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com
ScienceDirect
Hierarchical structure of bacterial-derived cellulose and
its impact on biomedical applications
Elizabeth M van Zyl and Jeannine M Coburn
Since its discovery in 1886, bacterial-derived cellulose has
become a highly researched biomaterial due to its unique
structural properties. These properties include fibrous structure
and robust stability through immense hydrogen bonding. The
hydrogen bonding and resulting hierarchical structure from
polymer chains to fibers can be controlled by altering bacteria
culture conditions. Low temperature and static culture of
cellulose producing microbes lead to the formation of a less
stable cellulose amorph, while agitated culture, increased
culture duration, alternative carbon sources, and the addition of
additives lead to the formation of cellulose with an increased
thermal stability. The unique structure of bacterial-derived
cellulose allows it to be used for living cell-based sensors,
vehicles for targeted cell delivery, and material for wound
dressings. This review discusses the recent findings on
bacterial-derived cellulose and cellulose synthase as a frame
for advanced functional biomaterials.
Address
Department of Biomedical Engineering, Worcester Polytechnic Institute,
Worcester, MA, United States
Corresponding author: Coburn, Jeannine M (jmcoburn@wpi.edu)
Current Opinion in Chemical Engineering 2019, 24:122–130
This review comes from a themed issue on Materials engineering
Edited by Jeannine M Coburn and David L Kaplan
For a complete overview see the Issue and the Editorial
Available online 17th May 2019
https://doi.org/10.1016/j.coche.2019.04.005
2211-3398/ã 2019 The Authors. Published by Elsevier Ltd. This is an
open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
Cellulose is produced by plants, bacteria (acetobacter,
acanthamoeba, and achromobacter spp.), algae (valonia,
chaetamorpha spp.) and fungi [3–5]. In plants, cellulose is
the structural component of plant cell walls and the fibers of
cotton [6]. Owing to its relative abundance and inexpensive
nature, cellulose has become a prominent material for
biomaterial research applications. Plant cellulose, however,
is synthesized in a matrix of contaminant molecules,
namely hemicelluloses, lignin, and pectin [7]. The percent-
age of cellulose found in plant materials ranges from 50% to
90%, necessitating purification through time consuming
Current Opinion in Chemical Engineering 2019, 24:122–130
and costly chemical processing that results in low cellulose
yields [6]. The additional cost and production steps
required to purify plant-based cellulose limit its utilization
in biomedical applications [7]. Alternatively, bacterial-
derived cellulose (BC) has been identified as a high-quality
pure cellulose, synthesized, and organized as twisted rib-
bons of micro-fibril bundles, requiring minimal purification
processing [10]. BC was first identified in 1886 by A.J.
Brown who observed ‘a jelly like translucent mass on the
surface of the culture fluid; this growth rapidly increases
until the whole surface of the liquid is covered with a
gelatinous membrane’ [11]. After performing composition
analysis, Brown described the membrane as cellulose that
was synthesized by a strain of bacteria that he named
Bacterium xylinum [11]. A rod-shaped aerobic Gram-nega-
tive bacteria, B. xylinum was later renamed Acetobacter
xylinum, thenGluconacetobacter xylinus, and is currently clas-
sified as Komagataeibacter xylinus [12,13]. Since Brown’s
discovery, BC has been extensively studied due to its ease
of fabrication, biocompatibility, high yield strength, and
water retention properties [14]. Realizing that there are
other cellulose-producing microbes, this review will focus
primarily on BC from Komagataeibacter ssp. as they are the
predominantly studied strains for biomedical applications
due to their high BC yield, purity, and crystallinity [15].
Bacterial-derived cellulose synthesis
The culture medium for cellulose-producing microbial
strains consists of a nitrogen and a carbon source [16]. The
carbon source is typically glucose but may also be other
carbon sources, such as sucrose, fructose, mannitol, molas-
ses, and fruit juice [17

