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Smart Bandage Technology

Jordan Davidson
School of Engineering
Robert Gordon University
j.davidson7@rgu.ac.uk

September 7, 2016
Abstract

This paper reviews the current literature pertaining to smart bandage technology and outlines a concept
design for a smart adhesive bandage. The concept of the ideal dressing is defined and potential biomarkers for
wound diagnostics are elucidated. Several sensor types, namely pH, temperature and oxygen, are discussed
and advantageous substrates are reviewed. Finally, a concept for a smart bandage technology is proposed
as a result of this literature review, which includes a three-sensor bandage to detect pH, temperature and
wound oxygenation and utilises carbon-based and polymer substrates. Near-field communication and radio
frequency identification technology is also recommended.

I. Introduction Table. 1 Potential Biomarkers

Would diagnostics remain an important as-


pect to health care and non-invasive methods • Bacterial load/specific microbial
for determining wound progress are continu- species/biofilms
ally required. The development of so-called
’Smart Bandages’ is therefore beneficial within • Cytokine release in response to specific
the clinical setting. This paper reviews the microbial antigens
literature pertaining to dressing requirements,
wound diagnostic criteria and smart bandage • DNA, e.g. gene polymorphisms to
technologies, biosensors and substrates and indicate susceptibility to disease, poor
proposes a new concept design for a smart healing or infection
bandage.
• Enzymes and their substrates, e.g. matrix
metalloproteinases and extracellular
II. Wound Diagnostics matrix

Wound healing is a complex biological phe- • Growth factors and hormones, e.g.
nomenon. Due to this complexity, there exists platelet-derived growth factor (PDGF),
an abundance of potential markers for both sex steroids (androgens/oestrogens) and
diagnostic and theranostic purposes. Such a thyroid hormones
list was compiled by Harding [1] and includes
markers such as bacterial, protein and hor- • Immunohistochemical markers, e.g.
monal loads as well as nutritional, Immunohis- integrins, chemokine receptors and trans-
tochemical, inflammatory and electrochemical forming growth factor beta II receptors to
markers. The full list is reproduced in Table 1. monitor healing status
below.

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Smart Bandage Technology

• Inflammatory mediators, e.g. cytokines the final cosmetic appearance of the


and interleukins to monitor healing sta- healed wound where this is relevant.’
tus and guide use of anti-inflammatory
treatments
These properties are shown in Table 2
• Nitric oxide for primary requirements and Table 3 for
secondary requirements.
• Nutritional factors, e.g. zinc, glutamine,
vitamins Table. 2 Ideal Dressing Primary Require-
ments
• pH of wound fluid
• Maintains the wound and the surround-
• Reactive oxygen species
ing skin in an optimum state of hydration
(this implies the ability to absorb exudate
• Temperature
effectively under compression)

• Transepidermal water loss from peri-


• Provides protection to the periwound
wound skin
skin from potentially irritant wound
exudate and excess moisture

• If self-adhesive, forms an effective water


III. Traditional Bandages and
resistant seal to the periwound skin,
The Ideal Dressing but is easily removable without causing
trauma or skin stripping
The concept of wound dressings and ban-
dages have been around for over 30,000 years
• Forms an effective bacterial barrier
[4] but only in the 1950s was the notion of the
(effectively contain exudate or cellu-
’Ideal Dressing’ proposed by Scales et. al [5].
lar debris to prevent the transmission of
It was understood then that a compromise
microorganisms into or out of the wound)
is required in wound treatment, as no single
bandage will be suitable for every wound [4].
• Conforms well to wound and limb
Furthermore, Scales et al. acknowledged the
limitations of materials technology at the time,
• Produces minimal pain during applica-
stating that with the materials present in 1956,
tion or removal as result of adherence to
production of an ideal dressing is impossible
the wound surface
[4].

• Free of toxic or irritant extractables


Thomas [6] proposed an updated definition
of wound healing, stating:
• Does not release particles or non-
‘The ideal dressing or dressing sys- biodegradable fibers into the wound
tem provides an environment within
the wound in which the objectives • Requires minimal disturbance or replace-
of the current phase of treatment ment
may be achieved in a timely and cost
effective manner without compromis- • Maintains the wound at optimum tem-
ing either patient safety or quality perature and pH
of life, or adversely affecting the
integrity of the periwound skin or

