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Biofilms and Impaired Wound Healing … 197
neutrophils also produce cytokines, which recruit and activate even more neutrophils, enhancing the inflammatory response. Cytokines such as TNF-a,
interleukin-1 (IL-1) and interleukin-6 (IL-6) have been found to be significantly
increased in wound fluid obtained from non-healing ulcers compared to healing
ulcers (Wallace and Stacey 1998; Trengove et al. 2000). Moreover, neutrophils
recruit macrophages from the bloods tream, which are also affected by the presence
of a biofilm.
Macrophages are functionall
y divided into two groups: the M1 and the M2
macrophages. M1 macrophages are pro-inflammatory and produce cytokines,
reactive oxygen species and phagocytize debris and microbes. M1 macrophages are
therefore sometimes termed ‘microbicidal’ macrophages. M2 macrophages are
reparative and produce polyamines which promote skin cell proliferation and
induce collagen production (Zhao et al. 2013; Motz et al. 2021; Sindrilaru and
Scharffetter-Kochanek 2013)
n normal wound healing, there is a regulated balance
. I
between M1 and M2 macrophages, but in biofilm-infected wounds, this balance
seems disrupted. Initially, the presence of bacteria causes a large infiltration of M1
macrophages into the wound, intensifying the inflammatory cytokine production
(Raziyeva et al. 2021). Yet, some in vitro studies have found that S. aureus biofilms
specifically can alter the ratio of M1 to M2 macrophages, by altering the macrophage gene expression away from the M1 phenotype towards the less microbicidal
M2 phenotype (Hanke et al. 2012; Thurlow et al. 2012). Moreover, one of these
studies observed that S. aureus biofilms caused a decreased macrophage migration
towards the biofilm and induced macrophage death by unknown mechanisms in an
in vivo mouse model (Thurlow et al. 2012). Lipopolysaccharides of bacterial origin
can also prevent macrophages from recognising apoptotic neutrophils destined for
engulfing. When the neutrophils are not properly cleared by the macrophages, this
leads to necrotic disintegration and further wound damage (Khandaker et al. 1998;
W
t et al. 2008). Studies have also found that microbial biofilms might disrupt
olcot
healing by interfering with the normal behaviour of human skin cells. In one study,
S. aureus biofilms were found to promote altered gene expressions in human skin
keratinocytes causing an upregulation of inflammatory genes and inducing the
production of several interleukins (Secor et al. 2011). In another study, an extracellular fibronectin-binding protein produced by S. aureus was found to slow the
migration of keratinocytes in vitro, thereby presenting another mechanism by which
microbes might restrict epithelialization (Kintarak et al. 2004)
Besides
changing phenotypic
responses and migration, biofilms may cause direct
.
damage to the skin and immune cells (Gajula et al. 2020). Rhamnolipids produced
by P. aeruginosa have been found to cause necrosis of neutrophils in vitro (Jensen
et al. 2007), as well as disruption of macrophage membranes, leading to decreased
phagocytosis (McClure and Schiller 1992). In high amounts, rhamnolipids have
also been correlated to increased microbial killing of macrophages (Chua et al.
2017). Furthermore, P. aeruginosa has been found to produce an exotoxin named
pyocyanin which drastically increases neutrophil apoptosis both in vitro and in a
murine animal model (Prince et al. 2008). Other unknown compounds in biofilm
conditioned media produced by S. aureus and P. aeruginosa have been found to be
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highly cytotoxic against keratinocytes (Kirker et al. 2009; Jeffery Marano et al.
2015). Transcriptome analyses of isolates obtained from chronic woun ds and joint
infections have found that many virulence factors are upregulated in microbes
isolated from infectious environments (Xu et al. 2016; Cornforth et al. 2018). Such
analyses have also shown that wound isolates expres s altered metabolic pathways
and upregulation of resistance genes. In general, biofilm in wounds survives well
due to several survival mechanisms, but that is outside the scope of this chapter and
has recently been reviewed elsewhere (Thaarup et al.
2022).
Disruption of Microenvironment
Microbial biofilms impair wound healing not only by affecting the skin and immune
cells but also by altering the microenvironment to an unfavourable state which does
not promote tissue regeneration. This is problematic, as a favourable wound
microenvironment has been described as the most important supporting factor in
achieving successful healing (Uluer et al. 2018).