,18,19]. The glucose is metabo-
lized through the pentose-phosphate cycle or the Krebs
cycle, depending on the physiological state of the culture
[20]. Cellulose production is regulated by oxygen supply
and is independent of carbon source concentration [21].
There are four key enzymatic steps in the synthesis of BC
as outlined in Figure 1a [20]. First, the glucose is phos-
phorylated by glucokinase forming glucose-6-phosphate
(Glc-6-P). Glc-6-P is isomerized to glucose-1-phosphate
(Glc-1-P) by phosphoglucomutase. Then uridine
diphosphoglucose (UDP-Glc) is synthesized by UDP-
Glc-phyrophosphorylate (UGPase), which can be utilized
by cellulose synthase for cellulose synthesis [1,22,23].
The cellulose synthase enzymatic reaction occurs via a
protein complex composed of two main bacterial-derived
cellulose synthase (Bcs) subunits: BcsA, an inner mem-
brane protein that is the first gene in the operon encoded
by bcsA; BcsB, a periplasmic protein that is anchored to
the inner wall and is the binding protein for c-di-GMP
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 Structure and synthesis of bacterial-derived cellulose van Zyl and Coburn 123

Figure 1

Protofibril Cellulose
Chains
b

a
C-di-GMP
activation

Glucose Units cellulose

glucokinase phosphoglucomutase UGPase
synthase

Glucose Glc-6-P Glc-1-P UDPGIc

Microfibril Cellulose
cytoplasm
Chains 1μm
periplasm
Bacteria
Culture
Amorphous
Medium
d c c
e Region c

β α a β α
Crystalline Region
b
γ γ
a Simple b
Triclinic Monoclinic
a≠b≠c a≠b≠c
Cellobiose Repeat Unit
α ≠ β ≠ γ ≠ 90° α = γ = 90° ≠ β

Current Opinion in Chemical Engineering

(a) Four key enzymatic steps that allow for cellulose production adapted from Refs. [1,2], (b) scanning electron microscopy (SEM) of BC
membrane showing the nanofibrous structure, (c) differences in inter and intra molecular bonds in cellulose Ia (red bonds), cellulose Ib (green
bonds), and the bonds that are in both amorphs (blue bonds) adapted from Refs. [8,9], (d) triclinic crystal structure of cellulose Ia, (e) monoclinic
crystal structure of cellulose Ib.

during cellulose synthase activation [24]. BcsB is required between 30–50 nm in diameter as shown in Figure 1b
for the catalytic activity of BcsA. These two enzymes [33,34]. The presence of several hydroxyl groups with
form a complex that is essential for cellulose synthesis similar reactivity and significant hydrogen bonding allows
[24,25,26
]. Two other subunits exist: BcsC, believed to for the formation of insoluble cellulose polysaccharide
be a transmembrane pore that allows for microfibril for- chains [30,35]. Inter-chain and intra-chain hydrogen bonds
mation by transporting glucan chains outside of the allow for the formation of stiffened polysaccharide chains
bacterium, and BcsD, a soluble protein present in the held together by weak van der Waals forces and form
periplasmic space that plays a role in the crystallization of layered sheets of cellulose [8]. These cellulose sheets
cellulose [26
,27,28,29
]. Purified BcsA and BcsB proteins are reinforced by dispersion forces between the stacked
are sufficient to catalyze cellulose synthesis; however, heterocyclic monomers rings [20].
mutations in BcsC and BcsD have been shown to greatly
decrease the yield of synthesized cellulose [30]. Recently, Bacteria can produce both the cellulose I and cellulose II
the cellulose synthesis and membrane translocation have structure, or parallel and anti-parallel cellulose chains,
been visualized by in crystallo methods providing signifi- respectively; though cellulose I is predominantly formed
cant understanding of the entire process that may be [36]. The cellulose II structure is primarily observed
utilized in the future for novel polysaccharide synthesis when cellulose I is mercerized, or alkali treated to break
by bacterium [31
]. bundled fibers down into microfibrils, then reassembled
which produces a more thermodynamically stable struc-
Bacterial-derived cellulose polymer and ture [20,37,38]. Cellulose I is further broken down into
membrane structure two different amorph structures: cellulose Ia and cellu-
Cellulose is a polysaccharide composed of b(1 ! 4) linked lose Ib. Cellulose Ia is a meta-stable phase of cellulose I
D-glucose monomer units present as pyranose rings, a cyclic with a triclinic unit cell (Figure 1d), while cellulose Ib is a
isomer that has five carbons and one oxygen in a ring of six stable phase of cellulose with a two chain monoclinic unit
atoms (Figure 1c). Cellulose synthesis occurs inside the cell (Figure 1e) [39]. When cellulose fibers are extruded
bacterium and is extruded as ribbon-like microfibers from the bacterium they orient randomly so the overall
between the outer and cytoplasmic membranes at a rate cellulose structure swaps and alternates between the
of 2 mm/min [32,33]. These 1.5 nm wide microfibers have different amorph phases of cellulose [8]. Cellulose Ia
the correct conformation that allows for bacterium-directed exhibits intra-molecular hydrogen bonding between
self-assembly into bundles of microfibrils that range O3–H ! O5’ and inter-molecular hydrogen bonding

