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REVIEW

Antibacterial Materials www.advhealthmat.de

Nanocellulose-Based Antibacterial Materials


Juanjuan Li, Ruitao Cha,* Kaiwen Mou, Xiaohui Zhao, Keying Long, Huize Luo,
Fengshan Zhou,* and Xingyu Jiang*

along with the abuse of antimicrobials,


In recent years, nanocellulose-based antimicrobial materials have attracted which threaten the health of billions of
a great deal of attention due to their unique and potentially useful features. people in the world. As the seriousness
In this review, several representative types of nanocellulose and modifica- of drug resistance of bacteria increases
rapidly, many studies have focused on
tion methods for antimicrobial applications are mainly focused on. Recent
developing antimicrobial materials that
literature related with the preparation and applications of nanocellulose-based prevent bacterial infection to overcome
antimicrobial materials is reviewed. The fabrication of nanocellulose-based drug resistance.[2]
antimicrobial materials for wound dressings, drug carriers, and packaging Nanocellulose have gained much atten-
materials is the focus of the research. The most important additives employed tion for antibacterial application because
in the preparation of nanocellulose-based antimicrobial materials are pre- of their remarkable physical properties,
special surface chemistry, and excel-
sented, such as antibiotics, metal, and metal oxide nanoparticles, as well lent biological properties.[3] Nanocellu-
as chitosan. These nanocellulose-based antimicrobial materials can benefit lose possess abundant hydroxyl groups,
many applications including wound dressings, drug carriers, and packaging which make them stable in water. There
materials. Finally, the challenges of industrial production and potentials for are mainly four kinds of nanocellulose,
development of nanocellulose-based antimicrobial materials are discussed. including nanocrystalline cellulose (NCC),
nanofibrillated cellulose (NFC), bacterial
cellulose (BC), and electrospun-cellulose
nanofibers (ESC).[4]
1. Introduction NCC is a class of rigid, hydrophilic, high in aspect ratio, and
rod-shaped crystal cellulose whiskers of 1–20 nm in diameter,
Antimicrobials have been used among both human beings and tens to hundreds of nanometers in length.[5] With a large
and animals to cure infectious diseases since the discovery surface area (150–250 m2 g−1) and low coefficient of thermal
of penicillin in 1929.[1] The drug-resistant bacteria appeared expansion, NCC shows great potential in tissue engineering,
fillers for injectable hydrogel, and drug carriers.[6] NFC is
isolated from cellulose-containing materials such as hemp
J. Li, H. Luo, Prof. F. Zhou fibers, wheat straws, and wood materials, which possess fine
Beijing Key Laboratory of Materials Utilization of Nonmetallic structure, high aspect ratio, large specific surface area, and
Minerals and Solid Wastes
good biocompatibility. NFC is applicable to the preparation of
National Laboratory of Mineral Materials
School of Materials Science and Technology multifunctional materials such as films, paper, foams, and aero-
China University of Geosciences (Beijing) gels with high porosity.[7] BC is known for numerous desirable
Beijing 100083, China properties, such as sustainability, biocompatibility, biodegrada-
E-mail: zhoufs@cugb.edu.cn bility, broad chemical-modification capability, and high surface
J. Li, Prof. R. Cha, X. Zhao, K. Long, Prof. X. Jiang area. BC is also the only nanocellulose that is produced and sold
Beijing Engineering Research Center for BioNanotechnology and
CAS Key Lab for Biological Effects of Nanomaterials and Nanosafety in large scales.[8] ESC is prepared by electrospinning and usu-
CAS Center for Excellence in Nanoscience ally in the form of films, and the raw materials of ESC include
National Center for NanoScience and Technology crystal whisker, cotton, and cellulose acetate. ESC has become
Beijing 100190, China useful for biomedical, filter, catalytic, and textile applications.[9]
E-mail: chart@nanoctr.cn; xingyujiang@nanoctr.cn
We described the preparation and application of the
K. Mou
nanocellulose-based antimicrobial materials (Figure 1).[2d,10]
CAS Key Laboratory of Bio-based Materials
Qingdao Institute of Bioenergy and Bioprocess Technology There are mainly four methods for preparing nanocellulose-
University of Chinese Academy of Sciences based antimicrobial materials, containing surface modifica-
Qingdao 266101, China tion, antibiotic addition, combination with nanomaterials, and
Prof. X. Jiang combination with antibacterial polymers. Several quaternary
Sino-Danish College, University of Chinese Academy of Sciences ammonium compounds, such as zwitterion betaines which
Beijing 100049, China
are essential for protein formation and DNA repair, have been
The ORCID identification number(s) for the author(s) of this article
can be found under https://doi.org/10.1002/adhm.201800334.
applied in the preparation of antibacterial materials.[11] Many
metal or metal oxide nanoparticles, such as gold, silver, copper,
DOI: 10.1002/adhm.201800334 copper oxide, zinc oxide, titanium dioxide, magnesium oxide

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Xingyu Jiang obtained his B.S.


at the University of Chicago
(1999), followed by an A.M.
(2001) and a Ph.D. (2004)
from Harvard University
(Chemistry), working with
Prof. George Whitesides. He
joined the NCNST in 2005
and has remained there since
then. His research interests
include surface chemistry on
the micro/nanoscale, develop-
ment of antibacterial nanoparticles, and their application
as wound dressings.

(DANFC) by sodium periodate oxidation, and found that the


antimicrobial activity of DANFC against both Staphylococcus
aureus and multidrug resistant (MDR) S. aureus increased with
the increase of aldehyde content (Figure 2).[15] DANFC also
displayed good biocompatibility toward mammalian cells, and
Figure 1. The preparation and application of nanocellulose-based
antimicrobial materials. showed good blood compatibility. We studied the healing effect
of DANFC in an animal model, and epithelial parakeratosis
nanoparticles, and cupper/titanium dioxide nanocomposites, was observed in both gauze group and DANFC group, but hair
are good candidates for antimicrobial applications.[12] Further- follicles and cuticular pegs appeared first in the wound tissue
more, many antimicrobial polymers are employed for antibacte- treated with DANFC mat on day 14. DANFC can accelerate
rial applications, for instance, chitosan and its derivatives are wound healing and enhance the formation of blood vessels and
good antibacterial agents.[13] Nanocellulose-based antimicrobial epithelium. Oxidized BC/silver composites prepared by reac-
materials can be used in many applications including drug car- tion between aldehyde compound and silver–ammino complex
riers, packaging materials, and wound dressing materials. showed significant antimicrobial property. The composites also
exhibited high biocompatibility, allowing the attachment and
growth of epidermal cells, which helps with wound repair.[16]
2. Methods for Preparation of Nanocellulose- TEMPO can link on the surface of nanocellulose under
aqueous condition, and then the hydroxyl group at C6 position
Based Antibacterial Materials
of nanocellulose will convert to aldehyde and carboxyl func-
2.1. Surface Modification on Nanocellulose tional groups.[17] TEMPO-BC/silver composite was prepared by
depositing silver nanoparticles on TEMPO-oxidized BC, which
Nanocellulose is composed of β-1, 4-glucose, and there are is a promising alternative for curing bacteriosis of shrimp.[18]
three active hydroxyls on C2, C3, and C6 positions of glu- Aldehyde-nanocellulose showed great potential in biomedical
copyranose ring. Nanocellulose can be easily modified on applications, whereas the regents and solvents which are used
these positions by oxidation, esterification, or etherification, during processing will affect the final products and environ-
which would introduce new functional groups. The functional ment. The best possibility to avoid toxic solvents is the usage of
groups with antimicrobial properties include aldehyde group water-soluble oxidant or other “green” oxidant.
and quaternary ammonium. These two kinds of nanocellulose
showed good antibacterial activity and biocompatibility.
2.1.2. Quaternized Nanocellulose

2.1.1. Aldehyde-Nanocellulose Antibacterial nanocellulose has been developed by grafting of


quaternary ammonium compounds. Quaternary ammonium
The aldehyde groups on nanocellulose are usually grafted compounds are the most widely used antimicrobial agents due
through oxidation by oxidants, such as periodate sodium and to their antibacterial properties, low toxicity, and environmental
2,2,6,6-tetramethylpiperidinyloxy (TEMPO). compatibility (Figure 3).[19]
The periodate oxidation is traditionally done in water, and Cationic porphrin (CP) was appended onto the surface
more periodate and longer oxidation time were used to achieve of NCC via the Cu (I)-catalyzed Huisgen–Meldal–Sharpless
higher aldehyde contents.[14] Periodate sodium can selectively “click” reaction, which was first proposed in 2001 and pro-
oxidize the hydroxyl group into aldehyde group on the C6 vides an excellent platform for biomedical applications.[20]
position of nanocellulose. We prepared 2,3-dialdehyde NFC NCC–CP showed excellent efficacy toward the photodynamic

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Figure 2.  Scheme of the experimental process of DANFC and its wound healing effect for the rat model. Reproduced with permission.[15] Copyright 2017,
the Royal Society of Chemistry.

inactivation of Mycobacterium smegmatis and S. aureus, albeit S. aureus.[29] Electrospuning of quaternized raw materials could
with only slight activity against Escherichia coli.[21] avoid the potential release of biocides from raw materials, which
NFC could be quaternized through grinding method and will provide benefit for the application of quaternized ESC.
high pressure homogenization. For example, after the cellulose
fibers were pretreated by sodium hydroxide and glycidyl trime-
thyl ammonium chloride (GTMAC) at 65 °C, NFC–GTM was 2.2. Addition of Antibiotic in Nanocellulose
synthesized by grinding.[22] Another kind of NFC–GTM was pre-
pared by high pressure homogenization of NFC and GTMAC, Antimicrobial properties of nanocellulose-based antimicrobial
which showed antimicrobial properties against E. coli, S. aureus, materials could be realized by adding antibiotics (Table 1). The
and Pseudomonas aeruginosa.[23] Compared with grinding method most frequently used antibiotics are shown in Figure 4.
which would damage the fiber badly and decrease its crystal- All the four kinds of nanocellulose are suitable for
linity, high pressure homogenization may be more suitable for synthesizing antibacterial materials.[31] For example, allicin-
preparing quaternized NFC with higher mechanical strength.[24] conjugated NCC can be attached on cellulose by a simple
BC-based antibacterial materials can be prepared by chemical conjugation, which showed durable antibacterial properties
reaction between BC and aminoalkyl groups, such as 3-amino- against S. aureus.[32] NFC hydrogel that contains polymyxin
propyltrimethoxysilane. BC membranes were grafted with ami- B can be prepared upon lyophilization.[33] In addition, ceftri-
noalkyl groups, which are lethal to E. coli and S. aureus, but no axone, chloromycetin,[34] ampicillin, and gentamycin[35] were
obvious toxicity to human adipose-derived mesenchymal stem added in BC to prepare antimicrobial materials. The 3D network
cells, as the cell viability was more than 70% after treated by the structure of BC is responsible for the largest holding capacity
membrane.[25] BC also plays a role in the development of sus- and sustained release of the antibiotic ceftriaxone.[36] ESC mat
tained-release material or efficient adsorbent for antibacterial with antimicrobial properties against E. coli and S. aureus was
applications. For example, BC mats which provided a sustained successfully prepared with poly(ε-caprolactone), cellulose acetate,
release of benzalkonium chloride (BKC) showed antimicrobial tetracycline hydrochloride, and dextran blend solution.[37]
properties against E. coli and S. aureus.[26] In addition, meth- In order to control the release rate and acquire better anti-
acryloyl oxyethyl dimethylbenzyl ammonium chloride-coated bacterial effect, clathration is an effective method for preparing
BC was applied to kill the E. coli in water.[27] antibiotic nanocellulose-based antibacterial materials. NCC was
Antibacterial ESC could be prepared by electrospinning of qua- functionalized with β-cyclodextrin (β-CD) by using succinic acid
ternized raw materials or dipping ESC into the solution of qua- and fumaric acid as bridging agents, which were able to release
ternary ammonium compounds. For instance, ESC with excellent antibacterial molecules for long periods of time. Consider-
antibacterial activities against E. coli and S. aureus was obtained ably sustained antibacterial activity against Bacillus subtilis was
by electrospuning of cellulose acetate which was modified by observed for NCC-CD compared with other materials.[40] Anti-
3-amino propyl trimethoxysilane (APTS) or 2,4-bi[(3-benzyl- microbial ESC was synthesized through electrospinning a blend
3-bimethylammonium)propylamino]-6-choro-1,3,5-triazine chlo- suspension of a novel β-CD modified N-halamine copolymer
ride (BBCTC).[28] Dipping ESC mats into 3-(trimethoxysilyl) and cellulose acetate. After chlorination treatment by sodium
propyldimethyl octadecylammonium chloride (AEM) could also hypochlorite, the chlorinated ESC showed good biocompat-
yield the ESC mats with excellent antibacterial activities against ibility and antibacterial properties against E. coli andS. aureus.[41]

