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Clinical and Antibiofilm Efficacy of Antimicrobial Hydrogels

This article reviews the clinical and antibiofilm efficacy of antimicrobial hydrogels in wound healing, emphasizing their role in managing biofilms that hinder recovery. While hydrogels are effective in treating various wound types, evidence supporting their efficacy against biofilms is limited, necessitating further research. Future studies should focus on improving in vivo biofilm models to better evaluate the effectiveness of these hydrogels in clinical settings.

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0% found this document useful (0 votes)
13 views9 pages

Clinical and Antibiofilm Efficacy of Antimicrobial Hydrogels

This article reviews the clinical and antibiofilm efficacy of antimicrobial hydrogels in wound healing, emphasizing their role in managing biofilms that hinder recovery. While hydrogels are effective in treating various wound types, evidence supporting their efficacy against biofilms is limited, necessitating further research. Future studies should focus on improving in vivo biofilm models to better evaluate the effectiveness of these hydrogels in clinical settings.

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elderj21
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Clinical and Antibiofilm Efficacy

of Antimicrobial Hydrogels

Simon Finnegan1,* and Steven L. Percival 2–4


1
Department of Chemistry, University of Sheffield, Sheffield, United Kingdom.
2
Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom.
3
Surface Science Research Centre, University of Liverpool, Liverpool, United Kingdom.
4
Scapa Healthcare, Manchester, United Kingdom.

Significance: Hydrogels have been shown to have a significant role to play in


wound healing. Hydrogels are used to assist in the management of dry, sloughy,
or necrotic wounds. However, recent scientific evidence has shown that biofilms
delay wound healing and increase a wound propensity to infection. It is therefore
essential that hydrogels incorporating antimicrobials demonstrate efficacy on
biofilms. Consequently, it is the aim of this article to review the efficacy of
hydrogels, incorporating antimicrobials, on wounds with specific reference to
Simon Finnegan, MCHEM their efficacy on biofilms.
Recent Advances: Technologies being developed for the management of wounds
Submitted for publication April 27, 2014. are rapidly expanding. In particularly next-generation hydrogels, incorporating
Accepted in revised form June 10, 2014. copolymers, have been reported to enable the smart release of antimicrobials.
*Correspondence: Department of Chem- This has led to the development of a more tailored patient-specific antimicrobial
istry, University of Sheffield, Dainton Building,
Brook Hill, Sheffield S3 7HF, United Kingdom hydrogel therapy.
(e-mail: [email protected]). Critical Issues: Evidence relating to the efficacy of hydrogels, incorporating
antimicrobials, on biofilms within both the in vitro and in vivo environments is
lacking.
Future Direction: Studies that investigate the efficacy of antimicrobial hydrogel
wound dressings on both in vivo and in vitro biofilms are important. However,
there is a significant need for better and more reproducible in vivo biofilm
models. Until this is possible, data generated from appropriate and represen-
tative in vitro models will help to assist researchers and clinicians in evaluating
antimicrobial and antibiofilm hydrogel technology for the extrapolation of effi-
cacy data relevant to biofilms present in the in vivo environment.

SCOPE AND SIGNIFICANCE specifically when used in the manage-


Microorganisms have detrimen- ment of at-risk or already infected
tal effects on wound healing by wounds and biofilms, based on cur-
affecting healing times, a patient’s re- rently available research publications.
covery time, risk of infection, and costs
to the health service. To help manage
wound healing, dressings, in particular TRANSLATIONAL RELEVANCE
hydrogels, are employed. However, the Chronic wounds are tissue injuries
efficacy of hydrogels on wound healing, that heal slowly or completely fail
and biofilms specifically, is poorly re- to heal. Generally, if a wound has not
searched and discussed. Consequently, healed beyond 12 weeks or the same
it is the intention of this article to re- wound reoccurs in a repetitive fash-
view the hydrogel platform and report ion, it will be classified as a chronic
on its effectiveness on wound healing wound.1 Such wounds fail to heal due

