Bacterial Cellulose Composites: Synthetic Strategies and Multiple Applications in Bio-Medical and Electro-Conductive Fields

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Bacterial cellulose composites: Synthetic strategies and multiple applications


in bio-medical and electro-conductive fields

Article  in  Biotechnology Journal · September 2015


DOI: 10.1002/biot.201500106

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Biotechnology Biotechnol. J. 2015, 10, 1847–1861 DOI 10.1002/biot.201500106
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Review

Bacterial cellulose composites: Synthetic strategies and multiple


applications in bio-medical and electro-conductive fields

Mazhar Ul-Islam1,2, Shaukat Khan1, Muhammad Wajid Ullah1 and Joong Kon Park1
1Department of Chemical Engineering, Kyungpook National University, Daegu, South Korea
2Department of Chemical Engineering, College of Engineering, Dhofar University, Salalah, Oman

Bacterial cellulose (BC), owing to its pure nature and impressive physicochemical properties, Received 11 JUN 2015
including high mechanical strength, crystallinity, porous fibrous structure, and liquid absorbing Revised 11 JUN 2015
capabilities, has emerged as an advanced biomaterial. To match the market demand and econom- Accepted 31 Aug 2015
ic values, BC has been produced through a number of synthetic routes, leading to slightly different
structural features and physical appearance. Chemical nature, porous geometry, and 3D fibrous
structure of BC make it an ideal material for composites synthesis that successfully overcome cer-
tain deficiencies of pure BC. In this review, we have focused various strategies developed for syn-
thesizing BC and BC composites. Reinforcement materials including nanoparticles and polymers
have enhanced the antimicrobial, conducting, magnetic, biocompatible, and mechanical proper-
ties of BC. Both pure BC and its composites have shown impressive applications in medical fields
and in the development of optoelectronic devices. Herein, we have given a special attention to
discuss its applications in the medical and electronic fields. In conclusion, BC and BC composites
have realistic potential to be used in future development of medical devices, artificial organs and
electronic and conducting materials. The contents discussed herein will provide an eye-catching
theme to the researchers concerned with practical applications of BC and BC composites.

Keywords: Bacterial cellulose · Biomedical · Composites · Optoelectronics · Synthetic strategies

1  I ntroduction applications in numerous fields, plant cellulose is asso-


ciated with some serious inadequacies. Among which,
Cellulose, the most abundant polymer on the earth surface the most important is its impure nature and the need
is primarily obtained from plants. Besides its intensive for intense pretreatments prior to utilization in various
applications. Bacterial cellulose (BC), a purified form of
cellulose, is produced by various types of bacterial species
Correspondence: Prof. Joong Kon Park, Department of Chemical Engineer- mainly belonging to the genus Acetobacter [1, 2]. BC con-
ing, School of Applied Chemical Engineering, Kyungpook National Univer- sists of microfibrils that are arranged in a 3D web-shaped
sity, Daegu 702-701, South Korea manner, providing a porous geometry and high mechani-
E-mail: parkjk@knu.ac.kr
cal strength [3, 4]. Compared to plant cellulose, BC pos-
Abbreviations: BC, bacterial cellulose; Ch, chitosan; CNTs, carbon nano- sesses a much higher crystallinity, liquid absorption
tubes; COL, collagen; ePTEE, expanded polytetrafluoroethylene; FE-SEM, capacity, and mechanical properties that make it an ideal
field emission scanning electron microscopy; GNPs, graphite nanoplatelets, biomaterial for numerous applications in the medical and
ITO, indium tin oxide; MMT, montmorrilonite; MWCNTs, multiwalled car- other industrial fields [5–7]. Although being a material of
bon nanotubes; (NH4)2S2O4, ammonium peroxydisulfate; OLEDs, organic prime importance in numerous fields, pure BC has certain
light emitting diodes; PANi, polyaniline; PBS, phosphate-buffered saline;
limitations that restrict its applications in several fields,
PEDOT:PSS, poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate);
PET, polyethylene terephthalate; PGA, polyglycolic acid; pHEMA, polyhy-
including the medical and electronic field [4, 8–10].
droxyethyl methacrylate; PLA, polylactic acid; pNIPAA, Poly N-isopropy- Since a few decades, the polymer composite technol-
lacrylamide; PVA, polyvinyl alcohol; QCM, quartz crystal microbalance; ogy has gained enormous fame. The limitations associ-
RGD, Arg-Gly-Asp; SBF, simulated body fluid ated with pure polymers themselves can be effectively

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overcome by the use of composites. Impregnation with ied biopolymer. While BC presents impressive structural
material of interest not only improves the existing proper- features and physiological behavior, serious economic
ties of polymers, but also provides additional features to and feasibility concerns remain regarding its production.
the polymer [8, 11]. In this scenario, several efforts have Besides the chemically synthesized medium, BC produc-
been made to synthesize BC composites using different tion has been established from numerous natural media.
materials and to improve its properties and applications The demand to control the cost of BC production led to
[3, 8, 12]. The motive towards BC composite synthesis has the use of various cheap and waste media [8]. Some of
been provided by its structural features and production these reported media include fruit juices, beer wastes,
procedure. During the production process, the micro- agriculture wastes, coconut, pineapple water, molasses,
fibrils are arranged in a web-shaped manner that can and sugar industry wastes.
encage numerous materials added to the culture medium. As described in the literature, BC is normally pro-
Besides, the porous fibril structure and hydrophilic nature duced at the air-liquid interface in the form of a gel. The
also facilitate the impregnation and attachment of materi- thickness of the produced BC depends upon the culture
als in the fibril network [8]. time and the presence of carbon sources in the medium.
BC composites showed much improved properties, BC microscopic studies indicate that it presents a web
leading to additional applications in the medical and shaped structure. The microfibrils obtained from the com-
other industrial fields. Impregnation with nanomaterials bination of cellulose chains are arranged in a 3D manner
having antibacterial properties, such as silver (Ag), zinc to form a net-like structure. As BC is produced at the air-
oxide (ZnO), titanium oxide (TiO2), antibacterial clays, liquid interface, newly produced microfibrils are added to
and some polymers have improved the antibacterial and the first layer, increasing the thickness of the BC layers.
biocompatible properties of BC and consequently, its Overall, the produced BC has a highly porous structure,
applications in medical fields [1, 3]. Similarly the addi- which presents high liquid absorption capabilities. The
tion of conducting materials, including CNTs, graphene morphology of the produced BC is mainly dependent on
oxide, PEDOT:PSS, and nanoparticles, provided BC with the production method [8]. Herein we summarize certain
conducting features [3, 8, 13]. approaches developed so far for BC production.
Currently, research is focused on the practical applica-
tion side. The materials, including composites, are mainly 2.1  Synthetic strategies for BC
synthesized for targeted applications. To this end, BC
composites have shown impressive results, specifically in The main motive behind producing BC through differ-
biomedical fields. BC and its composites have been used ent methods was its cost effective production. Being a
in applications, including wound healing, skin and tis- microbial product, the production is greatly dependent on
sue regeneration, healing under infectious environment, the bacterial activities and the fermentation technique.
development of artificial organs, blood vessels, and skin Initially, BC was synthesized through a static culture
substitutes [8, 14, 15]. Besides, conducting BC compos- technique, where BC mats were produced with varying
ites have been developed for application in electronics thickness. However, the fermentation was subjected to
and research is still in progress to produce conducting agitation techniques for which numerous reactors and
devices, displays, optoelectronics, sensors and bio-sen- fermenters were designed to enhance the production and
sors, and other advance materials using BC composites satisfy the commercial demands [17–20]. In addition to
as the base/substrate [4, 16]. its production, the physicochemical features of BC also
The current review describes the development made vary to a great extent with culturing technique and this
hitherto in BC producing techniques and the approaches explains why different methods were applied to obtain
adopted for its extensive applications. We summarized BC with specific properties. Some of the BC production
the developmental strategies for utilizing BC composites techniques are summarized in Fig. 1.
in the medical and conducting fields. Additionally, we
focused on describing the practical applications, includ- 2.1.1 Static cultures for BC films production
ing the use of BC and BC composites in the development BC films or pellicles produced through the static culture
of medical instruments and conducting devices. We hope technique are the most widely applicable form of BC.
that this review will catch the interest of the readers and BC films are produced through a very simple static cul-
will provide information regarding BC structure, develop- tivations strategy. In this method, containers are filled
ment, and practical applications. with sterilized growth medium and inoculated with a
freshly prepared preculture. The medium is then kept at
an optimum temperature range for different time intervals
2  B
 C production ranging from three to 15 days or more. The pellicles of BC
produced through static culture are shown in Fig. 1.
Since its initial production was reported more than a cen- In static culture, BC films are produced at the air-liquid
tury ago, BC has been established as one of the most stud- interface. The produced BC floats on the medium surface