Healthy skin is usually found to be slightly acidic with a pH in the range of 4.0–
6.0 (Schneider et al. 2007). Acidic skin environment deters the growth of many
pathogens and fungi, as they often need pH above 6.0 to grow. Unfortunately, the
pH of chronic wounds has often been found to be alkaline with a pH within the
range of 7.3–8.9 (Schneider et al. 2007). Moreover, healing has been reported to
progress at a reduced speed in wounds with an alkaline microenvironment (Leveen
et al. 1973; Tsukada et al. 1992). The alkalinity observed in chronic wounds is
thought to be partially due to tissue necrosis and bacterial activity. Many bacterial
wound species are able to produce ammonia, which in itself is a toxic compound
causing tissue damage but it also increases the wound pH (Leveen et al. 1973;
Percival et al. 2014). One study reported that the normal acidic environment of skin
became alkaline following the colonisation of microbes (Schneider et al. 2007).
Several in vitro experiments have corroborated that microbial growth in various
media types, even acidic media, often results in an alkaline microenvironment and
some studies have noted that co-cultures of bacteria increases the pH to a higher
degree than monocultures do (Kadam et al. 2021; Cendra et al. 2019). A study by
Hostacka et al. (2010) found that both P. aeruginosa and K. pneumoniae exhibited
increased biofilm production in vitro when exposed to an alkaline pH of 8.5.
A different study found that biofilms of P. aeruginosa produced larger amounts of
both alginate and proteases when grown at a pH of 8.0 (Harjai et al. 2005 ). In
general, alkaline wound environments support the continued degradation of skin
tissue while potentially promoting bacterial biofilm formation.
In vitro and ex vivo skin models have been used to investigate the effect of pH
on the behaviour of human immune cells. Such investigations generally find that
immune cells function best at neutral pH levels. According to one study, leukocyte
motility peaks at a pH of 7.5 (Percival et al. 2014), while another study found that
polymorphonuclear leukocytes (PMNs) showed the highest motility at pH levels
between 6.7 and 7.2 (Leblebicioglu et al. 1996). That same study also found that
Biofilms and Impaired Wound Healing … 199
phagocytosis of bacteria functioned best at a pH of 7.7. A later study by the same
group found that PMNs undergo apoptosis to a larger degree under alkaline conditions (Leblebicioglu and Walters 1999). Moreover, it has been observed that
macrophage production of TNF-a is increased at alkaline pH (Heming et al. 2001).
Unfortunately, tissue-destroying enzymes such as matrix metalloproteases and
collagenases also function best at alkaline pH, which further delays healing (Sch-
Percival et al. 2014).
neider et al.
2007;
Oxygen limitation is another microenvironmental factor that decreases the
healing potential of a woun
d. The hypoxic microenvironment observed in chronic
wounds is most likely due to the combined oxygen consumption of both immune
cells and microbes (Wu et al. 2018). Oxygen is a necessity for most cellular
functions, as it is involved in the creation of biological energy equivalents (Schreml
et al. 2010). It is also particularly vital for wound healing as it is needed for forming
new blood vessels, synthesising new collagen, cell proliferation and other reparative
processes (Schreml et al. 2010; Gottrup 2004). Oxygen is also used in the defence
mechanisms employed by the immune cells. Both neutrophils and macrophages
produce reactive oxygen species that are meant to defer bacterial contamination
(Trostrup et al. 2013). PMNs in particular are known for their ability to mount a
‘respiratory burst’, an essential component of the innate immune response, which is
the accelerated production of superoxide anions (Kolpen et al. 2010). Unfortunately, when produced in large amounts, reactive oxygen species cause oxidative
damage to both tissue and cells. They also function as important signalling molecules and increased levels promote a continuous infiltration of immune cells into the
wound (Zhao et al. 2016). Oxygen is also needed for the creation of nitric oxide
(NO), one of the most effective antioxidants found in wounds (Zhao et al. 2016).
M1 macrophages produce this antioxidant in an oxygen-dependant manner, so in
the hypoxic environment of chronic wounds, this antioxidant is often lacking, and
the balanced level of reactive oxygen species is disrupted. Finally, the alkaline pH
and anoxic environment of wounds are closely associated, as less oxygen is
available at high pH levels due to the Bohr effect, which states that oxygen is
released more readily from haemoglobin at low pH (Schneider et al. 2007).
Attention is often paid to wound temperatures and how they correlate with
healing. I
t is important to include bacterial biofilms in these considerations, as
bacterial behaviour has been found to be temperature-dependent in several instances.