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124 Materials engineering: bio-derived/bio-inspired materials
between O6–H ! O3’, while cellulose Ib exhibits intra-
molecular and inter-molecular hydrogen bonding
between O6’ ! H–O2’ as shown in Figure 1c [8]. Using
high resolution solid-state carbon-13 nuclear magnetic
resonance (13C NMR) to study the structure of cellulose
Ia and cellulose Ib, Vanderhart et al. showed that cellu-
lose Ia has singlets, or paired electrons, at the C-1 and
C-6, and a closely spaced doublet, or an unpaired electron,
at C-4 while cellulose Ib has doublets at C-1, C-4, and C-6
[40,41]. These NMR observations, along with the find-
ings that cellulose Ib is formed irreversibly from cellulose
Ia, which requires energy input into the system, indicates
that cellulose Ib is more thermodynamically stable than
cellulose Ia [8,42]. BC has the highest concentration of
cellulose Ia polymorph at 70%. Because cellulose Ia is
meta-stable, BC is less thermodynamically stable than
other types of cellulose that have an increased percentage
of cellulose Ib [43,44].
Culture conditions and cellulose structure
K. xylinus may be cultured under static or dynamic cul-
turing conditions that result in the formation of a variety
of material structures. Under static culturing, flat cellu-
lose pellicles form at the air-liquid interface of the culture
system as shown in Figure 2a. Since the cellulose forms at
the air-liquid interface under static conditions, a variety of
form factors can be fabricated based on oxygen exposure
including hollow tubes and transparent soft cellulose
[45,46]. Alternatively, in agitated culturing aggregated
cellulose shapes form as shown in Figure 2b; the shape
of the cellulose material formed varies depending on the
bacteria strain [47,48

