The Potential of WOUND HEALING BY MICROBIAL Cellulose

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International Journal of
CODEN: IJRSFP (USA)
Recent Scientific
International Journal of Recent Scientific Research Research
Vol. 13, Issue, 06 (A), pp. 1388-1400, June, 2022
ISSN: 0976-3031 DOI: 10.24327/IJRSR
Research Article
THE POTENTIAL OF WOUND HEALING BY MICROBIAL CELLULOSE
Nainika Srivastava, Shreya Jha and Subhrojyoti Ghosh
Department of Biotechnology, Heritage Institute of Technology, Kolkata 700107, India
DOI: http://dx.doi.org/10.24327/ijrsr.2022.1306.0295

ARTICLE INFO ABSTRACT

Article History: Microbial Cellulose refers to cellulose produced by certain strains of bacteria including Acetobacter
th
Received 12 March, 2022 xylinum or Gluconacetobacterxylinum. The lack of success of modern wound dressings and
Received in revised form 23rd increased instances of non-healing skin wounds have ultimately paved the way for searching for
April, 2022 biomaterials in wound dressing. Microbial Cellulose successfully addresses all these issues mainly
due to high water holding capacity and biocompatibility. One of the major challenges in Microbial
Accepted 7th May, 2022
Cellulose production is its low yield in bacterial cells and thus secondary materials have been
Published online 28th June, 2022
sought. This has led to increased scientific work in combining Microbial Cellulose with Nanofibers
Keywords: and Hydrogels. Additionally, the performance of Microbial Cellulose has been reported to be
increased with the incorporation of Mesenchymal Stem Cells or using combined therapies of
Microbial Cellulose (MC) Wound Healing irradiation. The purpose of this review is to summarize all the recent advances in Microbial
Wound Dressing Cellulose as a wound-healing material either with or without other secondary materials with detailed
mechanisms. Clinical performance and prospects have also been outlined.

Copyright © Nainika Srivastava et al, 2022, this is an open-access article distributed under the terms of the Creative Commons
Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is
properly cited.

INTRODUCTION The skin has many functions, such as protecting other organs
Human skin covers the entire surface of the body, which is the from pathogen invasion, dehydration, mechanical impact,
barrier between the human body and the outside world. It radiation, and chemicals. The skin also regulates body
affects the environment and plays an important role in temperature and is an integral part of the sensory system,
preventing pathogens from invading the human body[1]. But it serving as a reservoir of vitamin D synthesis [9,10]. Therefore,
is the most commonly injured part of the human body. When skin damage needs to be properly treated not only to restore its
injured, the connective tissue is exposed, triggering a series of appearance but also to restore its function as described above.
local cell and biochemical events that restore their integrity[2]. Therefore, special attention has been paid to the development
of biomaterials/structures suitable for wound care/healing[11].
The first reaction after an injury is to stop bleeding. It occurs at
the site of blood loss in the wound [3]. The second stage is The global wound care market was valued at US $ 17.49 billion
inflammation which lasts from 24 hours to 4-6 days, beginning in 2021. The market is projected to grow from US $ 18.51
with the release of proteolytic enzymes and pro-inflammatory billion in 2022 to the US $ 28.23 billion in 2029, showing a
cytokines from invasive immune cells into the wound area, CAGR of 6.2% over the forecast period [12].
where these inflammatory cells are reactive oxygen species In addition, of the various commercially available wound
(ROS) and it protects the organisms from bacterial infections care/biomaterials, wound dressings are the most widely used.
[4]. At this stage, all foreign bodies anddebris are removed Various forms of wound dressings have been developed,
from the wound bed by neutrophils and macrophages, including clear bandages, medical bandages, hydrogel
preventing infection [5]. In addition, the release of cytokines bandages, foam bandages, hydrophilic colloid bandages, and
and enzymes stimulates the growth of fibroblasts and film bandages [13,14,15].
myofibroblasts, and wound exudate provides the water needed
for healing [6,7]. The third stage is the proliferation stage Wound dressings play an essential role in the healing of some
where new granulation tissue is formed and grows in the types of open wounds, like chronic wounds, unless the moist,
wound area to form a new extracellular matrix. The final stage warm, and nutritious environment of the wound bed creates
of healing is remodeling. At this stage, the composition of the ideal conditions for microbial growth. Thus, the wound healing
matrix changes, collagen III replaces collagen I, and the tensile process can be hampered by bacterial colonization and
strength of the new tissue increases [3, 6, 8]. [Figure 1]