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Figure 3.  The frequently used quaternary ammoniums. CP. Reproduced with permission.[21] Copyright 2011, American Chemical Society; GTMAC.
Reproduced with permission.[22] Copyright 2016, Elsevier Ltd; BBCTC. Reproduced with permission.[28b] Copyright 2009, Elsevier Ltd; AEM. Repro-
duced with permission.[30a] Copyright 2015, Elsevier Ltd; BKC. Reproduced with permission.[30b] Copyright 2018, Elsevier Ltd; DMAE. Reproduced with
permission.[30c] Copyright 2012, Springer Nature; and APTS. Reproduced with permission.[30d] Copyright 2008, American Chemical Society.

Table 1. Antibiotics and their functions in nanocellulose-based


antimicrobial materials. The antibiotic consumption will reduce when combining
antibiotics with mats or hydrogels, which is effective for
Type Antibiotics Bacterial species Ref. reducing the risk of antibiotic-resistant infections.
NCC Allicin S. aureus [32]
NFC Polymyxin B P. aeruginosa; Serratia marcescens; [33]
2.3. Combination with Nanomaterials
S. typhimurium; E. coli; Enterobacter cloacae
BC Ceftriaxone S. aureus [36] Inorganic nanoparticles are widely used in nanocellulose-based
Chloromycetin S. aureus; Streptococcus pneumonia; E. coli [34] antimicrobial materials, such as noble metal nanoparticles and
Ampicillin S. aureus; P. aeruginosa; E. coli; E. faecalis [35] metal oxide nanoparticles. They would release from the com-
Gentamycin S. aureus; P. aeruginosa; E. coli; E. faecalis [35] posites and contact with the bacteria. The minimal inhibitory
concentration (MIC) of inorganic nanoparticles containing
Tetracycline S. aureus; E. coli [37]
nanocellulose-based materials is much lower than that of single
hydrochloride
metal or metal oxide nanoparticles, which is beneficial for
ESC Triclosan S. aureus; E. coli [38]
human beings and the environment.

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Figure 4.  The structure of antibiotics in nanocellulose-based antimicrobial materials. Polymyxin B. Reproduced with permission.[39a] Copyright 2011,
Elsevier Ltd; Ceftriaxone. Reproduced with permission.[39b] Copyright 2015, Elsevier Ltd; Chloromycetin. Reproduced with permission.[39c] Copyright 1949,
Elsevier Ltd; Ampicillin. Reproduced with permission.[39d] Copyright 2018, Elsevier Ltd; Gentamycin. Reproduced with permission.[39e] Copyright 1975,
American Chemical Society; and Tetracycline·HCl. Reproduced with permission.[39f ] Copyright 2016, Elsevier Ltd.

2.3.1. Silver/Gold Nanoparticles showed better efficacy against Gram-negative bacteria than most
of the antibiotics. It also possessed excellent physicochemical
Due to their unique properties including low-toxicity, photo- properties including water uptake capability, mechanical strain,
thermal effects, large specific surface area, versatility in surface and biocompatibility. The BC/Au-DAPT nanocomposite system is
modification, and polyvalent effects,[20d,42] our group studied a promising platform for treating superbug-infected wounds.[10a]
antibacterial properties of various gold nanoparticles, such as Silver nanoparticles have attracted tremendous amount of
4,6-diamino-2-pyrimidinethiol (DAPT) coated gold nanoparticles attention due to their broad antimicrobial spectrum.[45] These
(Au-DAPT).[43] Importantly, antimicrobial activity of Au-DAPT particles can kill bacteria. Silver nanoparticles are susceptible
nanoparticles will not induce any reactive oxygen species (ROS)- to destabilization or aggregation, which can affect their anti-
related process, which means that the nanoparticles are unlikely microbial activity.[46] Many approaches have been employed to
to induce bacterial resistance.[44] Au-DAPT nanoparticles incorpo- promote the antimicrobial activity of silver nanoparticles and
rated with BC were used as wound dressing (denoted as BC/Au- reduce their dosage for reducing cost. One is improving the
DAPT nanocomposite) for treating infected wounds (Figure 5). dispersity of silver nanoparticles in nanocellulose,[45a] because
On day 14 postoperation of the wounds, the sizes of the wounds well-dispersed silver nanoparticles could enhance the antibacte-
treated by BC/Au-DAPT nanocomposites were significantly rial activity with low-dosage.[47] Another one is controlling the
smaller than those of the BC-treated groups both for E. coli and release of silver nanoparticles.[48] The main issue with silver-
P. aeruginosa infected wound. BC/Au-DAPT nanocomposite based drugs is the rapid release of silver ions, which results in

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Figure 5.  The preparation of BC/Au-DAPT nanocomposite and its antibacterial mechanism. a) Schematic illustration of the preparation process of
the BC/Au-DAPT nanocomposites. Reproduced with permission.[10a] Copyright 2017, Wiley-VCH. b) The antibacterial mechanism of Au-DAPT nano-
particles. Au nanoparticles exert their antibiotic actions via sequestration of magnesium or calcium ions to disrupt the bacterial cell membrane (top
right corner). Reproduced with permission.[43a] Copyright 2010, American Chemical Society. Au nanoparticles induce the down-regulation of oxida-
tive phosphorylation pathway and ribosome pathways, and the transient up-regulation of chemotaxis (top left corner and bottom). Reproduced with
permission.[43b] Copyright 2013, the Royal Society of Chemistry.

high exposure concentrations of silver ions and inflicts adverse Silver-containing BC membranes can be prepared by micro-
effects upon human cells.[49] fluidic chips, freeze-drying, and in situ surface coating. BC/
NCC can serve as substrates, allowing glucose to reduce graphene oxide/silver nanoparticles with controlled-releasing
AgNO3 and NH3·H2O to produce silver nanoparticles at room and long-lasting antibacterial performance were fabricated
temperature (Figure 6a). The MIC of the generated silver by microfluidic approach, and the fibers were antibacterial
nanoparticles on NCC is much lower than that of commercial toward E. coli and S. aureus.[56] BC/sodium alginate–silver
silver nanoparticles, which is attributed to the good dispersion nanoparticles composites which synthesized by freeze-drying
of silver nanoparticles with the presence of NCC. NCC/silver showed excellent antibacterial activities and good biocompat-
showed good antibacterial activity against both E. coli, MDR ibility.[57] Furthermore, BC/silver nanocomposite of 3D porous
E. coli, S. aureus, and MDR S. aureus.[47] NCC/Ag nanocom- network structure showed good mechanical properties and
posites, such as films with antibacterial properties, could be water reabsorption capacity, as well as excellent antibacterial
prepared by melting or casting. For instance, films formed by effect on E. coli and S. aureus, for which the inhibition rate
alloying of NCC, silver nanoparticles, and poly(lactic acid) were was over 99%.[58] Multifunctional nanocellulose-based antimi-
antimicrobial against E. coli and S. aureus.[50] Ternary films were crobial materials were prepared through depositing silver nan-
prepared through casting NCC/silver nanohybrids and poly(3- oparticles on the iron oxide nanoparticle-containing BC, and
hydroxybutyrate-co-3-hydroxyvalerate) (PHBH). The films with the magnetic BC/silver nanocomposite possessed high antimi-
high silver contents showed dramatic improvements in antibac- crobial activity against E. coli and B. subtilis.[59]
terial properties and biocompatibility.[51] BC is also a good template for preparing silver nanopar-
An antibacterial and electrically conductive composite was ticles (Figure 6b).[52] Researchers either inject silver ion into
formed by generating catechol mediated silver nanoparticles BC or immerse BC in silver ion-containing solutions, thus
on the surface of NFC. The nanocomposite showed excellent silver nanoparticles were synthesized in situ and showed
antibacterial efficacy against both E. coli and S. aureus.[53] Anti- good antibacterial activity.[48,60] Silver nanoparticles self-
microbial nanomaterials were prepared via chemical reduc- assembled on the surface of BC, forming a stable and even
tion of silver ions in situ on NFC. The antibacterial activity distribution of silver nanoparticle. BC/silver exhibited signifi-
of cellulose membrane against E. coli and S. aureus was over cant antibacterial activity against S. aureus. It was applied in a
99.99%.[54] NFC/silver composite was formed through using second-degree rat wound model, and the wound flora showed
cationic NFC as solid supports for enzymes and silver nano- a significant reduction during the healing.[61] Silver ions
particles, and it showed sustained antibacterial effect towards were put in the Gluconacetobacter xylinum and induced the
E. coli. When immobilized lysozyme on the composite, it formation of silver/silver chloride nanoparticles by a biofac-
showed a moderate antimicrobial effect against both S. aureus tory, and the resultant nanocomposite displayed the desirable
and E. coli.[55] activity in inhibiting bacterial growth of S. aureus and E. coli

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Figure 6.  Preparation of silver containing nanocellulose-based antibacterial material. a) NCC-assisted generation of silver nanoparticles. Reproduced
with permission.[47] Copyright 2016, American Chemical Society. b) The scheme of the preparation process of TEMPO-BC/Ag nanocomposite. Repro-
duced with permission.[52] Copyright 2018, American Chemical Society.

