Appl Microbiol Biotechnol (2011) 91:1277–1286
DOI 10.1007/s00253-011-3432-y
MINI-REVIEW
Bacterial cellulose-based materials and medical devices:
current state and perspectives
Nathan Petersen & Paul Gatenholm
Received: 2 February 2011 / Revised: 9 May 2011 / Accepted: 2 June 2011 / Published online: 9 July 2011
# Springer-Verlag 2011
Abstract Bacterial cellulose (BC) is a unique and promis-
ing material for use as implants and scaffolds in tissue
engineering. It is composed of a pure cellulose nanofiber
mesh spun by bacteria. It is remarkable for its strength and
its ability to be engineered structurally and chemically at
nano-, micro-, and macroscales. Its high water content and
purity make the material biocompatible for multiple
medical applications. Its biocompatibility, mechanical
strength, chemical and morphologic controllability make it
a natural choice for use in the body in biomedical devices
with broader application than has yet been utilized. This
paper reviews the current state of understanding of bacterial
cellulose, known methods for controlling its physical and
chemical structure (e.g., porosity, fiber alignment, etc.),
biomedical applications for which it is currently being used,
or investigated for use, challenges yet to be overcome, and
future possibilities for BC.
N. Petersen
University of Virginia School of Medicine,
PO Box 800233, Charlottesville, VA 22908-0233, USA
P. Gatenholm (*)
Department of Chemical and Biological Engineering,
Chalmers University of Technology,
Kemivägen 4,
SE-412 96 Gothenburg, Sweden
e-mail: paul.gatenholm@chalmers.se
P. Gatenholm
School of Biomedical Engineering and Sciences,
Virginia Tech-Wake Forest University,
Blacksburg, VA 24061, USA
P. Gatenholm
BC Genesis, 2000 Kraft Dr,
Corporate Research Center at Virginia Tech,
Blacksburg, VA 24060, USA
Keywords Bacterial cellulose . Microbial cellulose .
Nanocellulose . Biocompatibility . Biomedical .
Acetobacter xylinum
Introduction
In recent years, natural polymers have gathered wide-
spread interest for use in biomedical materials and
devices for the various benefits each offers over its
synthetic polymer cousins. As materials naturally present
in the living organisms, with properties tailored to meet
specific needs of the organisms in which they reside,
they often carry with them certain native properties of
those respective tissues (Kim et al. 2008). Such natural
polymers as collagen, elastin, alginate, chitosan, starch,
and cellulose are widely present in natural organisms and have
all been investigated for various uses in tissue engineering
(Kim et al. 2008).
Among these, bacterial cellulose (BC) (sometimes referred
to as microbial cellulose or MC) has gained particular
interest more recently. Cellulose’s virtual ubiquity in nature in
organisms ranging from redwoods to plankton attests to its
biological utility, and its usefulness in biomedical and tissue
engineering applications is now becoming apparent as well
(Bodin 2007; Lau et al. 2007).
Plant cellulose has long been used in a variety of
medical applications ranging from cotton for hemostatic
wound dressings to sutures and renal dialysis membranes
(Hoenich 2006). Plant-based cellulose, though useful for
many applications, is not produced in a pure state. The
presence of lignin, hemicelluloses, and other molecules
requires intensive processes to prepare it for medical use. In
contrast, BC, while identical to plant cellulose in chemical
structure, is produced without contaminant molecules.
1278
Cellulose is produced by species of various genera of
bacteria including Acetobacter (renamed Gluconacetobacter),
Acanthamoeba, Achromobacter, Zoogloea, and others, the
most widely studied being Acetobacter, particularly the
species Acetobacter xylinum (Jung et al. 2007; Falcao et
al. 2008a; Ross et al. 1991; Klemm et al. 2001). BC’s high
tensile strength (Hutchens et al. 2006), purity, and biocom-
patibility (Helenius et al. 2006; Klemm et al. 2001) have all
contributed to growing interest in this natural polymer.
BC has a unique nanofibril network morphology which
mimics, to some extent, properties of the extracellular
matrix. Due to the hydrophilic nature of cellulose, the
material binds strongly water and behaves, thus, as a
hydrogel. In contrast to many synthetic polymers, BC is
biocompatible and exhibits tissue integration. It has
unique mechanical properties which are similar to soft tissues.