*Corresponding author: Nainika Srivastava


Department of Biotechnology, Heritage Institute of Technology, Kolkata 700107, India
International Journal of Recent Scientific Research Vol. 13, Issue, 06 (A), pp. 1388-1400, June, 2022

subsequent infection, which can induce an excessive and microbial cellulose can be tuned to have certain desired
prolonged inflammatory response from the host tissue[16]. properties. For example, the bacterium Acetobacter xylinum is
noted for its unique mechanical properties and its application in
It is very important that the ideal wound dressing matches its [24].
biocompatibility and bio-physicochemical properties. Most biotechnology, microbiology, and materials science
natural polymers are biocompatible, but often have poor me General Biochemical Pathway for Cellulose Synthesis
chanical properties and poor processability [17,18]. Cellulose-
based biomaterials are not only poorly biocompatible but their The synthesis of microbial cellulose is a multi-step process
physical, chemical, and mechanical properties are controlled. [Figure 2] involving two major mechanisms. The synthesis of
Various types of wound dressings have been developed from uridine diphosphoglucose (UDPGIc) is followed by the
cellulose-based biomaterials and have shown promising results polymerization of glucose into a long non-branched chain (β1
[19,20]. One such cellulose-based biomaterial is the Microbial → 4 glucan chain) by cellulose synthase. The details of
Cellulose (MC) which exhibits appropriate biocompatibility cellulose synthesis are widely documented [26,27]. The former
and biodegradability and has MC's unique physical and mechanism is well known, but the latter has not yet been
chemical properties such as ultrafine nanofiber network, high investigated. The formation of UDPGIc begins with carbon
crystallinity, high water retention, high tensile strength, so it is compounds (hexose, glycerol, dihydroxyacetone, pyruvate,
a biomaterial for wound healing[21]. dicarboxylic acid, etc.) entering the Krebs cycle,
gluconeogenesis, r pentose phosphate pathway, depending on
This review’s primary focus is to provide a comprehensive the available carbon sources. It is then catalyzed and
assessment of MC-based wound healing where we will phosphorylated, followed by isomerization of the intermediate.
elucidate the pathophysiology and the process of wound This process, known as UDPGIc pyrophosphorylase, converts
healing and the challenges related to it. Finally, MC based the compound to UDPGIc, a precursor to cellulose production.
wound healing system is reviewed, their strategies of
enhancement, clinical performance, and marketed products are
discussed, and the future perspectives are presented.

Fig 1 Stages of Wound Healing


The stages include- (a) Hemostasis, which is clotting of the blood; (b) Inflammation, where the release ofproteolytic enzymes and protection of
organism from microbial infections with the help of neutrophils and macrophages takes place; (c) Proliferation, where the formation of new
granulation tissue occurs; (d) Remodelling, where the composition of matrix changes and new tissue is formed.(Created by Biorender,22)

Cellulose The polymerization of glucose into the β1→4 glucan chain has
Microbial cellulose is an organic compound produced by been hypothesized to either involve a lipid intermediate [28] or
certain types of microorganisms (bacteria), predominantly not involve a lipid intermediate,[26] though structural
Acetobacter, Sarcina ventriculi, and Agrobacterium. Microbial enzymology studies and in vitro experiments indicate that
cellulose is characterized by high purity, strength, malleability, polymerization can occur by direct enzymatic transfer of a
and improved water retention [23]. In natural habitats, most glucosyl moiety from a nucleotide sugar to the growing
microorganisms (bacteria) synthesize extracellular polysaccharide[29]. A. xylinum usually converts carbon
polysaccharides such as cellulose to form a protective cover compounds into cellulose with around 50% efficiency[28].
around the cells. Although microbial cellulose is produced in Structure of Microbial Cellulose
nature, many methods are currently being explored as a large-
scale process to promote cellulose growth from laboratory The MC consists of twisted ribbon-shaped fibrils
cultures. By controlling the synthetic process, the resulting approximately 50100 nm wide and 38 nm thick [30, 31, 32,
33]. X-ray diffraction (XRD) shows that the size of microfibrils
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is associated with their crystallite size [34]. These ultrafine


ribbons are 19 μm long and form densely arranged structures
stabilized by extensive bonds between and within hydrogen
[35,36]. The average distance (pore diameter) between the
junctions of a typical MC film is calculated to be 0.523 ± 0.273
μm, and the direction of the segment as the average angle
formed between the x-axis and the segment is 85.64 ± 0.56 °
[37].
Fig 4 Microbial Cellulose microfibrils and its physical properties [51,52]
(a)Schematic diagram of Microbial Cellulosemicrofibrils;
(b)Physical properties of Microbial Cellulose