on agar plate or in liquid culture.[62] BC/silver composite composite showed antibacterial properties against S. aureus
was synthesized by hydrothermal in situ, and the composite and E. coli.[67]
can release the silver slowly to kill S. aureus.[63] The TEMPO
mediate BC (TOBC) was ion-exchanged in AgNO3 solution,
and silver nanoparticles with diameter of 16.5 nm were syn- 2.3.2. Metal Oxide Nanoparticles
thesized on TOBC nanofiber surfaces by thermal reduction
without using a reducing agent. The TOBC/silver composite Metal oxide nanoparticles such as titanium dioxide (TiO2),
exhibited high biocompatibility and showed significant anti- copper oxide (CuO), zinc oxide (ZnO), and magnesium oxide
bacterial activities of 100% and 99.2% against S. aureus and (MgO) were identified to exhibit antimicrobial activity (Table 2).
E. coli.[52] Antimicrobial property of TiO2 is related to its crystal struc-
ESC/silver antimicrobial materials can be prepared through ture, shape, and size distribution.[68] Oxidative stress via the
adding silver nanoparticles into raw materials, such as cellu- generation of ROS is a particularly important mechanism for
lose acetate, or putting the ESC in dispersion of silver nano- killing bacteria by TiO2 nanoparticles (anatase forms).[69] NCC/
particles. ESC/silver/silver ions showed better antibacterial TiO2 nanocomposites were developed by casting/evapora-
properties in comparison to single silver/silver ions in same tion of NCC, TiO2 nanoparticles, and wheat gluten, and NCC/
concentration.[64] Silver nanoparticles and microcrystalline TiO2 showed better antibacterial activity against Saccharomyces
cellulose combined through electrospinning, and the wound cervisiae, E. coli, and S. aureus compared to free coated paper.[70]
healing capabilities of ESC/silver improved because of the NFC/TiO2 nanocomposites were successfully produced by a
antibacterial activity of silver nanoparticles.[65] Silver nanopar- ‘‘green chemistry’’ approach in aqueous media. They showed
ticles were mixed with ESC from cellulose acetate to prepare antimicrobial properties against S. aureus and E. coli, and they
nanocomposite, and the composites were antimicrobial.[66] were stable under the UV irradiation.[71]
Antimicrobial ESC were prepared by electrospun of crystal CuO nanoparticles have been widely studied due to their
whiskers/poly (vinyl pyrrolidone)/silver nanoparticle, and the antimicrobial activities, biological, as well as chemical and

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Table 2.  Metal oxide in nanocellulose-based antimicrobial materials.

Metaloxide Type Bacterial species Mechanism Ref.


TiO2 NCC S. aureus The generation of ROS may be a particularly important mechanism for TiO2 nanoparticles [69–71]
E. coli (anatase forms), and then ROS causes site-specific DNA damage of bacteria
NFC S. aureus
E. coli
CuO NFC S. aureus CuO nanoparticles were implemented through crossing of nanoparticles from the bacteria [72–74]
E. coli cell membrane and then damaging the vital enzymes of bacteria
C. albicans
BC E. coli
ZnO NCC S. aureus ROS generation on the surface of the particles, zinc ion release causes membrane dysfunction [76–84,87]
E. coli and nanoparticles internalization
B. subtilis
E. coli
BC E. coli
E. coli
S. aureus
ESC S. aureus
E. coli
Citrobacter
S. aureus
E. coli
MgO NFC E. coli MgO nanoparticles damage the cell membrane and then cause the leakage of intracellular [85,86]
contents which in turn leads to death of the bacterial cells

physical properties.[72] The function of CuO nanoparticles was nocomposite foams with a maximum ZnO loading of 70 wt%
implemented through crossing of nanoparticles from the bac- was achieved by controlled hydrolysis and solvothermal crystal-
teria cell membrane and damaging the vital enzymes of bac- lization by using a BC aerogel as a template in a nonaqueous
teria.[73] NFC was coated with Cu/CuO nanoparticles through a polar medium. The bio-nanocomposite foams showed excellent
“green” reductive technique using the alcoholic extract of termi- antibacterial activity against E. coli.[80] BC/ZnO pellicle can also
nalia chebula fruit. NFC/CuO showed promising antimicrobial be synthesized by applying solution plasma to Zn ion without
activity against Staphyllococcus aureus, E. coli, and Candida albi- adding reducing agent, and ZnO simultaneously deposited into
cans, which was quite compatible with peripheral blood mono- a BC pellicle. The ZnO/BC pellicle has demonstrated strong
nuclear cells and mammalian red blood cells.[74] antibacterial activity without a photocatalytic reaction against
ZnO has outstanding optoelectronic properties, high catalytic both S. aureus and E. coli.[81] BC/ZnO nanocomposites were
activity against chemical and biological species, and strong anti- prepared by ultrasound irradiation with BC monolayer and
microbial properties against a wide range of pathogens. ROS multilayer films and 5 wt% ZnO nanoparticles. The multilayer
generation and the release of zinc ion will cause dysfunction of films are expected to achieve controlled release of ZnO. BC/
cell membrane.[75] NCC/ZnO nanocomposite was synthesized ZnO films showed good antibacterial activity against S. aureus
through in situ solution casting of dispersion containing NCC and E. coli.[82]
and ZnO nanoparticles. NCC/ZnO nanocomposite showed ZnO nanoparticles embedded ESC membrane from cel-
better antibacterial activity against both S. aureus and E. coli lulose acetate with multifunctional properties was pre-
compared to pure ZnO nanoparticles. The antibacterial activity pared through electrospinning method. The fibers exhibited
against S. aureus was stronger than E. coli.[76] Nanocomposites strong antibacterial activity against the S. aureus, E. coli,
were prepared with NCC, ZnO, and CeO2 nanoparticles by and Citrobacter.[83] ESC/ZnO membrane was fabricated by
using polyaniline as the binding agent. The bio-nanocomposite electrospinning from NCC, ZnO, and poly(3-hydroxy-butyrate-
was effective against both B. subtilis and E. coli.[77] co-3-hydroxy-valerate), and the membrane exhibited high
An excellent matrix for adsorbing ZnO nanoparticles was antibacterial efficiency of about 100% against both S. aureus
formed through dissolving BC in N-methylmorpholine-N-oxide. and E. coli.[84]
The BC/ZnO composite was biocompatible to animal osteo- MgO showed strong antibacterial activity due to its
blast cells, and showed excellent antimicrobial activity against alkalinity.[85] The antibacterial mechanism of MgO nanopar-
E. coli.[78] In another study, BC membrane was used as a matrix ticles is due to the generation of superoxide on the surface
for preparation of BC/ZnO sheet by ultrasonic-assisted in situ of these particles, and an increase in pH value by the hydra-
synthesis. BC/ZnO membrane showed antibacterial activity tion of MgO with water. MgO nanoparticles damaged the
against E. coli and S. aureus.[79] BC/ZnO membrane can be cell membrane and then caused the leakage of intracellular
formed without water. The assembly of porous BC/ZnO biona- contents, which in turn leads to death of the bacterial cells.

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NFC/MgO/regenerated cellulose films were prepared via 2.4. Compositions of Antibacterial Polymers and Nanocellulose
simple blending and casting processes. The film containing
30 wt% MgO showed excellent antibacterial activity against Polymers with antibacterial activities will combine with nano-
E. coli, and provided a promising pathway for manufacturing cellulose to form nanocellulose-based antimicrobial materials.
multifunctional and high-performance cellulose-based com- Antimicrobial polymers contain natural polymers (chitosan and
posite films.[86] amino acid) and synthetic polymers, for example, halogenated
Excessive use of metal or metal oxide nanoparticles will amines and guanidine salts. The antibacterial ability of these
cause bacterial resistance and environmental problems. To polymers was related to the protonation of amino groups.
reduce usage of nanoparticles and improve the antibacte-
rial efficiency of the nanocellulose-based antibacterial mate-
rials which contain metal or metal oxide nanoparticles, the 2.4.1. Natural Polymers
preparing conditions and properties of them still need to be
developed. For instance, increasing the specific surface area Chitosan, which is industrially produced from chitin, is the
and porosity of nanocellulose-based antibacterial materials are second most abundant polysaccharide in nature. Chitosan
practical methods to reduce nanoparticles consuming, and the is regarded as a natural antimicrobial compound against an
high specific surface area and porosity provide more opportu- extensive variety of microorganisms including bacteria, yeasts,
nities for nanocellulose-based antibacterial materials to contact and moulds.[94] Chitosan with low molecular weight will pass
with bacteria. through the cell membrane and combined with negatively
charged nucleic acid. Chitosan with high molecular weight
will adhere to the cell membrane and form a film on bacteria,
2.3.3. Graphene-Based Materials which will interdict the transport of nutrients. Chitosan was
functioned as a kind of chelating agent to adsorb metal ions,
Graphene oxide (GO) has an attracting and ever-growing interest which was essential for bacteria, and so forth.[95]
in antibacterial fields for its fascinating nanostructures.[88] GO NCC/chitosan nanopaper showed excellent antimicro-
showed high antibacterial activities against both Gram-negative bial activities against B. cereus and Salmonella typhimurium.
and Gram-positive bacteria compared with the antibacterial The presence of chitosan in the nanopaper enhanced the resist-
properties of four types of graphene-based materials. ance of paper to different microorganisms especially those that
NCC and reduced GO (rGO) were successfully synthesized cause food poisoning.[96] NCC/chitosan nanocomposite was
via acid hydrolysis and modified Hummer’s method. The NCC/ effective for killing E. coli and S. aureus, which was suitable for
rGO/poly-lactic acid (PLA) nanocomposite film, which was pre- saving meat and improving its shelf time.[97] NCC/chitosan/
pared by solution casting of the NCC/rGO and PLA, showed poly (vinyl pyrrolidone) composites were prepared by solution
distinct antibacterial efficacy against both S. aureus and E. coli, casting method. The composite showed good blood compat-
and the film also displayed negligible cytotoxicity of fibroblast ibility, high cell viability, and antimicrobial properties toward
cell line (NIH-3T3).[89] S. aureus and P. aeruginosa.[98]
BC/GO composites were synthesized by a mechanical NFC-based antibacterial films were prepared by incorpora-
mixing method using BC as a matrix. The BC/GO nanocom- tion with sodium alginate and benzalkonium chloride modified
posites showed a strong antimicrobial effect on S. cerevisiae due chitosan. The NFC/chitosan film exhibited antibacterial activity
to the effective contact between the nanofillers of the compos- against both E. coli and S. aureus.[99] Tricomponent film was
ites and the cell surfaces.[90] BC/GO/TiO2 composite was pre- synthesized by blending thermoplastic starch, chitosan, and
pared by filling GO/TiO2 nanoparticles into porous BC matrix. NFC. The tricomponent film possessed good thermal stability
The BC/GO/TiO2 composite showed no obvious cytotoxicity and mechanical performance, and showed antibacterial activity
antibacterial properties against S. aureus.[91] against S. aureus.[100]
BC/chitosan composites displayed excellent properties such
as high water holding capacity, ultrafine nanofiber network, high
2.3.4. Nanosilicates-Based Materials elastic modulus, and tensile strength.[101] The cumulative release
amounts of chitosan from the film were strongly depended on
Nanosilicates, such as montmorillonite, are composed of molecular weight of chitosan and pH of solution. BC/chitosan
two tetrahedral sheets of silica and a central octahedral sheet film was developed by immersing purified BC pellicles in 1.5–
of alumina. The particles are plate-shaped with an average 2.0% (w/v) acetic acid solutions containing chitosan of varying
diameter around 1 µm and a thickness of 9.6 nm, which has molecular weights. The film showed antimicrobial abilities
been widely used in medical fields for cleansing and protec- against S. aureus and Aspergillus niger, but did not show inhibi-
tion of skin with antibacterial activity. BC/montmorillonite tory effect on the growth of E. coli. The antibacterial activity
films with potent antibacterial activity and potential thera- against S. aureus of the film with the highest Mw chitosan
peutic value in wound healing and tissue regeneration were (263 000) was better than that of the others. The BC/chitosan
developed. The antibacterial activity of the film against E. coli film with the lowest Mw chitosan (141 000) promoted the growth
and S. aureus was excellent.[92] Multilayered membrane was of human skin cells more than those of the others.[102] BC/chi-
prepared by negatively charged NFC and positively charged tosan composite was obtained after dynamic culture of Glucoace-
CS/rectorite, which showed good antibacterial activity against tobacter xylinum and chitosan. The BC/chitosan composite with
E. coli.[93] high strength showed high antimicrobial activity against both

