GB2577493A

GB2577493A - Wound dressing

Info

Publication number: GB2577493A
Application number: GB1815586.1A
Authority: GB
Inventors: Zuberi Sheena; Newsome Christopher; John Kay Christopher
Original assignee: Sumitomo Chemical Co Ltd
Current assignee: Sumitomo Chemical Co Ltd
Priority date: 2018-09-25
Filing date: 2018-09-25
Publication date: 2020-04-01
Also published as: GB201815586D0

Abstract

A wound dressing has a flexible substrate 2 with a first face 3 and an opposing face 4. A first electrode 9 and a second electrode 10 are located on the first face, the first electrode defining a recessed area and the second electrode protruding into the recessed area. At least one of the electrodes is coated with an electrically conductive material for promoting a redox reaction. When a microcurrent flows at -0.45V the dressing generates hydrogen peroxide by reducing atmospheric oxygen dissolved in the coating. The coating may be a conjugated polymer such as PEDOT:PSS, and be topped with hydrogel. The dressing may include a Ag/AgCl reference electrode and a potentiostat. The first and second electrodes may interdigitate, or zig-zag (figure 7B), or form a circle within an annulus (figure 10), or otherwise interlock; they may be secured to the substrate by adhesive 5.

Description

Embodiments of the present invention relate to a wound dressing for electrochemically producing hydrogen peroxide for wound treatment.

Chronic wounds can be treated using reactive oxygen species (ROS), primarily hydrogen peroxide. The role of ROS in the wound healing response is reviewed in Dunnill et al.: "Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process", International Wound Journal, volume 14, pages 89-96 (2015). Wounds may io be exposed to different levels of hydrogen peroxide to adapt wound healing to a given stage and condition of the wound.

Electrochemical, conductive polymer-mediated, oxygen reduction pathway to hydrogen peroxide and/or water is known. In particular, it has been established that, for electropolymerized PEDOT cathode materials subjected to an applied voltage of about - 0.45 V between the cathode and an anode, approximately half of the current produces hydrogen peroxide and the balance produces water. However, at more negative voltages, e.g. -0.65 V, hydrogen peroxide will also be reduced to water, thereby reducing the overall amount of hydrogen peroxide produced by the electrochemical oxygen reduction reaction (for example, see Kerr et al. : "Influence of the Polymerization Method on the Oxygen Reduction Reaction Pathway on PEDOT", ECS Electrochemistry Letters, volume 2(3), pages F29-F31 (2013).

Dressings that include hydrogels and an electrochemical cell for the delivery of substances to intact skin, for example, a boil, or skin infection, or broken skin are also known. US 2015/025479 Al provides a skin dressing for delivery of a physiologically active precursor, the dressing comprising an electrochemical cell and a skin-contacting hydrogel layer that acts as a reservoir for an inactive precursor substance, wherein activation of the electrochemical cell triggers oxidation of the inactive precursor substance to produce a physiologically or antimicrobial active oxidised or reduced compound which is capable of diffusing towards the skin surface. However the dressings disclosed in this document are non-polymeric systems.

WO 2005/068016 Al discloses a patch for transdermal or intradermal delivery of a substance, the patch comprising an electrochemical cell having at least two electrodes positioned on one side of the patch, the electrodes being configured for delivering an electric current through the skin, and a conductive hydrogel which comprises the substance to be delivered and which is, in use, located between at least one of the electrodes and the skin surface.

US 5 211 827 A discloses an electrochemical cell that employs an anode, an analyte, a cathode, a catholyte, and a membrane separating the anolyte from the catholyte, the membrane comprising a nonporous solid composite material that is formed from a hydrogel dispersed through an inert matrix material. Films formed from this electrical cell can be used as a protective interface between the dermis or epidermis and the environment, and may be applied as a standard wound type dressing.

These dressings, however, may have one or more drawbacks. For example, a dressing may not produce a sufficient quantity of hydrogen peroxide required to treat a wound. 15 A dressing may not produce hydrogen peroxide evenly over a treated area. A dressing may not be able to reduce the amount of hydrogen peroxide over time.

SUMMARY

A summary of aspects of certain embodiments disclosed herein is set forth below. It should be understood that these aspects are presented merely to provide the reader with a brief summary of these certain embodiments and that these aspects are not intended to limit the scope of this disclosure. Indeed, this disclosure may encompass a variety of aspects and/or a combination of aspects that may not be set forth.