Pathophysiology of Wounds
Wound healing is a complex, multi-step, multifactorial process
that includes: various cells, signals, and biochemicals. Wound
healing stages include hemostasis, inflammation, proliferation,
and remodeling, in which different cells and signals/stimuli are
involved.
When cell integrity is compromised ortissue is destroyed,
physical, mechanical, or metabolic problems cause wounds
[41], which destroy the function of the skin. Wound healing is
a complex process as many factors can affect the wound,
including the type of wound (e.g., dry, acute, chronic, and
exudate) and the patient's condition (e.g., anemia and diabetes).
The classification of skin scars is either chronic or chronic
acute and depends on the nature of the healing process during
Fig 2 Biochemical Pathway for Cellulose Synthesis[25] that period. Burns and incisions cause acute wounds. Here, the
Synthesis of microbial cellulose is a multi-step process involving the synthesis healing bond is related to the number of skins layer andskin
of uridine diphosphoglucose (UDPGlc) followed by polymerization of glucose
into β1 → 4 glucan chain by cellulose synthase.
size [42,43]. Wounds are normal with the development of
hypertrophic scars (HS) known as a fibroproliferative disorder.
Cellulose produced under static conditions produces a leather- Hypertrophic scars are confined to the edges of the original
like membrane that supports a population of cells of the wound bed and keloids extend beyond these boundaries. It is
xylinum species. These pellicles[Figure 3]are composed of believed that excessive movement across joints, underlying
overlapping and intertwined cellulose ribbons that form a grid bone structure, or excessive tension due to loss of tissue can
of parallel but chaotic planes [23]. play a role in the development of these particular scars. Keloids
are also common in patients with dark skin[44,45].
The exact mechanism by which these scars are formed is
unknown, but abnormal or hyperactive fibroblasts have been
found in keloids. These fibroblasts produce large amounts of
collagen, elastin, fibronectin, and proteoglycans and overreact
to stimuli. This response may be associated with the
upregulation of insulin-like growth factor receptors on keloid
fibroblasts. Insulin-like growth factor stimulates collagen
production. Unlike normal scars, the collagen deposited on
keloids is randomized and may play a role in extending beyond
the edges of the wound[44,45].
Hypertrophic scar collagen is bundled and arranged in a wavy
pattern parallel to the epithelial surface. This slightly organized
Fig 3 MC Pellicle [38] pattern distinguishes hypertrophic scars from the disordered
A wet microbial cellulose pellicle being removed from a culture. alignment found in keloids. Unlike keloid fibroblasts,
hypertrophic scar fibroblasts usually respond to growth factors
Adjacent strands of cellulose mats branch and connect to a and producea slight excess of collagen. Hypertrophic scars also
greater extent than is common in static cultures, compared to contain the unique modular structure of alpha-smooth muscle
cellulose produced in agitated cultures. Under agitated actin myofibroblasts, as well as those involved in scar
conditions, increased branching is observed in the form of contraction. Hypertrophic scars are thought to heal over time,
fibrous strands and irregular particles that are completely but keloids do not[44,45].
dispersed in the culture broth [39]. In addition, moving MCs
combine to form a grid-like pattern [40]. The schematic MC
microfibril model and its physical properties are shown in the
figure[Figure 4].