The nanofibrils can guide cells, and BC is therefore very
attractive as a scaffold for tissue engineering.
BC mimics extracellular matrix
The nanofibril architecture of BC bears certain felicitous
similarities with extracellular matrix components, particularly
with collagen. Both cellulose and collagen are often the
primary mechanical support structures for their respective
tissues of origin. Collagen and BC fibers are similar in size,
both approximately 100 nm in diameter (Bäckdahl et al. 2006,
Fig. 1). Like bacterial cellulose, collagen is assembled
extracellularly from precursor molecules into polymer
chains. Some researchers have even investigated BC as a
“collagen-like” material (Kramer et al. 2006). In biomedical
applications, BC is being investigated for some of the same
uses as collagen, such as cell matrices. Yet, BC may have the
advantage over collagen in immunologic nonreactivity.
Proteins are particularly recognizable to the immune system
and prone to triggering immunologic responses, whereas BC
has the distinct advantage as a polysaccharide of being less
immune-stimulatory. A recent study using the dorsal
skinfold chamber model showed good tissue integration
Fig. 1 SEM images of umbilical
cord collagen (a) and bacterial
cellulose (b) showing structural
similarity. Prepared by Karnov-
sky fixation. Bar=2 μm in a and
b. Used with permission from
Bäckdahl et al. 2006
Appl Microbiol Biotechnol (2011) 91:1277–1286
and production of extracellular matrix around BC implant
(Esguerra et al. 2010). One of the concerns when using
materials produced in microbial processes is potential
presence of endotoxins which might be residues from
bacterial cell wall. The endotoxin levels in the water incubated
with the porous cellulose scaffold were determined to be less
than 0.1 endotoxin units (EU)/ml (Bodin et al. 2010). The
limit for endotoxin set by the Food and Drug Adminis-
tration (FDA) for medical devices is 0.5 EU/ml. BC
material has recently received FDA approval for use by Xylos
Corporation ® as Xylos ® Vessel Guard, Xylos ® Porous
Surgical Mesh, MTA ™ Surgical Sheet, and Securian ™
Tissue Reinforcement Matrix.
In a recent in vitro study of blood compatibility of
vascular grafts made of BC in comparison with conven-
tionally used graft materials, the complement activation
parameters (sC3a and sC5b-9) were much higher for BC
(Fink et al. 2011). The systematic study of the effect of BC
on complement activation and immune response should be
carried out in the future since there is no correlation
between complement activation observation and overall
immune response for BC materials.
Biocompatibility
The biocompatibility of cellulose-based materials (e.g.,
cellulose sponge) has been investigated and demonstrated
successfully in the past (Martson et al. 1999; Miyamoto
et al. 1989; Martson et al. 1998a, b; Izeboud 1992;
Bowry and Rintelen 1998; Fig. 1). BC biocompatibility
studies performed to date have likewise shown promising
results. Helenius et al. (2006)in an in vivo study of
subcutaneous bacterial cellulose implantation in rats found
that after 12 weeks, no fibrotic capsule or giant cells were
detectable by microscopy, indicating no foreign body
reaction (Fig. 2). Furthermore, macroscopically, no red-
ness, swelling, or exudate developed around the implan-
tation sites. Other studies have also demonstrated
biocompatibility of BC (Klemm et al. 2001; Wouk et
al. 1998; Schumann et al. 2008).
Appl Microbiol Biotechnol (2011) 91:1277–1286
Fig. 2 a One week after implantation, BC showed little foreign body
reaction. Used with permission from Helenius et al. 2006. b
Magnification of the porous side of BC showing infiltration of
Biodegradability
Cellulose degradation occurs by hydrolysis. However,
because of its compact structure, it is highly resistant to
degradation. Neither stomach acid nor the hydrolyzing
enzymes of the human GI tract (e.g., amylase) are
capable of significantly affecting cellulose for Figs. 2 and 3.