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Table. 3 Ideal Dressing Secondary Re- ambiguous signal. Uric acid has been demon-
quirements strated to be elevated in wound fluid from
chronic venous leg ulcers and its relative con-
centrations correlating with wound chronicity
• Possesses antimicrobial activity, capable
by Fernandez et al. [10], [11].
of combating localized infection
Kassal et al. [11] have taken this concept
• Has odor-absorbing/combating proper- further in their development of a smart ban-
ties dage with wireless connectivity for uric acid
biosensing, in which the electrochemical UA
• Has ability to remove or inactivate prote- biosensor displayed strong analytical perfor-
olytic enzymes in chronic wound fluid mance in vitro, with respect to sensitivity, se-
lectivity, operational stability, and robustness.
• Possesses haemostatic activity These in vitro experiments were performed by
dispensing 200 micro-L of phosphate-buffered
• Exhibits effective wound-cleansing (de- saline onto the sensing area of the bandage.
briding) activity Moreover, Kassal et al. undertook mechanical
stress testing of the bandage, complete with
sensor in order to approximate the impact of
mechanical deformation likely to be experi-
IV. Towards Smart Bandages: enced when the bandage is in situ. It was
found that repeated bending stress did not
Literature Review have a significant impact of the electrochem-
McLister et al. have reviewed the electrochem- ical response of the smart bandage biosensor.
ical approaches to the development of smart The biosensor itself was fabricated via screen-
bandages [5] as well as new developments printing Prussian blue modified carbon elec-
of smart bandage technologies for wound di- trodes onto a commercial bandage. The smart
agnostic purposes [6]. In their former re- bandage then connects to a potentiostat which
view, a focus on electroanalytical approaches, has been developed for use with mobile and
namely pH, baceterial metabolites, endoge- wearable biosensors specifically and has fur-
nous wound biomarkers, volatile organic em- ther been integrated with wireless capability.
misons and temperature. This approach is in The measured current output from the biosen-
concordance with Narayan, [7], who remarked sor is proportional to the uric acid concentra-
that he dominant detection mechanism for an- tion and this data can then be sent, upon re-
alytes in biofluid sample is the electrochem- quest, to a computer or smart device via radio
ical assessment and Badodkar and Wang [8], frequency identification or near-field commu-
stating that amperometry and potentiometry nications, respectively.
methods have been commonly implemented
in the application of wearable biosensor devel- VI. Temperature Sensors
opment for bodily fluids.
It has been demonstrated that a developing di-
V. pH Sensors abetic foot ulcer may be anticipated by an in-
crease of temperature in the area at risk [12].
Various approaches have been proposed for Moreover, similar temperature-based behavior
pH sensor development in the context of smart has been observed in bedsores as well as for
bandage technology. Phair et al. [9] developed pressure ulcers [13].
a disposable in situ pH sensor, such that the Moser and Gijis [14] developed a flexi-
system exploits the pH dependence of the en- ble temperature sensor based on a micro-
dogenous biomarker uric acid, yielding an un- patterned thin-film platinum resistor and in-

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corporated a biocompatible high-temperature- VII. Oxygen Sensors


resistant polyimide material, with potential
applications in the characterisation of the Mostafalu et al. [29] designed a smart bandage
thermo-ablation process of tumours. Further, with a primary functionality for continuous
they anticipate that a small size, flat shape, monitoring of wound oxygenation through
and high flexibility variation of the sensor de- the utilisation of off-the-shelf electronic com-
veloped will open possibilities for temperature ponents and hydrogel, which was used as an
measurement applications. epidermal layer through which oxygen can
easily diffuse and reach an oxygen sensor. It
Matzeu et al. [15] have investigated the was shown that the flexible oxygen sensors,
application of wireless sensors for skin electrochemical galvanic cells implemented on
temperature monitoring through the use parylene, had ample sensitivity and linear out-
of a conducting film with a temperature- put. The bandage material was 3D-printed
dependant resistivity measured by an RFID using an elastomer of advantageous mechani-
tag. A polymeric nanocomposite based on cal properties (tensile strength, flexibility, and
carbon nanotubes (CNT) was utilised as the stretchability) called TangoPlus.
sensing film. Matzeu et al. published an ad- The oxygen sensor output was found to be
ditional paper [16] on this subject, reporting linear with increase in oxygen content, in ac-
the fabrication of a temperature sensor based cordance with accepted theory. In addition,
on multi-walled carbon nanotubes/styreneb- concerns over environmental oxygen diffusing
(ethylene-co-butylene)-b-styrene triblock through the hydrogel and influencing the oxy-
copolymer composite, in which the results left gen sensors was addressed by using a cast in
the authors optimistic regarding feasibility a bandage that stabilizes the oxygen sensor
of realizing nanocomposite films with tem- with contributions from environmental fluctu-
perature sensitivities comparable to that of ations to oxygen to be identical across many
common thermistors. measurements. This allowed for sensor cal-
ibration via microcontroller programming in
Carbon nanotubes are of particular inter- each wound environment. The authors further
est within the context of biosensors, due to suggested that the printed circuit board used
their advantageous mechanical, electrical and in their design could be replaced with flexible
thermal properties [17], [18]. Indeed, the PCB and hence provide more feasibility in de-
use of carbon nanotubes for the realization veloping more complicated designs.
of miniaturized temperature sensors has been
suggested by [19], [20] and [21].
VIII. Additional Sensor Substrate
Experimentally, nanoscale reinforcement of Materials
polymers has been shown to remarkably
change the properties of materials [22], and Graphene has received a large research inter-
the afore mentioned advantageous characteris- est since its discovery in 2004 by Geim and
tics shown by carbon nanotubes indicated that Novoselof [30] and by virtue of its high elec-
their incorporation into polymeric matrices tron conductivity [31], fast heterogeneous elec-
could allow for the creation of new nanostruc- tron transfer rate at edges of sheets and defects
tured materials characterised by unique prop- on the basal plane [32], [33], large surface area
erties [23], [24], [25], [26]. Moreover, carbon [34], and cheap and simple fabrication [35].
nanotubes with semi-conducting or metallic Further, it is suitable for electrochemical appli-
qualities have shown a resistivity as strictly a cations such as smart bandage technology [36];
function of temperature, thus rendering them indeed, graphene has already been identified
of interest in the development of small-scale as holding great potential for electrochemical
temperature sensors [27], [28]. sensing and biosensing by [37, 38].