]. Toyosaki et al. determined that
some strains of Acetobacter were more suited for agitated
culture and consistently produced more stable cellulose
than other strains [47]. The increased shear stress in
agitated culture increases the solid material dispersion
Figure 2
(a)
(a) Cellulose membrane or pellicle, (b) cellulose aggregates.
Current Opinion in Chemical Engineering 2019, 24:122–130
in the culture and has been seen to increase both bacteria
growth and cellulose synthesis rates [47,49]. However,
mutations can occur in some strains that leads to non-
cellulose producing cultures [47]. Inoculum volume, or
the volume of microbe suspension used to propagate into
a larger volume culture, also impacts the cellulose spheres
formed. Hu et al. showed that with increased inoculum
volume there is decreased space between individual
bacterium, decreasing the number of cellulose spheres
formed as adjacent bacteria synthesis aggregates fuse
together [50].
Tanskul et al. isolated a strain of cellulose-producing
bacteria, Rhodococcus sp. MI 2, from ripe fruit and vege-
tables [51]. The bacteria were either cultured under static
conditions, in a rotating shaker at 180 rpm, or with a
magnetic stirrer all at 25 C. Under static conditions the
cellulose produced was three-dimensional intercon-
nected net-like structured pellicles. While under rotating
conditions the cellulose produced was tapioca-pearls/
irregular aggregate shapes. Under stirring conditions,
the cellulose produced was feather like shapes and aggre-
gates [51]. The altered culturing conditions not only
affected the macro-structure of the cellulose materials,
it also changed the inter-molecular and intra-molecular
structure of BC. Using SEM, Watanabe et al. showed that
both static and agitated culture produce cellulose that
have similar fibrous structures [52]. However, X-ray dif-
fractometry (XRD) showed that agitated culture resulted
in cellulose with smaller crystal sizes, and a lower degree
of polymerization, crystallinity, and cellulose Ia percent-
age [52]. A correlation between crystal size and percent of
cellulose Ia formed was identified that suggests agitated
culture interferes with the crystallization process of BC,
resulting in smaller crystallite formation and thus
preferentially inducing the formation of cellulose
(b)
Current Opinion in Chemical Engineering
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 Structure and synthesis of bacterial-derived cellulose van Zyl and Coburn 125

Ib [48

,52,53]. This indicates that under agitated culture

Agitated: large irregular shapes

Aggregate diameter: 5–22 mm

Stirred: large irregular shapes

conditions more thermodynamically stable cellulose is

Stirred: feather-like shapes

Strains produced BC with

Aggregate Number: 0–55
produced. In static culture under low culture tempera-

Agitated: small granules

Static: reticular pellicle

Static: reticular pellicle

tures, between 10 C and 36 C, increased cellulose Ia

varying properties
content has been observed [54]. In both static and agi-
tated conditions, structural variations of BC pellicles have

Other result
been observed with different cellulose producing
K. xylinus strains [48

]. Singhsa et al. performed XRD
analysis on cellulose pellicles, produced by five different

–
–
–
–
strains, harvested after seven days of culture. Three of the

Agitated: 10900
five strains produced cellulose with a 20% higher degree

2156.2–2342.2
Static: 14400
of crystallinity and an average of 1 nm larger crystallites
than the other two strains. The difference in crystallite
size indicates that the three strains produced less thermo-

DP
dynamically stable cellulose due to their increased

–
–
–
cellulose Ia content [48

].

Agitated: 41–74%
Static: 55–81%
Agitated: 72%

Agitated: 84%

80.6%–75.7%
A trickling bed reactor was used as an alternative culture

Static: 80%

Static: 89%
Crystallinity
method that allows for the input of fresh medium with
minimal disruption to the culture. Using this fermenta-
tion method, Lu et al. analyzed the thermal decomposi-

–
tion behavior by thermogravimetric analysis (TGA) of

Cellulose Ia content

Agitated: 66–77%
cellulose produced in a trickle bed reactor, static condi-

Static: 73–82%
Agitated: 61%

Agitated: 71%
From 56–72%
tions, or agitated conditions [55]. The static and agitated

Static: 73%

Static: 76%
cellulose samples showed two endothermic peaks while
the trickle bed reactor sample had two exothermic peaks
resulting in cellulose formation with an increased thermal
–

–
–
stability than cellulose formed in static or agitated cul-

10% starter volume

ture. Additionally, Fourier-transform infrared spectros-
1–16% v/v starter
Inoculum volume

copy (FTIR) absorption peaks indicated that the trickle

10% v/v starter

2% v/v starter

5% v/v starter

5% v/v starter
bed reactor resulted in the formation of cellulose with an
increased hydrogen bond associating degree than other
culture methods [55].