Embodiments of the present disclosure provide a wound dressing comprising a flexible substrate having a first and second opposite faces, first and second electrodes disposed over the first face wherein the first electrode defines a recessed area and the second electrode comprises a protruding area extending into the recessed area and a coating on at least one of the first and/or second electrode for promoting a redox reaction, the coating(s) comprising a conductive material.

In some embodiments, the first and second electrodes are coplanar. In some embodiments, the wound dressing has a ratio of an area of the first electrode to an area of the second electrode is 2:1. In some embodiments the wound dressing has a ratio of an area of the first electrode to an area of the second electrode is greater than 2:1.

In some embodiments, the first and second electrodes are interdigitated. in some embodiments, the first and second electrodes have the same dimensions. In some embodiments, the first electrode has different dimensions to the second electrode.

Tn some embodiments, the fingers of the first and second electrodes have the same widths. Tn some embodiments, the widths of the fingers of the first electrode are different to the widths of the fingers of the second electrode. In some embodiments, the fingers of the first and second electrodes have the same lengths. In some embodiments, the lengths of the fingers of the first electrode are different to the lengths of the fingers of the second electrode. In some embodiments, the interstitial spaces of the first and so second electrodes have the same widths. In some embodiments, the interstitial space widths of the first electrode are different to the interstitial space widths of the second electrode.

In some embodiments, the first electrodes has the same shape to the second electrode. In some embodiments, the first electrode has a different shape to the second electrode.

Tn some embodiments, the fingers of the first and second electrodes are arranged in a repeating configuration.

In some embodiments, the wound dressing has a size of 2 cm x 4 cm. In some embodiments, the wound dressing has a size of 5 cm x 10 cm. In some embodiments, the wound dressing has a size of 20 cm x 40 cm.

In some embodiments, the wound dressing has a first adhesion layer disposed on the first face of the substrate and the first electrode and a second adhesion layer is disposed on the first face of the substrate and the second electrode and the adhesion layer is electrically conductive.

In some embodiments, the wound dressing has a first adhesion layer disposed on the first face of the substrate and the first electrode and a second adhesion layer disposed on the first face of the substrate and the second electrode and the adhesion layer is electrically insulating.

In some embodiments, the wound dressing has an adhesion layer disposed on the first face of the substrate and the first and second electrodes and the adhesion layer is 3° electrically insulating. -3 -

In some embodiments, an edge of the first electrode and an edge of the second electrode are straight.

In some embodiments, an edge of the first electrode and an edge of the second electrode have a boustrophedonic shape and interlock each other.

In some embodiments, an edge of the first electrode and an edge of the second electrode have a zig-zag shape and interlock each other.

Tn some embodiments, an edge of the first electrode and an edge of the second electrode have a sinusoidal-like shape and interlock each other.

In some embodiments, the first and second electrodes have a generally circular shape.

ro In some embodiments, the wound dressing further comprises a power source and a switch wherein the power source is connectable to the first and second electrodes using the switch.

In some embodiments, a hydrogel is disposed on top of the coating.

In some embodiments, the conductive material is biocompatible. In some embodiments, the conductive material is a conjugated polymer. In some embodiments, the conductive material is poly(3,4-ethylenedioxythiophene). In some embodiments, the conductive material is poly(3,4-ethylenedioxythiophene):polystyrene sulfonate.

In some embodiments, the wound dressing further comprises a reference electrode and a potentiostat. -4 -

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure is described in conjunction with the appended figures. It is emphasized that, in accordance with the standard practice in the industry, various features are not drawn to scale. In fact, the dimensions of the various features may be arbitrarily increased or reduced for clarity of discussion.

In the appended figures, similar components and/or features may have the same reference label. Further, various components of the same type may be distinguished by following the reference label by a dash and a second label that distinguishes among the similar components. If only the first reference label is used in the specification, the io description is applicable to any one of the similar components having the same first reference label irrespective of the second reference label.