One study measured biofilm production at two different temperatures and found that
3 out of 4 tested V. cholera strains, that were isolated from a hospital setting,
produced more biofilm at 30 °C compared to 37 °C (Hoštacká et al. 2010). The same
study found that this was also true for 3 out of 4 tested P. aeruginosa strains. Other
studies have found that the optimal temperature for P. aeruginosa biofilm production
is highly strain-dependent, with some strains producing the most robust biofilms at
20 °C (Kim et al. 2020)
ene expression patterns and microbial virulence factors
. G
have also been found to be temperature regulated (Bisht et al. 2021).
While the temperature of chronic wounds or the adjacent skin is often measured,
an unequi
vocal answer to an optimum temperature for healing is hard to come by.
On one hand, hypothermic wounds are often reported to heal slower than
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normothermic wounds, and colder wounds have been reported to have a worse
wound bed score (Kurz et al. 1996; Lin et al. 2021; Dini et al. 2015). Hypothermia
leads to thermoregulatory vasoconstriction, which limits the supply of oxygen to
the wound site (Kurz et al. 1996). Moreover, neutrophil killing of microbes has
been found to be reduced when the temperature was lowered from 37 to 30 °C
(Allen et al. 1997). PMN locomotion is also significantly decreased in cold temperatures (Nahas et al.
1971).W
hen the effects of cold wound temperatures are
considered together with the observations that some bacterial strains produce larger
amounts of biofilm in a colder microenvironment, it seems that warm wound
temperatures would always be favourable. Yet, several studies interpret local
increased wound temperature as a negative sign that signifies the presence of an
infection. Armstrong et al. (2006) found that patients with a significant temperature
increase above 10 °F (5 °C) of the affected limb compared to the unaffected limb
had a less favourable clin ical outcome. Another study that included data from 112
patients found that wounds with elevated temperature compared to the opposing
limb were far more likely to have moderate or heavy bacterial growth (Woo and
Sibbald
2009). Finally, Chanmugam et al. (2017) found that infected wounds
showed higher wound bed and periwound temperatures relative to the opposing
limb, compared to wounds which were inflamed but not infected. The same study
also observed how efficient antibiotic treatment caused a notable lowering of the
temperature. These studies suggest that a moderate wound temperature increase
might signify inflammation and progressio n of healing whereas a high wound
temperature increase could signify infection. This vi
ew is supported by the study of
Lin et al. (2021) who found that non-infected pressure ulcers with higher temperatures healed faster than those with lower temperatures.
Detection Methods
Biofilm Detection Issues
There are several inherent issues with detecting biofilms in wounds. These issues
are connected to the intrinsic nature of microbial biofilms in the chronic wound
environment. The first challenge, which is also the largest issue, is the random and
heterogeneous spatial distribution of biofilms in wounds. This has been observed in
several studies of chronic wounds, in which the spatial distribution was investigated
(Thomsen et al. 2010; Fazli et al. 2009; Travis et al. 2020). Such studies have
shown that not only is the abundance of a single species substantially different from
one surface area to another, but the number of species between different locations
may also vary significantly. These studies exemplify the randomness and heterogenic distribution of wound biofilms, which in turn imposes complications on their
detection. Fazli et al. (2009) investigated the depth distrib ution of biofilm aggregates of S. aureus and P. aeruginosa within chronic venous leg ulcers by using
confocal microscopy in combination with peptide nucleic acid-based fluorescence
Biofilms and Impaired Wound Healing … 201
in situ hybridization (PNA-FISH). By measuring the distance from the wound
exterior to the observed bacterial aggregates, they could determine the mean distance from the wound surface for each species. They found that S. aureus was
located 20–30 µm from the surfa ce of the wound, whilst P. aeruginosa was located
deeper within the tissue, around 50–60 µm from the wound surface. This study
illustrates the problem with detection methods that rely on routinely used surface
ing, as biofilm aggregates may be absent from the surface of a wound while
wabb
s
still inhabiting deeper regions in the wound tissue. Dunyach-Remy et al. (2014)
i
nvestigated the bacterial species found in 20 diabetic ulcers. They took both surface swabs and deep-tissue biopsies and analysed the samples using PCR coupled
to denaturing gradient gel electrophoreses (DGGE). They found that a significantly
larger number of species were present in the deeper tissues than in the surface swab
samples, once again emphasizing the importance of considering the depth distribution of wound biofilms.