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1400, June, 2022

The Rate off Healing Is Calculated As Equation [46]: Open wounds provide a suitable environment for bacterial
colonization [57].. Open wounds are usually contaminated with
Percentage of Healing (%)
pathogens from the environment
environment[58]. Gram-positive bacteria
Wound area on a particular day predominate in the early stages of chronic wound formation,
=1 − ×100 while Gram-negative
negative bacteria are found deep in the skin and
Wound area on day zero
cause significant tissue damage [59]. Bacterial infections are
The normal mechanism of wound healing may be interrupted the most common clinical complications associated with skin
due to various factors that prolong healing time[47].time For diseases and play an important role in delaying the healing
example, for severe chronic wounds, physiological changes can process [56]In
In addition, it causeshighmorbidity and mortality
occur in the wound, which produces excess exudate that inpatients [60]. Therefore,
re, skin function should be restored by
destroys tissue proteases from wound contamination [48]. immediate covering with a wound dressing to prevent
moreover, chronic wounds, burns, and diabetic ulcers are on contamination and promote skin healing [61]. To this end,
the rise at the time of relaxation.
elaxation. High levels of exudate are one natural and synthetic wound dressings with antibacterial
example. Found in burns, this provides a favorable properties have been developedloped in various forms such as
environment for bacterial growth [49].. The presence of these sponges, hydrogels, foils, and membranes.
bacteria causes wound inflammation through pro-inflammatory
pro Wound Healing Using Mc
manifestations of cytokines [50].. The degree of inflammation
prevents the formation of granulation tissue in the wound area In 1980, Farah and Ring first reported the use of MC as a
from degradable due to high metalloproteinase (MMP) wound dressing material [62,63]
,63]. In vivo experiments revealed
content.ECM components and resulting in delayed wound that MC films reduced inflammation along with suitable wound
healing[53].. In addition, diabetic wounds show dilation healing protection propertiesmaking it an excellent material for wound
time due to dry, insensitive properties. Therefore, diabetic dressing and in making artificial skin in comparison to skin
wounds are prone to skin infections [54]. grafting [64]. Other
ther wound dressings and healing properties
include high water-holding
holding capacity, excellent gas, and liquid
Wound Healing Challenges- The Microbial Contamination permeability, and tissue biocompatibility [65,66]. MC can be
Bacteria can naturallycolonize both biological and non-
non very effective in burn wounds because it also has better heat
biological surfaces [55].. When microorganisms settle in a absorption and pain reduction.
patient with severe burns, the immune system can be
compromised andthe skin barrier can be physically
physica destroyed
[56].

Fig 5 MC based Nanofibers & Hydrogels


1. MC based Nanofiber: Here, first silver nanoparticle is prepared and then it is combined with bacterial cellulose. The comb
combination is utilized to make
Nanofiber Composites. Thereafter, they are directly applied to the wounded site. This allows the slow and continuous release of silver nanoparticles at the
wounded site which has significant antimicrobial properties. 2. MC based Hydrogels: Here, chitosan is first prepared from chichitin by deacetylation process. Next,
it is combined with microbial cellulose. Thereafter, it is crosslinked with glutaradehyde and loaded with specific antimicrobial drugs to make a hydrogel. On
application to the wounded site, the hydrogel releases the drugs and results in wound healing. (Crea
(Created with Biorender)