Cellulases are required to hydrolyze the β-1,4 D-glucose
linkages of cellulose. These are not possessed by
animals, but are made by many types of fungus and
bacteria. Termites and ruminants like cattle, horses, and
deer host symbiotic cellulase-secreting bacteria in their
GI tracts which allow them to degrade cellulose into
simple glucose (Garrett and Grisham 2005). This is ideal
for some applications, and problematic for others. Within
the human body, say, as an implant, there are simply no
mechanisms for the large-scale breakdown of cellulose.
Nonenzymatic, spontaneous hydrolysis of the cellulose
chains may perhaps account for slow breakdown of
unaltered BC within the human body, though this is
admittedly conjecture and has not been adequately
studied or described elsewhere in print to the best
knowledge of the authors. Some work has been made,
however, in altering BC such that it can be degraded in
the human body (discussed below under “Looking
forward” Section).
Fig. 3 SEM micrographs of
freeze-dried BC. The compact
surface at the oxygen-rich side
(a) and a cross section of the
less compact surface of the
oxygen-poor side (b). Used with
permission from reference
Helenius et al. 2006
1279
fibroblasts into the BC network. Twelve weeks postimplantation.
Arrowheads indicate collagen synthesized by fibroblasts. Ladewig's
trichrome stain. Used with permission from Helenius et al. 2006
Macrostructure control
The ability to control the physical structure at the macro,
micro, and even nanoscales is another important character-
istic of BC with diverse potential biomedical applications.
BC-producing bacteria are directable using a variety of
techniques to ultimately produce virtually any shape or
form. Furthermore, advances are being made on the micro
and nanoscales in successfully controlling such properties
as surface chemistry, porosity, and fiber orientation.
Research into BC’s unique properties in each of these areas
has led to a promising array of techniques being used for
various biomedical applications.
Bacterial cellulose has traditionally been fabricated into
flat sheets (such as pellicles) and particles. Pellicles (the flat
BC disc formed when a test tube is used as the cultivation
container) and larger sheets are formed by static cultivation
on the surface of a liquid culture medium (Fig. 3, Fig. 4a).
In agitated cultures, bacterial cellulose forms small par-
ticles of various sizes and shapes (e.g., spherical,
ellipsoidal, “stellate”) ranging in size from 10 μm to
several millimeters (Bäckdahl 2008; Czaja et al. 2004).
The overall network of the microbial cellulose is similar in
the two forms though static cultures show higher crystal-
linity and degree of polymerization (Bäckdahl 2008;
Watanabe et al. 1998).
1280
Fig. 4 a BC sheet. b Tubular
cellulose grown on branched
silicone tubing. Image b
used with permission from
Bodin et al. 2007a
Hollow BC tubes have more recently been utilized (Bodin
et al. 2007a; Fig. 4). In this process, gas-permeable tubing
through which oxygen is passed is surrounded by culture
medium, and the aerobic bacteria spin BC around the tubing.
These are currently the primary macrostructural designs into
which BC is made for existing biomedical applications,
though there is potential for culturing BC in virtually any
desired shape by using oxygen-permeable molds. BC has in
fact been cultured into far more complex shapes such as a
seamless human glove (White and Brown Jr. 1989).
Porosity
One concern raised in the past with bacterial cellulose is
that the density of its mesh prevented cell migration into
the material (Fig. 5). As scaffolding for cell growth is an
area of great interest in BC research with broad potential
for biomedical applications (e.g., bone graft, skin graft,
artificial cartilage, etc.), increasing BC’s native porosity has
been a focused area of research. Any application requiring
complete integration of cells throughout a BC structural
matrix would require cellular permeability. In nature, it
behooves BC to be impenetrable to invading bacterial cells
(Klemm et al. 2005; Ross et al. 1991; Hutchens et al. 2006).
And an in vivo study noted integration of fibroblasts into
native BC to be superficial at best (Helenius et al. 2006).
Production of artificially porous BC has been achieved with
the use of various methods, most notably porogens.
Fig. 5 Left fully developed
network of BC nanofibers.
