Chitosan-Based Dressing Materials
for Problematic Wound
Management
Ji-Ung Park, Eun-Ho Song, Seol-Ha Jeong,
Juha Song, Hyoun-Ee Kim, and Sukwha Kim
Abstract
Wound healing is a complex mechanism
involving a variety of factors and is a repre-
sentative process of tissue growth and regen-
eration in our body. Surface-based interactions
between the dressing material and the wound
may significantly influence the healing phase.
Advances in understanding the mechanism of
wound healing have led to the development of
numerous dressing materials that can acceler-
ate the healing process. However, these mate-
rials have a passive role in wound healing. It is
therefore necessary to develop novel wound
dressing materials, especially effective for
clinically problematic wounds. Chitosan-­
based dressing materials are considered suit-
Authors Ji-Ung Park and Eun-Ho Song have been equally
contributed to this chapter.
J.-U. Park
Department of Plastic and Reconstructive Surgery,
Seoul National University Boramae Hospital,
Seoul, South Korea
E.-H. Song · S.-H. Jeong
Department of Materials Science and Engineering,
Seoul National University, Seoul, South Korea
J. Song
School of Chemical and Biomedical Engineering,
Nanyang Technological University,
Singapore, Singapore
© Springer Nature Singapore Pte Ltd. 2018
H. J. Chun et al. (eds.), Novel Biomaterials for Regenerative Medicine, Advances in Experimental
Medicine and Biology 1077, https://doi.org/10.1007/978-981-13-0947-2_28
28
able for clinically problematic wounds as they
exhibit several characteristic features, such as
facilitating hemostasis, enhanced wound heal-
ing during the inflammatory and proliferative
phases, antimicrobial effect, etc. Here, we
review the current status of clinically available
dressing materials and studies on the biologi-
cal characteristics of chitosan, and discuss the
potential applications of chitosan in multi-­
functional dressing materials for accelarated
wound healing.
Keywords
Wound healing · Dressing materials ·
Chitosan
H.-E. Kim (*)
Department of Materials Science and Engineering,
Seoul National University, Seoul, South Korea
Biomedical Implant Convergence Research Center,
Advanced Institutes of Convergence Technology,
Suwon, South Korea
e-mail: kimsw@snu.ac.kr
S. Kim (*)
Department of Plastic and Reconstructive Surgery,
Seoul National University College of Medicine,
Seoul, South Korea
e-mail: kimhe@snu.ac.kr
527
528 J.-U. Park et al.

28.1 O
 verview of Wound Healing overlapping stages in which the effects of several
and Dressing Materials cellular components and cytokines play a role in
recovering the normal continuity of and replace-
28.1.1 Wound Healing Process ment of tissue defect. In particular, during the
inflammatory phase, inflammatory cells are
Wounds are sites where repair of damaged tissue actively recruited to the wound site and play
occurs. It is important to maintain homeostasis at important roles in the secretion of growth factors
wound sites. Non-healing problematic chronic such as transforming growth factor-beta (TGF-­
wounds develop due to local or systemic causes, β), platelet-derived growth factor (PDGF), and
such as infection, trauma, and aging [33, 62]. The insulin-like growth factor-1 [18, 20]. Moreover,
process of wound healing involves a cascade of during the proliferative phase, the fibroblast den-
consecutive biochemical and cellular responses sity significantly increases because fibroblasts
that is generally divided into four phases: hemo- are recruited to the wound by growth factors
stasis, inflammatory phase, proliferative phase released by the inflammatory cells. From this
(including fibroplasia, neovascularization, for- perspective, the type of dressing material used for
mation of granulation tissue, and re-­wound treatment is critical since surface interac-
epithelialization), and finally, the formation of tions between the dressing material and the
extracellular matrix and maturation of tissues [6, wound may significantly influence the healing
55]. phase, including cell recruitment and cytokine
The wound healing process is complex, and a production [10, 18].
wound dressing needs to meet certain require-
ments to successfully regenerate the tissue.