398 j ADVANCES IN WOUND CARE, VOLUME 4, NUMBER 7


Copyright ª 2015 by Mary Ann Liebert, Inc. DOI: 10.1089/wound.2014.0556
ANTIBIOFILM EFFICACY OF ANTIMICROBIAL HYDROGELS 399

to repeated tissue insults or underlying physiological excessive polymorphonucleocyte and metallopro-


conditions, such as diabetes, persistent infections, tease levels (in particular, matrix metalloproteases
poor primary treatment, and other patient-related [MMPs]-2 and -9), microbial wound bioburden, and
factors.2 Further the risk of these wounds becoming more recently evidence of a virulent biofilm.12
infected is high due to the presence and coloniza- A biofilm is defined as a community of microor-
tion of endogenous and exogenous microorganisms2 ganisms attached to a surface, or each other, which
growing both within the planktonic and biofilm becomes encased in a self-generated extracellular
phenotypic states. matrix, referred to as the extracellular polymeric
substance, which is fundamentally composed of
CLINICAL RELEVANCE polysaccharides, proteins, glycoproteins, extracel-
lular DNA, and metal ions.
Hydrogel wound dressings contain water (typi-
Wound dressings, in particular hydrogels, are a
cally between 70% and 90%)3 and have been shown
standard treatment required for the management
to have a significant role to play in wound heal-
of wounds and are used for both the donation of
ing.4,5 They are generally utilized in the manage-
fluids in dry wounds and the removal of excessive
ment of sloughy or necrotic wounds given their
levels of wound exudate in wetter wounds. Wound
requirement for moisture. They are non-reactive
dressings are classified in a number of ways de-
with biological tissue, have a high permeability to
pending on their function: first, whether they func-
metabolites, and are non-irritant.6 Hydrogels have
tion to help debride, treat at-risk or infected wounds,
the ability to absorb fluid thousands of times their
provide an occlusive environment, or absorb exudate
dry weight.7 Since these gels are used in all wound
at the wound site13; second, on the type of material
types, their rheological profile is such that they
used, that is, hydrocolloid, alginate, or collagen13;
stay in place after application to the wound and can
and third, on the physical form of the dressing, that
remain in situ for relatively long periods of time.8
is, an ointment, film, foam, fiber, or a hydrogel.14
Hydrogels are water-retaining, swelling hydro-
BACKGROUND philic materials made from polymers or a combi-
Enormous gaps still remain in our knowledge nation of polymers, which can be either synthetic or
regarding the etiology (origin) and pathogene- natural in origin. As examples poly(methacrylates)
sis (mechanism) of chronic wounds. In general, all and polyvinylpyrrolidone are typically used poly-
chronic wounds are categorized into three groups: mers. Dressings, such as Nu-gel ( Johnson and
venous ulcers, pressure ulcers, and diabetic ulcers. Johnson) and Purilon (Coloplast), use hydrogel
These three types of chronic wounds upon first in- alginate combinations. Hydrogels can be applied
spection would appear to have little in common and either as an amorphous gel or as elastic, solid sheets
have been addressed previously as separate con- or films. Although hydrogels are very similar to
ditions. However, examining their commonalities hydrocolloids, hydrogels have subtle differences
in more detail leads to the hypothesis that human in action. Hydrocolloids are a type of dressing con-
chronic wounds may not have a unique defect in- taining gel-forming agents, such as sodium carboxy-
dividual to each group but they represent a com- methylcellulose (NaCMC) and gelatin, often in
bination of common factors.9 Each component of combination with elastomers and adhesives and ap-
pathogenesis, including biofilm virulence, is dam- plied to a carrier. In the presence of wound exudate,
aging to wound healing, but collectively they com- hydrocolloids absorb liquid and form a gel while hy-
pletely overwhelm the natural healing response. drogels are a water containing gel already upon ap-
Mustoe and colleagues10 have previously proposed plication. In the intact state, most hydrocolloids are
this theory of unification of causes. However, the impermeable to water vapor, but as the gelling pro-
treatment of chronic wounds should be addressed cess takes place, the dressing becomes progressively
on an individual basis. more permeable.15 Hydrogels are typically cross-
The management of chronic wounds is a complex linked and produced in free radical reactions These
process compounded by underlying pathophysiol- are summarised schematically in figure 1.
ogies and neuropathies. Many chronic wounds are
characterized by chronic inflammation resulting
in the release of cytotoxic enzymes, free radicals, DISCUSSION OF FINDINGS
and inflammatory mediators that can cause dam- AND RELEVANT LITERATURE
age to the host tissues if not properly controlled.11 Hydrogels
A state of prolonged inflammation can be initiated The use of hydrogels as debriding agents in di-
and augmented by a number of factors, including abetic foot ulcers was included in the Cochrane
400 FINNEGAN AND PERCIVAL