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Chee and Pumera [39] compared the per- lowing for the film to be used for detection of
formance of chemically-modified graphenes additional analytes, such as glucose and oxy-
to glassy carbons and edge plane pyrolytic gen.
graphite using uric acid. The authors found
that thermally-reduced graphene oxide pro-
IX. Proposed Design
vided the most sensitive and selective re-
sponse but also found that it was among In the literature reviewed, common wound
the least linear and reproducible. Graphite diagnostic markers include used in smart ban-
oxide, graphene oxide, chemically reduced dage technologies included pH, temperature
graphene oxide and electrochemically re- and tissue oxygenation; however, a technology
duced graphene oxide were found to gener- with multiple integrated sensors has not been
ally exhibited higher sensitivity but poorer re- investigated. Moreover, the use of carbon-
producibility and selectivity than glassy car- based substrates such as graphene, carbon
bons and edge plane pyrolytic graphite. The nanotubes or carbon-loaded polymer films,
authors conclude that applications of these combined with radio frequency identification
chemically-modified graphenes for advanced or near-field communications capabilities
diagnostics is conceivable. Furthermore, Sa- would produce a novel technology for clinical
hatiya et al. [40] described an approach to diagnosis. Thus, the following concept has
the fabrication of flexible electronics using so- been generated and is shown in Figures 1 and
lar exfoliated reduced graphene oxide (SrGO) 2.
and graphene flakes as the sensing materials
for developing the sensors on a polyimide sub-
strate. With regard to temperature sensing,
both SrGO- and graphene flake-based devices
displayed negative temperature coefficient val-
ues greater than those seen by various com-
mercial sensors, thus indicating graphene on
polyimide can be effectively used as a high
sensitive infrared photodetector and wearable
temperature sensing platform in a clinical set-
ting.
Phair et al. [41] investigated butyl grafted Figure 1: Smart Bandage Concept: Expanded View
polyethylene film loaded with carbon as a
mechanically flexible conductive substrate for Figure 1 shows an exploded view of the
electrochemical sensing applications for smart bandage, with the hydrogel layer in blue,
bandage development. It was concluded that a pH sensor on a carbon-based substrate
given the high degree of morphological flex- in green, a oxygen sensor on a parylene
ibility present in wound sites, a composite substrate in blue and a temperature sensor
mesh offers mechanical flexibility sufficient for on a carbon-based substrate in red. The final
purpose and that that the film exhibits the re- layer is a self adhesive polymer. Absorption
quired electroanalytical properties for use in a and porous layers are not shown but may
clinical setting. Moreover, other carbon-based be included as required. Figure 2 shows the
substrates, such as nanotubes and graphene contracted view of the bandage.
previously addressed, have financial limita-
tions with regard to material costs and mass The concept shown in Fig.1 and Fig.2 con-
manufacturing that are not present in carbon tains the basic structure of the smart ban-
loaded polyethylene film. The authors con- dage, including the three afore mentioned sen-
jecture electrochemical mesh modifications al- sors, utilising carbon-based substrates, such

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• Mechanically flexible polymer/elastomer


for self-adhesive layer.

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