Moreover, nowadays, increase in unfavorable 28.1.2 Problematic Clinical Wounds
and delayed healing conditions, such as diabetic and Wound Dressing
foot, pressure ulcers, and venous ulcers that alter
the normal wound healing process, have led to With the rapidly growing elderly population,
challenging problems associated with non-­ delayed wound healing has significantly
healing chronic wounds and increased socioeco- increased because chronic diseases such as dia-
nomic suffering [44, 51]. The delay in wound betes, pressure ulcers, and venous ulcers often
healing is a disorganization of coordinated bio- hinder the normal wound healing processes [4,
logical responses to tissue injury that results in 22]. Diabetes affects 200  million people world-
tissue contraction, epithelialization, and restora- wide and the number is expected to increase to
tion. Under unfavorable conditions, the self-­ more than 300 million people in 20 years. More
perpetuating inflammatory cascade may result in than 15% of diabetics have a diabetic foot, and
increased tissue destruction and necrosis rather over a million people undergo leg amputation
than healing. Moreover, the longer it takes for annually due to unhealed wounds [41]. The inci-
spontaneous wound healing, the worse the out- dence of pressure ulcers is steadily increasing
come usually is, with an increasing likelihood of due to the increased number of patients with limb
developing not only hypertrophic scarring and paralysis caused by cerebrovascular disease and
unsightly alterations in pigmentation, but also generalized placebo caused by aging. In Europe,
secondary infections and even sepsis [6, 8, 20]. the cost of treating bedsores is >500  million
Wound healing begins with the creation of the euros annually, and bedsores have been reported
wound itself, and is mediated by extravasated to be included in the top four illnesses in terms of
cytokines and various cells from the injured cost. In hospitals, the incidence of pressure ulcers
blood vessels at the wound site. Each phase is approximately 11% [40, 52]. In the United
exhibits dominant biochemical reactions that are States, more than 2  million people suffer from
associated with specific cells. Moreover, the pro- burns each year and the cost of treating burns is
cess of wound healing is a consecutive flow of reportedly >1  billion dollars. The patients with
28  Chitosan-Based Dressing Materials for Problematic Wound Management
the most severe burns require long-term in-­
patient care, and severe burns have led to a high
rate of mortality due to secondary infections
through the wounds and excessive blood loss [17,
26].
Although definite surgical treatments (which
include debridement, skin grafting, or flaps) are
often required for treatment of problematic
wounds such as severe burns, appropriate wound
dressing is a critical part of successful healing
that supports complex wound healing processes.
Therefore, the development of functional wound
dressings for the acceleration of wound healing is
necessary to minimize the duration of wound
healing and reduce the associated medical cost,
in addition to protecting the damaged area against
dehydration and infection.
28.1.3 Currently Used Wound
Dressing Materials
The maintenance of homeostasis is critical for
the treatment of various problematic, non-healing
clinical wounds. To treat wounds in clinical
patients, an ideal wound dressing needs to inhibit
exogenous microorganisms and prevent bacterial
growth, maintain a controlled moist environment,
allow gaseous exchange and promote fluid drain-
age, and possess a soft and flexible texture with
biocompatibility and certain strength.
Recently, commercialized dressing materials
composed of synthetic polyurethane foam, embed-
ded hydrogel, or hydrocolloids have been clini-
cally used. However, these materials only satisfy
one or few of the required standard characteristics
of an ideal wound dressing and play a passive and
limited role in wound healing [11, 18].
Various dressing materials have been devel-
oped from conventional dressing methods such as
the use of gauzes and biological dressing materi-
als such as polyurethane foam, hydrocolloids,
hydrofibers, hydrogels, and alginate [10, 28].
The gauze is a simple and inexpensive mate-
rial to use in a stopgap method, but is often
implemented as a dressing. However, there is
pain associated with the dressing change, the
529
wound gets desiccated, and the moist environ-
ment is not maintained. Commercially produced
polyurethane foam include Medifoam® (Ildong
Pharmaceutical, Seoul, Korea), Allevin® (Smith
and Nephew, London, UK), Biatain® (Coloplast,
Fredensborg, Denmark), and Versiva® (Convatec,
Chester, UK) [21]. Polyurethane foam is widely
used due to its ability to absorb the exudate, non-­
adherence to the wound surface, and minimized
interference with cellular activity. However, it
can aggravate infected wounds and has no special
function other than to absorb the exudate [46].
Hydrocolloid agents, including Duoderm®
(Convatec) and Comfeel® (Coloplast), exhibit
wound protection and necrotic degradation, but
also cause cellular damage on the wound surface
due to stickiness when removed and are inade-
quate to use when there is a large amount of exu-
date. Hydrofiber materials include Aquacell-Ag®
(Convatec) and Acticoat® (Smith and Nephew).