–
–
–
Culture duration also effects the thermodynamic stability
A. xylinum subsp. Sucrofermentans BPR2001 [52]

K. xylinus (KY, TISTR, 086, 428, 975, 1011) [48

]

of the BC. Increased culture time increased the number

G. intermedius BC-41(3–15 days of culture) [57]

G. xylinus BRP 2004 (7–21 days of culture) [56]
of microfibril bundles formed due to an increase in
G. xylinus JCM 9730 (ATCC 700178) [50]
Structural differences in BC due to altered culture conditions

hydrogen bonding, resulting in increased cellulose stabil-

ity [56]. Additionally, the FTIR spectra showed increased
A. xylinum NQ5 (ATCC 53582) [53]

hydrogen bond intensity with increased culture time up

until 14 days of culture [56]. Shi et al. found that the
degree of polymerization (DP) of the produced cellulose,
Rhodococcus sp. MI2 [51]

determined by viscometry, was 2,342.2 after three days of

culture but decreased up until nine days of culture,
A. xylinum 998 [51]

resulting in a low of 2,156.2, where the DP then started

A. xylinum [54]
Bacteria strain

to increase again. This suggests that BC may be more

stable after nine days of culture [57]. These studies are
further summarized in Table 1.

Changes in BC yield and marginal changes in structure

Culture temp (36–10 )

have also been observed when using alternative carbon

sources in the culture medium [58]. The cellulose yield,
Agitated culture

when produced using glycerol as a carbon source, was

Culture time

found to be 1.5 times higher than with glucose as the

Variables
Table 1

carbon source [58]. Using XRD, the cellulose produced

with glycerol as a carbon source had a crystallinity index
of 78% versus 88% with glucose as a carbon source [58].

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126 Materials engineering: bio-derived/bio-inspired materials
Another study found that glucose, mannitol, and fructose
resulted in a higher cellulose yield in the first 48 hours of
culture as compared to glycerol and sucrose, but that
glycerol and sucrose resulted in a higher cellulose yield
after 96 hours of culture [59]. 13C-NMR showed no dif-
ference in crystallinity, cellulose Ia, or cellulose Ib, for
cellulose produced on different carbon sources and for
different incubation times. However, SEM images
showed that pellicles formed with glycerol and fructose
carbon sources had a microfibril directionality not seen in
the pellicles grown with other carbon sources [59]. Addi-
tionally, mannitol was found to support high cellulose
yields. TGA of the samples showed that mannitol had a
higher maximum decomposition temperature when com-
pared to sucrose and thus an increased thermal stability.
Increased crystallinity of cellulose produced with manni-
tol as a carbon source is believed to explain the thermal
degradation behavior that was observed [60]. These stud-
ies are further summarized in Table 2. Additionally, Fang
and Catchmark found that the use of galactose as a carbon
source allows for the incorporation of non-cellulosic poly-
saccharides in the cellulosic network which decreased the
crystallinity and crystal size of the cellulose produced
[61]. This incorporation is believed to be through surface
coating or self-aggregation [61]. The production of non-
cellulosic polysaccharides as well as the altered structure
of cellulose produced with alternative sugars as a carbon
source suggests that natural molecular incorporation and
hybrid cellulose formation is possible.
Hybrid cellulose formation is further supported by the
observation that N-acetylglucosamine (GlcNAc) can be
incorporation in the bacterial-synthesized polymer form-
ing lysozyme-susceptible pellicles [62,63]. Yadav et al.
further indicated that GlcNAc uptake and incorporation is
possible through not only innate mechanisms, as indi-
cated by previous studies, but also by genetically
engineering he bacteria. When isolating the gene
Table 2
Structural differences in BC due to altered carbon sources
Bacteria strain Carbon source
G. xylinus (ATCC 10245) [58] Glucose
*Yield calculated in comparison to 1% glucose Fructose
Inositol
Glycerol
G. xylinus (ATCC 53524) [59] Fructose
Glucose
Glycerol
Mannitol
G. xylinus (PTCC 1734) [60] Mannitol
Food-grade Sucrose
Sucrose
Date Syrup
Glucose
*
Yield calculated in comparison to 1% glucose (set to 100% yield).
Current Opinion in Chemical Engineering 2019, 24:122–130
required for metabolisms of GlcNAc, molecular incorpo-
ration of GlcNAc was observed by wild type G. xylinus
[64]. Genetically engineered G. xylinus expressing an
operon from Candida albicans that allows for the produc-
tion of cytoplasmic UDP-GlcNAc monomers results in
the production of hybrid cellulose composed of both
glucose and GlcNAc. XRD determined that the hybrid
cellulose contained both cellulose Ia and cellulose II, a
less crystalline cellulose amorph. Complete degradation
with lysozymes further supported that GlcNAc was incor-
porated [65]. Having genetic control of the BC production
allows for not only the creation of degradable cellulose
but also genetically engineering functionalized cellulose.
Florea et al. functionalized the cellulose pellicles by
engineering expression vectors that allow for fusion of
proteins to short cellulose-binding domains (CBDs) that
tightly bind to cellulose fibers. Binding of CBD super-
folder green fluorescent protein (CBD-sfGFP) extracted
from Escherichia coli, produced a fivefold increase in
cellulose binding than green fluorescent protein (GFP)
alone [66