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Figure 1.  Bacterial cellulose production under static and agitated conditions. Various bioreactors for production under agitated conditions. Figure has
been reproduced from Shi et al. [91] with permission from Elsevier.

due to the entrapped CO2 generated from the bacte- mixing of the oxygen in the medium. Thus, this method
rial metabolism. BC thickness increases with the culture was the first approach used to enhance BC production.
time, provided that the medium contains glucose or other The irregular shaped BC pellets obtained through
carbon sources. Since BC is produced at the surface, the shaking culture are much different from the mats obtained
overall BC production is directly related to the surface through static culture. Usually, the produced pellets are
area of the air-liquid interface [21]. While providing BC spherical in shape. However, their size and geometry vary
for multiple applications, the static culture method is a with the rotational speed [22]. The size of the produced
very slow process and has the lowest production rate. The pellets also varies with the agitation speed. These fibers
biggest problem in static culture methods is the limited are synthesized throughout the medium and get attached
oxygen supply specifically to the cells beneath the growth to each other, forming a mass of cellulose. However, the
of the surface BC layer. fast rotation speed defines their symmetry and internal
To overcome this inadequacy, fed batch culturing structure. The structural analysis conducted through FE-
was introduced in static cultures. The issue of carbon SEM revealed that cellulose spheres produced at 200 rpm
source depletion can be addressed using this strategy were hollow, while spheres produced at 150  rpm were
and the production rate can be enhanced with culture solid [22].
time. Besides, there are efforts illustrating the develop- Along with the irregular shape of produced BC, the
ment of novel reactors that can produce BC through static second major problem associated with submerged fer-
cultures with a much higher efficiency [18]. mentation is the accumulation of non-BC-producing
mutants [23]. In this regard, certain bacterial species
2.1.2  Shaking cultures for BC pellets production withstand more effectively the mutant generation effect
BC production is a slow and continuous process. Once and result in higher BC production. For example, Gluco-
begun, the newly produced microfibrils attach to the nacetobacter xylinus BPR2001 produced 1.8-fold more
growing layer, thus, increasing the thickness in static BC than the commonly used strain, G. xylinus (ATCC®
cultures. The produced gel shaped pellicles attain the 23769). Similarly, the use of other bacterial strains also
shape of the container surface. However, the geometry led to an increase in BC production in shaking cultures
of the produced BC is quite different when produced by [12, 23, 24].
shaking culture. Due to continuous shaking, BC does not
grow in the form of a steady layer and instead forms small 2.1.3  Agitated culture for producing BC granules
irregular shaped pellets. In shaking cultures, BC produc- The third important technique that was used to enhance
tion can occur throughout the medium due to continuous BC production was high-speed agitation cultures in spe-

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cially designed reactors/fermenters. Once the basic syn- 3  BC composite