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E. coli and S. aureus.[103] BC/chitosan composite showed signifi- polymerization. The nanocomposite film was antimicrobial
cant inhibition on the growth of E. coli and S. aureus, and the against B. subtilis and E. coli.[116]
wound treated with BC/chitosan epithelialized and regenerated Additionally, antimicrobial ESC mats were prepared from cellu-
faster than those treated with BC or Tegaderm.[104] lose acetate by adding poly [5,5-dimethyl-3-(3′-triethoxysilylpropyl)
Antibacterial ESC was manufactured from wet-spinning of hydantoin] to the cellulose acetate solution via electrospinning
crystal whiskers and hydroxypropyl chitosan, and the ESC exhib- technique followed with curing, and then exposing to diluted
ited excellent antibacterial activities against both S. aureus and sodium hypochlorite. The chlorinated ESC mat had excellent anti-
E. coli.[105] Another antimicrobial ESC was prepared by chitosan bacterial effect against S. aureus and E. coli.[117]
and cellulose acetate. Nanostructured membranes of cellulose
acetate and chitosan/poly(ethylene oxide) were prepared by
electrospinning, and they have significant antimicrobial activity 2.5. Composition of Other Molecules and Nanocellulose
against E. coli and Propionibacterium acnes.[106] When depositing
chitosan and pectin/organic rectorite on ESC surface from cel- Lysozyme will hydrolyze peptidoglycan of the bacterial cell
lulose acetate by a layer-by-layer technique, the diameters of wall,[118] which is composed of kinds of amino acid.[119] NCC/
the inhibition zone increased from 7.6 to 15.8 mm for E. coli, lysozyme was prepared by conjugating lysozyme with NCC by
and from 7.4 to 14.2 mm for S. aureus.[107] Multilayer-ESC mat a carbodiimide cross-linker, and it had good antifungal and
was fabricated by quaternized carboxymethyl chitosan, organic antibacterial effects against standard strains of C. albicans,
rectorite, and cellulose acetate. The antibacterial activity of ESC A. niger, S. aureus, and E. coli.[120]
mat against E. coli and S. aureus increased with the number of NFC/lysozyme films were prepared by immobilization of
coating layers and the incorporation of organic rectorite.[108] lysozyme on NFC, and they can act as a minor component
Polylysine consists of 20–35 lysine residues with multiva- in the formulation of release devices for reducing the release
lent cations, which would destroy the structure of microbial rate of active molecules from the main polymer network.[121]
cell membrane and inhibit the proliferation of Gram-positive Nisin and other lysozyme will release from the three aerogels,
and Gram-negative bacteria such as E. coli and S. aureus.[109] which inhibit the growth of Enterococcus faecalis, Clostridium
BC/polylysine nanofiber was prepared by immersing wet BC tyrobutyricum, and Micrococcus lysodeikticus.[33] Solid supports
pellicles in polylysine solution followed by cross-linking with for enzymes and silver nanoparticles with a sustained anti-
polyamide. The nanofiber exhibited antibacterial activity against bacterial effect were prepared from aqueous dispersions of
both E. coli and S. aureus.[110] Bacteriostatic sausage casing with anionic lysozyme and cationic NFC. The solid supports were
antibacterial properties was made with BC and polylysine by nontoxic and biodegradable, which are a suitable support for
making BC into the casing after immersion in lysine solution. bioactive materials, and are effective in protecting and retaining
The casing exhibited antibacterial activity against S. aureus.[111] enzymatic activity as well as antibacterial activities.[55]
Besides, ESC mats were prepared by adding positively
charged lysozyme and rectorite composites into negatively
2.4.2. Synthetic Polymers charged electrospun cellulose acetate. The antimicrobial effect
of the ESC mats was enhanced by rectorite.[122] Anti-infective
In addition to natural polymers, the synthetic polymers can bandages were formed by a cell lytic enzyme, lysostaphin,
also be combined with nanocellulose to prepare antimicrobial with specific bactericidal activity. The ESC/lysostaphin showed
composites, containing polypyrrole and polyhexamethylene activity against S. aureus in an in vitro skin model with low
biguanide (PHB). Cell membrane of bacteria will be destroyed by toxicity toward keratinocytes.[123]
the adhesion of polymers, which results in the death of bacteria. Bovine lactoferrin is a glycoprotein with ≈80 kDa, which
PHB is known as a broad spectrum antimicrobial agent possesses a wide range of activities, such as antimicrobial,
against both Gram-negative and Gram-positive bacteria. The immunoregulatory, and anticancer.[124] Bovine lactoferrin can
nanocellulose/PHB dressing has been reported to reduce also be combined with nanocellulose to prepare antibacterial
biofilm and promote granulation tissue in wound without composites. The functionalized films were assessed as edible
irritation.[112] BC/PHB/sericin membrane showed low inflam- antimicrobial packaging, which is able to contact with highly
mation response, and potentially reduced wound size with high perishable foods, specifically fresh sausage as a model of meat
extent of collagen formation. The membrane possessed antimi- products. BC/bovine lactoferrin films showed bactericidal
crobial property and could prevent the wound infection due to efficiency against E. coli and S. aureus.[125]
the antibacterial activity of polyhexamethylene biguanide and As a kind of typical natural antibiotics, propolis shows broad-
wound healing activity of sericin, which was suitable for wound spectrum antibacterial properties. BC/propolis demonstrated
healing, additionally, BC/PHB showed antimicrobial activity the potent antimicrobial activity and wound healing properties.
against S. aureus.[113] ESC mats were synthesized by PHB, cellu- The propolis could be adsorbed on BC, which would promote
lose acetate, and polyester urethane through electrostatic spin- wound healing and tissue reconstruction.[126] BC/manuka honey
ning, which can promote wound healing.[114] composites also showed anti-inflammatory and antibacterial
Nanocomposite was prepared by cellulose acetate incorpo- function properties, and it would promote tissue growth.[127]
rating with polymethacrylamide-modified NCC. The composite At present, the research on the addition of natural antibac-
films had excellent antibacterial properties against both E. coli terial molecules in the preparation of nanocellulose-based
and S. aureus.[115] A composite film based on NFC, polyvinyl antibacterial materials is still in the early stage. There is no
alcohol, and polypyrrole was synthesized in situ by a chemical doubt that the discovery of more natural antibacterial molecules

Adv. Healthcare Mater. 2018, 1800334 1800334  (10 of 16) © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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will promote the emergence of nanocellulose-based antibacte- culture medium, and the BC/chitosan composite with high
rial materials and reduce environmental pollution. strength showed high antimicrobial activity against both E. coli
and S. aureus.[103] Another BC/chitosan composite also showed
significant inhibition on the growth of E. coli and S. aureus. The
3. Application of Nanocellulose-Based wound treated with BC/chitosan epithelialized and regenerated
faster than those treated with BC or Tegaderm (a transparent
Antimicrobial Materials
medical dressing manufactured by 3M).[104]
Nanocellulose-based antimicrobial materials can be used for many
applications, such as wound dressing, drug carriers, and pack-
aging materials. Nanocellulose-based antimicrobial materials are 3.2. Drug Carriers
sources-extensive, easily degradable, and can be easily prepared.
Nanocellulose-based materials can serve as carriers for phar-
maceuticals and drug-releasing scaffolds.[132] A core–shell
3.1. Wound Dressing Materials nanofiber drug carrier was fabricated via blend and coaxial
electrospinning of carboxymethyl cellulose and poly(ethylene
Wound dressings made from nanocellulose are developed for oxide).[31b] Tetracycline hydrochloride served as a drug model
acceleration of wound healing by minimizing wound infec- incorporated within these nanofibers. The drug release from
tion and controlling the appropriate wound environment.[128] the optimized core–shell nanofibers was much slower than
BC based wound dressings were effective in the treatment of that from blend nanofibers, which sustained for 72 h with only
chronic nonhealing wounds in clinical studies. BC based wound 26.06% burst release within the first 30 min. The drug-loaded
dressings have been associated with reducing pain, improving core–shell nanofibers showed excellent bactericidal activity
wound cleansing, and accelerating wound healing.[129] BC based against a wide range of bacteria. Similarly, nanofiber drug car-
dressings have ultrafine fiber structures with high capability to riers were fabricated by coaxial electrospinning of sodium car-
absorb and retain large amount of water (more than 200 times boxymethyl cellulose with methyl acrylate and poly(ethylene
of its dry state), bringing the high capacity to absorb wound oxide).[31a] The tetracycline hydrochloride loaded into the opti-
exudate and controlling moist environment over the wound.[130] mized core–shell nanofiber as a drug mode. The nanofiber with
Their nanoporous structures allow the easy transportation of smooth and beadless morphology showed sustained release
active molecules or compounds to the wound, and the high ability, and could kill a wide range of bacteria efficiently.
tensile strength and flexibility make them to be a good barrier
for wound protection. In addition, they have cooling effect with
high purity and nontoxicity, which can reduce pain.[131] How- 3.3. Packaging Materials
ever, BC itself does not possess any antimicrobial activity for the
prevention of wound infections. In order to endow antimicro- The maintenance of the food safety and quality assurance are
bial properties in BC, various studies have fabricated BC-com- crucial for the food industry. The biodegradable packaging
posites with different antimicrobial substances. BC/Au-DAPT materials that can vastly increase the barrier property and
nanocomposites were used for treating bacterially infected extend shelf life are necessary.[133] Nanocellulose-based anti-
wounds, with smaller sizes of the wounds compared with that microbial material is one of the most promising materials for
of the BC groups. The BC/Au-DAPT nanocomposite system is a food packaging. We manufactured biodegradable films with
promising platform for treating superbug-infected wounds.[10a] improved barrier and mechanical properties, and they could
BC nanocomposites with strong antibacterial activity were function as packaging materials with antibacterial properties
prepared using in situ biosynthesis by adding chitosan to the (Figure 7a).[134] The film played an equivalent role in the storage

Figure 7.  Preparation of packaging materials. a) The schematic of casting process for films. Reproduced with permission.[134] Copyright 2015, the Royal Society
of Chemistry. b) Preparation scheme of NFC/chitosan–BKC biocomposite-incorporated sodium alginate film. Reproduced with permission.[51] Copyright 2017,
Elsevier Ltd.