Moody reported on the use of a hydrogel dressing to


treat a chronic leg ulcer for a patient who could not
tolerate even reduced compression therapy due to
pain; the hydrogel helped reduce the pain consider-
ably to allow for therapy to continue.19
Many hydrogels reside in the market place, in-
cluding amorphous gels and gel dressings. Examples
include NuGel ( Johnson & Johnson), GranuGel
and DuoDERM Gel (ConvaTec), Intrasite (Smith
& Nephew), and AquaForm (Maersk), Prontosan
Figure 1. Schematic methods used in the formation of crosslinked hy- (B. Braun), Hydrosorb (including Aquaclear; Hart-
drogels by free radical reactions, including a variety of polymerizations and mann), Purilon gel (Smith & Nephew), Curafil
crosslinking of water-soluble polymers. Examples include crosslinked
and Curagel (Covidien), Hypergel (Mölnlycke
polyhydroxyethylmethacrylate (PHEMA) and polyethylene glycol (PEG)
hydrogels. Health Care), Spenco 2nd Skin (Spenco Medical UK
Ltd.), SoloSite gel (Smith & Nephew), Solugel
( Johnson & Johnson), and Sterigel (Seton Health-
Review by Smith.16 This review highlighted that care). A major point of differentiation between prod-
hydrogels increased the healing rate of diabetic ucts is in their absorbent properties and ability to
foot ulcers compared to gauze and standard wound donate fluid. There is a continuing and growing need
care. However, it was unclear whether this effect for hydrogels containing antimicrobials for the use of
was due to debridement or the intrinsic properties those wounds that are at risk of infection, infected, or
of hydrogels. Furthermore, the follow-up period to ‘‘biofilm infected.’’ The most commonly used antimi-
these trials was relatively short and restrictions crobials added to hydrogels include silver, iodine, and
may have occurred as a consequence of the self- polyhexamethylene biguanide (PHMB). The efficacy
application of the dressings by the patients. Yet, in of these antimicrobial-based hydrogels on wound
other randomized control trials, hydrogels have healing, microbes, and biofilm will be discussed.
been reported to be equal to, or superior in terms of
fluid absorption and odor control17 when compared Silver hydrogels and biofilms
with various hydrocolloid dressings.15 This demon- Some currently available silver hydrogels include
strates that, when compared with a hydrocolloid SilvaSorb (Medline), Elta Silver Gel (Elta Skin
dressing, a synthetic polymer hydrogel dressing and Wound Care), Silver Shield and Silver-Sept
performed more favorably in terms of overall clinical (Anacapa Technologies), Gentell Silver Hydrogel
performance based on its ability to aid autolytic de- (Gentell), DermaSyn/Ag (DermaRite Industries),
bridement; however, healing rates were comparable SilverMed (MPM Medical, Inc.), ReliaMed Silver
for the two dressings. Thomas et al.17 reported Hydrogel (ReliaMed), and Silver Genesis Colloidal
findings that a hydropolymer dressing outperformed Silver Hydrogel (Silver Genesis). Efficacy of anti-
a hydrocolloid dressing in terms of dressing leakage microbial hydrogels on biofilms will be discussed
and odor control in the treatment of leg ulcers and where research is available.
pressure sores. An earlier study by Geronemus It has long been known that ionic silver possesses
and Robins documented the ability of hydrogel antimicrobial properties. Silver is available in a
dressings to promote reepithelialization of wounds, number of therapeutic preparations, including col-
using a pig wound model, by up to 44% when com- loidal silver suspensions, a dilute salt solution (0.5%
pared with control untreated wounds.15 In a more silver nitrate solution), creams, and in modern wound
recent study, hydrogels were found to be superior dressings. Preparations including silver sulfadiazine
to a conservative treatment with povidone-iodine- and silver nitrate are commonly used for wound in-
soaked gauze, facilitating the rapid epithelialization fections, with antimicrobial efficacy reported on
of pressure ulcers in 27 patients.18 Also evaluated in Pseudomonas-aeruginosa-related infections.20–22
this study was the safety and efficacy of a hydrogel A number of studies have investigated the effec-
dressing in comparison to a hydrocolloid dress- tiveness of silver hydrogels in the treatment of
ing and wet-to-moist gauze. They found that, while wounds. Boonkaew et al. compared the antimicrobial
each dressing was satisfactory in providing an en- efficacy of a novel silver hydrogel dressing compared
vironment favorable to healing, the hydrogel dress- with two commonly used dressings (Acticoat and
ing proved superior in terms of; visualization of the PolyMem Silver).23 The silver hydrogel dressing was
wound, nonadhesiveness, cooling effect, ease of ap- composed of 2-acrylamido-2-methylpropane sulfonic
plication, and conformability.18 A further study by acid sodium salt with silver nanoparticles. To com-
ANTIBIOFILM EFFICACY OF ANTIMICROBIAL HYDROGELS 401

