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ScienceDirect
Nanocellulose, a tiny fiber with huge applications
Tiffany Abitbol1,3, Amit Rivkin1,3, Yifeng Cao 1,3, Yuval Nevo1,
Eldho Abraham1, Tal Ben-Shalom1, Shaul Lapidot2 and
Oded Shoseyov1
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.
Addresses
1
Robert H. Smith Faculty of Agriculture, Food and Environment, The
Hebrew University of Jerusalem, Rehovot 76100, Israel
2
Melodea Ltd, Rehovot 76100, Israel
Corresponding author: Shoseyov, Oded (shoseyov@agri.huji.ac.il)
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.
Introduction
Increased 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
Current Opinion in Biotechnology 2016, 39:76–88
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
100 nm
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 photonics
Nanocellulose 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 Margaritaria
nobilis fruit.
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CNF BC
100 nm 5 µm
Current Opinion in Biotechnology
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
Current Opinion in Biotechnology 2016, 39:76–88
78 Nanobiotechnology

Figure 2

(a) (b)

1 2 3

CNC Suspension CNC/Organosilica Mesoporous PPV coated

P/2 Composite Organosilica Organosilica

Natural light views UV light view

50 μm 10 mm

Mesoporous Organosilica PPV/Organosilica PPV/Organosilica

(c) (d)

100
2% CNC/0.2% ZnO
90 2% CNC/0.4% ZnO
80 5% CNC/0.5% ZnO
5% CNC/1% ZnO
% Transmittance

70
5% CNC/1% ZnO (100 μm)
60 2% CNC/2% ZnO
5% CNC/2.5% ZnO
50
6% CNC/2.5% ZnO
40 5% CNC/3% ZnO
30 5% CNC/5% ZnO
8.75% CNC/5% ZnO (100 μm)
20
10

500 nm 0
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 foams
CNC 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

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 Nanocellulose, a tiny fiber with huge applications Abitbol et al. 79
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 functionalization
The 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
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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 materials
Nanocellulose, including CNCs and CNFs, is extensively
used as a filler in thermoplastic polymeric matrices to
Current Opinion in Biotechnology 2016, 39:76–88
80 Nanobiotechnology

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 [79]
reinforcement
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]

pH sensitive, CO2 controlled flocculation [87]

R1=H, Me

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 composites
The 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

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 Nanocellulose, a tiny fiber with huge applications Abitbol et al. 81

Table 2

Summary of recent advances in nanocellulose-thermoplastic composites

Nanocellulose Polymer component Manufacturing technique Applications

type
CNCs Methylcellulose Hydrogel by aqueous Thermoreversible and tunable nanocellulose-based
dispersion hydrogels [101]
Plasticized starch Solution casting Transparent materials [102]
Starch Blending [103], solution Air permeable, resistant, surface-sized paper [103],
casting [104] 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 Solution casting and Interface melting [109]
lauroyl chloride thermorpressing
PC Matsterbatch melt extrusion Optical devices [110]
process
PC based polyurethane blend Solution casting Smart actuators and sensors [80]
Ethylene-co-vinyl acetate Solution mixing and Transparent, rubbery materials [111]
rubber vulcanization
PU Solution casting High temperature biomedical devices [112]
CNFs Polyethylene glycol PEG-g-CNF ribbons by Ultra-high tensile strength and modulus for
stretching hydrogel optoelectronic and medical devices [113]
Amorphous dialcohol Oxidation + reduction of CNF Barrier films [114]
cellulose surface
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- Injection molding Light-weight and high performance materials for
terephthalate) defense, infrastructure and energy [127]
BC Poly(ethylene oxide) based Solution casting Transparent biocomposites [128]
block copolymer
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 applications
Nanocellulose 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

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82 Nanobiotechnology
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.
Current Opinion in Biotechnology 2016, 39:76–88
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].
Conclusions
Although 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.
Acknowledgments
The authors thank David Ernst Weber for design of the table of contents
graphic, and the Minerva Center for Biohybrid Complex Systems for
support. TA is grateful to the Azrieli Foundation for the award of an Azrieli
Fellowship, and YC and EA acknowledge the PBC post-doctoral fellowship
for funding. This work was partially supported by a Minerva Grant and two
FP7 programs: BRIMEE (608910) and NCCFOAM (604003-2). In addition,
the authors would like to thank the Hebrew University Center for
Nanoscience and Nanotechnology.
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