White bar=2 μm. Right BC
network with attached
smooth muscle cell. White
bar=2 μm (courtesy: Henrik
Bäckdahl)
Appl Microbiol Biotechnol (2011) 91:1277–1286
Porogens are materials initially incorporated into a
material as space holders which can subsequently be
removed without significantly disturbing the material
(Fig. 6). Such porogens as salt, paraffin, ice, gelatin, and
sugar have been used in various polymeric materials to
achieve porosity (Bäckdahl et al. 2008a, b). The same
process has also been applied to BC. Bäckdahl et al.
investigated potato starch and paraffin wax as porogens in
BC tubes. They found they could vary pore size and
interconnectivity by controlling the size of the paraffin
particles and by heat treating the initial paraffin wax
particles at specific temperatures to create partial particle
fusion (Bäckdahl et al. 2008a, b). Successful attachment of
smooth muscle cells inside the pores was also demon-
strated (Bäckdahl et al. 2008a). A different approach by
Rambo et al. (2008)for application in BC sheets used a
template with pins of varying diameters (60–300 μm) to
create porosity.
It has been noted that in addition to simply creating
space for cell migration, the actual geometry at the nano
and microscales affects cell behavior. For example, in
bone grafts and scaffolds, the geometry of the microen-
vironment around osteoprogenitor cells directs the prog-
ress of osteoinduction (Habibovic et al. 2005). Precise
control of bacterial cellulose structure and porosity at the
micro and nanoscales, then, is of significance for applica-
tions of BC as a cell scaffolding and deserves further
research.
Appl Microbiol Biotechnol (2011) 91:1277–1286
Fig. 6 SEM of microporosity-engineered BC. White bar=200 μm.
Used with permission from Bäckdahl et al. 2008a
Orientation
BC is naturally anisotropic in the culturing plane. Since
bacterial motion is random, the resulting BC network is a
cobweb of randomly oriented cellulose nanofibers. Although
despite this randomness of fiber orientation, the material is still
quite strong, for some applications it could be helpful to
achieve an isotropic material with improved mechanical
properties along a specific direction. Several advances have
been made towards this end. The earliest known example of
achieving BC fiber alignment, to the knowledge of these
authors, involved using a scaffolding of nematic ordered
cellulose with aligned cellulose fibers to direct the pathway of
travel of A. xylinum bacteria parallel to the orientation of the
scaffolding (Kondo et al. 2002). Using microfluidic channels,
Wang et al. (2008) were able to demonstrate some ability to
direct bacteria motion and thus fiber alignment. Putra et al.
(2008a) showed that A. xylinum grown on ridged polydime-
thylsiloxane led to BC with uniaxial alignment of the
nanofibers. When grown on oxygen-permeable silicone
tubes, BC seems to naturally orient itself preferentially along
the longitudinal axis of the tube (Putra et al. 2008b). Also, a
honeycomb pattern of BC nanofibers was achieved using
honeycomb-patterned microgrooves in an agarose film (Uraki
et al. 2007). Such control of nanofiber alignment has the
potential to make bacterial cellulose an isotropic material with
enhanced mechanical properties along a specified axis. More
recently, in a process called dielectrophoretic microweaving, a
charge is induced in A. xylinum and bacteria motion is
directed by the application of an external electromagnetic
field. The result is alignment of BC nanofibers along
electromagnetic field lines (Sano et al. 2010).
Modification
There are a variety of other methods for modifying BC that
are of great potential use in biomedical applications.
1281
Chemical treatments, irradiation, and impregnation with
biologically active molecules or metals are all being
investigated and offer potential usefulness in biomedical
applications.
The possible chemical modifications are too numerous to
count, but a few examples are listed here. Phosphorylation
followed by treatment with simulated body fluid induces
hydroxyapatite crystal growth on BC (Wan et al. 2007).
This has potential application in stimulating osteoblast/
osteoclast seeding for bone scaffolding. Phosphorylated
BC can also be used as an adsorbent for metal ions
(Oshima, et al. 2008). Acetylation to form cellulose acetate
has been shown to increase BC crystallinity and lead to
greater thermal stability (Barud et al. 2008b). Addition of
sulfate groups by hydrolysis of BC with sulfuric acid also
changes thermal stability (Roman and Winter 2004).
Alkaline pretreatment (e.g., with NaOH) makes BC more
susceptible to cellulase degradation (Jung et al. 2008).
Pentafluorobenzoylation produces lipophobic/hydrophobic
BC materials (Cunha et al. 2007). The list is virtually
unlimited, and constantly growing.