Figure IA is a schematic side view of a first wound dressing able to electrochemically produce hydrogen peroxide; Figure iB is a schematic side view of a second wound dressing able to electrochemically /5 produce hydrogen peroxide; Figure 2 is a schematic diagram of a conventional op-amp potentiostat circuit for use in the wound dressing shown in Figure 1.; Figure 3 is a plan view of a first coplanar electrode arrangement; Figure 4 is a plan view of a second coplanar electrode arrangement; Figure 5 is a plan view of a third coplanar electrode arrangement; Figure 6 is a plan view of a fourth coplanar electrode arrangement; Figure 7A is a plan view of a first alternative electrode finger layout; Figure 7B is a plan view of a second alternative electrode finger layout; Figure 7C is a plan view of a third alternative electrode finger layout; Figure 8 is a plan view of a fifth coplanar electrode; Figure 9 is a plan view of a sixth coplanar electrode; -5 -Figure fo is a plan view of a seventh coplanar electrode; Figure 11 is a table of hydrogen peroxide release; Figure 12 are graphs of current against time for a coplanar electrode; and

DETAILED DESCRIPTION

Overview Figures iA and 113 provide schematic side views of a first and a second wound dressing able to electrochemically produce hydrogen peroxide.

The wound dressing 1 generally takes the form of a flat, flexible pad which can be ro applied to an open wound (not shown), such as a laceration, abrasion or avulsion, so as to aid healing of the wound. A wound may include an ulcer, a deep ulcer, a burn, a boil and cuts. The wounds may or may not be infected.

The dressing 1 includes a thin, flexible substrate 2 having first and second opposite faces 3, 4. The first face 3 is intended to face the wound (not shown) and so maybe /5 referred to as the "front face" or simply "front". The second face 4 is intended to face the atmosphere and so maybe referred to as the "back face" or simply "back".

The substrate 2 is formed from a biocompatible plastic polymer. The biocompatible plastic polymer may be a polyamide, a polyurethane, a polystyrene, a polyvinyl chloride, a polypropylene, a polyethylene, a polyethylene napthalate (PEN), poly(ethylene-vinyl acetate) and polyethylene terephthalate (PET). The biocompatible plastic polymer is preferably a polyurethane polymer.

The dressing 1 includes a thin adhesion-promoting layer 5 (which may also be referred to as an "adhesion layer") disposed over the first face 3 of the substrate 2 and an electrode arrangement 8 which includes first and second flat, interdigitated co-planar electrodes 9, 10 disposed on the adhesion layer 5. The electrode arrangement 8 may include further electrodes. As used herein, a layer disposed "over" another layer as used herein means that the two layers are directly adjacent or spaced apart by one or more intervening layers. The term "over" does not imply any specific orientation in relation to any axis. -6 -

The dressing 1 will have dimensions suitable for treating a wound. Typically, the wound dressing will have a size in the order of centimetres, optionally from about i x 1 cm up to about 5o cm x so cm. For example, this may be 2 cm x 4 cm, or 5 cm x 10 cm, but it may also be 20 cm x 40 cm. The wound dressing may be any shape. For example, the wound dressing 1 may be square, rectangular, triangular or circular. The wound dressing 1 may have an irregular shape. The wound dressing 1 may have a shape that matches the wound shape. Sizes as given herein are a width of the wound dressing at its widest point and a length at its longest point.

In some embodiments of the present disclosure, the adhesion layer 5 may be an electrically insulating material. if the adhesion layer 5 is electrically insulating, the adhesion layer may be in contact with first and second electrodes 9, 10 of the electrode arrangement 8 simultaneously. In other embodiments of the present disclosure, a first adhesion layer 5, may be in contact with the first electrode 9 and a second adhesion layer 5, may be in contact with the second electrode 10. First and second adhesion layers Si, 52 are not in contact with each other and may be either electrically conducting or electrically insulating.

The adhesion layer 5 helps adhesion of the electrode arrangement 8 and the substrate 2. The adhesion layer 5 is preferably formed from a metal and has a thickness of between 1 and 20 nm.

The first and/or second electrode 9, 10 has a coating 15 for promoting a red ox reaction. The coating 15 takes the form of a conductive material. In some embodiments a hydrogel (not shown) may be disposed on the conductive material coating 15. The conductive material may be dispersed within a hydrogel (not shown). In some embodiments, the conductive material may be biocompatible. In some embodiments, the conductive material may be a conjugated polymer. In some embodiments the conductive conjugated polymer may be poly(3,4-ethylenedioxythiophene) (PEDOT). In other embodiments, the conductive conjugated polymer may be poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS).