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The pain can be diminished by proper moisture control at the cells (HaCaT) as compared to never-dried MC (ND-MC) [87].
wounded site thereby retaining the humidity at the wounded Moreover, Kingkaew et al. have impregnated chitosan into
site and preventing dehydration of the wound dressing has MC, and the MC/chitosan composite film displayed high
inspired renewed interest among researchers [67,68]. antibacterial skills and promoted the pores and skin
keratinocytes and fibroblasts at unique concentrations of
Combination of MC and Nanofibers
chitosan [88]. Thereafter, Li et al. delivered hyaluronan (HA)
Two most common strategies used in MC based wound healing to MC, and the MC/HA composite film speeded up recovery
applications are (i) the usage of MC nanofibrous shape loaded and confirmed tremendous tissue restoration in Wistar rats in
with a model drug or antibacterial nanoparticles, and (ii) vivo [89]. Not only this, butKeskin et al. also extensively
nanofibrous dressing in which MC is mixed with some other utilized impregnated keratin in MC, and the effects revealed
herbal or synthetic polymers without or with chemical or that keratinocytes and fibroblasts had been greater connected to
bodily modifications [69-72]. Being a biocompatible the composite dressing [90]. Apart from these, Radu et al.
biomaterial, MC has been combined with silver nanoparticles included keratin in BCM, and the keratin/BCM aggregate
which have antimicrobial properties to make nanofiber displayed regeneration potential in rabbits' dorsal burnt wounds
composites [73]. The slow and continual release of silver in vivo [91]. Lin et al. used dextran in an MC hydrogel and
nanoparticles was not at all harmful to human cells but instead located that it improved wound recovery in C57BL/6 mice in
has prolonged antimicrobial activity [74,75]. [Figure 5] vivo in comparison to a moist MC industrial dressing and a
dried film dressing called Tegaderm [92]. Qiao et al. included
Combination of MC And Hydrogels
arginine into microporous microbial cellulose (MOMC) and
Hydrogels find extensive use in wound healing applications proved that MC/arginine has a right-away position in wound
since they have high water holding capacity, can be easily recovery via ways of means of improving fibroblast and
loaded with drugs along with embedded skin cells, and have keratinocyte migration and proliferation [93]. In addition to
been shown to have no adverse inflammatory response these, Farideh et al. included arginine into MC-primarily based
[76,77,78]. In vitro experiments were carried out by either on nanofibers (MC-NF) and located that Arg/MCNF led to
loading human epidermal keratinocytes with-based hydrogels quicker wound closure and recovery than MCNF alone. Better
[79] or by fabricating semi-interpreting networks (semi-IPN) reepithelization and angiogenesis had been attributed to this
hydrogels on MC and chitosan and subsequent wound healing [94]. Qiao et al. grafted arginine with microporous oxidized
efficiency was analyzed [80]. The results revealed proper MC (MOBC), which stepped forward fibroblast and endothelial
thermal and mechanical stability, significant anti-bacterial cell proliferation and migration [93]. Moreover, Lin et al.
activity along with an overall acceleration in wound healing located that including dextran in MC and creating an
[79,80].[Figure 5] MC/dextran hydrogel improved fibroblast cell proliferation and
hastened wound recovery in comparison to the use of moist
Performance of MC Based Wound Dressing- In Vivo And In
MC [94]. Silk sericin (SS) turned into included in the MC via
Vitro
way of means of Lamboni et al., and the BC/SS composite
In vitro experiments had been carried out by many researchers. improved fibroblast film proliferation and wound recovery
Volova et al. had loaded the fibroblast cells on 3- [95]. Lin et al. used dextran in MC hydrogel and located that
hydroxybutyric and 4-hydroxybutyric acids P(3HB/4HB)/ MC moist MC industrial dressing and dried film called Tegaderm
composite dressing film which prolonged wound healing slowed wound recovery in C57BL/6 mice in vivo [92].
because of the vending of epidermal epithelization [81]. Apart
Prospect of Using Mc In Wound Healing
from this, in a Sprague Dawley rat, Mohamad et al. grafted AA
onto MC, and the MC/AA hydrogel expanded wound Skin wound healing is a complicated process that involves
recuperation and extended fibroblast proliferation and many distinct tissues, cell types, and matrix components
epithelization in vivo [82]. Incorporating human epidermal [96,97]. An ideal modern wound healing material should be
keratinocytes (HEK) and human dermal fibroblasts (HDF) into non-toxic, non-pyrogenic, biocompatible, able to provide a
MC/AA hydrogel improved the recuperation price and collagen barrier against infection and control fluid loss, reduce pain,
deposition, consistent with Mohamad et al [83]. In addition to create and maintain a moist wound environment, easy
these, Moraes et al. found that incorporating collagen into the introduction of medicine to the wound, able to absorb exudates
MC membrane ended in higher wound recuperation and faster during the inflammatory phase [98] should create an optimal
tissue regeneration in rat dorsal wounds in vitro whilst as environment for epidermal regeneration [97-102]. MC has been
compared to industrial collagenous ointment [84]. The demonstrated to show all these properties and is hence
incorporation of HACC and CoL-I into MC was proven to considered an ideal material in wound healing systems.
assist the proliferation and unfolding of NIH3T3 cells and
Methods to Improve the Performance of the Mc Based
HUVECs [85]. Tang et al. have incorporated hyaluronic acid
Wound Healing
(HA) into MC hydrogel and confirmed better L9292 cell
viability for MC/HA composite than MC alone which turned Incorporation of Mesenchymal Stem Cells (MSCS)