thetic mechanism of BC production was clear, the impor-
tance of culture media, oxygen, and cells was determined. Both natural and synthetic composite materials are cur-
Simple static and shaking culture cannot bring about the rently in demand for almost all industrialized processes,
perfect mixing and distribution of oxygen in the culture owing to their impressive features. In composites, the
medium. Furthermore, these former two culture methods base is a matrix acting as a scaffold, while reinforcement
are basically working in batch fermentation techniques. materials impart additional features to the matrix [8]. A
Therein, the supplementation with additional nutrients is wide variety of both matrices and reinforcing materials
usually difficult and the process is stopped after one batch allows the synthesis of numerous composites through a
of BC production. All these issues were affecting the broad range of synthetic techniques. Polymers, including
industrialization of BC. The agitation cultures were there- biopolymers have been impregnated with a great number
fore introduced. BC was produced in specially designed of reinforcement materials to synthesize multifunctional
reactors, where the mixing of oxygen and timely supple- composites [30, 31].
mentation of nutrients or culture medium is assured. The BC is an excellent biopolymer for the synthesis of com-
BC produced in this culture system is in the form of small posites. There are two major driving forces for the syn-
sized granules. The fast rotation speed and moving shafts thesis of BC composites. First, the outstanding structural
of the reactors do not allow the produced BC to accumu- features of BC are ideal for the synthesis of its composites
late in the form of large pellets. Owing to the initial suc- with various materials. The nicely arranged web shaped
cess of agitation cultures, numerous bio-reactors were fibrous network structure of BC fibers can encage nano-
developed with slightly different operation conditions. particles, thus working as a matrix. Besides, the presence
Some of these are summarized below. of hydrogen bonded sites on cellulose chains allows inter-
In 1997, Chao et al. introduced the first air-lift bio- action with other polymers to form strong composites [6,
reactor that can be operated using a low power supply 7, 32]. Secondly, pure BC lacks certain features that limit
and can enhance BC production [25]. In this particular its applications in different fields. For instance, pure BC
design, air is continuously supplied from the bottom side does not present antibacterial, magnetic, and conducting
that circulates inside the culture medium. The proper properties. This is a drawback in designing BC based
oxygen supply to the cells is one of the keys to enhance medical or conducting devices. [8].
the production. They reported 3.8 g after 67 h of culture To date, there have been numerous reports on the syn-
with a slightly modified air lift bioreactor [26]. Jung et al. thesis of BC composites with multiple materials to attain
introduced a novel reactor with spin filters for enhancing BC with increased mechanical strength, biocompatibil-
the production in agitated cultures [27]. The bioreactor ity, bactericidal activities, conductivity, and magnetic
consisted of a six flat-blade turbine impeller along with properties [33–35]. Based on the intended application and
a spin filter surrounded by a stainless steel mesh, whose suitability of material impregnation, different methods
bottom was attached to the agitator shaft. BC production have been developed to synthetize BC composites. The
was improved (4.7 g/L) and was about three times higher most common method used for biopolymer composite
than the conventional jar fermentation [27]. The first synthesis is the initial addition of reinforcement materials
rotating disk bioreactor for BC production was reported to the culture medium (in situ composite synthesis). BC
by Serafica et al. in 2002 [28]. The rotating disc bioreac- composites have been synthesized with polymers, includ-
tor is composed of several circular disks accumulated on ing chitosan, gelatin, poly-3-hydroxybutyrate, nanoma-
a rotating central shaft and an inlet for inoculation. The terials, CNTs, and other solid particles, including clays
main objective of this bioreactor design was the homo- and silica [7, 8, 28] using the in situ composite synthetic
geneity of the produced BC, which cannot be achieved strategy. The reinforcement materials impregnate well
with agitation and airlift bioreactors. During the process, inside the growing BC fibrils. The effectiveness of in situ
the disc area is half embedded inside the medium, while composite synthetic strategy has been hindered by the
the other half is exposed to air. While rotating, the disc antibacterial nature of reinforcement materials that kill
surface alternatively interacts with air and liquid medium, the BC producing cells as well as the insolubility of various
allowing the adhesion of BC to the disc surface and pro- materials in culture media.
viding BC with additional mechanical strength. Recently, The second approach adopted to cope with the dis-
much improved bioreactors, including immobilized-cell crepancies of the in situ method was the post-synthetic
reactors, hollow fiber reactors, and cell recycle reactors, modification of BC with reinforcement materials. The
have been employed to improve BC production. Cheng et approach is termed the ex situ composite synthetic strat-
al. reported 7.05 g/L BC production using plastic compos- egy. As mentioned earlier, the web shaped porous geom-
ite biofilm reactors [29]. etry of BC provides space for impregnation of different
materials inside its surface. Polymer solution and suspen-
sions of nanoparticles when treated with BC films pen-
etrate inside the BC matrix. Depending upon their chemi-

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cal nature, the materials are physically encaged either 4.2  Macrostructure control and orientation
within BC fibers or they form chemical bonding with the
cellulose chains [6–8]. A number of BC composites have BC structure, both in wet and dry form, presents excit-
been produced through ex situ synthesis strategy. These ing features. Generally, the produced BC is in the form of
include BC composites with chitosan, gelatin, polyethyl- a gel, which can be directly utilized in the medical field
ene glycol, silver nanoparticles, gold nanoparticles, and and for separation purposes. Furthermore, its physical
CNTs [33–37]. The major limitation of this strategy is structure is flexible enough to be controlled at the macro,
that only particles of specified size can penetrate inside micro, and even nanoscale level. By varying the growth
the BC fibers. Besides, hydrophobic materials cannot be and culture conditions, the BC producing microorgan-
combined with BC through this approach. isms can be directed to produce BC in several shapes or
Recently, the most advance strategy adopted allows forms such as flat sheets, pellets, and granules [8]. Stud-
the synthesis of BC composites from dissolved BC solu- ies have shown that several characteristic features of BC
tion. BC dissolved in some specific solvents can be such as surface chemistry, porosity, and fiber orientation
regenerated in the form of films and fibers [3, 7]. Using this can be optimized at the micro and nanoscale. This mac-
particular strategy, reinforcement materials are added to rostructure control offers great advantages in developing
the dissolved BC solution to produce a homogenous com- BC for multiple applications [14, 15, 39].
posite solution. Films or regenerated BC is then casted In nature, BC shows an anisotropic pattern in the
from the composite solution to produce BC composites. culturing plane. This randomness of cellulose fibers could
This strategy seems more effective as materials of differ- be attributed to the bacterial motion in the culture medi-
ent nature and size can be mixed in the BC solution. BC um. Despite this random behavior of cellulose fibers, the
composites with nanoparticles, including ZnO and TiO2, overall cellulose structure is quite compact and strong. It
have been synthesized by using this new technique [1, 3]. can achieve a comparable isotropic alignment and has
The composition of matrix and reinforcement materials as been proven useful for several applications. Wang et al.
well as their homogenous distribution can be easily con- optimized the bacterial motion using the microfluidic
trolled using this strategy. The major drawback with this channels and successfully obtained aligned BC fibers
particular strategy is the difficulties in the dissolution of [40]. Uraki et al. obtained a honeycomb pattern of BC by
BC. In fact, BC is insoluble in water as well as in the most using honeycomb-patterned microgrooves in an agarose
widely used organic solvents [38]. film [41].

4.3  Porosity and liquid absorbing capabilities


4  I nspiring features for multiple applications
of BC BC presents a certain level of porosity that differs largely,
depending upon its production and treatment processes.
BC possesses several unique features such as ultrafine The porous geometry provides an ideal environment
fibrous structure, biocompatibility, porosity, crystallinity, for the absorption of liquids, including water, solutions,
transparency, and biodegradability. All these features media, or wound exudates. Although the existing poros-
make BC an important material for applications in the ity of BC is convincing for certain applications, it is still
medical as well as various industrial fields. Herein, we low, limiting its use in a wide range of medical applica-
briefly discuss a few of these features. tions. In general, this feature of BC is advantageous since
it prevents the invasion of microbial cells, but, from the
4.1  Ultrafine thin fibrous structure biomedical application perspective, it is a limitation that
prevents the penetration of mammalian cells [42].
The wide spread applications of BC starts from its unique Currently, artificially porous BC is developed through
structure itself. Pure BC has a fine network of ultra-thin various strategies such as the use of porogens. A porogen
fibers. These are well arranged and giving a firm appear- is any material (e.g. salt, paraffin, ice, gelatin, and sugar)
ance to BC. The fibers are arranged in a web shaped that is initially incorporated into BC as a space holder,
manner. The cross sectional morphology observed by which is later on removed without disturbing the native
microscopy shows that fibers are arranged in layers. chemical and molecular structure [39]. In their study,
The arrangement of cellulose fibers is the basic reason Bäckdahl et al. investigated potato starch and paraffin
of its higher crystalline properties as well as mechanical wax as porogens in BC tubes and successfully altered
strength. The microfibril arrangement plays a vital role in the pore size and interconnectivity by controlling the
the development of BC for applications in optoelectronic size of the paraffin particles. Moreover, partial particle
devices and medical instruments [1, 8]. fusion was created by heat-treating the initial paraffin
wax particles at specific temperatures. They successfully
attached the smooth muscle cells inside the pores [39].