The first electrode 9 serves as a working electrode and the second electrode 10 provides a counter electrode.

The working electrode 9 and counter electrode 10 are connected to a power source 16. The power source 16 may be a battery, provided with a switch. -7 -

Oxygen from the atmosphere diffuses through the substrate layer 2 from the back face 4 to the front face 3, passes through the adhesion layer 5 and electrode arrangement 8 before dissolving in the coating 15. When a current is applied to the electrodes, the oxygen is reduced to hydrogen peroxide at the working electrode 9. The electrolytically-produced hydrogen peroxide is then in contact with the wound (not shown).

A voltage regulator circuit (not shown) may be included to apply the appropriate potential to the working electrode 9. Alternatively, a constant current device (not shown) may be included to provide a constant current at the working electrode 9 during operation. The current at the working electrode 9 during operation is typically in the /0 region of 5 RA to 0.5 mA, and is preferably about 50RA.

The oxygen reduction reaction at the coating 15 depends on the potential. At -o.45V (using a Ag/AgCI reference), it is expected that about half of the current produces hydrogen peroxide and half produces water. At more negative potentials, depending on how the coating 15 is prepared, the proportion producing water may increase.

Therefore, for optimum production of hydrogen peroxide, a voltage applied between the working electrode 9 and counter electrode 10 is selected to be close to -0.45V using a Ag/AgCI reference.

At potentials below -o.45V, for example -o.65V versus Ag/AgC1, hydrogen peroxide is further reduced to water. Therefore, wound levels of hydrogen peroxide may be lowered by selecting a lower voltage potential.

The wound dressing 1 is finite.

Figure 2 is a schematic diagram of a conventional op-amp potentiostat circuit for use in the wound dressing shown in Figure 1.

In some embodiments, a control circuit 20 which is functionally equivalent to a potentiostat may be employed to control the potential at the working electrode 9. Other transistor circuits may be used. A greater degree of potential control can be achieved using three electrodes including a working electrode 9, a counter electrode 10 and a reference electrode 21.

In certain embodiments, the wound dressing 1 incudes a reference electrode 21. If the 30 wound dressing 1 includes a reference electrode 21, then the reference electrode 21 is positioned closer to the working electrode 9 than the counter electrode 10. The -8 -reference electrode 21 may be disposed in a space in the centre of the working electrode 9. The reference electrode 21 may take the form of a thin silver film having an area of a few mm2. The reference electrode 21 may be coated with AgCI.

Referring still to Figure 2, an op-amp potentiostat circuit 20 may comprise a control signal generator 22, first and second resistors 24, 25, and first and second operational amplifiers 26, 27. The control signal generator 22 is connected via the first resistor 24 to the negative terminal of the first operational amplifier 26. The control signal generator 22 is also connected via the first and second resistors 24, 25 to the output of the second operational amplifier 27. The second operational amplifier 27 is configured to produce negative feedback. The positive terminal of the second operational amplifier 27 is connected to the reference electrode 21. The output of the first operational amplifier 26 is connected to the counter electrode 10. The positive terminal of the first operational amplifier 26 and the working cathode 9 are connected to ground.

For hydrogen peroxide reduction and sensing, lowering the overpotential can help to reduce the magnitude of the potentials used. Lowering the overpotential can be achieved by modifying the conductive material in the coating 15 with a doping agent (not shown) such as Meldola Blue. Using such a doping agent can enable detection of hydrogen peroxide in the range of 5 to 120 pM, which encompasses the physiologically relevant range, is possible.

Electrode geometry Figure 3 is a plan view of a first coplanar electrode arrangement. In Figure 3, a first coplanar electrode configuration 8, is shown. The first and second electrodes 9, 10 are generally interdigitated.

The first electrode 9 includes a first strip 3o (or "line") providing a common electrode portion running in a first direction and a set of first fingers 31 extending from the first strip 3o in a second, transverse (for example perpendicular) direction to respective distal ends 32. The first fingers 31 are straight. In a similar way, the second electrode 10 includes a second strip 35 providing a common electrode portion running in the first direction and a set of second fingers 36 extending from the second strip 35 in a transverse direction, past the first fingers 31 and towards the first strip 30, to respective distal ends 37. The second fingers 36 are straight. The first fingers 31 and the second -9 -fingers 34 are interleaved. Preferably, the first fingers 31 run up to, but do not touch, the second strip 35. Likewise, the second fingers 36 run up to, but do not touch, the first strip 3o thereby helping to increase overlap.