pare the antimicrobial efficacy of each dressing, three pare and contrast currently available antimicro-
different antimicrobial tests were used: disc diffu- bial dressings. The dressings that were evaluated
sion, broth culture, and the Live/Dead Baclight included Cadesorb, Idoflex, Alisite, Acticoat,
bacterial viability assay against P. aeruginosa, Medihoney, Curity, Tegaderm, SilvaSorb,
Meticillin-sensitive Staphylococcus aureus, Acineto- Prontosan, Triadine, and Aquacel. The bio-
bacter baumannii, Candida albicans, Meticillin- film was subjected to pretreatment with gentami-
resistant S. aureus, and vancomycin-resistant cin for 24 h to gain antibacterial resistance. The
enterococci. Acticoat was reported to be the most study was conducted over a 24 h time period. The
efficacious dressing, with a zone of inhibition rang- study concluded that the ability of antimicrobial
ing from 13.9 to 18.4 mm. Acticoat reduced the mi- wound dressings to kill mature biofilms varies
crobial inocula below the limit of detection and widely with time of exposure, number of applica-
reduced microbial viability by 99% within 4 h. Poly- tions, moisture level, and release profile. However,
Mem Silver had no zone of inhibition for most of the researchers did conclude that taking into ac-
the evaluated test microorganisms, and it also count the large degree of variables SilvaSorb and
showed poor antimicrobial activity in the broth cul- Iodoflex were the most effective in reducing the
ture and Live/Dead Baclight assays. The silver mature biofilm by a log of five.28
hydrogel reduced most of the tested microbes below
Iodine hydrogels and biofilms
the detection limit and decreased bacterial viability
Vogt et al.29 undertook a monocentric, random-
by 94–99% after 24 h exposure.23
ized, observer-blinded, phase III study of a poly (N-
Shuffitt et al. reported on the ability of SilvaSorb
vinylpyrrolidone) (PVP)–iodine preparation hydro-
to deliver ionic silver and moisture to the wound
gel containing a 3% iodine concentration (Repithel)
bed, as a result the dressing only required changing
to study the effect on epithelialization in patients
three days after application. The increase in appli-
receiving meshed skin grafts. Grafts of 167 patients
cation time resulted in an overall reduced bioburden.
(donor site defects, burn wounds, or chronic defects)
This case series demonstrated a cost-effective and
were dressed either with Repithel (n = 83) covered
clinically effective method of treatment.24 Glat et al.
with a gauze ( Jelonet), or Jelonet-gauze only (n = 84)
also presented a study on SilvaSorb (Medline
until healing. The grafts that received Repithel
Industries, Inc.) compared with silvadene (King
healed significantly earlier (9.4 vs. 12.4 days;
Pharmaceuticals), a silver sulfadiazine cream, dem-
p < 0.0001) and faster than controls, as measured by
onstrating the efficacy of SilvaSorb in the treatment
neo-epithelialization of mesh holes between days 7
of partial-thickness burns.25 Recently Simcock and
and 11 (91.20 – 22.8% vs. 82.3% – 28.6, p < 0.001).29
May conducted a study on split-skin graft recon-
Further, Beukelman et al.30 tested PVP-ILH, Re-
struction of scalp defects using a decellularized ex-
pithel, on its ability to reduce the inflammatory re-
tracellular matrix biomaterial, with application of
sponse. The study showed that PVP-ILH reduced
SilvaSorb after application to successfully stop in-
the amount of free superoxide anions and helped
fection at the site of reconstruction.26
promote ‘‘normal’’ wound healing.30
Zelen et al.27 compared the healing characteris-
Mishra and Chaudhary tested numerous hy-
tics of diabetic foot ulcers treated with dehydrated
drogels that had incorporated povidone-iodine
human amniotic membrane allografts (EpiFix;
(PVP-I) showing that its release could be tailored by
MiMedx) versus SilvaSorb ( Medline Industries,
hydrogel composition leading to improved wound
Inc.). An international review board–approved,
healing.31 Homann et al. demonstrated the efficacy
prospective, randomized, single-center clinical
of a novel PVP-I-loaded liposome hydrogel in a
trial was performed. Included were patients with
randomized controlled trial compared with silver
a diabetic foot ulcer of at least 4-week duration,
sulfadiazine cream treatment. The liposome PVP-I
without infection, and having adequate arterial per-
hydrogel resulted in significantly faster, complete
fusion. Patients were randomized to receive Silva-
healing of the burn wounds compared with silver
Sorb alone or with the addition of EpiFix. In the
sulfadiazine cream (9.9 – 4.5 vs. 11.3 – 4.9 days;
SilvaSorb group alone (n = 12) and the EpiFix group
p < 0.015). Local tolerability was also noted to be
(n = 13), wounds reduced in size by a mean of
good; handling and change of dressing were also
32.0% – 47.3% versus 97.1% – 7.0% ( p < 0.001) after 4
rated as easy.32
weeks. Patients treated with EpiFix achieved supe-
rior healing rates over standard treatment alone.27 PHMB hydrogels and biofilms
In a recent comprehensive comparative study on The antimicrobial activity of PHMB owes itself
biofilms, Phillips et al.28 used an ex vivo porcine to its molecular shape and charge. Where PHMB
skin explant, P. aeruginosa biofilm model to com- causes an irreversible loss of essential cellular
402 FINNEGAN AND PERCIVAL