attributed to the extended floor density and smoother floor [86].
One of the most recent advances in wound healing research is
In the case of in vivo experiments, it was Khan et al. who first
the incorporation of MSCs into MC structure to enhance the
blended gelatin porogens with microporous regenerated
efficacy of the wound healing system. In this regard, several
microbial cellulose (rMC), and the rMC/gelatin confirmed
researchers tried and carried out a plethora of ways including
higher wound closure and recovery of around 60% in
either introduction of Acrylic Acid (AA) into MC to make a
comparison to that of MC alone in vivo in C57BL/6 mice and
hydrogel and subsequent loading with Human Epidermal
supported the adhesion and proliferation of human keratinocyte
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Keratinocytes (HEK) or Human Dermal Fibroblasts (HDF) Combined Therapies of MC and Irradiation
[103], or the seeding of Adipose Stem Cells (ADCs)
Grafting of AA on MC hydrogel using either electron beam
[104]/rabbit Bone Marrow Mesenchymal Stem Cells (rBMSCs)
[114] or microwave irradiation significantly reduced the
[105]/human Urine-derived Stem Cells (hUSCs) [106] into MC
adhesiveness of the wound dressing along with increased
structure which significantly increased the healing rate and had
wound closer rate and faster healing [115]. This led researchers
a faster tissue regeneration potential.
to conclude that the combination of MC with phototherapy
Immobilization of Growth Factors could accelerate the wound healing process [116-118].
This is another strategy adopted for increasing the performance Clinical Performance- Mc Based Wound Dressing In Drug
of MC-based wound healing material. By stimulating Delivery System
angiogenesis and wound healing, the growth factors generated
The MC-based wound dressing operates as a drug delivery
by cells play a vital role in wound healing mechanisms as well
system (DDS) where various narcotics, as well as
as in increased fibroblast activity [107], influenced by cellular
macromolecules, are charged. An ordinarily high-level area, as
proliferation to accelerate the healing of the wound [108]. In
well as hydroxyl groups current, are able of intermolecular and
vivo experiments involved basic Fibroblast Growth Factor
synthetic interactions are to the incorporation of large bio-
(bFGF)/human Epidermal Growth Factor (hEGF)
macromolecules and nanoparticles [119,120]. The micro-
[109]/Vascular Endothelial Growth Factor (VEGF) [110] on
porosity of MC structure gives slow-moving discharge of
MC hydrogel or scaffold with subsequent application to the
narcotics within the clustered hurt with lengthy-permanent
wounded site.[Figure 6]
antibiotic action against bacterial growth [121]. Though, that
ought to not influence the regular wound cure trial.
The natural feature is not enough to encounter the demand in
getting dressed materials. The MC acts as a physical barrier
against bacterial incursion and misses opposed-bacterial
qualities to impede bacterial infection itself[122,123] which
reduces the efficacy of MC in the therapy of highly polluted
cuts. As DDS, the effectiveness of MC could be upgraded by
taking advantage of H2O uptake to charge MC with
antimicrobial operatives like antibiotics[124]. For that goal,
anti-inflammatory and antimicrobial drugs like diclofenac as
well as ibuprofen[125], antibiotic nanomaterials like
silver(Ag+), Zinc Oxide(ZnO), graphene oxide(GO), as well as
titanium oxide(TiO2), as well as special polymers are generally
integrated within the MC-based wound treating[126,127,128].
Antimicrobial Nanomaterials
A few antimicrobial nanomaterials have been integrated within
MC wound dressing to increase efficacy. The Microbial
Cellulose (MC)/ZnO compound had more well-disposed
antibiotic features as well as cell adherence than pure MC[129].
Moreover, the MC/ZnO scaffold exposed substantial cure
effectiveness as well as tissue reclamation in the burn mic
model in vivo in Balbvermins than that of pure MC dressing
scaffold[130] because of antibiotic properties of Zn as well as
Fig 6 MSCs and Growth factors incorporated Wound Healing
its affirmative strike proliferation of keratinocytes. The
in Diabetic Foot Ulcer Treatment[111]
The figure illustrates the wound healing process in the Diabetic foot ulcer ZnO/carboxyl MC membrane reduced wound closure, reducing
treatment by incorporating mesenchymal stem cells and immobilizing growth the inflammatory response in vivo in BalB/c vermins, and was
factors. possibly found to be a non-irritant to the skin in vivo in the
Nano- And Micropatterning dorsal skin of New Zealand pallid bunny[131]. That was
possibly by cause of antibiotic properties, which quick re-
It is known from published works of literature that the micro epithelialization and wound contraction.
and nanoscale surface morphology of the ECM is responsible
for triggering physical signals which affect cellular interactions Antimicrobial Drugs
[112]. The distribution and architecture of collagen in the ECM The charging of MC-based wound dressing with a few
also affect wound healing efficiency. Having known that, antibiotic narcotics was used to increase the efficacy of MC-
scientists either patterned MC with 10µm stripes [112] or based wound dressing. The planting of penicillin out upon the
modified the surface of porous micropatterned MC by arginine- restored microbial starch demonstrated great wound cure
glycine-aspartate-serine (RGDS) which formed dense collagen effectiveness in vivo in females than in MC[132]. That was
on the surface of Human Skin Fibroblasts (HSF) significantly owing to the antibiotic properties of the restored microbial
reduced scar size in in-vivo experiments leading to an cellulose wound dressing. The charging of microbial cellulose
accelerated wound healing response [113]. sheet with povi done-iodine(PI) as well as polihexamide