Silver-containing hydrofibers possess antimicro-
bial effect to a certain degree, but after use, the
debris of the fiber adheres and gets invaginated
into the wound and exhibits cytotoxicity against
important cell components needed for wound
healing, such as keratinocytes and fibroblasts,
implying that hydrofibers have limited applica-
tion in common cases [12, 24, 37]. In addition,
various hydrogel components including alginate
are used to promote wound healing. Currently,
the commercially available hydrogels are Intrasite
Gel® (Smith and Nephew), Purilion gel®
(Coloplast), and Kaltostat® (Convatec).
28.1.4 Development of Chitosan-­
Based Dressing Material
Currently available dressing materials can be
adapted according to the characteristics of the
wound to promote wound healing. However, it is
necessary to develop a more active and functional
dressing material for effective wound healing.
The most common approaches for developing
new and improved wound dressing materials
include synthesizing and modifying biocompati-
ble materials. Studies have attempted to develop
530
various materials that are effective in wound
healing such as hydrocolloids, hydrofibers, algi-
nate, etc. [11, 18, 34]. Among them, chitosan and
its composite materials have gained considerable
attention because of their biocompatible and non-
toxic characteristics, flexibility, and distinctive
strength. Across various fields, several studies
have been conducted to improve the biological
and mechanical properties of chitosan by com-
bining it with other organic or inorganic materi-
als [14, 15, 36, 38, 43]. However, the wound
healing capabilities in these studies have not been
extensively compared with widely used commer-
cial dressing materials, providing limited infor-
mation from a practical perspective [19].
28.2 Chitosan as a Natural
Polymer
28.2.1 Characteristics of Chitosan
Chitin was first discovered as an insoluble mate-
rial obtained from mushrooms by Henri
Bracoonot in 1811 [31]. Subsequently, it was also
discovered in various organisms, namely in the
outer skeleton of crustaceans (crabs, lobsters,
shelfish, and shrimp), shell of insects, and even in
the cell walls of mycelial fungi [45]. Chitosan, a
derivative of chitin, is a natural polysaccharide
composed of β (1–4) glycosidic bond-linked
D-glucoamine and N-acetyl-D-glucosamine. The
degrees of deacetylation (DDA) are key factors
that determine the physical property of chitosan.
Highly deacetylated chitosan has numerous free
amine groups, making it sensitive to pH varia-
tion. Amines from chitosan chains are uncharged
over pH 6.3 while they are protonized in acidic
conditions under pH 6.3, suggesting that chitosan
has the potential of being used as an advanced
drug delivery system, which can selectively
release drugs at certain pH levels [53]. Chitosan
is also biodegradable. It is mainly degraded by
lysozyme, which is present in human body fluids
and tissues. The degradation time is related to the
DDA and the copolymer type of chitosan. Higher
DDA induces slower degradation rates (chitosan
with >90% DDA could not be degraded by lyso-
J.-U. Park et al.
zyme), and a block-type copolymer exhibits
faster degradation mechanics than a random-type
copolymer [53].
28.2.2 Chitosan-Based Biomaterials
Chitosan has been widely used in versatile bio-
medical applications, including guided bone
regeneration (GBR) membranes carrying drugs,
hemostatic agents, and antimicrobial agents.
GBR is dominantly applied in dental surgery to
support hard tissue growth and integration. It
needs to be biocompatible, exclude unwanted
cells, and provide the space to allow tissue
ingrowth. Chitosan is a biocompatible natural
polymer and it can be fabricated into membrane
form with interconnected pores where tissues
permeate into the membrane, facilitaitng bone
regeneration. Recently, efforts to develop
improved chitosan-based GBR were conducted
by applying other osteoconductive biomaterials
(for e.g., silica, hydroxyapatite, and other natural
polymers (for e.g., fibroin) or protein-based
growth factors (for e.g., bone morphogenetic pro-
tein-­2 (BMP-2)) to chitosan membrane. Chitosan/
fibroin-hydroxyapatite composite was prepared
as a GBR membrane in a rabbit calvarial model
for 8 weeks. It was effective in terms of new bone
formation and inflammatory response, compara-
tive to commercially available collagen mem-
brane (Bio-Gide) [60]. Similarly, chitosan
hybridized with silica xerogel induced mineral-
ization in physiological conditions, enhanced
biological properties (such as alkaline phospha-
tase activity, indices of differentiation and prolif-
eration of ATCC pre-osteoblasts. and promoted
bone regeneration significantly in vivo [36].