components due to damage caused to the cytoplasm was used for 3 days to prevent pes equinus and to
membrane. PHMB has also been found to prevent let the ankle joint rest. Change in wound size (cm2),
the efflux pump and so the microbe is unable to incidence of local infection, wound bed character-
reduce the levels of antimicrobial present within istics, and pain levels (measured on a 0–10 pedi-
it.33 Therefore, microorganisms are not known to atric pain scale) were assessed at 3-day intervals
adapt to PHMB and no known resistance has yet during the 14-day treatment period. Satisfaction
been documented.34 with the dressing was also evaluated. Twenty chil-
The precise mechanism of action of PHMB on dren (mean age = 5.6 – 1.33 years) were recruited
bacteria still remains unclear.34 An example of into the study and included in the analysis. The
a PHMB-containing hydrogel is Suprasorb X + mean baseline wound area was 8.60 – 6.57 cm2. The
PHMB.35 Bruckner et al.36 performed a study on 40 mean time to complete wound closure was 12.95 –
patients, each suffering from delayed wound healing 7.69 days with a mean total of 4.70 – 1.56 visits. The
for at least 3 weeks, and signs of critical colonization/ mean pain score was 9.55 – 0.69, compared with
infection to determine the efficacy of Suprasorb X + 0.15 – 0.37 on day 14 ( p < 0.003). At the second visit
PHMB. The progress of wound healing was evaluated (after 3 days), 17 of the 20 children were reported to
by a colorimetric method. In 32 out of 40 patients, the be free of pain. No cases of local infection were noted.
share of granulation tissue was increased, as a result The evaluation also showed that it was well toler-
of sufficient reduction of bacterial colonization (gran- ated and achieved good healing outcome.37
ulation tissue start point is 12% – 18% and endpoint is Galitz et al.38 compared the potency of pain and
79% – 24% in 27 – 25 days; n = 40). However, in five the microbial reduction of chronic wounds in a
patients no progress was measured, all of these controlled, randomized, multicentric comparative
wounds were infected with P. aeruginosa with signs of study over a period of 28 days on 21 patients using
biofilm formation.35 BWD-PHMB and a typical silver dressing as a
Consultants36 undertook a cohort study to evalu- comparison. The results of which were inconclusive
ate the clinical efficacy of a polyhexanide-containing in terms of reduction in microbial burden. The pain
biocellulose dressing, Suprasorb X + PHMB (Loh- in changing dressings was noted to be reduced when
mann and rauscher GmbH), for the eradication of using the Suprasorb X + PHMB dressing. Haem-
biofilms in nonhealing wounds. The study consisted merle et al. compared treatment of a polihexanide-
of 28 patients, aged over 18 years, who presented at containing biocellulose wound dressing (BWD +
an outpatient wound clinic with nonhealing, locally PHMB) to silver dressings (Ag) in 38 painful, criti-
infected, and/or critically colonized wounds of various cally colonized or locally infected wounds. Although
etiologies that showed clinical signs of biofilm. The BWD + PHMB and Ag were effective in reducing
patients were prospectively followed for a maximum pain and bacterial burden, the BWD + PHMB was
of 24 weeks or until healing for analysis of safety and stated as being significantly faster at removing the
efficacy endpoints. critical bacterial load from the colonized wounds.39
Evolution of wound size was conducted with Lenselink and Andriessen,40 however, conducted
tracings and standardized digital photographs as a study on the efficacy of Suprasorb X + PHMB on
well as for determining healing rates. At 24 weeks, patients visiting an outpatient clinic with nonheal-
12 wounds (75%) had healed (complete epithelial- ing wounds of various etiologies that showed clinical
ization with no drainage). Of those wounds that signs of biofilm inhabitancy.40,41 Suprasorb X +
had not closed, the mean wound area had reduced PHMB dressing changes took place two to three
by 61% by week 24. Ten patients (63%) had a good times per week, depending on the wound condition
reduction in biofilm presence, 5 (32%) scored mod- and exudate production, and patients were followed
erate, and 1 (6%) had no reduction noted at week until healing. Reduction of the biofilm was scored on
24, concluding that the PHMB-containing bio- a three-point scale (good/moderate/poor). Reduction
cellulose dressing seems to be suitable for lightly- in wound size was also scored on a three-point scale,
to-moderately exuding wounds.36 using planimetry and photographs. Interestingly
Spits and Van Gent37 conducted a similar study 60% of the 25 patients included in the study had a
to evaluate the clinical benefits, primarily tolera- good reduction in biofilm size and a good reduction in
bility and reduction in pain levels, associated with wound area. These results indicated that Suprasorb
the use of a PHMB-impregnated biosynthetic cel- X + PHMB has the ability to reduce biofilm burden in
lulose dressing (Suprasorb X + PHMB) on pediatric patients with chronic wounds.40 Further, Lenselink
heel lacerations in particular. A PHMB-impreg- and Andriessen performed a similar study in 201142
nated biocellulose dressing was applied and left in that reinforced the efficacy of Suprasorb X + PHMB
situ until epithelialization occurred. A cork splint toward biofilm eradication. Twenty-eight patients,
ANTIBIOFILM EFFICACY OF ANTIMICROBIAL HYDROGELS 403