Another challenge is the large vari
alike in terms o
f species amount and composition. Thomsen et al. (2010) investi-
ety of species. No two wounds are going to be
gated 14 venous ulcers using molecular detection methods and found an average of
5.4 species per wound, while Price et al. (2011) found an average of 20.9 bacterial
genera per wound when investigating 13 chronic wounds of different aetiology. The
situation is further complicated as both viruses and fungi have been isolated from
chronic wounds and their role in the infectious microenvironment has yet to be
elucidated (Wolcott et al. 2009; Xu and Hsia 2018). A small number of biofilms
obtained from wound samples have previously been found to be multispecies,
which causes further complications (James et al. 2008; Johani et al. 2017; Malone
et al. 2017b; Choi et al. 2019). Detection methods targeted toward specific species
or compo unds produced solely by a limited group of microbes will fall short under
these circumstances. Yet, the detection of specific species is not without merit, as
the presence of certain microbes has been found to significantly affect healing
outcomes. Madsen et al. (1996) analysed 59 venous leg ulcers and found that ulcers
containing P. aeruginosa increased in size compared to those that did not. They
also observed that ulcers containing S. aureus or haemolytic streptococci healed
more slowly than ulcers without. More recent studies have confirmed this trend that
the presence of either P. aeruginosa or S. aureus leads to a worse healing outcome
(Gjødsbøl et al. 2006; Kalan et al. in press).
The large variety of wound microbes also complicates methods based on the
detection of
extracellular polymeric substances (EPS) produced by the microbes. In
general terms, EPS is described to consist of proteins, lipids, exopolysaccharides
and extracellular DNA (eDNA), although this description might only be true for
in vitro biofilms (Koo and Yamada 2016). To our knowledge, no thorough
examination has been performed that analyses the EPS produced in chronic wounds
and the actual content of the in vivo wound EPS might differ. Some researchers
suggest that wound microbes are likely to incorporate host materials such as
collagen into their
and
et al.
2017).
It is important to note that there is no one specific EPS composition, as
biofilm, which could alter the function and structure (Trivedi
fibrin
different species and even different strains of the same species have been found to
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secrete EPS components of vastly different types and amounts (Hobley et al. 2015).
One study analysed several strains of Streptococcus thermophilus all grown in the
same medium and found that EPS production, proteolytic activity and monosaccharide composition varied widely between strains (Aslim et al. 2006).
One final difficulty in detecting biofilms in wounds is that the number of
pathogens present might be minuscule and therefore below various detection limits
sholtetal. 2009).However
(Bjarn
the presence of even a small number of bacteria
,
in a wound can cause an infection, as the bacteria are able to proliferate, resulting in
a large biofilm and subsequently causing a delayed healing response. Detection
methods that depend on large quantities of microbes being present should thus be
careful with ruling out the possibility of infection.
Conventional Detection Methods
Current conventional detection methods can be divided into three groups: direct
culturing methods, molecular analyses, and imaging methods. Direct culturing
techniques assess the viability of the microbes found in a wound. When performed
non-invasively, the sample is taken with a surface swab that is run across either part
of a wound or sometimes the whole wound surface. While this method is cheap, fast
to perform and easy to do in most hospital settings, the results are usually
incomplete and cultures often take 24 h or more before they are visible. The bacterial numbers tend to be underestimated and the species found often do not match
the ones found using molecular methods (Davies et al. 2004; Xu et al. 2020;
Malone et al. 2017c). Results vary greatly depending on the type of swab, the media
used for incubation, the incubation conditions including oxygen and temperature,
and the duration of incubation (Jakobsen et al. 2021). All these factors need to be
considered when comparing results between institutions or different hospitals, as
standard practices might differ. As mentioned earlier, wound biofilms exist in
deeper layers of the tissue, and superficial swabs are therefore unlikely to reach
these. Moreover, superficial swabs may by accident sample commensal skin
microbes. Finally, and perhaps the most important point related to traditional culturing techniques is the presence of a wound biofilm cannot be proven using these
methods.
Molecular methods are often deemed more accurate than culturing methods
since molecular methods have the possibility to detect microbes, such as anaerobes
or slow-growing variants that often can not be detected using traditional culturing
(Dowd et al. 2008). Molecular techniques can be performed on both non-invasive
surface swab samples or on wound biopsies that are invasive to acquire. Molecular
methods used for detecting wound pathogens include 16S rRNA sequencing,
Bacterial Tag-Encoded FLX Amplicon Pyrosequencing (bTEFAP) Partial Ribosomal Amplification and Pyrosequ encing (PRAPS), Full Ribosomal Amplification,
Cloning and Sanger sequencing (FRACS), Partial Ribosomal Amplification, DGGE
and Sanger sequencing (PRADS), Whole Genome Sequencing (WGS) and mRNA
sequencing (Cornforth et al. 2018; Malone et al. 2017c). Major concerns when
Biofilms and Impaired Wound Healing … 203
using molecular methods include the possibility of DNA contamination from the
environment, the amplification of molecular material from dead microbes and
finally: the presence of a biofilm can also not be proven using the majority of these
methods. mRNA sequencing is the one exception to most of these limitations.