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(PHMB) showed both disinfectant properties as well as high Overview of Commercialisation Ability of the Mc for Wound
biocompatibility in human keratinocytes[133]. The charging of Care Products
MC with PHMB as well as polyethylene glycol(PEG)
The wound cure rate of sure functionalized Microbial starch-
demonstrated a quick wound cure capability for
based wound dressing is possibly pictured in the table of
PHMB/PEG/MC in vivo in vermins than other for-profit
contents given below. As per observation, the altered Microbial
wound dressings[134]. The fluconazole/never-desiccated
cellulose-based wound dressing demonstrated a higher
microbial cellulose membrane was highly capable of healing
percentage of hurt cure than pure MC-based wound treating,
incinerate cuts in vivo in Wistar rat cuts.
commercial film dressing[146,147,148], gauze[149,150], as
Antimicrobial Polymers well as silver sulfadiazine[151,152,153] as well as pure
MC[154,155,156]. Though functionalizedMC has possibly
Certain special polymers with antibiotic qualities have been
shown possible supporting properties to be utilized as hurt
used to better the efficacy of MC-based wound dressing. The
treatment, especially for burn cuts, there goes on a bit wound
thymol/MC demonstrated considerably enhanced wound cure
dressings market akin bacterial nanocellulose[148], Nano-
effectiveness in Wistar rats in vivo as opposed to pure MC
skinas well as CelMat[157]. Despitestudies examining that the
scaffold[135]. That was possibly attributed to its antibiotic
function and modification of pure and simple Microbialstarch-
properties, which reduced burning and improved hurt closing.
based for-profit products could increase their in-vitro as well as
Opposed- Inflammatory Operative in vivo cure rates as hurt treatment, there are alive hardly any
products. For instance, PHMB-functionalized MC got
The procedure of hurt cure is possibly energetic and
acquainted as Suprasorb X has been commercialized as wound
burdensome comprising different phases. The end product of
dressing[158]. Another commercialized hurt treatment is
thrombin is possibly cyclooxygenase (COX-2), and its level is
Biofill which was possibly utilized as interim skin, which
possibly elevated after skin harm. That enhances the transfer
diminished infection, upgraded the cure rate, and lightened
and proliferation of cells[136]. Brassolatti et al. possess
ache[159]. Another commercialized interim skin is Membracel
lidocaine on MC film and increased the resistant expression of
for burns and sores. CommercializedxCellhas possibly
COX-2. Also, the skin appendices in the wound site
utilizedtreatment for venous ulceration cuts for ache ease as
demonstrated a gentle inflammatory penetration, which
well as quick granulation. Further, Nanoderm and Nanoderm
supported the wound burn cure[137]. The immobilization of
Ag have been efficient in stopping infections due to their
betulin diphosphate(BDP) as an anti-inflammatory agent on the
antimicrobial properties. Nanoskin was possibly covered by
MC/ZnO exposed an efficient wound cure in vivo in Wistar
longstanding cuts for suppressing the entry of microorganisms.
rats than MC which was ascribed to the combined effects of
At last, the commercialized MC hurt treating CelMat has been
marked down oxidative strain and governed oxygenation[138].
demoed to delete wreckage after tidying[160,161].
The charging of microbial cellulose with sericin along with
polyhexamethylene biguanide (PHMB) exposed that Future Prospects & Conclusion
MC/sericin/PHMB lowered ache and decreased the long-
The hurt cure is a complicated, energetic procedure with
standing burning in vivo in Wistar rats as opposed to for-profit
various taking part in cells, biochemical molecules, as well as
of it Bactigras[139].
signaling pathways. A few endogenous, as well as exogenous
Natural Therapeutics impeding elements, influence the procedure, like severe
inflammatory responses, pathogenic corruptions, wound bed
Native products such as plants have possibly demonstrated a
parchedness, ambers, as well as oxygen permeability. The
tremendous good capability to be utilized in renewed getting
passive wound cure/treating biomaterials exclusively serve as
dressing materials[140]. The combination of Microbial starch
the bodily constructions, which avoid microbial incursion as
membrane with the propolis extract was possibly found to
well as fine-tune the wound bed's humidity at the optimal
showcase considerably higher cure capacity in vivo in diabetic
situation. Wounds akin to infected hurt, diabetic sores, as well
vermins role models for against-inflammatory functions and
incinerated wounds, need bodily care as well as organic
backing in vivo epithelization [141]. Curcumin charging on
interventions which are non-existent with the idle hurt-
Microbial Cellulose(MC) considerably upgraded cure patterns
cure/treating biomaterials.
than MC in vivo in the Balbvermins wound burn model[142].
The micro colloidal Zanthoxylum acanthopodium(MZA) was Microbial-cellulose-based biomaterials are possibly efficient
possibly charged on the MC filaments, as well as that for the cure of wounds for their diversification, tuneable bodily,
demonstrated a higher cure rate in vivo in tan rats than MC by synthetic, automatic, and biological acts, convenience, price
cause of improving vascularization as well as antibiotic rise, and biocompatibility. Cellulose-based biocompoundsare
properties also as reduced inflammatory reactions[143]. The glamorous for wound-cure/treating materials because of their
incorporation of Vaccariaasegetalis extract (vaccarin), as well process ability to numerous structures like nano/microfibers,
as the MC membrane, demonstrated a faster wound cure in the hydrogels, and colloids. Their hydrophilic nature has been used
rat skin model in vivo than the MC membrane unique for the to fine-tune the performance of different naturesas well as a
forming of heavy newborn subcutaneous tissue as well as fabricated hurt cure or otherwise treating materials. A few
squamous epithelium[144]. Further, the encapsulation of matrix bioactive molecules similar to sooner drugs, vitamins, growth
metalloproteinase 9 si-RNA (si-MMP-9) within the MC- hyper elements, peptides, as well as native materials have been
branched cationic polysaccharide (MC-HCP) led to anapparent brought to the wound site by applying starch-based structures.
wound cure rate in vivo rat diabetic wound[145]. The biodegradation of MC-based biomaterials is possibly
challenging, which is possibly nota biggie for wound