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this review, we focused on describing its application in


the medical field and in developing conducting devices.
Pure BC naturally presents certain features that drive its
multiple applications. Herein, we will summarize the driv-
ing features for these applications.

5.1  Medical applications of BC and BC composites


Figure 2.  Illustration of the cell adhesion biocompatible behavior of BC
and BC composites. Fibroblast cell attachment on BC surface (A), confo-
cal microscopy images of MC3T3-E1 osteoprogenitor cells seeded on BC The above-mentioned structural features and physico-
scaffolds (B) Optical micrographs of HEK cells for one day of culture in chemical properties of BC offer several exciting appli-
nanocomposite of BC-Hap; and (C). The figure is modified from Khan et cations in the biomedical field. Some of the biomedical
al., 2015 [3] (A), Bäckdahl et al., 2006 [62] (B) and Grande et al., 2009 (C). applications of BC include topical covering for severe
wounds, artificial skin, coverings for nerve surgery, dura-
mater prosthesis, and arterial stent coating [15]. Biopro-
4.4  Biocompatibility cess®, XCell®, BASYC®, and Biofill® are few of the impor-
tant products that are already available commercially for
BC biocompatibility is defined as its ability to remain in topical application in wound healing [14, 47].
contact with living tissues without causing any toxic or all- Studies have shown that BC could be effectively
ergic side effects. BC biocompatibility is directly associa- used as wound dressing material to reduce pain and the
ted with its higher liquid absorbing capabilities that assist regeneration time of the damaged tissue, ease wound
the prolonged and sustainable growth of living cells. Seve- observation and drug application, and accelerate the
ral studies reported moderate to strong levels of biocompa- epithelialization process [14, 15]. Due to its high water
tibility against different cells [43, 44]. Helenius et al. in their holding capacity and slow release rate, it serves as an
in vivo study demonstrated BC biocompatibility in rats by ideal moisturizer during wound healing by maintaining
subcutaneous implantation for 12 weeks. The microscopic a proper water balance. Similarly, owing to its unique
results demonstrated the complete absence of any fibrotic structural and physico-mechanical features, it can serve
capsules or giant cells, indicating no foreign body reaction. as support material (scaffold) for the skin regeneration
Moreover, no redness, swelling, or exudates developed process [8, 15]. It supports the adhesion and prolifer­
around the implantation sites was shown by macroscopic ation of epithelial cells (Fig. 2) and thus, could serve as a
observations [45]. The biocompatible behavior of pure BC semi-permanent artificial skin. Moreover, this developed
and BC composites has been observed against various ani- graft could be used as an autograft during the grafting
mal and human cells (Fig. 2). However, in certain cases, the process for severe damaged skin tissues [15]. BC has
biocompatibility is not up to the desired levels and, thus, shown a remarkable potential in bone tissue regeneration.
further enhancement is required. One of the solutions to During this process, the scar tissue formation at healing
achieve this goal is the development of BC composite with sites is prevented through the implantation of a barrier
biocompatible materials. A great success has been achie- membrane that keeps fibroblasts away, allowing slower
ved in this regard and we will discuss it later. osteogenesis to take place [15]. Some of the impressive
applications of BC and BC composites are illustrated in
4.5  Biodegradability Fig. 3 and 4.
BC composites with several polymeric and non-poly-
BC biodegradation, due to its high degree of crystallin- meric compounds and nanomaterials have been prepared
ity and compact structure, is the most difficult feature to to impart antimicrobial, antifungal, tissue regeneration,
achieve in order to meet the requirements for biomedi- and biocompatible properties to BC [6, 7, 34, 48]. BC
cal applications. Since the cellulase enzyme required for composite with chitosan (BC-Ch) displayed higher water-
its degradation does not exist in mammalian cells, an holding capacities and retained water for a long time with
alternative strategy for its degradation is needed. Li et al. very slow water release [31]. Consequently, it enhan-
reported the enhanced degradation of BC in vitro through ced the biocompatibility, cell adhesion, and proliferation
periodate oxidation [46]. Because of this treatment, BC properties of BC and showed better results as a wound
became biodegradable in water, PBS, and SBF, while the dressing material and as a scaffold in tissue engineering
original network structure of BC remained intact. [34, 49]. Kim et al. found that BC composite with gelatin
showed fibroblast adhesion and proliferation when provi-
ded with the appropriate growth conditions. Moreover,
5  A
 pplications of BC and BC composites the biocompatibility was also improved compared to pure
BC and the developed scaffolds were bioactive, indicating
BC has been used extensively in different fields. In fact, their potential for wound dressing [34]. The composite
it is quite hard to summarize its potential applications. In of BC with polyvinyl alcohol (PVA) with controllable

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Figure 3.  Illustration of various biomed-


ical applications of BC-based biomateri-
als and medical devices

mechanical and anisotropic features was found useful to devices [14, 49]. Some of their applications include their
replace cardiovascular and other connective tissues [50]. use as artificial skin, vascular grafts, scaffolds for tissue
BC-collagen (BC-COL) composites have been developed engineering, artificial blood vessels, medical pads and
for potential tissue engineering applications through an dental implants, artificial cornea, heart valve prosthesis,
in situ composite synthesis strategy. These composites artificial urethra, artificial bone, artificial cartilage, artifi-
enhanced the mechanical properties of COL and the cell cial porcine knee menisci, and deliveries of drug, hormo-
adhesion properties of BC and hence, can be effectively ne and proteins. Table 1 represents BC based biomaterials
used for biomedical applications [51]. The BC composite used for several medical applications. Biofill, a membrane
with silver (Ag) nanoparticles has been found very useful prepared from BC, is used as a temporary skin substitute
against many bacterial and fungal species. As a result, the for patients with burns and ulcers [33]. Instead of discus-
healing process becomes safer and faster. BC composites sing the generalized applications in this review, we will
with metallic oxide (BC-TiO2 and BC-ZnO) also possess focus on few examples, indicating the use of BC and BC
excellent antibacterial properties and hence, can be uti- composites in the development of medical devices and
lized for various biomedical applications [1, 52]. BC com- biomaterials.
posites with clay materials such as MMT displayed tre-
mendous potential as biomedical materials by enhancing 5.2.1  Scaffold
BC mechanical properties and conferring antibacterial The success of tissue regeneration requires the devel-
properties, and wound healing potential to BC [6, 7, 53]. opment of a three dimensional scaffold that provides
the structural support for cell attachment, spreading,
5.2  B
 C and BC-composite based biomedical migration, proliferation, differentiation, and shape of the
materials and devices developing tissue. Pure BC is not biodegradable by
mammalian cells due to the absence of cellulase. Li et al.
BC and BC based composites have been used for the developed a method involving the periodate oxidation of
development of numerous biomaterials and medical BC by which the scaffold could be developed and is read-