BC impregnation with antimicrobial materials or drugs
is another area of research for biomedical applications.
BC impregnation with silver has been investigated
because of silver’s innate antimicrobial properties (Barud
et al. 2008a). Others have worked towards developing
BC as a drug delivery mechanism by incorporating drug
molecules into the BC membrane allowing gradual
release of the drug (Nguyen et al. 2008; Klechkovskaya
et al. 2008; Stoica-Guzun et al. 2007). And electron beam
irradiation has been used to modify diffusion character-
istics of BC and potentially lengthen drug release time
(Stoica-Guzun et al. 2007).
Native BC fosters only very limited cell–BC interactions.
However, various surface modifications of native BC have
been used to direct cell–BC interactions towards specifically
desired ends. Treatment of native BC with xyloglucan–RGD
conjugate has been shown to promote endothelial cell
adhesion and proliferation (Bodin and Ahrenstedt 2007).
Also, Kalaskar et al. (2008) demonstrated that cell spreading
on BC and the cells’ morphology could be directed by
the esterification of amino acids to the BC network.
Aromatic amino acids in particular (especially tryptophan)
enhance cell spreading on BC. Furthermore, hydroxyap-
atite crystal growth on BC has been shown to induce
osteoblast proliferation, differentiation, and attachment
(Hutmacher et al. 2007).
Clinical applications
Many exciting developments have occurred in practical
applications for bacterial cellulose in the biomedical field.
1282
One of BC’s best known biomedical applications is as a
topical covering for severe wounds. Others include artificial
skin, coverings for nerve surgery, dura mater prosthesis, and
arterial stent coating (Czaja et al. 2007). Previous reviews
(Klemm et al. 2006; Czaja et al. 2006; Czaja et al. 2007,
Shih 2010; Gatenholm and Klemm 2010) have discussed
many of these applications. We will revisit some of these
topics and discuss recent further developments.
Bioprocess®, XCell®, and Biofill® are products already
available commercially for topical application in wound
healing (Fontana et al. 1990; Czaja, et al. 2006; Fig. 7).
Studies have shown BC to be superior to conventional
wound dressings in terms of exudate retention, reducing
wound pain, accelerating reepithelialization and healing
times, reducing wound infection rates, ease of wound
inspection (because of its semitransparency), and in
reducing scarring (Fontana et al. 1990; Czaja, et al. 2006;
Czaja et al. 2007). It has the benefit of comforming
remarkably well to almost any contour and is an ideal
moisturizing applicant as it can maintain a proper water
balance by either absorbing or releasing fluid according to
the behavior of the wound.
Thanks to its unique network structure, high water
content, and mechanical characteristics, BC could poten-
tially be used not just as a wound healing treatment, but as
a scaffold seeded with epithelial cells. In this roll, it could
potentially be grafted as a semipermanent artificial skin and
induce epithelial recovery even after the severest epithelial
damage. Autografting is the treatment of choice for skin
damage covering large areas. Other skin substitutes, such
as cadaver-harvested skin substitutes, may also be used
when autografting is not an option (Czaja et al. 2007). A
cell-seeded BC skin substitute could be an improved
alternative to autografting for patients with severe skin
damage (e.g., burn victims, Stevens–Johnson syndrome, etc.).
The use of BC tubes as blood vessels and for nerve
surgery has not yet reached clinical trials in humans, but
there have been very promising results in animal studies. A
Fig. 7 Topical BC application for wound healing. Used with
permission from Czaja et al. 2007
Appl Microbiol Biotechnol (2011) 91:1277–1286
recent study of BASYC® small caliber blood vessel
replacements in five mice (carotid artery) and eight pigs
(carotid artery) demonstrated patency in all of the mice
endoprosthesis after 1 year and seven of the eight pig
prostheses after 90 days. Epithelialization of the internal
lining of the prosthesis was also observed histologically as
well as the development of three distinct structural layers
mirroring the normal three-layer structure of native arteries
(Schumann et al. 2008). Other studies of BC tube prosthesis
for rat blood vessels (carotid arteries and jugular veins)
have also showed patency of all implants at their
conclusion (Klemm et al. 2001; Wurdinger et al. 2000).