again from an outpatient wound clinic with non- taining propyl and benzyl side chains with vitamin E
healing, locally infected, and/or critically colonized moiety into physically crosslinked networks of
wounds of various etiologies that showed clinical ‘‘ABA’’-type polycarbonate and poly(ethylene glycol)
signs of biofilm were included in the study. Sixteen triblock copolymers. In vitro antimicrobial stud-
patients (9 women), with a mean age of 60.9 – 21.6 ies revealed that the more hydrophobic [VE/
years, were included in the analysis. The patients BnCl(1:30)]-loaded hydrogels generally exhibited
were prospectively followed for a maximum of 24 better antimicrobial/antifungal effects compared
weeks or until healing for analysis of safety and ef- with their counterpart VE/PrBr(1:30) as lower
ficacy endpoints. Wound size was conducted with minimum bactericidal concentrations (MBCs) were
standardized digital photographs for determining observed in Staphylococcus, Escherichia coli, and C.
healing rates. After 24 weeks, 75% had healed albicans. Similar trends were observed for the
(complete epithelialization with no drainage) and of treatment of biofilms where VE/BnCl(1:30)-loaded
those wounds that had not closed, the mean wound hydrogels displayed better efficiency with regards to
area had reduced by 61% at week 24, 63% had a good eradication of biomass and reduction of microbe vi-
reduction of the biofilm, 32% scored moderate, and ability of the biofilms. These hydrogels also dis-
one had no reduction noted at week 24.42 played excellent compatibility with human dermal
fibroblasts with cell viability > 80% after treatment
New-generation hydrogels and biofilms
with hydrogels loaded with cationic polymers at
Hydrogels containing endopeptidase enzymes,
minimum biocidal concentrations (MBCs).44
which are used to cleave denatured proteins and
Other hydrogels have been reported with prom-
superoxide-dismutase-containing hydrogels, have
ising results, which include oxygen-generating hy-
demonstrated positive effects on wound healing.
drogels,45 thermoresponsive hydrogels,46 semi-inter
Further, a biphosphonate-functionalized hydrogel
penetrating networks hydrogel silver nanocompos-
was reported to inhibit the action of MMPs in
ities,47 and hydrogels incorporating synergistic
chronic wound fluid.43
agents for enhanced antibiofilm activity.48
Lee et al.44 reported on the development of
novel biodegradable hydrogels from vitamin E-
functionalized polycarbonates for antimicrobial SUMMARY
applications. These hydrogels were formed by in- Within this review a host of hydrogels as a
corporating positively charged polycarbonates con- platform containing a variety of antimicrobials in

Figure 2. Currently available antimicrobial-incorporated hydrogel wound dressings.