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Table 3.  Recent reports on toxicology experiments and conclusions for nanocellulose. on both cellular and genetic level as well as
in vivo organ and animal experiments. Sur-
Type Toxicological experiment Conclusion Ref. face grafting of positive charged molecules
NCC Human MG-63 cells Low toxicity [51] or oxidation by strong oxidant molecules
Hemolysis assay Highly hemocompatible [98]
on nanocellulose can introduce biologically
Mouse fibroblasts Good biocompatibility active building blocks, which may contribute
to the potential of nanocellulose being used
NFC Human microvascular endothelial cell Good biocompatibility [15]
as antibacterial materials.[101b]
Animal wounds Promote the growth of hair follicles
Renal adenocarcinoma cells Good biocompatibility [136]
Mouse embryo fibroblasts Cell proliferation promoted [137] 5. Challenges
BC Mouse embryo fibroblasts Good biocompatibility [128]
The nanocellulose-based antibacterial
Human fibroblast cell High biocompatibility [113b]
materials are interesting, innovative, and
Human umbilical vein endothelial cells Good biocompatibility [10a] challenging. As a new kind of biomedical
Animal wounds Promote wound repair material, nanocellulose has captured the
A second-degree rat wound model The wound flora showed a [61] attention of many companies, and it has
significant reduction made huge progress. Several companies and
Human embryo kidney 293 Good biocompatibility [19a] institutes have realized large-scale prepara-
tion of nanocellulose, and they are mainly
ESC Human fibroblasts Good biocompatibility [31a]
located in US, Canada, China, Japan, and
An in vitro skin model Keratinocytes Good biocompatibility [123]
Sweden.[139] As a represent company, the Cel-
Mouse fibroblasts Excellent adhesion ability [138] luForce located in Canada developed a pilot-
scale production line for preparing NCC by
sulphuric acid hydrolysis at 2012, and the
of cakes with preservative film. We also prepared a kind of sau- capacity is 1000 kg d−1.[140] The US Forest Service established
sage casing by NCC and collagen, and the casing possesses a factory for preparing NCC (sulphuric acid hydrolysis, 10 kg
high strength of extension and elongation, which can extend d−1) in 2012. China International Travel Service Co. Ltd built
shelf life of sausage. [10c] We prepared NCC/ alkyl ketene dimer a production line for preparing NCC (100 kg d−1) in 2013.[141]
(AKD) emulsion as the sizing agent for surface-sized cellulosic Hangzhou Yuhan Technology Co., Ltd. has achieved preparing
paper, and the mechanical and multiple barrier properties were nanocellulose (phosphoric acid activation, 250 kg d−1).[142]
improved.[135] NCC/PHBH/silver nanocomposites showed high Innventia in Sweden started the first device for preparing NFC
antibacterial ratio of 99.9% with good barrier property and in 2011 (100 kg d−1). The factory of the US Forest Service also
lower migration levels in food simulants, which was suitable produced NFC (mechanical grinding, 1000 kg d−1) in 2012. Oji
for food packaging.[51] The NFC/chitosan–BKC biocomposite- Paper and Mitsubishi Chemical launched studies about com-
incorporated sodium alginate film exhibited remarkable anti- mercial film of NFC in 2013.[143]
bacterial activity against S. aureus and certain antibacterial Although a number of organizations have made consider-
activity against E. coli, which would be a promising material for able progress in the preparation of nanocellulose in pilot plants
food packaging. The tensile strength of the composite sodium over the last years, the industrial production of nanocellulose is
alginate film increased about 225% when the loading of NFC/ still not achieved. The large scale preparation of nanocellulose
chitosan–BKC biocomposite was 10 wt% (Figure 7b).[99] These by green method with low-energy and low cost is an issue with
innovations would solve two problems at once: assisting in great challenge.
cutting down packaging waste and in reducing the number of There are many challenges for the efficient and economical
food-borne illnesses. applications of nanocellulose-based antibacterial materials,
such as lacking of molding technics of mats and films for
wound dressing and packaging materials. Unlike cellulose
4. Biocompatibility for Nanocellulose-Based pulp, nanocellulose with smaller size is not suitable for wet-
end formation in papermaking. Contrary to true solution of
Antibacterial Materials
cellulose, the casting of nanocellulose dispersion needs further
Biocompatibility is the ability of a material existing in harmony study because it only uses water as solvent. How to rapidly pre-
with tissue without causing deleterious changes, which is an pare the low basis weight film is also important for low-concen-
essential requirement for biomedical materials. Nanocellu- tration nanocellulose dispersion.
lose can be generally considered to be broadly biocompatible,
invoking only moderate foreign body responses in vivo. A com-
prehensive assessment of the toxicology research for nanocel- 6. Conclusion
lulose and nanocellulose-based biocomposites was developed in
recent twenty years. Table 3 summarizes recent reports on toxi- The aim of this review is to outline the current state of research
cology experiments and conclusions for nanocellulose. There is and future development of nanocellulose in antibacterial appli-
no evidence for serious influence or damage of nanocellulose cation through the discussion of selected examples. There are

Adv. Healthcare Mater. 2018, 1800334 1800334  (12 of 16) © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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mainly four methods for preparation of nanocellulose-based [4] a) C. Aulin, G. Salazar-Alvarez, T. Lindstrom, Nanoscale 2012,
antibacterial materials, and these materials possess great applica- 4, 6622; b) A. Hakeem, F. Zahid, R. Duan, M. Asif, T. Zhang,
tion as wound dressing, drug carriers, and packaging materials. Z. Zhang, Y. Cheng, X. Lou, F. Xia, Nanoscale 2016, 8, 5089;
Nanocellulose-based antibacterial materials possess remarkable c) C. S. R. Freire, S. C. M. Fernandes, A. J. D. Silvestre, C. P. Neto,
Holzforschung 2013, 67, 603; d) L. Chen, C. Lai, R. Marchewka,
features that surpass those of synthetic polymer-based antibacte-
R. M. Berry, K. C. Tam, Nanoscale 2016, 8, 13288; e) X. Yao, W. Yu,
rial materials, including plentiful, convenient, and low-cost. It is X. Xu, F. Chen, Q. Fu, Nanoscale 2015, 7, 3959; f) K. Gao, Z. Shao,
essential to develop the green method with low-energy and low X. Wu, X. Wang, Y. Zhang, W. Wang, F. Wang, Nanoscale 2013, 5,
cost for nanocellulose, which is beneficial to pave the way for 5307; g) Y. R. Kang, Y. L. Li, F. Hou, Y. Y. Wen, D. Su, Nanoscale
greater acceptance of nanocellulose as a commercially available 2012, 4, 3248.
material. For their application of nanocellulose-based antibac- [5] E. Morales-Narvaez, H. Golmohammadi, T. Naghdi, H. Yousefi,
terial material, the moulding technics and devise for mats and U. Kostiv, D. Horak, N. Pourreza, A. Merkoci, ACS Nano 2015, 9,
films are the important impactors. If we can further improve the 7296.
mechanical property of nanocellulose-based antibacterial mate- [6] a) B. Wang, A. Walther, ACS Nano 2015, 9, 10637; b) R. M. Parker,
rials, they may be environmentally friendly and more extensive B. Frka-Petesic, G. Guidetti, G. Kamita, G. Consani, C. Abell,
S. Vignolini, ACS Nano 2016, 10, 8443.
for application as filters and clothes in the future. We believe
[7] a) M. Zammarano, P. H. Maupin, L. P. Sung, J. W. Gilman,
that nanocellulose will get more attention to realize their poten- E. D. McCarthy, Y. S. Kim, D. M. Fox, ACS Nano 2011, 5, 3391;
tial as antibacterial materials and benefit the development of b) H. Zhu, Y. Li, Z. Fang, J. Xu, F. Cao, J. Wan, C. Preston, B. Yang,
new kinds of antibacterial materials. We hope that our ideas in L. Hu, ACS Nano 2014, 8, 3606.
this review will offer help in promoting the development and [8] a) Y. J. Kang, S. J. Chun, S. S. Lee, B. Y. Kim, J. H. Kim, H. Chung,
application of nanocellulose-based antibacterial materials. S. Y. Lee, W. Kim, ACS Nano 2012, 6, 6400; b) S. Bottan, F. Robotti,
P. Jayathissa, A. Hogglin, N. Bahamonde, J. A. Heredia-Guerrero,
I. S. Bayer, A. Scarpellini, H. Merker, N. Lindenblatt, D. Poulikakos,
A. Ferrari, ACS Nano 2015, 9, 206.
Acknowledgements [9] K. Roemhild, C. Wiegand, U. C. Hipler, T. Heinze,
The authors thank the Ministry of Science and Technology of China Macromol. Rapid. Commun. 2013, 34, 1767.
(grant no. 2013YQ190467), Chinese Academy of Sciences (grant nos. [10] a) Y. Li, Y. Tian, W. Zheng, Y. Feng, R. Huang, J. Shao, R. Tang,
XDA09030305 and 121D11KYSB20170026), and the National Science P. Wang, Y. Jia, J. Zhang, W. Zheng, G. Yang, X. Jiang, Small 2017,
Foundation of China (grant nos. 81361140345, 21535001, 81730051, and 13, 1700130; b) K. Long, R. Cha, Y. Zhang, J. Li, F. Ren, X. Jiang,
21761142006) for financial support. Cellulose 2017, 85, 1; c) Y. Zhang, Q. Zhao, H. Wang, X. Jiang,
R. Cha, Carbohydr. Polym. 2017, 164, 358.
[11] a) S. B. Zhang, X. H. Yang, B. Tang, L. J. Yuan, K. Wang, X. Y. Liu,
X. L. Zhu, J. N. Li, Z. C. Ge, S. G. Chen, Chem. Eng. J. 2018,
Conflict of Interest 336, 123; b) S. G. Chen, L. J. Yuan, Q. Q. Li, J. N. Li, X. L. Zhu,
Y. G. Jiang, O. Sha, X. H. Yang, J. H. Xin, J. X. Wang, F. J. Stadler,
The authors declare no conflict of interest.
P. Huang, Small 2016, 12, 3516.
[12] a) B. Heli, E. Morales-Narvaez, H. Golmohammadi, A. Ajji,
A. Merkoci, Nanoscale 2016, 8, 7984; b) A. Llorens, E. Lloret,
Keywords P. A. Picouet, R. Trbojevich, A. Fernandez, Trends Food Sci. Technol.
2012, 24, 19; c) S. G. Chen, Y. J. Guo, S. J. Chen, Z. C. Ge,
bacterial cellulose, electrospun nanofibers, nanocellulose, H. P. Yang, J. N. Tang, Mater. Lett. 2012, 83, 154; d) S. G. Chen,
nanocrystalline cellulose, nanofibrillated cellulose Y. J. Guo, H. Q. Zhong, S. J. Chen, J. A. Li, Z. C. Ge, J. N. Tang,
Chem. Eng. J. 2014, 256, 238.
Received: March 30, 2018 [13] a) G. Wang, Z. Xing, X. Zeng, C. Feng, D. T. McCarthy, A. Deletic,
Revised: May 18, 2018 X. Zhang, Nanoscale 2016, 8, 18050; b) A. Khan, T. Huq,
Published online: R. A. Khan, B. Riedl, M. Lacroix, Crit. Rev. Food Sci. Nutr. 2014, 54,
163; c) K. Xu, C. Liu, K. Kang, Z. Zheng, S. Wang, Z. Tang, W. Yang,
Compos. Sci. Technol. 2018, 154, 8; d) D. Zhu, H. H. Cheng,
J. N. Li, W. W. Zhang, Y. Y. Shen, S. J. Chen, Z. C. Ge, S. G. Chen,
[1] A. Fleming, Br. J. Exp. Pathol. 1929, 10, 226. Mater. Sci. Eng., C 2016, 61, 79; e) Y. X. Chen, J. N. Li, Q. Q. Li,
[2] a) X. Yang, J. Yang, L. Wang, B. Ran, Y. Jia, L. Zhang, G. Yang, Y. Y. Shen, Z. C. Ge, W. W. Zhang, S. G. Chen, Carbohydr. Polym.
H. Shao, X. Jiang, ACS Nano 2017, 11, 5737; b) R. H. Dong, 2016, 143, 246.
Y. X. Jia, C. C. Qin, L. Zhan, X. Yan, L. Cui, Y. Zhou, X. Jiang, [14] J. Sirvio, U. Hyvakko, H. Liimatainen, J. Niinimaki, O. Hormi,
Y. Z. Long, Nanoscale 2016, 8, 3482; c) J. A. Delezuk, D. E. Ramirez- Carbohydr. Polym. 2011, 83, 1293.
Herrera, B. Esteban-Fernandez de Avila, J. Wang, Nanoscale 2017, [15] K. Mou, J. Li, Y. Wang, R. Cha, X. Jiang, J. Mater. Chem. B 2017, 5,
9, 2195; d) W. Zheng, Y. Jia, W. Chen, G. Wang, X. Guo, X. Jiang, 7876.
ACS Appl. Mater. Interfaces 2017, 9, 21181. [16] X. Wen, Y. Zheng, J. Wu, T. Zhang, X. Chen, Rare Metal Mater. Eng.
[3] a) K. Liu, L. Chen, L. Huang, Y. Ni, B. Sun, Carbohydr. Polym. 2014, 43, 220.
2015, 117, 996; b) K. Liu, H. Liang, J. Nasrallah, L. Chen, [17] X. Cao, B. Ding, J. Yu, S. S. Al-Deyab, Carbohydr. Polym. 2013, 92, 571.
L. Huang, Y. Ni, Carbohydr. Polym. 2016, 142, 183; c) J. Y. Zhu, [18] S. Elayaraja, K. Zagorsek, F. Li, J. Xiang, Carbohydr. Polym. 2017,
X. Pan, R. S. Zalesny, J. Appl. Microbiol. Biotechnol. 2010, 87, 847; 166, 329.
d) J. Y. Zhu, X. S. Zhuang, Prog. Energy Combust. Sci. 2012, 38, 583; [19] a) W. Shao, J. Wu, H. Liu, S. Ye, L. Jiang, X. Liu, Carbohydr. Polym.
e) Q. Wang, J. Y. Zhu, Tappi J. 2015, 14, 167; f) Z. J. Shi, X. Gao, 2017, 178, 270; b) W. Z. Xu, G. Gao, J. F. Kadla, Cellulose 2013, 20,
M. W. Ullah, S. X. Li, Q. Wang, G. Yang, Biomaterials 2016, 111, 40. 1187.