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Figure 4.  Transparent BC nanocompos-


ite films and their application as sub-
strate for OLED fabrication. Transparent
acetylated BC film (A), BC acrylic nano-
composite film (B), OLED fabricated on
transparent BC films (C) and (D). Fig-
ures modified from Ifuku et al., 2007 [73]
(A), Nogi and Yano, 2008 [74] (B and C)
and Ummartyotin et al., 2011 [77] (D)

ily biodegraded in water, phosphate-buffered saline, and BC and PVA using the freeze-thaw method. They made
simulated body fluid [46]. a hydrogel composite by impregnating various amounts
A review of the literature reveals that the earlier of PVA into a transparent BC polymer matrix and charac-
attempts of developing scaffolds with biodegradable terized its various features. The key features of the com-
materials were overshadowed by several limitations such posite that played an important role in the development
as a higher degradation rate of scaffold material compared of the artificial cornea included the water content, light
to the growth rate of cells. This issue could be address transmittance, structure, thermal stability, and mechani-
through the development of permanent scaffolds by using cal properties. The presence of large amount of hydroxyl
more biocompatible, porous, and highly resistant materi- groups on the two components ensured the interfacial
als. To date, several materials have been evaluated for interactions through hydrogen bonding that resulted in
such purposes such as PGA, PLA, PVA, pHEMA, and the desirable adhesion at the BC-PVA interface. They
poly(N-isopropylacrylamide) (pNIPAA) [54]. Currently, the found that the optical properties, thermal stabilities, and
development of BC based scaffolds is receiving a lot of mechanical characteristics of the BC-PVA composites
interest due to its non-toxic nature and ability to be used met the requirements of artificial cornea materials and,
as implanted material or as a substrate. It has been exten- thus, proved to be a promising biomaterial candidate for
sively evaluated as a scaffold material both in native and cornea replacement.
modified forms. However, the native BC could not support
cell growth due to its limited biocompatibility. However, 5.2.3  Heart valves
upon soaking in serum and electrolytic solution such as The development of artificial heart valves is another area
sodium hydroxide, the cells readily started to adhere and of interest in BC applications in the biomedical field.
proliferate on BC-based scaffolds [55]. Currently, two types of valve replacements are in prac-
tice, porcine valves presenting a limited lifespan and
5.2.2  Cornea mechanical heart valves, which have longer lifespan, but
Wang et al. developed a biocompatible, flexible, and one- require lifelong blood thinning medication and thus cause
piece artificial cornea [56]. In their study, they attempted increased shear forces on red blood cells, cell rupture,
to develop an artificial cornea using BC based composite and associated anemia. These issues could be addressed
with polyvinyl alcohol (PVA). PVA is more stable, while by developing BC composite-based heart valves. Millon
BC is biocompatible and possesses high mechanical and Wan developed a BC-PVA composite that possesses
properties. Therefore, a composite was developed from mechanical features comparable to native heart leaflets.

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In their study, they showed that the stress-strain proper- be used as a substitute for chemically synthetic materi-
ties of porcine aorta are matched by one of the BC-PVA als such as vinyon, Teflon, and synthetic fiber Dacron to
[50]. In another study, Mohammadi also developed BC- synthesize artificial blood vessels since it carries a lower
PVA composites for the production of heart valve leaflets risk of blood clot formation (Table  1). Moreover, it pos-
to mimic the non-linear mechanical properties displayed sesses high mechanical features appropriate for shape
by porcine heart valves and their anisotropic behavior. retention and tear resistance. When processed into a film
He achieved this goal by applying a controlled strain to or sheet, BC has shown remarkable mechanical strength
the sample, while undergoing low-temperature thermal compared with many organic sheets like polypropylene,
cycling in order to induce oriented mechanical features polyethylene terephthalate, or cellophane. Thus, tubular-
[57]. shaped BC could serve as an attractive candidate as a
Fink et al. evaluated the hemocompatibility of BC- blood vessel replacement [44]. Upon interaction with
based vascular graft tubes and compared them with the blood, BC does not cause any toxic effect and, thus,
commercial grafts of PET and ePTEE. They observed can serve as a useful element for synthesizing artificial
that BC-based grafts did not induce plasma coagulation, blood vessels. The BC fibers support the growth and
but rather induced the slowest coagulation cascade [58]. proliferation of smooth muscle, endothelial, and fibroblast
Moreover, Andrade et al. further addressed this issue by cells that ultimately create a viable artificial blood vessel.
coating BC with the tripeptide RGD to assist endotheli- Moreover, its high mechanical properties such as tensile
alization and thus, improve BC hemocompatibility [59]. strength and flexibility assist in withstanding the high
pressure generated by the circulatory system. A BC-
5.2.4  Blood vessels based PVA nanocomposite has displayed the required
Artificial blood vessels are tube-like materials made from medical features for the development of artificial blood
synthetic materials to restore the blood circulation in case vessels with the desired medical properties owing to its
of blockage of coronary vessels near the heart. BC could high biocompatibility.

Table. 1.  Illustration of recent research on BC and BC-based biomaterials for biomedical applications

BC/BC-composite Application Improved features Reference


BC films Substitution of diseased arteries Substantial permeability to water and [88]
and blood vessels high water holding capacity and
mechanical strength, improved
biocompatibility, low surface roughness
and minimized blood clotting
BC tubes (BASYC®) Synthetic blood vessels in High mechanical strength and [44]
microsurgery moldability, smooth inner surface
BC membrane Scaffold for mammalian cell High permeability [55]
BC sheet impregnated with drugs Wound care Highly nanoporous, allows transfer [14, 89]
of antibiotics or medicines, acts as a
physical barrier against external
infections, accelerated wound healing,
improved mechanical properties
BC-chitosan and silver nanoparticles Skin tissue regeneration Antibacterial activity, improved [89]
mechanical properties and flexibility,
improved transparency
BC-MMT Wound healing Improved mechanical and thermal [6, 53]
properties, antimicrobial activity
BC-hydroxyapatite Cartilage and bone tissue Improved mechanical features and [90]
regeneration and engineering biocompataibility
BC-chitosan Wound healing, scaffold, and Highly nonporous, high water holding [14, 31]
skin burns and slow water release features, high
mechanical properties, enhanced
biocompatibility, cell adhesion and
proliferation
BC-gelatin Wound dressing Improved fibroblast adhesion and [34]
proliferation