The fingers 31, 36 of the first and second electrodes 9, 10 have first and second lengths L, lo respectively and have first and second widths w,, AN, respectively. In this case, the first and second lengths 1,12 are the same. In this case, the first and second widths w,, w2 are the same.

The fingers 31, 36 of the first and second electrodes 9, to have first and second interstitial spaces 33, 38, each having a width 51, so respectively, in between each finger.

rci In this case, the first and second interstitial space widths s,, s2 are the same.

The first and second electrodes 9, 10 have areas a1, an respectively. In this case, the first and second areas at, a, are the same. The first and second electrodes 9, 10 may have the same shape and the same size.

The first and second electrodes 9, 10 have edges 4o, 41 respectively.

The arrangement of the first coplanar electrode configuration 8, allows hydrogen peroxide (11202) to be produced uniformly over the whole surface of the first electrode 9.

Figure 4 is a plan view of a second coplanar electrode arrangement. In Figure 4, a second coplanar electrode configuration 82 is shown.

The second coplanar electrode configuration 8, is the same as the first coplanar electrode configuration 8, except that the width w, of the first fingers 31 are wider than the width w2 of the second fingers 36, the interstitial space widths s2 of the second electrode 10 are greater than the interstitial space widths si of the first electrode 9 and the area a, of the first electrode 9 is greater than area ao of the second electrode 10.

The width w, of the first fingers 31 may be twice the width w2 of the second fingers 36. The width w, of the first fingers 31 may be more than twice the width w, of the second fingers 36. In some embodiments, the area at may be twice the size of the area a2. In other embodiments, the area a, may be more than twice the size of the area an.

-10 -The second coplanar electrode configuration 82 may produce more hydrogen peroxide than the first coplanar electrode configuration 8, when a current flows between the first and second electrodes 9, 10 due to a higher a, to a, ratio.

Figure 5 is a plan view of a third coplanar electrode arrangement.

In Figure 5, a third coplanar electrode configuration 83 is shown.

The third coplanar electrode configuration 83 is the same as the first coplanar electrode configuration 81 except that there is a greater number of the plurality of fingers 31, 36 on the first and second electrodes 9, 10 respectively.

The greater number of electrode fingers 31, 36 present in the third coplanar electrode so configuration 83 allows a greater length of the first electrode edge 4o to be in close proximity to the second electrode edge 41 than in the first coplanar electrode configuration 8,. This has the effect of increased hydrogen peroxide production when a current flows between the first and second electrodes 9, 10.

Figure 6 is a plan view of a fourth coplanar electrode arrangement.

/5 In Figure 6, a fourth coplanar electrode configuration 84 is shown.

The fourth coplanar electrode configuration 84 is the same as the second coplanar electrode configuration 82 except that there is a greater number of the plurality of fingers 31, 36 on the first and second electrodes 9, 10 respectively, and that there is one more finger 36 on the second electrode 10 than on the first electrode 9. The extra finger 36 allows the fingers 36 of the second electrode 10 to surround each of the fingers 31 of the first electrode 9. With this arrangement, a greater amount of the first electrode edge 40 is in close proximity to the second electrode edge 41. An increased amount of the first electrode edge 4o in close proximity to the second electrode edge 41 increases the amount of hydrogen peroxide production when a current flows between the first and second electrodes 9, 10.

Referring to Figures 4, 7A, 7B and 7C, a first finger 31 and second finger 36 pair 45 are isolated. The plurality of first electrode fingers 31 and plurality of second electrode fingers 36 may have different shapes.

Figure 7A is a plan view of a first alternative electrode finger layout.

In some embodiments, for example in Figure 7A, the first electrode edge 4o along the plurality of first electrode fingers 31 moves boustrophedonically along the length 1,. The second electrode edge 41 along the plurality of second electrode fingers 36 moves boustrophedonically along the length L. The pair 45 of fingers is arranged so that the boustrophedonic patterns follow closely to each other and the distance d between the edges 4o, 41 of each finger is near constant.

Figure 7B is a plan view of a second alternative electrode finger layout.