mRNA degrades rather fast and will therefore only be found from alive and
metabolically active microbes, while dormant microbes might not be detected using
mRNA
sequencing. Moreover, mRNA sequencing might be able to determine
whether the isolated strains were growing in a biofilm or not. In vitro studies have
been performed comparing planktonic cells to biofilm-growing cells and specific
expression patterns have been observed (Dötsch et al. 2012; Rumbo-Feal et al.
2013). In the future, perhaps mRNA sequencing of wound microbes could be used
to determine whether the isolates were growing in a biofilm or not. Yet, some
studies have observed how chronic wounds with a high clinical infection score
contain surprisingly small amounts of bacterial mRNA (Fritz et al. 2022).
Finally, imaging techniques such as confocal laser scanning microscopy
(CLSM) or scanning electron microscopy (SEM) can be performed. However, for
both of these methods, wound biopsies will need to be acquired making them more
invasive than detection
methods that can use surface swab samples. Using SEM ,
microcolonies can be observed and the presence of EPS be confirmed (Johan i et al.
2017). Using CLSM, universal probes or species-specific probes can be utilized to
confirm microbial aggregates of both unknown and particular species. Specific
stains have been developed that target different components of the biofilm EPS such
as polysaccharides, glycoproteins or eDNA (Neut et al. 2011; Oates et al. 2014;
er
Schlaf
and Meyer 2017). Although direct visualization of biofilms is currently
seen as the gold standard for proving biofilm presence in a wound, these methods
also have several limitations (Kvich et al. 2020 ). Imaging techniques carry the risk
of false-negative results, as the investigated biopsy samples might not contain any
biofilm aggregates due to the random and patchy distribution of biofilms in wounds.
These imaging techniques also require expensive and specialized equipment
making them unsuitable to use in routine diagnostics at hospitals.
Novel Sensor-Based Detection Methods
Novel detection methods are often based on wearable sensors. Sensors have been
reported to cause minimal patient inconvenience and wearable sensors incorporated
into dress
needs to be taken (Pusta et al. 2022). These sensors are able to detect various
biological markers which broadly can be divided into three categories (see Fig. 1
Indirec
the infection status and wound healing prospects. Microbe markers that directly
detect microbes or pathogens within the wound. This can also include the detection
of a secreted product of microbial origin. Finally, biofilm markers, including EPS
matrix components, as well as microbe secreted products that are only produced by
biofilm residing bacteria. There is an overlap between microbe markers and biofilm
ings can limit the need for bandage removal every time a measurement
t infection markers that monitor the microenvironment and correlate this to
).
204 I. C. Thaarup and T. Bjarnsholt
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Fig. 1 Novel detection methods based on the measurement of infection markers. These markers
can broadly be divided into three categories: indirect infection markers, microbe markers and
biofilm markers. Some overlap can occur between the different markers. Illustrated wound is
shown to contain both biofilm and single cells of the rod-morphology, but all morphological cell
types can be found in wounds, in addition to fungi and viruses. Figure created using
BioRender.com
markers in regards to density regulated compound production, which is sometimes
inferred to be equal to biofilm production (see Table 1 for an overview of
sensor-based detection methods). Alternatively, instead of using biological sensors,
non-invasive imaging techniques are being developed, which can detect the presence of microbes and microbial compounds within a wound, without the need to
take samples.
Monitoring microenvironmental changes in the wound is a way to indirectly
determine if there is an infection present. As described above, the presence of an
infection cause changes to both wound
Moreover, the immune response will
temperature, pH and oxygen levels.
be altered in the presence of pathogens and by
observing the actions of the immune cells it can be determined if an infection is
present. Antibodies produced by the body have been investigated as they might
function as suitable detection markers. The antimicrobial peptide alpha defensin has
already been shown to be a sensitive and specific marker for discovering infection
in periprosthetic joint infections, however, while this antibody is produced against a
wide spectrum of microbes it is not biofilm specific (Deirmengian et al. 2015). Gao
et al. (2021) developed a multiplexed immunosensor which was able to d etect
several immune system signalling molecules in the collected wound exudate.