Adv. Healthcare Mater. 2018, 1800334 1800334  (13 of 16) © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.advancedsciencenews.com www.advhealthmat.de

[20] a) B. Ran, Y. L. Xianyu, M. L. Dong, Y. P. Chen, Z. Y. Qian, [40] D. O. Castro, N. Tabary, B. Martel, A. Gandini, N. Belgacem,
X. Y. Jiang, Anal. Chem. 2017, 89, 6114; b) Y. Chen, Y. Xianyu, J. Bras, Mater. Sci. Eng., C 2016, 69, 1018.
J. Wu, B. Yin, X. Jiang, Theranostics 2016, 6, 969; c) Y. L. Xianyu, [41] R. Li, J. F. Dou, Q. Y. Jiang, X. H. Ren, J. Funct. Mater. 2013, 44,
X. Y. Jiang, Curr. Opin. Chem. Eng. 2014, 4, 144; d) Y. Xianyu, 3455.
Z. Wang, X. Jiang, ACS Nano 2014, 8, 12741; e) Y. Zhou, S. Wang, [42] a) Y. Zhao, Z. Wang, W. Zhang, X. Jiang, Nanoscale 2010, 2, 2114;
K. Zhang, X. Jiang, Angew. Chem., Int. Ed. 2008, 47, 7454; b) X. Yang, N. Wang, L. Zhang, L. Dai, H. Shao, X. Jiang, Nanoscale
f) K. Zhu, Y. Zhang, S. He, W. Chen, J. Shen, Z. Wang, X. Jiang, 2017, 9, 4770.
Anal. Chem. 2012, 84, 4267; g) W. Qu, Y. Liu, D. Liu, Z. Wang, [43] a) Y. Zhao, Y. Tian, Y. Cui, W. Liu, W. Ma, X. Jiang, J. Am. Chem. Soc.
X. Jiang, Angew. Chem., Int. Ed. 2011, 50, 3442; h) Y. Guo, 2010, 132, 12349; b) Y. Zhao, X. Jiang, Nanoscale 2013, 5, 8340;
Y. Zhang, H. Shao, Z. Wang, X. Wang, X. Jiang, Anal. Chem. 2014, c) Y. Zhao, Z. Chen, Y. Chen, J. Xu, J. Li, X. Jiang, J. Am. Chem. Soc.
86, 8530. 2013, 135, 12940; d) X. Y. Jiang, Y. Y. Zhao, Y. Tian, W. W. Liu,
[21] E. Feese, H. Sadeghifar, H. S. Gracz, D. S. Argyropoulos, W. Zhang (National Center for Nanoscience and Technology),
R. A. Ghiladi, Biomacromolecules 2011, 12, 3528. CN102188383-A, 2010.
[22] S. Saini, C. Y. Falco, M. N. Belgacem, J. Bras, Carbohydr. Polym. [44] Y. Zhao, C. Ye, W. Liu, R. Chen, X. Jiang, Angew Chem., Int. Ed.
2016, 135, 239. 2014, 53, 8127.
[23] a) A. Chaker, S. Boufi, Carbohydr. Polym. 2015, 131, 224; b) [45] a) Y. Tian, J. Qi, W. Zhang, Q. Cai, X. Jiang, ACS
H. Zhang, X. Zeng, J. Xie, Z. Li, H. Li, Carbohydr. Polym. 2016, 136, Appl. Mater. Interfaces 2014, 6, 12038; b) X. Ma, Y. Zhao, X. Jiang,
493. W. Liu, S. Liu, Z. Tang, Phys. Chem. Chem. Phys. 2012, 13, 2531;
[24] a) X. Zhuo, C. Liu, R. Pan, X. Dong, Y. Li, ACS Sustainable c) X. Hu, Y. Zhao, Z. Hu, A. Saran, S. Hou, T. Wen, W. Liu, Y. Ji,
Chem. Eng. 2017, 5, 4414; b) O. Nechyporchuk, M. N. Belgacem, X. Jiang, X. Wu, Nano Res. 2013, 6, 822.
J. Bras, Ind. Crops Prod. 2016, 93, 2. [46] H. Wang, W. Meng, Z. Liu, J. Funct. Mater. 2013, 44, 677.
[25] P. M. Favi, R. S. Benson, N. R. Neilsen, R. L. Hammonds, [47] S. Wang, J. Sun, Y. Jia, L. Yang, N. Wang, Y. Xianyu, W. Chen, X. Li,
C. C. Bates, C. P. Stephens, M. S. Dhar, Mater. Sci. Eng., C 2013, R. Cha, X. Jiang, Biomacromolecules 2016, 17, 2472.
33, 1935. [48] J. Wu, Y. D. Zheng, S. Gao, J. Guo, Q. Y. Cui, X. Ding, X. H. Chen,
[26] a) B. Wei, G. Yang, F. Hong, Carbohydr. Polym. 2011, 84, 533; b) Chem. Res. Chin. Univ. 2013, 34, 210.
B. V. Mohite, R. K. Suryawanshi, S. V. Patil, Cell Chem. Technol. [49] J. Gagnon, M. J. D. Clift, D. Vanhecke, I. E. Widnersson,
2016, 50, 219; c) B. Wei, G. Yang, F. Hong, presented at International S. L. Abram, A. Petri-Fink, R. A. Caruso, B. Rothen-Rutishauser,
Forum on Biomedical Textile Materials, Shanghai, May 2010. K. M. Fromm, J. Mater. Chem. B 2016, 4, 1166.
[27] D. N. Lu, X. R. Zhou, X. D. Xing, X. G. Wang, Z. Liu, Acta [50] E. Fortunati, I. Armentano, Q. Zhou, A. Iannoni, E. Saino, L. Visai,
Polym. Sin. 2004, 25, 107. L. A. Berglund, J. M. Kenny, Carbohydr. Polym. 2012, 87, 1596.
[28] a) R. Li, Q. Jiang, X. Ren, Z. Xie, T. S. Huang, J. Ind. Eng. Chem. [51] H. Zhang, H. Y. Yu, C. Wang, J. Yao, Carbohydr. Polym. 2017, 173,
2015, 27, 315; b) A. Hou, M. Zhou, X. Wang, Carbohydr. Polym. 7.
2009, 75, 328. [52] C. N. Wu, S. C. Fuh, S. P. Lin, Y. Y. Lin, H. Y. Chen, J. M. Liu,
[29] P. Kampeerapappun, Chiang Mai. J. Sci. 2012, 39, 712. K. C. Cheng, Biomacromolecules 2018, 19, 544.
[30] a) J. Yang, D. Hu, W. Li, S. Yi, Chem. Eng. J. 2015, 267, 93; [53] H. L. Nguyen, Y. Jo, M. Cha, Y. Cha, D. Yoon, N. Sanandiya,
b) S. M. Kimura, K. Yonemitsu, Y. Ohtsu, A. Sasao, H. Tsutsumi, E. Prajatelistia, D. Oh, D. Hwang, Polymers 2016, 8, 102.
S. Furukawa, Y. Nishitani, Legal Med. 2018, 32, 48; c) H. Y. Ahn, [54] R. Jung, Y. Kim, H. S. Kim, H. J. Jin, J. Biomater. Sci.,Polym. Ed.
J. Kim, M. Gong, Macromol. Res. 2012, 20, 174; d) R. M. Pasternack, 2009, 20, 311.
S. R. Amy, Y. J. Chabal, Langmuir 2008, 24, 12963. [55] K. M. A. Uddin, H. Orelma, P. Mohammadi, M. Borghei, J. Laine,
[31] a) A. Esmaeili, M. Haseli, Carbohydr. Polym. 2017, 173, 645; M. Linder, O. J. Rojas, Cellulose 2017, 24, 2837.
b) A. Esmaeili, M. Haseli, Mater. Sci. Eng., C 2017, 77, 1117. [56] C. Chen, T. Zhang, B. Dai, H. Zhang, X. Chen, J. Yang, J. Liu,
[32] R. Jafary, M. K. Mehrizi, S. H. Hekmatimoghaddam, A. Jebali, D. Sun, ACS Sustainable Chem. Eng. 2016, 4, 6534.
J. Text. Inst. 2015, 106, 683. [57] W. Shao, H. Liu, X. Liu, S. Wang, J. Wu, R. Zhang, H. Min,
[33] P. Campia, E. Ponzini, B. Rossi, S. Farris, T. Silvetti, L. Merlini, M. Huang, Carbohydr. Polym. 2015, 132, 351.
M. Brasca, R. Grandori, Y. M. Galante, Carbohydr. Polym. 2017, [58] N. Yan, Y. Zhou, Y. Zheng, S. Qiao, Q. Yu, Z. Lia, H. Lua, RSC Adv.
158, 102. 2015, 5, 97467.
[34] N. T. Lacin, Int. J. Biol. Macromol. 2014, 67, 22. [59] M. Sureshkumar, D. Y. Siswanto, C. K. Lee, J. Mater. Chem. 2010,
[35] E. Kaplan, T. Ince, E. Yorulmaz, F. Yener, E. Harputlu, N. T. Lacin, 20, 6948.
J. Biomater. Tissue Eng. 2014, 4, 543. [60] a) D. Sun, J. Yang, J. Li, L. Zhou, J. Yu, J. Biomed. Eng. 2009, 26,
[36] S. C. Lazarini, R. de Aquino, A. C. Amaral, F. C. A. Corbi, 1034; b) J. Luan, J. Wu, Y. Zheng, W. Song, G. Wang, J. Guo,
P. P. Corbi, H. S. Barud, W. R. Lustri, Cellulose 2016, 23, 737. X. Ding, Biomed. Mater. 2012, 7, 065006.
[37] N. Liao, A. R. Unnithan, M. K. Joshi, A. P. Tiwari, S. T. Hong, [61] J. Wu, Y. Zheng, X. Wen, Q. Lin, X. Chen, Z. Wu, Biomed. Mater.
C. H. Park, C. S. Kim, Colloids Surf., A 2015, 469, 194. 2014, 9, 035005.
[38] D. E. Rodriguez-Felix, M. M. Castillo-Ortega, A. L. Najera-Luna, [62] C. Liu, D. Yang, Y. Wang, J. Shi, Z. Jiang, J. Nanopart. Res. 2012, 14,
A. G. Montano-Figueroa, I. Y. Lopez-Pena, T. Del Castillo-Castro, 1084.
F. Rodriguez-Felix, J. M. Quiroz-Castillo, P. J. Herrera-Franco, [63] G. Yang, J. Xie, Y. Deng, Y. Bian, F. Hong, Carbohydr. Polym. 2012,
Curr. Drug Delivery 2016, 13, 49. 87, 2482.
[39] a) M. Shaheen, J. Li, A. C. Ross, J. C. Vederas, S. E. Jensen, [64] a) J. Feng, Q. Shi, W. Li, X. Shu, A. Chen, X. Xie, X. Huang,
Chem. Biol. 2011, 18, 1640; b) Y. Tian, L. Lu, D. Zhang, Cellulose 2014, 21, 4557; b) Y. Zheng, C. Cai, F. Zhang, J. Monty,
J. Li, Y. Feng, C. Hu, J. Pharmaceut. Biomed. 2015, 102, 326; R. J. Linhardt, T. J. Simmons, Nanotechnology 2016, 27, 055102;
c) J. E. Smadel, Am. J. Med. 1949, 7, 671; d) Z. Yu, R. Y. Lai, Talanta c) D. Shi, F. Wang, T. Lan, Y. Zhang, Z. Shao, Cellulose 2016, 23,
2018, 176, 619; e) T. L. Nagabhushan, P. J. L. Daniels, R. S. Jaret, 1899.
J. B. Morton, J. Org. Chem. 1975, 40, 2835; f) S. Hashemikia, [65] J. Quiros, S. Gonzalo, B. Jalvo, K. Boltes, J. Antonio Perdigon-
N. Hemmatinejad, E. Ahmadi, M. Montazer, Mater. Sci. Eng., C Melon, R. Rosal, Sci. Total Environ. 2016, 563, 912.
2016, 59, 429. [66] J. Song, N. L. Birbach, J. P. Hinestroza, Cellulose 2012, 19, 411.