]. Additionally, functional proteins can also be
bound to CBDs allowing for the development of function-
alized BC-based materials [66

].
Additives and alternative nitrogen sources
As with alternative carbon sources, the nitrogen source
and additives in the culture medium can also influence
the structure of the cellulose formed. Shi et al. studied the
effects of medium formulations on the DP of the cellulose
formed by Gluconacetobacter intermedius BC-41. The DP of
cellulose produced in A9 medium (glucose, yeast, pep-
tone, Na2HPO412H2O, corn syrup, acetic acid, alcohol)
was 22.9% higher than that produced in Schenk and
Hildebrandt (SH) medium (glucose, peptone, yeast,
Na2HPO412H2O, citric acid) [57]. The addition of
2,6-dichlorobenzonitrile, a cellulose synthesis inhibitor,
promoted the production of cellulose II instead of the
more commonly produced cellulose I [36]. Additionally,
Yield Cellulose Ia (%) Crystallinity (%)
*
100% – 88%
95%* – 86%
85%* – 75%
155%* – 78%
1.78 g/L 61% 85%
1.89 g/L 62% 80%
0.82 g/L 60% 80%
2.04 g/L 65% 90%
5.7% – 65.5%
1.3% – –
2.4% – 63.2%
4.7% – –
3.4% – –
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 Structure and synthesis of bacterial-derived cellulose van Zyl and Coburn 127
Table 3
Structural differences in BC due to altered additives and nitrogen sources
Bacteria strain Additive/nitrogen source
G. intermedius BC-41 [57] Schenk Hildebrant (SH) medium –
A9 medium – –
G. xylinus (ATCC 10245, IFO 13693, HS medium
IFO 13772, IFO 13773, HS medium + lignosulfonate
IFO 14815, IFO 15237) [58]
A. xylinum (ATCC 700178) [70] Corn steep liquor with fructose
(control medium)
0.5% Avicel
0.5% CMC
0.5% Sodium alginate
0.2% Agar
the most common carbon source for BC production is
glucose. However, Zhong et al. determined that only
19.05% of initial cultured glucose was incorporated into
cellulose while 40.03% was converted into gluconic acid
byproduct [67]. This increase in gluconic acid negatively
impacts cellulose production due to the decreased pH of
the culture [68]. The addition of lignosulfonate inhibits
gluconic acid formation in the culture allowing for
increased cellulose production with increased crystallin-
ity and decreased amorphous regions [69]. A variety of
alternative additives have been testing in microbial cul-
ture to promote cellulose yield while retaining the
material’s unique properties. Agar, carboxymethylcellu-
lose (CMC), microcrystalline cellulose, and sodium algi-
nate were all individually tested to promote cellulose
production [70]. The addition of CMC resulted the
production of a more thermodynamically stable cellulose
amorph as well as the highest cellulose yield [70]. These
studies are further summarized in Table 3.
Brief applications
BC’s bacterial origin have led to biocompatibility and
immunogenic concerns. However, sterilized BC has been
found to be biocompatible in both in vivo and in vitro
testing [71,72]. For detailed information on the biocom-
patibility analysis of BC, readers may consult references
[9,73–75]. The unique structure and biocompatibility of
BC opens the doors to a wide variety of biomedical
applications. The close-fitting microstructure of BC sup-
ports entrapment of E. coli while allowing for the perme-
ability of analyte molecules. This encapsulated system
allowed for the development of a cell-based living sensor
system that, as a proof of concept, expressed a dual-color
riboswitch causing the E. coli to fluoresce either green or
red in the presence of a target analyte [76]. Bacterial-
derived cellulose has also been researched as a vehicle for
directed cell delivery [77
]. Bacterial cellulose/acrylic acid
hydrogels have been investigated as a wound dressing and
cell carrier for partial-thickness burn wounds [77
]. The
hydrogels allowed for the rapid attachment of cells but
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Yield Cellulose Ia (%) Crystallinity index /% DP
– – 1613.3
– 2301.7
0.114 – 0.3036 g/30 m L 43–44 3.02–3.95 –
0.2178–0.4896 g/30 m L 42–44 3.53–4.0 –
1.25 g/L – 85% –
4.5 g/L – – –
7.25 g/L – 83.3% –
1 g/L – – –
4.5 g/L – – –
also allowed the cells to migrate from the hydrogel into
the wound site [77
]. Another study modified the materi-
al’s chemical composition by crosslinking dextran to the
cellulose. This modification promoted and enhanced cell
proliferation more than unmodified cellulose and may be
a promising hydrogel-based wound dressing [78]. By wet
stretching BC pellicle, alignment of cellulose nanofibers
has been observed, resulting in a highly transparent film
with a tensile strength of roughly 1.0 GPa [79]. The
increase in mechanical strength provides utility for BC
in soft tissue applications such as anterior cruciate
ligament reconstruction [80].
A number of BC composite materials have also been
investigated. Hybrid composite wound dressings com-
prised of BC and a copolymer of 3-hydroxybutyric and
4-hydroxybutyric acids [P(3HB/4HB)] have been shown
to be an effective vehicle for drug delivery in would
dressing applications [81