Tn some embodiments, for example in Figure 7B, the first electrode edge 4o' along the plurality of first electrode fingers 31 moves in a zig-zag pattern along the length I, The /0 second electrode edge 41' along the plurality of second electrode fingers 36 moves in a zig-zag pattern along the length L. The pair 45 of fingers is arranged so that the zig-zag patterns follow closely to each other and the distance d' between the edges 40', 41' along each finger is near constant.

Figure 7C is a plan view of a third alternative electrode finger layout.

In some embodiments, for example in Figure 7C, the first electrode edge 4o" along the plurality of first electrode fingers 31 moves sinusoidally, or sinusoidal-like, along the length L. The second electrode edge 41" along the plurality of second electrode fingers 36 moves sinusoidally, or sinusoidal-like, along the length 12. The pair 45 of fingers is arranged so that the sinusoidal patterns follow closely to each other and the distance d" between the edges 4o", 41" along each finger is near constant.

These three arrangements of the plurality of first and second electrode fingers 31, 36 increases the amount of the first electrode edge 4o in close proximity to the second electrode edge 41.

Figure 8 is a plan view of a fifth coplanar electrode.

Tn Figure 8, a fifth coplanar electrode configuration 85 is shown.

The first electrode 9 is generally square or rectangular with rounded corners. The second electrode to surrounds the first electrode 9.

In some embodiments, the first electrode 9 includes a plurality of interstitial spaces 33 cut from an edge 4otowards the centre defining a set of first fingers 31. The second electrode to has a plurality of fingers 36 which protrude into the plurality of strips 5o -12 -cut out of the first electrode 9. The first and second electrodes 9, 10 may have curved edges 40, 41 or straight edges 40, 41, or a combination of curved and straight edges 40, 41. The first electrode area a, may be greater than the second electrode area a,. The ratio of the first electrode area a, to the second electrode area a, may be 8:1. The ratio of the first electrode area a, to the second electrode area a2 may be greater than 8:1.

Figure 9 is a plan view of a sixth coplanar electrode.

In Figure 9, a sixth coplanar configuration 86 is shown.

The first electrode 9 is generally square or rectangular with rounded corners. The second electrode 10 is surrounded by the first electrode 9.

In some embodiments, the first electrode 9 includes an interstitial space 33 cut from an edge 4o towards the centre defining a set of first fingers 31. The second electrode 10 has a single finger 36 which protrudes into the strip 55 cut out of the first electrode 9. The first electrode area a, may be greater than the second electrode area a,. The ratio of the first electrode area a, to the second electrode area a2 may be 8:1. The ratio of the first electrode area a, to the second electrode area a2 may be 8:1. The ratio of the first electrode area a, to the second electrode area a2 may be greater than 8:1.

Figure in is a plan view of a seventh coplanar electrode.

In Figure 10, a seventh coplanar configuration 87 is shown.

The first electrode 9 is generally circular, having a circular recessed area in the centre of the electrode forming a first interstitial space 33. The second electrode 10 is also generally circular and protrudes into the recessed area of the first electrode 9. The ratio of the second electrode area a, to the first electrode area a, may be 8:1. The ratio of the second electrode area a, to the first electrode area a, may be greater than 8:1.

Experimentation and results Electropoiymerisation of PEDOT 3,4-Ethylenedioxythiophene (EDOT), and polystyrene sulfonate (PSS) in water:ethanol (3:2) was added p-toluenesulfonic acid portion-wise to a solution of sodium paratoluenesulfonate (NaPTS) until a pH of 2 was reached (Table 1).

-13 -Material Amount in a Amount in a lomL 2omL 1120:Et0H 1120:Et0H solution solution o.i.M NaPTS 194 mg 388 mg o.005M EDOT 71 mg 142 mg 0.01M PSS 20 mg 41 mg

Table 1

The PEDOT electrodeposition was carried out using a three-electrode cell as described by Kerr et al. : "Influence of the Polymerization Method on the Oxygen Reduction Reaction Pathway on PEDOT", ECS Electrochemistry Letters, volume 2(3), pages F29-F31 (2013) where ITO/Au was the working electrode, Pt the counter electrode and Ag/AgCI as the reference electrode.