The tubes also improved outcomes in nerve surgery when
placed around suture sights, presumably by reducing
invasion of connective tissue (Klemm et al. 2001). There
has also been progress in seeding BC tubes with human
cells and growing a urothelial lining for use as urinary
conduits. These urothelial-lined BC tubes seemed to do
well after 2 weeks’ implantation (Bodin et al. 2010).
BC has shown some utility for guided tissue regeneration
of bone. Like in nerve surgery, in this process, scar tissue
formation in healing sites is prevented by implantation of
a barrier membrane which keeps out fibroblasts and
allows the slower process of osteogenesis to occur. BC
membranes have been successfully used in this application
(Czaja et al. 2007).
Recently, BC has also been investigated as a potential
bone tissue scaffold. Bone is made of a matrix comprised
largely of collagen which is mineralized by hydroxyapatite.
This lends stiffness and strength to the composite. BC, as a
collagen-like material, could in theory, substitute for
collagen in a biomimetically engineered bone construct.
Calcium phosphate minerals (such as hydroxyapatite) are
known to increase osteoblastic differentiation of progen-
itor cells, increase cell alkaline phosphatase activity, and
generally promote bone tissue formation (Stevens, et al.
2008; Sibilla, et al. 2006; Ducheyne and Qiu 1999). Thus,
in attempts to create a BC-based biomimetic bone
scaffold, BC has been mineralized with hydroxyapatite
crystals. Many other factors, however, such as scaffold
porosity (Hutmacher et al. 2007; Stylios et al. 2007),
nanoscale topography (Stevens, et al. 2008), and hydroxy-
apatite crystal size (Smith et al. 2006) also affect the
adhesion, differentiation, and proliferation of osteogenic
cells (Dulgar-Tulloch et al. 2009; Ducheyne and Qiu 1999;
Habibovic et al. 2005). The ideal BC bone scaffold will
require the optimization of each of these parameters. An
initial experiment of hydroxyapatite/BC constructs seeded
with human bone marrow stem cells showed promising
results such as enhanced cell attachment, proliferation, and
differentiation compared to cells seeded on unmodified
BC (Hutmacher et al. 2007; Fang et al. 2009). Ongoing
work in the control of BC porosity, nanoscale topography,
Appl Microbiol Biotechnol (2011) 91:1277–1286
and hydroxyapatite crystal size will help bring the ultimate
goal of a functional, implantable, BC bone tissue scaffold
closer to realization.
Another area of development is the potential for BC
use in artificial heart valves. Millon and Wan (2006) in
their research on BC composites showed that a biocom-
patible polyvinyl alcohol–bacterial cellulose composite
possessed mechanical stress–strain characteristics compa-
rable to native heart valve leaflets, but that relax faster
than native valves and to a lower residual stress. Currently,
standard valve replacements are either porcine heart
valves, which have a limited lifespan, or mechanical heart
valves, which last longer but require lifelong blood
thinning medication and cause increased shear forces on
red blood cells, cell rupture, and associated anemia. A BC
composite material could be a highly desirable alternative
to current treatment options.
Researchers in Brazil have tested bacterial cellulose
created by Zoogloea species for repairing abdominal wall
defects in rats. Though some hopeful results were
obtained, an initial challenge is that the nanoscale
porosity of native BC was insufficient to permit the
desired level of integration with surrounding tissue
(Falcao et al. 2008a, b). Advances in creating porosity in
BC may help solve this problem.
The favorable comparison between properties of carti-
lage and BC has led to investigations into BC use for
cartilage replacement. A recent study of a BC composite
demonstrated superior properties using a bacterial cellulose/
poly(dimethyl acrylamide) double network gel and con-
cluded that it could potentially be used as a cartilage
substitute (Azuma et al. 2007). Another study demonstrated
BC’s potential utility as a cartilage scaffold, noting that it
surpassed alginate and plastic in supporting chondrocyte
migration and proliferation (Svensson et al. 2005). Bodin et
al. (2007b) found unmodified BC to be similar to porcine
knee menisci in young’s modulus at compression loads of
2 kPa and superior to a simultaneously tested collagen-
based material, though natural menisci surpassed BC at
higher loads. Improved characteristics may be achievable
by directing BC fibril orientation (now conceivably
possible thanks to advances mentioned above), through
BC composites, impregnation with proteoglycans to mirror
normal meniscus composition and reduce BC dessication
under loading, or by incorporating human chondrocytes
into the BC matrix during culturing.