]. While gelatin/BC composites
have shown potential for guided tissue regeneration
applications and mineralization possibilities [82]. BC
modified with chitosan has been investigated for surgical
mesh, enzyme immobilization, and antimicrobial applica-
tions [72,83,84]. Jia et al. found that BC chitosan compo-
sites resulted in a decrease in material crystallinity and
thermal stability and an increase in antimicrobial proper-
ties [85]. Lysozyme susceptible sutures, composed of
regenerated chitin reinforced with BC nanocrystals, were
found to accelerate would healing [86

]. Additionally,
lysozyme susceptible BC has been shown to provide
hMSCs with an environment that promotes type II
collagen and aggrecan, markers for chondrogenesis [87].
Conclusions
The unique structure and purity of BC, along with the
prospects of increased degradation make it an ideal mate-
rial for increased biomedical research and application.
The hierarchical structure of BC is highly dependent
on culture conditions, such as culture movement, car-
bon/nitrogen sources, and culture additives, which affects
Current Opinion in Chemical Engineering 2019, 24:122–130
128 Materials engineering: bio-derived/bio-inspired materials
structural properties including crystallinity and DP. This
characteristic of BC synthesis allows for the formation of
BC with tunable properties. This along with the forma-
tion of hybrid cellulosic materials that are degradable by
mammalian enzymes will allow for the development of
novel BC-based materials for a wider range of applica-
tions, specifically applications that require material
degradation in vivo. Overall the mechanical and biocom-
patible properties of BC make it an attractive material for
biomedical applications.
Conflict of interest statement
Nothing declared.
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Current Opinion in Chemical Engineering 2019, 24:122–130
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