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5.2.5  Bone and cartilage ing materials. BC composites with multiwalled carbon
Naturally, the bone is composed of a collagen matrix nanotubes (MWCNTs) were synthesized by dipping a
reinforced with hydroxyapatite (HAp). The bone regen- BC pellicle in an aqueous MWCNT dispersion contain-
eration through healing in case of some severe damage ing a surfactant [68]. The electrical conductivity of the
is often a very difficult process and, thus, bone transplant BC pellicles containing well-dispersed and embedded
or substitute is required. The comparable features of BC MWCNTs was found to be approximately 1.4 × 10-1 S/cm.
with cartilage open new gateways for the development of Initially, these composites presented a relatively low
BC-based grafts for damaged bone and cartilage. BC has optical transparency that was later improved by
served as a useful scaffold for the regeneration of bone incorporating an aqueous silk fibroin solution into BC
and cartilage tissues owing to its biocompatibility, high membranes. The resultant composite films possess good
tensile strength, fine fibril network, high crystallinity, and optical transparency with a transmittance of 70.3% at
moldability into three-dimensional structures (Zimmer- 550  nm and electrical conductivity of 2.1  ×  10-3  S/cm.
mann et al., 2011). Moreover, it can support the growth In another recent study, GNPs were incorporated into
of several types of cells such as endothelial cells, smooth pristine BC membranes to impart electrical conductivity.
muscle cells, and chondrocytes and does not cause any BC membrane with 8.7  wt% GNPs showed electrical
toxic effect to these cells. A study of BC as a cartilage conductivity of 4.5 S/cm [70].
substitute showed that it surpassed alginate and plastic BC composites with PANi, a highly conducting poly-
in supporting chondrocyte migration and proliferation mer, have been extensively investigated [63–70]. Hu
[60]. Another study showed the development of BC com- et al. reported the in situ synthesis of PANi in the BC
posite with poly(dimethylacrylamide) in the form of a matrix by polymerization of aniline in the presence of
double network gel and concluded that it could potentially ammonium persulfate as an oxidant [67]. The obtained
be used as a cartilage substitute [61]. However, a major BC-PANi nanocomposites showed excellent electrical
limitation associated with BC is that nanofibrils form a conductivity of 5.5  ×  10-2  S/cm and good mechanical
dense mesh that can limit cell infiltration [62]. This issue properties [67]. Interfacial polymerization led to improved
was resolved through the introduction of pores into BC electrical conductivity of PANi/BC composites and the
using porogens [39]. electrical conductivity was raised to 3.8  ×  10-1  S/cm
[71]. The BC conductive composite films combine the
5.3  A
 pplications of BC and BC composites electronic characteristics of conducting polymers and
in electro-conducting fields nanomaterials with the excellent mechanical properties
of the BC matrix. These can be used in optoelectronics,
BC has been investigated for the preparation of conduct- including flexible electrodes, flexible displays, and other
ing composites for application in electrical devices, elec- electronic devices (Fig. 4).
tronic papers, and display devices [63–67]. Some groups
have reported BC conducting composites with conduct- 5.3.2  Optically transparent films
ing nanomaterials such as CNTs [68], graphene [69], and Optically transparent BC has been coated with ITO and
graphite nanoplatelets [70]. However, the first BC con- applied as flexible substrate to replace ITO-glass in opto-
ducting polymer composite was prepared by the in situ electronic devices such as organic light emitting diodes
oxidative polymerization of pyrrole (Py) on a BC polymer (OLEDs) [72]. However, the BC membrane only transmits
matrix and a conductance of 1 S/cm was achieved [63]. 40% light at 550  nm. Thus, many researchers devoted
BC conducting composites with polyan PANi have also their time to improve the optical transparency of BC.
been synthesized by the in situ polymerization of ANi in Optical transparency of BC has been greatly enhanced
the presence of (NH4)2S2O4 and iron III chloride (FeCl3) as through various chemical modifications for optoelectronic
the oxidizing agent [63–66]. The BC-PANi showed good applications. BC nanofibers were acetylated to enhance
conducting properties, was suggested for applications the properties of optically transparent composites of
in biosensors, flexible electronics, and work as platform acrylic resin. Acetylation decreased the refractive index
substrates to evaluate the effect of electrical signals on of cellulose and the regular transmittance of composites
cell activity and to guide enviable cell function for tissue (63% BC nanofibers) was improved [73]. Foldable and
engineering applications. Herein, we review the potential ultralow-coefficient of thermal expansion (CTE) (4 ppm/K)
applications of functional BC nanocomposites with a spe- transparent BC nanocomposites have been prepared with
cial focus on optoelectronics, biosensors, photocatalytic, acrylic resin. This BC nanocomposite exhibited a high
and magnetically active membranes. optical transparency with a regular transmittance at a
wavelength of 600 nm of 81.3%. The substrates reinforced
5.3.1  Electro-conductive films with this unique assembly of cellulose nanofibers have
Static cultures produce BC in the form of films, which a minimum bending radius; they can be folded or bent
are non-conductive in nature. The conducting feature without damage. These nanocomposites are expected to
can be introduced in BC by combining it with conduct- shift the electronics display industry from the traditional