Chitosan is also widely used as a hemostatic
agent. Its use as a hemostatic agent or dressing
membrane was approved in the USA due to its
potential to modulate cell mechanisms and
induce rapid blood clotting. The functional NH3+
groups of cationic chitosan enhances platelet
aggregation, which results in clot formation.
Celox (Medtrade products Ltd., Cheshire, UK) is
currently used as a commercial chitosan-based
hemostatic agent for severe hemorrhage [42]. It
28  Chitosan-Based Dressing Materials for Problematic Wound Management
was already used in emergency situations (such
as severe bleeding during cardiothoracic surgery)
and military settings. Recently, to enhace throm-
bosis and hemostasis, composite systems (devel-
oped by incorporating zinc ion, cellulose, and
kaolin with chitin) have been developed to pro-
duce synergistic effects [29, 47, 63] In addition,
based on the applications, various types of com-
posite systems were developed, including porous
microspheres for deep and irregular shapes of
surgical sites and dressings for covering large
areas.
Chitosan exhibits antimicrobial effects against
gram-negative bacteria. The primary amines of
chitosan disrupt the outer membranes of bacteria,
destroying the metabolism effectively.
Furthermore, chitosan is a prime polymer to dis-
perse and stabilize inorganic nano-particles, such
as silver nano-particles (NPs), which possess
anti-microbial effects against sulfur and phos-
phorous present in the microbial cells. Chitosan
is also considered biocidal and has been proposed
as a parasitic control agent against Lernaea cypr-
inacea, which is frequently found in gold fish
(Carassius auratus) aquaria during the spring
[2]. Chitosan-silver NPs composite system was
also incorporated in electrospun mats in which
silver NPs were dispersed homogeneously inside
the chitosan fiber and exhibited anti-bacterial
effects, especially against Escherichia coli [1].
28.2.3 Chitosan-Based Composite
Biomaterials
Chitosan is extensively used in composite sys-
tems with other natural polymers, synthetic poly-
mers, inorganic particles, drugs, or growth
factors. For application in the dairy industry, a
silica/chitosan composite was developed to
immobilize β-galactosidase to increase its stabil-
ity [54]. Chitosan phosphatic thermosensitive
hydrogels—which hold significant potential for
minimum injury surgery by regulating the applied
heat—were developed using nano-noble Ag@Pd
particles [3]. A chitosan/gelatin composite (CG)
was developed as a hemostatic agent [32]. CG
exhibited excellent liquid absorption and pro-
531
moted platelet aggregation significantly under in
vitro conditions. Its hemostatic property was fur-
ther verified in greater detail using in vivo bleed-
ing models (rabbit ear artery injury model and
rabbit liver injury model). CG was effective in
inducing rapid blot clot formation and swiftly
reducing bleeding. In addition, the bony defect
healing capability of BMP-2-loaded chitosan/sil-
ica hybrid membrane was demonstrated in in
vitro and in vivo studies [35]. Hybrid systems
exhibited higher affinity for BMP-2 as a drug car-
rier to deliver growth factors in a sustained man-
ner. The hybrid system synergetically improved
osteoconductivity in GBR, accelerating new
bone formation in the regions of defects.
Chitosan/silica hybrid also showed great perfor-
mance as a dressing membrane in wound healing.
As nano-scale silica was incorporated in chitosan
by sol-gel process, its biological property was
enhanced in terms of cellular responses, which
accelerated the healing process in vivo. Silicon
ion released from hybrid systems and the bioac-
tive chitosan-based hybrid membrane itself pro-
moted fibroblast (L929) proliferation in vitro.
When the hybrid dressing was used in an in vivo
study, wound closure was accelerated, cellularity
level was lowered, TGF-β and α-smooth muscle
actin densities increased, and the newly formed
collagen matrix was aligned, organized uni-
formly and dense, as determined from in vivo
immunohistology assays [50].
28.3 Chitosan-Based Dressing
Materials
28.3.1 Functional Benefits
of Chitosan as a Dressing
Material
Chitosan has been reported to accelerate wound
healing in all stages. It prohibits hemorrage by
inducing thrombosis, enhances the function of
inflammatory cells (polymorphonuclear leuko-
cytes (PMNs) and macrophages), and activates
the fibroblasts to form new collagen matrix in the
regions of tissue defects [6]. Furthermore, the
chitosan membrane is able to maintain a
532
p­hysiologically moist microenvironment that
promotes healing and formation of granulation
tissue and achieves hemostasis. Due to its high
potential as an ideal healing agent, chitosan-
based products have been commercially fabri-
cated and studied [16, 30, 64]. However, there are
concerns regarding its low bioactivity (when it is
used in vivo) and the unsatisfactory maintenance
of the chitosan framework, particularly in the
moist condition [27]. Therefore, the development
of an efficient chitosan composite system for
accelerated wound healing in problematic clini-
cal wounds continues to remain a major
challenge.