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cure/treating applications. They are readily taken out from the 10. Joodaki, H.; Panzer, M.B. Skin mechanical properties
wound bed after causing the needed effect. and modeling: A review. Proc. Inst. Mech. Eng. Part H
2018, 232, 323–343.
The application of venomous crosslinking operatives is about
11. Gonzalez, A.C.d.O.; Costa, T.F.; Andrade, Z.d.A.;
interest in making biocompatible cellulose-based hydrogels.
Medrado, A.R.A.P. Wound healing-A literature review.
Accordingly, the development of secure, efficacious, and
An. Bras. Dermatol. 2016,91, 614–620.
biocompatible cross linking approaches is possibly needed for
12. https://www.google.com/amp/s/www.fortunebusinessins
the manufacturing of hydrogel-based biomaterials with
ights.com/amp/wound-care-market-103268
convenient physicochemical as well as biological features. The
13. Nour, S.; Baheiraei, N.; Imani, R.; Khodaei, M.;
combination of cell healing notion with starch-based wound-
Alizadeh, A.; Rabiee, N.; Moazzeni, S.M. A review of
cure biomaterials as the cell-charged structures is possibly
accelerated wound healingapproaches Biomaterial-
giving hope to intensify the cure trial in long-standing wounds.
assisted tissue remodeling. J. Mater. Sci. Mater. Med.
Declaration 2019, 30, 120.
14. Ehterami, A.; Salehi, M.; Farzamfar, S.; Samadian, H.;
The authors declare that they have equal contributions to the
Vaez, A.; Sahrapeyma, H.; Ghorbani, S. A promising
completion of this paper. Figures1 and 5 have been created by
wound dressing basedon alginate hydrogels containing
the authors by using the Biorender application
vitamin D3 cross-linked by calcium carbonate/d-
(https://biorender.com/). They have no competing interests.
glucono--lactone. Biomed. Eng. Lett. 2020,10, 309.
The guidance of our professor, Dr. Nandan Kumar Jana and the
15. Mohammadinejad, R.; Maleki, H.; Larrañeta, E.;
support of the Department of Biotechnology, Heritage Institute
Fajardo, A.R.; Nik, A.B.; Shavandi, A.; Sheikhi, A.;
of Technology, Kolkata is gratefully acknowledged. This work
Ghorbanpour, M.; Farokhi,M.; Govindh, P. Status and
has received no specific grant from any funding agency.
future scope of plant-based green hydrogels in
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How to cite this article:


Nainika Srivastava et al.2022, The Potential of Wound Healing By Microbial Cellulose. Int J Recent Sci Res. 13(06), pp. 1388-
1400. DOI: http://dx.doi.org/10.24327/ijrsr.2022.1306.0295

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