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batch process to the much anticipated, more cost-effec- water absorption [77]. Besides offering protection against
tive continuous roll-to-roll manufacturing process [74]. water absorption, the SiO layer additionally provides
Optically transparent BC/polycaprolactone (PCL) nano- smoothness to the surface. Together, the use of SiO and
composites have been prepared by impregnation of PCL ferrofluid solution can reduce the BC surface smoothness
acetone solution into dried BC membranes. The optical to 5 nm [78].
transparency of the BC/PCL membrane is increased in BC composites in various composition were prepared
comparison with pristine BC. The good transparency of with polyurethane (PU) based resin. After fabrication,
the BC/PCL was attributed to the PCL nano-sized spheru- these composites were applied as substrate for flexible
lites, which are smaller than the wavelength of visible OLED displays [76]. The composite illustrated very high
light and practically free of light scattering. The novel BC/ visible light transmittance reaching up to 80%. Along with
PCL membrane could be used as a substrate for prepara- high transparency, these compounds exhibited much
tion of fully biocompatible flexible display devices [75]. higher thermal stability (up to 150ºC). Once fabricated on
Synthesis of BC and polyurethane (PU)-based nanocom- substrate, the OLED presented a maximum current effi-
posites have been reported and applied as a substrate ciency of 0.085 cd/A and power efficiency of 0.021 lm/W
for flexible OLED display devices. The visible light trans- at 200 cd/m2. This study suggested that BC nanocompos-
mittance of the nanocomposite film was 80%. The nano- ite could be an astounding material as substrate for the
composites showed thermal stability up to 150ºC, while future development of flexible OLED displays.
their dimensional stability in terms of CTE was less than
20 ppm/K. The OLED, fabricated on the substrate through 5.3.4  Sensors
the thermal evaporation technique, presented the highest Its chemical structure (presence of hydroxyl groups),
current efficiency of 0.085 cd/A and power efficiency of physical appearance (porous geometry with high surface
0.021 lm/W at 200 cd/m2, while retaining its flexible fea- area) and physiology (extensive absorption capabilities)
ture. The authors concluded that BC/PU nanocomposites make BC an ideal material to be used as a moisturizer
are promising materials for the development of substrate or gas sensor. Combination with the QCM system, BC
for flexible OLED display devices [76]. membrane coating could depict a perfect view to be used
Besides BC, plant cellulose has also been utilized in designing remarkably sensitive humidity and gas sen-
for the synthesis of transparent membranes for applica- sors. Hu et al. reported the fabrication of a very stable and
tion in different fields, including optoelectronics. Highly sensitive humidity sensor composed of QCM coated BC
transparent conductive networks have been fabricated films [79]. It was observed that the sensors possessed fine
on a cellulose nanopaper. Uniform coating of the conduc- sensing features and doubled in magnitude with increas-
tive nanomaterials such as silver nanowires (AgNWs) and ing (5–97%) relative humidity (RH). Besides, the Log(f)
CNT was achieved by simple filtration of their aqueous also illustrated good linearity (20–97% RH) and the sensor
dispersion through the cellulose nanopaper, which acts possessed a good reversible behavior and lasting stabil-
both as a filter and as a transparent flexible substrate. The ity. The gas sensitivity of BC membranes could be further
as-prepared AgNW networks on the nanopaper present enhanced by introducing alternate detective components
a sheet resistance of 12 Ω sq-1 with an optical transpar- to BC. In a study, Hu and coworker developed formalde-
ency of 88%. These results indicated that the ‘filtration hyde sensors based on PEI/BC membranes coated QCM
coating’ provides uniformly connected conductive net- [80]. PEI was added as an additional detective material
works because of drainage in the perpendicular direction to reinforce the interaction of formaldehyde molecules
through paper nanopores. Furthermore, the conductive and sensing materials. Test conducted with 1–100 ppm
networks strongly adhered to the nanopaper substrate of formaldehyde illustrated that the sensors exhibited a
and provided foldability with negligible changes in elec- high sensitivity and selectively together with a good lin-
trical conductivity. These optically transparent compos- earity. This strategy is not limited to a particular detective
ites of BC and cellulose are expected to lead the way to material or gases, but can be widely used with different
a wider use of different optically transparent polymers detective materials and for detecting different gases. BC
in optoelectronic devices such as substrates for flexible composites with gold nanoparticles (BC-Au) have been
displays. used for enzyme immobilization and glucose biosensor
fabrication [56, 81]. A biosensor composed of horseradish
5.3.3  Flexible displays peroxidase (HRP)/Au-BC nanocomposite displayed out-
BC has been used as a substrate in the development of standing results, including a wider linear range, narrow
several flexible displays. The major inevitable adjust- detection limits, and quick response toward hydrogen
ments required in BC are surface smoothness and control- peroxide, suggesting that Au-BC nanocomposite could
lable hygroscopicity prior to its use in the fabrication of be a suitable matrix for enzyme immobilization [81].
OLEDs. Ummartyotin et al. suggested the deposition of
SiO thin films through plasma enhanced chemical vapor
deposition that can act as a transparent barrier against

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5.3.5  Magnetically responsive films BC films with hydrophobic and lipophobic surfaces
BC, which is inherently a non-magnetic biopolymer, and magnetic properties can be used in electronic actua-
was rendered magnetic by the infiltration of various tors, for information storage, in magnetographic printing,
nanomaterials for electromagnetic applications (Fig.  5). and in electromagnetic shielding coating. Fluorination
Magnetically responsive BC sheets have been prepared of the magnetic Fe3O4/BC membrane resulted in sur-
with magnetite (Fe3O4) nanoparticles by using an in situ face modification from amphiphilic to amphiphobic and
co-precipitation method (Fig. 5). The saturation magneti- showed the highest water contact angle (WCA) of 130º.
zation of the magnetic bacterial cellulose sheets ranged These superparamagnetic membranes can be applied
from 1.92 to 26.20 emu/g at 300 K and ranged from 2.96 in electronic actuators [86]. High particle loading in the
to 28.10 emu/g at 100 K [82]. BC flexible magnetic sheets BC magnetic nanocomposite films resulted in the trans-
have been prepared by in situ synthesis of the Fe3O4 nan- formation from a highly porous and flexible, magnetically
oparticles coated with PEG. These uniform nanocompos- actuating aerogel to a solid and stiff magnetic nanopa-
ites exhibited a saturation magnetization of 40.58 emu/g. per [87]. The precipitation of ferromagnetic cobalt ferrite
Additionally, the sheets exhibited striking flexibility and nanoparticles on BC resulted in dry, lightweight, 98%
mechanical properties [83]. Flexible magnetic BC mem- porous and flexible membranes that can be actuated by
branes have also been prepared by impregnation of the a small household magnet. Owing to their flexibility and
never dried BC pellicles with ferric chloride, followed by high porosity, these aerogels are expected to be used in
reduction with sodium bisulfite and alkaline treatment microfluidics devices and as electronic actuators [87].
for magnetite precipitation. The magnetite nanoparti-
cles in the BC pellicles presented a super paramagnetic
behavior with a saturation magnetization in the range of 6  Concluding remarks and future prospects
60  emu/g and coercive force around 15  Oe. This super
paramagnetic property is of great interest for applica- Recently, research interest in BC has tremendously
tion in nonlinear optics, clinical applications as contrast increased. BC impressive applications, synthetic routes,
agents for magnetic resonance imaging, hyperthermia market demand, economic feasibility, deficiencies, and
and cell separation, and sensors [84]. BC has also been composites synthetic strategies are the diverse factors
made magnetic by the infiltration of Ni-nanoparticles that contribute to the expansion of the BC research area.
via a simple aqueous phase salt reduction method. The Currently, the focus is mainly shifting towards the practi-
resulting hydrogel exhibited different magnetic behav- cal applications of BC and BC composites, in develop-
iors due to two distinct size distributions varying from ing artificial organs, conducting materials, and display
3.2 nm to 140 nm for the Ni nanoparticles. The dominant devices using BC as a substrate material.
interparticle interactions between the smaller nano-sized The structural modification (specifically chemical) of
particles resulted in a spin glass-like behavior, while the BC to enhance the interaction with the living body is
small fraction of larger particles exhibited a ferromagnetic among the possible future strategies that will exceedingly
response with a coercivity varying between 60  G and boost the application of BC. This can not only provide an
110 G [85]. insight for developing biomedical devices, but can also

Figure 5.  (A) Schematic illustration of


the synthesis process for the magneti-
cally responsive BC films, (B) illustration
of response by magnetically actuated
BC films to the applied magnetic field.
(C) SEM image of freeze dried magnetic
aerogel with cobalt ferride nanaoparti-
cles. (D) Aerogel actuation with magnet,
water absorption and recovery. Figure
modified from Zheng et al., 2013 [83];
Olsson et al., 2010 [87].