404 FINNEGAN AND PERCIVAL

the treatment of acute and infected wounds have


TAKE-HOME MESSAGE
been addressed, with references to the past, cur-
 Hydrogels are used to assist in the management of dry,
rent, and future use of this type of wound dress-
sloughy, or necrotic wounds.
ing. It is difficult to formulate an opinion on which
antimicrobial-containing hydrogel is the obvious  More comparative studies between wound dressing plat-
forms are needed with standardized procedures being put
choice for future treatment of wounds. However, it
in place to facilitate more meaningful conclusions to be
is fair to say that the choice of hydrogel is highly
drawn from literature in the future.
biased toward the type of patient and underlying
pathologies, wound type, and location. Further the  Some initial biofilm studies that involve some antimicrobial
choice of antimicrobial hydrogel will also depend on hydrogels show good efficacy.
the virulence and microbiology of the biofilm and  Significant clinical- and biofilm-related research is urgently
the amount of exudate being produced by the needed on antimicrobial hydrogels.
wound. What is clearly evident and highlighted in
this article is that there is presently a lack of good
scientific evidence regarding the efficacy of anti-
microbial hydrogels on biofilms and healing rates. ABOUT THE AUTHORS
This area was reviewed recently by Valle and col- Simon Finnegan obtained his Biological
leagues49 who concluded that they did not identify Chemistry MCHEM in 2010 from the University of
any studies that assessed wound healing rates in a Sheffield, United Kingdom and has now under-
meaningful manner. Not only for hydrogels but for taken a DTC-TERM PhD position at the University
composite dressings, specialty absorptive dress- of Sheffield. Designing novel silicone wound con-
ings, contact layer dressings impregnated gauzes, tact layers to be used in wound dressings in colla-
or dressings with debriding agents. Concluding boration with Scapa healthcare.
this was due to the high risk of bias, inconsistent Professor Steven L. Percival holds a PhD in
results, selective outcome reporting, and/or im- microbiology and biofilms, a BSc in Applied Biolo-
precise estimates. Consequently significant clini- gical Sciences, Post graduate Certificate in Edu-
cal- and biofilm-related research is urgently needed cation, diploma in Business Administration, an
on hydrogels and their effectiveness in wound care. MSc in Public Health, and an MSc in Medical and
The treatment of acute and infected wounds have Molecular Microbiology. Was a senior university
been addressed, with references to the past, cur- lecturer in medical microbiology, Head of the Bio-
rent, and future use of this type of wound dressing’. film Research Group and later the positions of Di-
Figure 2 has the currently commercially available rector of R&D and Chief Scientific Officer at
antimicrobial-incorporated hydrogel wound dres- Aseptica, Inc., and senior clinical fellowships at the
sings summarised. Centres for Disease Control, Atlanta, and Leeds
Teaching Hospitals Trust. Held senior manage-
ment R&D and innovation positions at Bristol
ACKNOWLEDGMENTS
Myers Squibb, Conva Tec, Advanced Medical So-
AND FUNDING SOURCES
lutions Plc. Held an honorary Professorship in the
Simon Finnegan is funded by a joint PhD stu-
medical school at West Virginia University. In
dentship between Sheffield University and Scapa
2011, joined Scapa Healthcare Plc as Vice Pre-
Healthcare.
sident of Global Healthcare R&D and was awarded
an honorary Professor in the Institute of Ageing
AUTHOR DISCLOSURE AND GHOSTWRITING and Chronic Disease and the Surface Science Re-
All authors have nothing to disclose. No ghost- search Centre at the University of Liverpool,
writers were used to write this article. United Kingdom.
ANTIBIOFILM EFFICACY OF ANTIMICROBIAL HYDROGELS 405

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406 FINNEGAN AND PERCIVAL

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PVP ¼ poly(N-vinylpyrrolidone)

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