Other uses of BC less documented in the literature but
for which patents are held include BC contact lenses
(Levinson and Glonek 2008) and BC-producing bacteria as
a dietary supplement for combating diabetes (Park et al. 2004).
In the latter case, BC-producing Lactobacillus and
Acetobacter species were described as potential dietary
supplements wherein the gut is artificially populated with
1283
bacteria that would take in simple sugars converting them
to nondigestible (and osmotically relatively inert) cellulose
(dietary fiber).
Looking forward
Research in BC has led to significant advancement in recent
years with the promise of even greater advances likely yet to
come. As mentioned, cellulose in the human body is slowly
biodegradable at best (Czaja et al. 2007; Lau et al. 2007). For
certain applications (e.g., heart valves, meniscus) cellular
vitalization of a permanent, nondegraded scaffold may be
adequate. For others, a bioresorbable matrix that can be
replaced by natural tissue over time may be best (e.g., bone).
It is known that oxidized cellulose is rendered more
vulnerable to hydrolysis and therefore potentially degradable
by the human body. Some research on enhancing
nonbacterial cellulose biodegradability through oxidation
has been published (Laurence et al. 2005; Singh et al. 1979).
Li et al. (2009) have also recently published findings on
improving BC’s degradability in vitro (in water, phosphate-
buffered saline, and simulated body fluid) through periodate
oxidation. Multiple patents describing oxidation of BC to
create biodegradable BC material are also held (Harris et
al. 2010; Kumar and Dang 2010; Saferstein and Serafica
2010; Kumar and Dong 2009; Kumar 2004), and Xylos
Corporation currently markets an oxidized BC resorbable
product. However, to the authors’ best knowledge, no in
vivo studies on enhanced BC biodegradability through
oxidation treatment have been published in the literature to
date. BC modification to enhance and control biodegradabil-
ity, especially in vivo biodegradability, merits further study.
Further in vivo biocompatibility studies are likewise needed.
While initial results are promising, further research of
measurements of such markers as complement activation
and coagulability is yet needed.
Chemical modification for improved interaction with
the human body is one area with tremendous potential
for opening the way for broader use in medical devices.
Covalent attachment of biologically active ligand mole-
cules to a BC framework can enhance and alter BC
characteristics for specific applications. Pharmaceuticals,
anticoagulants or coagulation cascade factors, growth
factors, and angiogenic factors are all of great potential
(if not indispensible) use for preparing BC for specific
purposes. Long-term patency of small-caliber BC blood
vessels, for example, is more likely to be successful with
the presence of the anticoagulant factors expressed on the
endothelium of normal blood vessels. Strides are being
made towards use of BC as a tissue scaffold for cartilage,
bone, skin epithelium, and various types of endothelium.
Chemical modification also has promise for aiding in this area
1284
of research. Cell–BC interactions are complex and will yet
require further in vitro and in vivo studies.
Techniques for producing BC in different shapes and
sizes beyond just sheets and tubes will also allow for
wider applications of BC. Improved techniques for
incorporating and controlling porosity in various shapes
of BC will be necessary for cell-seeding and use of BC
as a tissue scaffold. Control of BC fiber orientation will
open new possibilities for enhanced mechanical proper-
ties. Further control of cell–BC interactions through BC
macro and microstructure control will also be of paramount
importance.
Finally, lack of general awareness of BC, in general, as a
feasible biomedical material is a hindrance to its application
and use. While not new, it has yet to reach large-scale
recognition. Part of this problem is the questionable nature
of large-scale production techniques of a material created
by a living organism. Creating controlled, reliable, repro-
ducible, production techniques will be essential to ultimate
FDA approval for new applications and will help pave the
way for greater acceptance of BC as the commercially
available material for biomedical applications it has such
possibility to be.
Acknowledgments ICTAS funding, Project 555053 Bone Healing is
acknowledged for financial support.
Author disclosure statement Dr. Gatenholm is a cofounder of
Arterion but no longer associated with the company. He is also
cofounder of BC Genesis.
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