials have been employed to this end, with loading into

the nanocellulose structures based either on physical

adsorption or chemical conjugation.


The mechanical properties, water contents and good

biocompatibility, make BC the most attractive form of

nanocellulose for tissue replacement. While several

examples show early stage results for soft tissue applica-

tions [147,159,192–194], blood vessel replacements are by

far the most promising and relevant with significant

benefits compared to clinically available synthetic mate-

rials [195–199].

Fluorescent labeling of nanocellulose with a variety of

fluorophores is of emerging interest in bio-imaging, target-

ing and sensing applications [33,81,82,200]. Finally,

CNC-based systems are also compelling as mechanically

adaptive materials for intracortical microelectrode applica-

tions. The first report of this nature described CNC-based

microprobes which exhibited switchable mechanical prop-

erties from wet to dry [201�].

ConclusionsAlthough the topic of nanocellulose (CNCs, CNFs, and

BC) has been intensively researched over the past

2+ decades, the room for new developments, particularly

in the fields of coatings and medical devices, clearly

exists. Pushing the boundaries of nanocellulose further

into flexible electronics, optical devices, and high perfor-

mance functional plastics, to create organic materials with

tunable, ‘smart’, and biomimetic characteristics will be of

particular interest for the future, especially as cost-effective

commercial sources of nanocellulose continue to emerge.

Currently, the applications of nanocellulose may be some-

what limited by availability and cost, however the outlook

is promising as more and more companies and researchers

look toward these particles for solutions to existing chal-

lenges.

AcknowledgmentsThe authors thank David Ernst Weber for design of the table of contentsgraphic, and the Minerva Center for Biohybrid Complex Systems forsupport. TA is grateful to the Azrieli Foundation for the award of an AzrieliFellowship, and YC and EA acknowledge the PBC post-doctoral fellowshipfor funding. This work was partially supported by a Minerva Grant and twoFP7 programs: BRIMEE (608910) and NCCFOAM (604003-2). In addition,the authors would like to thank the Hebrew University Center forNanoscience and Nanotechnology.

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201.�

Harris JP, Capadona JR, Miller RH, Healy BC, Shanmuganathan K,Rowan SJ, Weder C, Tyler DJ: Mechanically adaptiveintracortical implants improve the proximity of neuronal cellbodies. J Neural Eng 2011 http://dx.doi.org/10.1088/1741-2560/8/6/066011.

This work describes the preparation and performance of mechanicallyadaptive microelectrodes, emphasizing the potential of nanocellulosecomposites to overcome mechanical mismatches between electrodesand cortical tissue. A system that can decouple the mechanical andsurface chemistry components of the neural response is demonstrated.

































http://dx.doi.org/10.1088/1748-6041/7/6/065006

http://dx.doi.org/10.1007/s11051-012-1084-1




















































































http://dx.doi.org/10.1088/1741-2560/8/6/066011

http://dx.doi.org/10.1088/1741-2560/8/6/066011

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