28.3.1.1 Hemostasis
Hemostasis is the first step in the wound healing
process. Hemorrhage is controlled by two essen-
tial components: platelets and fibrin. Platelets are
composed of alpha granules containing crucial
signaling proteins, such as PDGF and TGF-β, to
initiate the wound healing cascade by attracting
inflammatory cells to the wound sites [6].
Chitosan helps in the process by inducing an
intrinsic pathway of coagulation. Positively
charged polymeric chains of chitosan gather neg-
atively charged cell membranes of erythrocytes
by electrostatic interactions, leading to agglutina-
tion of erythrocytes, formation of a plug at the
site of tissue defects and prevention of severe
bleeding [13]. Based on the hemostatic property
of chitosan, a collagen sponge coated with chito-
san/calcium pyrophosphate nanoflowers was
developed. The nanoflower-coated collagen
sponge promoted hemoglobin adsorption and
platelet adhesion in vitro and reduced the time
required for hemostasis and the extent of bleed-
ing significantly in an in vivo hepatic trauma
model and a ear artery model as well [67].
28.3.1.2 Acceleration of Wound
Healing Process
Based on the DDA, chitosan exhibits different
cytotoxicities to keratinocytes and human skin
fibroblasts. Chitosan with high DDA (89%) stim-
ulated the proliferation of fibroblasts but inhib-
ited human keratinocyte mitogenesis in vitro
J.-U. Park et al.
[25]. In an in vitro cell viability study using
HaCaT (a cell line of human keratinocyte), it was
found that chitosan promoted the release of cyto-
kines from the HaCaT cells to induce apoptic cell
death [66]. PMNs, which characteristically react
to foreign bodies, were not affected by chitosan
when PMNs were isolated in the membrane and
reactive oxygen species (ROS) were detected
[57]. However, it was reported that chitosan-­
treated wounds exhibited severe infiltration of
PMNs in the early proliferation stage, and granu-
lation was more distinctive at a later stage [64].
Collagen production also increased, as demon-
strated by immunohistochemical analysis.
Moreover, in open skin wounds, chitosan ban-
dage increased the epithelialization rate and
deposition of organized collagen in the dermis,
and reduced the number of inflammatory cells
significantly in vivo.
28.3.1.3 Antimicrobial Effect
of Chitosan
Chitosan with molecular weight (MW) < 305 kDa
exhibited antimicrobial activity against both,
gram-negative and gram-positive barcteria [69].
High MW chitosan exhibited an enhanced anti-
microbial effect against gram-positive
Staphylococcus aureus, whereas low MW chito-
san showed a high antimicrobial activity against
gram-negative E. coli. It was suggested that chi-
tosan exhibits antimicrobial effects by two mech-
anisms in their study: (1) the chitosan polymer
chain blocks the nutrients entering through the
bacterial membrane, and (2) low MW chitosan
enters the bacterial cell wall through pervasion
and disrupts the physiological activities of bacte-
ria. The first mechanism is predominantly
observed in gram-positive bacteria and the sec-
ond mechanism is seen in gram-negative bacte-
ria. The antibacterial property of chitosan can be
further enhanced by adding other drugs or nano
particles. Vancomycin and daptomycin were suc-
cessfully loaded on chitosan films to alleviate
infections after bone fractures, and silver nano-­
particles were incorporated in wound dressing
material, especially in cases of infected wounds
[59, 65].
28  Chitosan-Based Dressing Materials for Problematic Wound Management
28.3.1.4 Chitosan Composite
Dressing Materials
Chitosan-based dressing materials can be
enhanced by incorporating antimicrobial or bio-
active inorganic particles and grafting biopoly-
mers in the chitosan chain. Chitosan dressing
incorporated with zinc oxide and silver nanopar-
ticles exhibited enhanced antibacterial activity
that inhibited representative bacteria (such as S.
aureus, E. coli, and Pseudomonas aeruginosa),
indicating its potential as a dressing material for
infected wounds [39]. Chitosan/titanium oxide
(TiO2) composite improved fibroblast prolifera-
tion, induced the expression of fibroblast markers
(TGF-β, fibroblast growth factor-2, collagen type
I, delta like non-canonical notch ligand 1, and
proliferating cell nuclear antigen), and showed
significant antibacterial effects [7]. Furthermore,
the composite could induce an accelerated heal-
ing rate by activating the fibroblast signaling
pathway during the inherent healing cascade.