Adv. Healthcare Mater. 2018, 1800334 1800334  (14 of 16) © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.advancedsciencenews.com www.advhealthmat.de

[67] S. Huang, L. Zhou, M. C. Li, Q. Wu, Y. Kojima, D. Zhou, Materials [100] L. C. Tome, S. C. M. Fernandes, D. S. Perez, P. Sadocco,
2016, 9, 523. A. J. D. Silvestre, C. Pascoal Neto, I. M. Marrucho, C. S. R. Freire,
[68] F. Haghighi, R. Mohammadi, P. Mohammadi, Hosseinkhani, Cellulose 2013, 20, 1807.
R. Shidpour, Infect. Epidemiol. Med. 2013, 1, 33. [101] a) Y. Huang, C. Zhu, J. Yang, Y. Nie, C. Chen, D. Sun, Cellulose
[69] W. Liu, P. Su, S. Chen, N. Wang, Y. Ma, Y. Liu, J. Wang, Z. Zhang, 2013, 21, 1; b) N. Lin, A. Dufresne, Eur. Polym. J. 2014, 59, 302.
H. Li, T. J. Webster, Nanoscale 2014, 6, 9050. [102] J. Kingkaew, S. Kirdponpattara, N. Sanchavanakit, P. Pavasant,
[70] N. A. El-Wakil, E. A. Hassan, R. E. Abou-Zeid, A. Dufresne, M. Phisalaphong, Biotechnol. Bioprocess. Eng. 2014, 19, 534.
Carbohydr. Polym. 2015, 124, 337. [103] P. Zhang, L. Chen, Q. Zhang, F. F. Hong, Front. Microbiol. 2016, 7,
[71] O. L. Galkina, K. Onneby, P. Huang, V. K. Ivanov, A. V. Agafonov, 260.
G. A. Seisenbaeva, V. G. Kessler, J. Mater. Chem. B 2015, 3, 7125. [104] W. C. Lin, C. C. Lien, H. J. Yeh, C. M. Yu, S. H. Hsu,
[72] L. Muthulakshmi, N. Rajini, H. Nellaiah, T. Kathiresan, M. Jawaid, Carbohydr. Polym. 2013, 94, 603.
A. V. Rajulu, Int. J. Biol. Macromol. 2017, 95, 1064. [105] a) X. Lu, S. Tang, B. Huang, X. Shen, F. Hong, Fibers Polym. 2013,
[73] M. Natan, O. Gutman, R. Lavi, S. Margel, E. Banin, ACS Nano 14, 935; b) N. Ardila, N. Medina, M. Arkoun, M. C. Heuzey, A. Ajji,
2015, 9, 1175. C. J. Panchal, Cellulose 2016, 23, 3089.
[74] S. Barua, G. Das, L. Aidew, A. K. Buragohain, N. Karak, RSC Adv. [106] K. Segala, S. V. Guerra Nista, L. Cordi, M. T. Marques Bizarria,
2013, 3, 14997. J. de Avila Junior, S. A. Kleinubing, D. C. Cruz, M. Brocchi,
[75] a) K. R. Raghupathi, R. T. Koodali, A. C. Manna, Langmuir L. M. Ferrareso Lona, N. E. Duran Caballero, L. H. Innocentini
2011, 27, 4020; b) Y. Xie, Y. He, P. L. Irwin, T. Jin, X. Shi, Mei, Braz. J. Pharm. Sci. 2015, 51, 911.
Appl. Environ. Microbiol. 2011, 77, 2325. [107] S. Xin, X. Li, Z. Ma, Z. Lei, J. Zhao, S. Pan, X. Zhou, H. Deng,
[76] K. Lefatshe, C. M. Muiva, L. P. Kebaabetswe, Carbohydr. Polym. Carbohydr. Polym. 2013, 92, 1880.
2017, 164, 301. [108] L. Jiang, Y. Lu, X. Liu, H. Tu, J. Zhang, X. Shi, H. Deng, Y. Du,
[77] B. K. Nath, C. Chaliha, E. Kalita, M. C. Kalita, Carbohydr. Polym. Carbohydr. Polym. 2015, 121, 428.
2016, 148, 397. [109] M. T. Santini, C. Cametti, P. L. Indovina, G. Morelli, G. Donelli,
[78] M. Ul-Islam, W. A. Khattak, M. W. Ullah, S. Khan, J. K. Park, J. Biomed. Mater. Res., Part A 1997, 35, 165.
Cellulose 2014, 21, 433. [110] C. Gao, T. Yan, J. Du, F. He, H. Luo, Y. Wan, Food Hydrocolloids
[79] C. Katepetch, R. Rujiravanit, H. Tamura, Cellulose 2013, 20, 1275. 2014, 36, 204.
[80] P. Wang, J. Zhao, R. Xuan, Y. Wang, C. Zou, Z. Zhang, Y. Wan, [111] H. Zhu, S. Jia, H. Yang, W. Tang, Y. Jia, Z. Tan, Food Sci. Biotechnol.
Y. Xu, Dalton Trans. 2014, 43, 6762. 2010, 19, 1479.
[81] N. Janpetch, N. Saito, R. Rujiravanit, Carbohydr. Polym. 2016, 148, [112] E. Lenselink, A. Riessen, J. Wound Care 2011, 20, 536.
335. [113] a) S. Napavichayanun, R. Yamdech, P. Aramwit,
[82] F. S. Jebel, H. Almasi, Carbohydr. Polym. 2016, 149, 8. Arch. Dermatol. Res. 2016, 308, 123; b) C. Wiegand, S. Moritz,
[83] S. Anitha, B. Brabu, D. J. Thiruvadigal, C. Gopalakrishnan, N. Hessler, D. Kralisch, F. Wesarg, F. A. Mueller, D. Fischer,
T. S. Natarajan, Carbohydr. Polym. 2013, 97, 856. U. C. Hipler, J. Mater. Sci.: Mater. Med. 2015, 26, 1.
[84] S. Y. H. Abdalkarim, H. Y. Yu, D. Wang, J. Yao, Cellulose 2017, 24, [114] X. Liu, T. Lin, Y. Gao, Z. Xu, C. Huang, G. Yao, L. Jiang, Y. Tang,
2925. X. Wang, J. Biomed. Mater. Res., Part B 2012, 100B, 1556.
[85] E. Rabie, J. C. Serem, H. M. Oberholzer, A. R. M. Gaspar, [115] Y. Liu, L. Li, N. Pan, Y. Wang, X. Ren, Z. Xie, G. Buschle-Diller,
M. J. Bester, Ultrastruct. Pathol. 2016, 40, 107. T. S. Huang, Polym. Adv. Technol. 2017, 28, 463.
[86] J. Zhao, X. Zhang, R. Tu, C. Lu, X. He, W. Zhang, Cellulose 2014, [116] B. Bideau, J. Bras, S. Saini, C. Daneault, E. Loranger,
21, 1859. Mater. Sci. Eng., C 2016, 69, 977.
[87] C. Pittarate, T. Yoovidhya, W. Srichumpuang, N. Intasanta, [117] Q. Jiang, Z. Jiang, K. Ma, R. Li, J. Du, Z. Xie, X. Ren, T. S. Huang,
S. Wongsasulak, Polym. J. 2011, 43, 978. J. Mater. Sci. 2014, 49, 6734.
[88] J. Zhu, J. Wang, J. Hou, Y. Zhang, J. Liu, B. Van der Bruggen, [118] N. Kandemir, A. Yemeniciogwlu, Ç. Mecitogwlu, Z. S. Elmaci,
J. Mater. Chem. A 2017, 5, 6776. A. Arslanogwlu, Y. Goksungur, T. Baysal, Food Technol. Biotechnol.
[89] N. Pal, P. Dubey, P. Gopinath, K. Pal, Int. J. Biol. Macromol. 2017, 2005, 43, 343.
95, 94. [119] B. A. Russell, B. Jachimska, P. Komorek, P. A. Mulheran, Y. Chen,
[90] X. N. Yang, D. D. Xue, J. Y. Li, M. Liu, S. R. Jia, L. Q. Chu, F. Wahid, Phys. Chem. Chem. Phys. 2017, 19, 7228.
Y. M. Zhang, C. Zhong, Carbohydr. Polym. 2016, 136, 1152. [120] A. Jebali, S. Hekmatimoghaddam, A. Behzadi, I. Rezapor,
[91] L. P. Liu, X. N. Yang, L. Ye, D. D. Xue, M. Liu, S. R. Jia, Y. Hou, B. H. Mohammadi, T. Jasemizad, S. A. Yasini, M. Javadzadeh,