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enhance the attachment of biological molecules (prote-


ins, enzymes, and drugs) to be used in medical applica- Mazhar Ul-Islam obtained his M.S.
tions. Besides, by enhancing the attachment capabilities degree in Organic Chemistry from the
through chemical modifications, numerous materials of Institute of Chemical Sciences Univer-
pharmaceutical nature can be utilized in combination sity of Peshawar, Pakistan in 2006. In
with BC for specific applications. 2009 he joined the lab of Biochemical
Among optoelectronic applications, the major hurdle Engineering, Department of Chemical
is the non-conductivity and lower transparency level of Engineering at Kyungpook National
BC. However, chemical modifications can also help in University and completed his Ph.D.
this regard. BC acetylation can result in a much more in 2012. He worked as post doctorate
transparent film that could prove vital in the development fellow and contract professor for two years in the same institute. Cur-
of electronic devices. rently he is working as Assistant professor in department of chemical
The currently established composite synthesis stra- engineering, Dhofar University, Salalah, Oman. His research expertise
tegies are still facing hurdles in combining several vital is mainly in synthesis of nanobiopolymeric composite materials for
materials homogenously with the BC matrix. In this case, biomedical applications.
the recent approach of BC dissolution and regener­ation
can be proved effective if some easy BC dissolution
methods are developed. The success in attaining homo-
genous BC composites can lead towards the future deve-
lopment of electronic papers, displays, LEDs, and various Joong Kon Park is a professor at the
optoelectronic devices. Department of Chemical Engineer-
ing of Kyungpook National Univer-
sity (South Korea). He received a B.S.
This research was supported by the Basic Science degree (Seoul National University,
Research Program through the National Research Founda- Korea), M.S. and Ph.D. (KAIST, Korea)
tion (NRF) of Korea, funded by the Ministry of Education, all in chemical engineering and was a
Science and Technology (NRF-2014-R1A1A2055756). postdoctoral fellow at the University
Additionally, it was supported by the BK21 plus (2014- of Michigan (USA). He served as the
2019) Korea, (21A.2013-1800001). vice president of the Korean Society of Biotechnology and Bioengineer-
ing, and currently works as the editor-in-chief of the Korean Journal of
The authors declare no financial or commercial conflict Chemical Engineering. His research interests include biological sepa-
of interest. ration and purification, biofuels, biopolymers, and nano-biopolymer
composite materials.

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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 1861


Cover illustration
This special issue, in collaboration with the Asian Federation of Biotechnology and edited
by Professors Yoon-Mo Koo and Penjit Srinophakun , covers advances in bioprocess
­engineering. Several articles in this issue discuss different aspects of lignocellulose-based
biorefining. Miscanthus (shown on the cover) is one example of a plant whose lignocellu-
losic ­biomass can be used for bioethanol production. © M. Schuppich, Fotolia.com

Biotechnology Journal – list of articles published in the December 2015 issue.

Editorial Review
Bioprocess beyond the large scale production Aggregating tags for column-free protein purification
Yoon-Mo Koo and Penjit Srinophakun Zhanglin Lin, Qing Zhao, Lei Xing, Bihong Zhou and
http://dx.doi.org/10.1002/biot.201500618 Xu Wang
http://dx.doi.org/10.1002/biot.201500299
Editorial
Biotechnology Journal 10 year Anniversary – Research Article
Thank you for your continued support Fatty acid hydration activity of a recombinant Escherichia coli-
Jing Zhu based biocatalyst is improved through targeting the oleate
http://dx.doi.org/10.1002/biot.201500624 hydratase into the periplasm
Sang-Min Jung, Joo-Hyun Seo, Jung-Hoo Lee,
BiotecVisions Jin-Byung Park and Jin-Ho Seo
Beyond Asian Biotechnology: Collaboration between Asia http://dx.doi.org/10.1002/biot.201500141
and Europe
Hyun Jung Kim Research Article
http://dx.doi.org/10.1002/biot.201500623 Understanding β-mannanase from Streptomyces sp. CS147 and
its potential application in lignocellulose based biorefining
BiotecVisions Hah Y. Yoo, G. C. Pradeep, Soo K. Lee, Don H. Park,
European’s Biochemical Engineering to face the megatrends Seung S. Cho, Yun H. Choi, Jin C. Yoo and Seung W. Kim
and associated challenges beyond 2020 http://dx.doi.org/10.1002/biot.201500150
Guilherme Ferreira
http://dx.doi.org/10.1002/biot.201500627 Research Article
Improved growth and ethanol fermentation of Saccharomyces
Review cerevisiae in the presence of acetic acid by overexpression
Bacterial cellulose composites: Synthetic strategies and of SET5 and PPR1
multiple applications in bio-medical and electro-conductive Ming-Ming Zhang, Xin-Qing Zhao, Cheng Cheng and
fields Feng-Wu Bai
Mazhar Ul-Islam, Shaukat Khan, Muhammad Wajid Ullah http://dx.doi.org/10.1002/biot.201500508
and Joong Kon Park
http://dx.doi.org/10.1002/biot.201500106 Research Article
Enhanced hydrolysis of lignocellulosic biomass: Bi-functional
Review enzyme complexes expressed in Pichia pastoris improve
Incorporating unnatural amino acids to engineer biocatalysts bioethanol production from Miscanthus sinensis
for industrial bioprocess applications Sang Kyu Shin, Jeong Eun Hyeon, Young In Kim, Dea Hee
Yuvaraj Ravikumar, Saravanan Prabhu Nadarajan, Kang, Seung Wook Kim, Chulhwan Park and Sung Ok Han
Tae Hyeon Yoo, Chong-Soon Lee and Hyungdon Yun http://dx.doi.org/10.1002/biot.201500081
http://dx.doi.org/10.1002/biot.201500153

© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.biotechnology-journal.com


Research Article Research Article
Phenolic compounds: Strong inhibitors derived from Dual utilization of NADPH and NADH cofactors enhances
lignocellulosic hydrolysate for 2,3-butanediol production xylitol production in engineered Saccharomyces cerevisiae
by Enterobacter aerogenes Jung-Hyun Jo, Sun-Young Oh, Hyeun-Soo Lee,
Sang Jun Lee, Ju Hun Lee, Xiaoguang Yang, Sung Bong Kim, Yong-Cheol Park and Jin-Ho Seo
Ja Hyun Lee, Hah Young Yoo, Chulhwan Park and http://dx.doi.org/10.1002/biot.201500068
Seung Wook Kim
http://dx.doi.org/10.1002/biot.201500090 Biotech Method
Phosphonium alkyl PEG sulfate ionic liquids as coating
Research Article materials for activation of Burkholderia cepacia lipase
Salt tolerant chromatography provides salt tolerance Yui Matsubara, Shiho Kadotani, Takashi Nishihara,
and a better selectivity for protein monomer separations Yoshichika Hikino, Yukinobu Fukaya, Toshiki Nokami and
Noriko Yoshimoto, Daisuke Itoh, Yu Isakari, Ales Podgornik Toshiyuki Itoh
and Shuichi Yamamoto http://dx.doi.org/10.1002/biot.201500413
http://dx.doi.org/10.1002/biot.201400550

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