Sericin extracted from silk fiber was also blended
with chitosan as a form of electrospun fiber mats
[68]. Sericin provided antioxidant, hydrophilic
(to absorb moisture), and antibacterial functions
to the chitosan membrane, enhancing the poten-
tial of chitosan as a dressing material. An algi-
nate/chitosan-based bi-layer composite could
deliver ciprofloxacin hydrochloride continually
[23]. The chitosan membrane was present in the
exterior of the bi-layer composite to prevent bac-
terial invasion and control the water vapor trans-
mission ratio, and the inner part of the bi-layer
composite consisted of an alginate scaffold,
which contained drugs, and drains the exudates
from the wounds. Chitosan-silica hybridized
membrane coupled with sol-gel technique is also
another promising chitosan composite dressing
material [49]. It successfully performed wound
closure for a full-thickness porcine wound model,
accelerated the healing rate, and improved epi-
thelialization, fibroblast proliferation, collagen
formation, and inflammatory cell infiltration
histologically.
28.3.1.5 Scaffold for Drug Delivery
Local-drug delivery systems are beneficial for
wound dressing to achieve a high concentration
533
of drugs at the target sites, while lowering the
total amount of serum needed, compared with
whole body dosing, which could induce systemic
toxicity [11]. Melatonin-loaded chitosan/
Pluronic® F127 microspheres were developed as
an innovative antimicrobial dressing [56].
Melatonin was entrapped in the microspheres to
potentiate chitosan antimicrobial activity against
S. aureus and five clinical methicillin-resistant S.
aureus (MRSA) strains, without inducing any
deteriorating effects on the composite biocom-
patibility with skin keratinocytes and fibroblasts.
Levofloxacin (Levo, fluoroquinolones, approved
in 1996 by the FDA) was successfully delivered
through a grafted derivative of chitosan with
2-hydroxyethylacrylate (CS-g-PHEA) to kill
methicillin-susceptible S. aureus, MRSA, and P.
aeruginosa [58]. The chitosan/CS-g-PHEA com-
posite shows conisderable promise in wound
infection management and exhibits tolerability,
safety, and antibacterial activity as a potential
wound dressing material. Chitosan scaffolds con-
taining growth factors, which can accelerate the
healing stage by intervening in the healing cas-
cade directly, were also studied. Chitosan-bFGF
scaffold accelerated wound closure in pressure
ulcers in an aged mouse model, enhanced angio-
genic functions by delivering growth factors, and
elevated neutrophil levels, which contributes to
the proteolytic conditions of pressure ulcers [48].
28.3.2 Clinical Applications
of Chitosan-Based Dressing
Materials
The wound healing proficiency of chitosan-based
dressing was further demonstrated through clini-
cal study in the human body. Azad et  al. con-
ducted a clinical study using a mesh-type chitosan
membrane (with DDA 75%), incorporated with
other protein and mineral contents, and a MW of
1500 kDa [5]. The clinical results obtained post-­
treatment with the mesh chitosan matrix were in
alignment with the results of an in vivo animal
test, in terms of efficient adherence, hemostasis,
healing rate, and re-epithelialization, and the
mesh chitosan matrix was found to be ­significantly
534 J.-U. Park et al.

better than Bactigras®, a chlorhexidine acetate- rior biocompatibility and bioactivity, while
impregnated tulle gras, used as the control. It pro- exhibited accelerated wound healing. In future, it
moted faster healing and re-organized the is important to develop standardized prototypes
collagen matrix into healthy and highly accept- of chitosan-based dressing materials, and to
able new skin. In another study, clinically treat- prove their effectiveness in wound healing in
ing skin graft donor sites using N-carboxybutyl humans through clinical trials for various clinical
chitosan showed that vascularization and histoar- wounds. Chitosan-based dressing materials have
chitectural order improved and the number of significant potential for use as multi-functioning
inflammatory cells decreased in the chitosan- dressing materials, which provide an effective
treated sites [9]. Stone et al. evaluated the healing wound healing environment in problematic clini-
effects of a chitosan dressing called Hyphecan cal wounds.
(Hainan Kangda Marine Biomedical Corporation,
Hong Kong, China) in a clinical study [61].
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