L. Q. Chu, C. Zhong, Carbohydr. Polym. 2017, 174, 1078. A. Amiri, M. Soltani, Z. Rezaei, N. Sedighi, M. Seyfi, M. Rezaei,
[92] M. Ul-Islam, T. Khan, W. A. Khattak, J. K. Park, Cellulose 2013, 20, M. Sayadi, Cellulose 2013, 20, 2897.
589. [121] a) C. A. Cozzolino, F. Nilsson, M. Iotti, B. Sacchi, A. Piga, S. Farris,
[93] H. Deng, X. Wang, P. Liu, B. Ding, Y. Du, G. Li, X. Hu, J. Yang, Colloids Surf., B 2013, 110, 208; b) J. Xie, Z. Tang, J. Wang, C. Chen,
Carbohydr. Polym. 2011, 83, 239. Y. Zhang (Univ Shanghai Ocean), CN107057127-A, 2017.
[94] K. W. Kim, B. J. Min, Y. T. Kim, R. M. Kimmel, K. Cooksey, S. I. Park, [122] W. Li, X. Li, Q. Wang, Y. Pan, T. Wang, H. Wang, R. Song, H. Deng,
LWT–Food Sci. Technol. 2011, 44, 565. Carbohydr. Polym. 2014, 99, 218.
[95] S. Tokura, K. Ueno, S. Miyazaki, N. Nishi, Macromol. Symp. 1997, [123] J. Miao, R. C. Pangule, E. E. Paskaleva, E. E. Hwang, R. S. Kane,
120, 1. R. J. Linhardt, J. S. Dordick, Biomaterials 2011, 32, 9557.
[96] M. A. El-Samahy, S. A. A. Mohamed, M. H. A. Rehim, [124] J. Rybarczyk, E. Kieckens, D. Vanrompay, E. Cox, Vet. Microbiol.
M. E. Mohram, Carbohydr. Polym. 2017, 168, 212. 2017, 202, 23.
[97] D. Dehnad, H. Mirzaei, Z. Emam-Djomeh, S. M. Jafari, S. Dadashi, [125] J. Padrao, S. Goncalves, J. P. Silva, V. Sencadas, S. Lanceros-
Carbohydr. Polym. 2014, 109, 148. Mendez, A. C. Pinheiro, A. A. Vicente, L. R. Rodrigues, F. Dourado,
[98] R. Poonguzhali, S. K. Basha, V. S. Kumari, Int. J. Biol. Macromol. Food Hydrocolloids 2016, 58, 126.
2017, 74, 1. [126] H. d. S. Barud, A. M. de Araujo Junior, S. Saska, L. B. Mestieri,
[99] K. Liu, X. Lin, L. Chen, L. Huang, S. Cao, H. Wang, J. Agric. Food J. A. Duarte Bonini Campos, R. M. de Freitas, N. U. Ferreira,
Chem. 2013, 61, 6562. A. P. Nascimento, F. G. Miguel, M. M. d. O. Lima Leite Vaz,

Adv. Healthcare Mater. 2018, 1800334 1800334  (15 of 16) © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.advancedsciencenews.com www.advhealthmat.de

E. A. Barizon, F. Marquele-Oliveira, A. M. Minarelli Gaspar, [135] L. Yang, S. Lu, J. Li, F. Zhang, R. Cha, Carbohydr. Polym. 2016, 136,
S. J. Lima Ribeiro, A. A. Berretta, J. Evidence-Based Complementary 1035.
Altern. Med. 2013, 2013, 703024. [136] K. Littunen, J. Snoei de Castro, A. Samoylenko, Q. Xu, S. Quaggin,
[127] X. Yang, L. Fan, L. Ma, Y. Wang, S. Lin, F. Yu, X. Pan, G. Luo, S. Vainio, J. Seppala, Eur. Polym. J. 2016, 75, 116.
D. Zhang, H. Wang, Mater. Des. 2017, 119, 76. [137] X. Wang, F. Cheng, J. Liu, J. H. Smatt, D. Gepperth, M. Lastusaari,
[128] a) L. M. P. Sampaio, J. Padrao, J. Faria, J. P. Silva, C. J. Silva, C. Xu, L. Hupa, Acta Biomater. 2016, 46, 286.
F. Dourado, A. Zille, Carbohydr. Polym. 2016, 145, 1; b) H. Pan [138] A. R. Unnithan, G. Gnanasekaran, Y. Sathishkumar, Y. S. Lee,
(Huizhong Int Medical Equip Beijing Co. Ltd), CN106806934-A, C. S. Kim, Carbohydr. Polym. 2014, 102, 884.
2017; c) Z. Li (Suzhou Lingkete New Materials Co. Ltd), [139] a) A. N. Netravali, K. Qiu (Univ Cornell), WO2010135234-A2;
CN107397975-A, 2017; d) K. Lu, Z. Zhuang, H. Tang (Guangdong WO2010135234-A3; US2012129228-A1; US8541001-B2;
Taibao Medical Sci Technology), CN206026745-U, 2017. US2014083327-A1; US9499686-B2, 2010; b) R. Berry,
[129] A. Piatkowski, N. Drummer, A. Riessen, D. Ulrich, N. Pallua, Burns A. Granger (Celluforce Inc), WO2014190428-A1; CA2913359-A1;
2011, 37, 800. EP3004247-A1; US2016108236-A1; US9796849-B2, 2014;
[130] W. Czaja, A. Krystynowicz, S. Bielecki, R. M. Brown, Biomaterials c) M. W. Feng, X. Wang, Y. Zhang, S. Raymond, R. Berry (Celluforce
2006, 27, 145. Inc), WO2015117237-A1; CA2938518-A1; US2016355710-A1;
[131] T. Eberlein, G. Haemmerle, M. Signer, U. Gruber-Moesenbacher, EP3105298-A1; EP3105298-A4, 2015; d) W. Y. Hamad, S. Atifi,
J. Traber, M. Mittlboeck, M. Abel, R. Strohal, J. Wound Care 2012, R. M. Berry (Celluforce Inc), WO2014138976-A1; CA2905200-A1;
21, 18. EP2970639-A1; US2016024264-A1; JP2016518465-W;
[132] a) T. Retsina, K. Nelson, L. Hill, V. Pylkkanen, T. Galliford, EP2970639-A4, 2014; e) Y. B. Wen, D. Cheng, Y. H. Ni, X. H. Zhu,
T. J. Galliford (Api Intellectual Property Holdings Llc), X. Y. An, X. C. Jiang (Tianjin Univ Sci & Technol), CN103275336-B,
WO2017192476-A1; US2017328003-A1, 2017; b) K. Nelson, 2013; f) I. Kajanto (Upm-Kymmene Corp), WO2011080386-A1;
T. Retsina, V. Pylkkanen, R. Oconnor (Api Intellectual Property FI200906417-A; FI122145-B1; CA2781757-A1; EP2519689-A1;
Holdings Llc), US2016281298-A1, 2016. US2012291974-A1; CN102791924-A; JP2013516553-W;
[133] a) J. Li, K. Chen, B. Wang, X. Tian, J. Zeng, J. Xu, W. Gao (Univ EP2519689-B1; EP2519689-A4, 2011.
South China Technology), CN107540858-A, 2018; b) Z. Chen, [140] A. Czyzewski, Firm roots for NCC production, Engineer, 2012.
Y. Hu, J. Zhang, S. Shen, X. Ye (Nanjing Fengyuan New Material [141] H. Lan, G. K. Li, A. G. Liu, X. M. Li (China International Travel
Technology), CN107383401-A, 2017; c) S. Chen, X. Chen (Fuzhou Service Co. Ltd), CN201210593534, 2012.
Yongxin Plastic Packing Supplies), CN106905598-A, 2017. [142] B. B. Shi (Yuhan Technology Co., Ltd.), CN201410403739.7, 2014.
[134] S. Cheng, Y. Zhang, R. Cha, J. Yang, X. Jiang, Nanoscale 2016, 8, 973. [143] D. Sandquist, Appita J. 2013, 66, 156.

Adv. Healthcare Mater. 2018, 1800334 1800334  (16 of 16) © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

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