Among the measured signalling molecules were TNF-a, IL-6 and IL-8 which have
previously been observed to be increased in non-healing ulcers (Wallace and Stacey
1998; Trengove et al. 2000; Edsberg et al. 2012). The immunosensor was tested
in situ in a wounded mouse model and subsequently on wound exudate retrieved
Biofilms and Impaired Wound Healing … 205
Table 1 Table presenting the sensor-based detection methods mentioned in this chapter
Type of
marker
Indirect
infection
Indirect
infection
Indirect
infection
Indirect
infection
Indirect
infection
Indirect
infection
Indirect
infection
Indirect
infection
Indirect
infection
and
microbe
Indirect
infection
and
microbe
Indirect
infection
and
microbe
References Markers measured Details Tested in
Vu et al. (2020) pH A multilayered wound alkalinity
Tamayol et al.
(2016)
Pan et al.
(2019)
Shukla et al.
(2014)
al.
Dini et
(2015)
and
Woo
Sibbald (2009)
Fierheller and
Sibbald (2010)
He et al. (2020) Oxygen Wound dressings with
Gao
et al.
(2021)
Sharifuzzaman
et al. (2020)
Simoska et al.
(2020)
pH pH-responsive hydrogel fibres
pH Curcumin was loaded into a
pH Wound pH measured by litmus
Temperature Using
Temperature A handheld infrared
ature A handheld
Temper
TNFa, IL-6,
TGF, S. aureus cell
wall epitopes,
temperature and pH
pH, uric acid,
temperature
Pyocyanin, uric acid,
nitric oxide
IL-8,
monitoring system was
developed that changed colour
based on the detected pH
were developed which changed
colour based on the pH. The
measurement could be read
using a smartphone
fibrous material and exhibited
colour changes based on the pH.
Measurements could be read
using a smartphone app
paper was correlated to the type
of organism present
an infrared camera,
wound temperatures were
measured and correlated to
wound bed score
thermometer was used to assess
wounds together with bacterial
culturing methods
used to measure wound
temperature
incorporated methylene
were developed. The
turned yellow due to oxygen
depletion
Measurements were performed
using multiplex biosensors in a
mouse wound model and in
human wound exudate samples
A
smart bandage with
laser-guided graphene electrode
sensors were used
pH, uric acid
The bandage was tested on
wound exudate samples
Flexible carbon
ultramicroelectrode arrays were
used to detect infection markers
thermometer was
blue
dressings
to measure
and temperature.
humans or
on human
samples?
No
No
No
Yes
Yes
Yes
Yes
No
Yes
Yes
No
(continued)
206 I. C. Thaarup and T. Bjarnsholt
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Table 1 (continued)
Type of
marker
Indirect
infection
and
microbe
Microbe Sharp et al.
Microbe Kassal et al.
Microbe Roy et al.
Microbe Jarošová et al.
Microbe Zhou et al.
Microbe Thet et al.
Microbe Thet et al.
Biofilm Li et al. (2014) Uncharacterised EPS
References Markers measured Details Tested in
Ashley et al.
(2019)
(2008)
(2015)
(2021)
(2019)
(2018)
(2016)
(2020)
Lactic acid, oxygen A flexible electrochemical
Uric acid A sensor added to carbon fibre
Uric acid A smart bandage was created by
S. aureus DNA A dressing was developed which
Uric acid, pyocyanin Electrodes were developed
Toxins A wound dressing that changed
Toxins Presents a wound dressing with
Toxins Swab from a wound was added
components
biosensor was developed, which
could detect both lactate and
oxygen. It was designed to be
able to be integrated into wound
bandages
mesh was used to measure uric
acid in whole blood, serum and
wound fluid
screen printing an amperometric
biosensor directly on a wound
dressing
was based on a composite of
zeolitic imidazolate framework
and carbon nitride conjugated
with S.aureus probe-DNA
which could monitor changes in
uric acid and pyocyanin levels
colour and released
antimicrobials in response to
bacterial toxins was developed
and tested on a mouse wound
model
a lipid-encapsulated fl uorescent
dye, which was released when in
contact with bacterial toxins.
Tested on an ex vivo porcine
model
to a liposome-encapsulated
fluorescent dye, which was
released when in contact with
bacterial toxins
A gold-particle based
multichannel nanosensor was
developed, which detected
various EPS components,
creating different patterns
depending on the specific
species that produced the EPS
humans or
on human
samples?
No
Yes
No
No
No
No
No
Yes
No
(continued)
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