Hydrogen Peroxide Generation A three electrode set-up comprising an indium-tin oxide (ITO)/Au/PEDOT working electrode, an ITO/Au counter electrode and a Ag/AgC1 reference electrode, is immersed io in a phosphate-buffered saline (PBS) solution. Hydrogen peroxide (H202) is generated by applying a constant voltage of -0.45 V between the reference and the working electrode. After a period of 90 minutes, the concentration of FLO° generated was quantified using a colorimetric peroxide assay kit.

Figure 11 is a table of hydrogen peroxide release.

An interdigitated electrode arrangement 82 with a first to second electrode area ai, a2 ratio of 2:1 and a total area of 1.28 cm2 generates hydrogen peroxide at a rate of 6.5 pM/minute/cm2. When a bridging material, for example Mepitel® Gauze, is interposed between the electrode arrangement 82 and a PBS solution mimicking wound fluid, hydrogen peroxide is generated at a rate of 10.6 µM/minute/cm2. A square electrode arrangement with a first to second electrode area ratio of 8:1 and a total area of 2.7 cm2 generates hydrogen peroxide at a rate of 3.4 pM/minute/cm2. When a bridging material, for example Mepitel® Gauze, is interposed between the square electrode arrangement and a PBS solution mimicking wound fluid, hydrogen peroxide is generated at a rate of 5.8 pM/minute/cm2.

-14 -Figure 12 are graphs of current against time for four coplanar electrode layouts.

Referring to Figure 12, amperometric traces of current during the 90 minute hydrogen peroxide generation period are plotted for two example electrode configurations. During the recording of the traces, the electrodes are adjacent to a silicone mesh that acts as a bridging material between the device and the PBS solution. The recordings are taken while the PBS solution is being stirred and not stirred.

A first trace 5o is from an example of a known square-like electrode configuration used in a wound dressing having an 8:1 first electrode area a, to second electrode area a2 ratio where a second electrode io is a thin strip adjacent to the four sides of a ro substantially square first electrode 9. A second trace 51 is from the same square electrode configuration as the first trace 51, but where the wound-mimicking PBS solution is also stirred during the experiment. A third trace 52 is from the second electrode configuration 82, having a 2:1 first electrode area a, to second electrode area a2 ratio, and the first electrode 9 and the second electrode 10 are interdigitated. A fourth trace 53 is also from the second electrode configurations 82, but where the wound-mimicking PBS solution is also stirred during the experiment.

Referring still to Figure 12, the second electrode configuration 82, having interdigitated electrodes and a first to second electrode area a1, a, ratio of 2:1, has a higher current flowing between the first and second electrodes 9, 10, for the majority of the 90 minute period. The higher the current flowing between the first and second electrodes 9, 10, results in a greater amount of hydrogen peroxide being generated. When the PBS solution is stirred the current increases and a greater amount of hydrogen peroxide is produced compared to the non-stirred control.

Modifications It will be appreciated that various modifications may be made to the embodiments hereinbefore described. Such modifications may involve equivalent and other features which are already known in the design, manufacture and use of wound dressings and component parts thereof and which may be used instead of or in addition to features already described herein. Features of one embodiment may be replaced or supplemented by features of another embodiment.

Although claims have been formulated in this application to particular combinations of features, it should be understood that the scope of the disclosure of the present -15 -invention also includes any novel features or any novel combination of features disclosed herein either explicitly or implicitly or any generalization thereof, whether or not it relates to the same invention as presently claimed in any claim and whether or not it mitigates any or all of the same technical problems as does the present invention.

The applicants hereby give notice that new claims may be formulated to such features and/or combinations of such features during the prosecution of the present application or of any further application derived therefrom. -i6-

Claims

CLAIMS1. A wound dressing (1) comprising: a flexible substrate (2) having a first and second opposite faces (3, 4); first and second electrodes (9, io) disposed over the first face (3) wherein 5 the first electrode defines a recessed area and the second electrode comprises a protruding area extending into the recessed area; and a coating (15) on at least one of the first and/or second electrode for promoting a redox reaction, the coating(s) comprising a conductive material.
2. The wound dressing of claim 1, wherein the first and second electrodes (9, io) are coplanar.
3. The wound dressing of claim 1 or 2, wherein a ratio of an area (a,) of the first electrode (9) to an area (a2) of the second electrode (16) is 2:1.
4. The wound dressing of claim 1 or 2, wherein a ratio of an area (a1) of the first electrode (9) to an area (a2) of the second electrode (io) is greater than 2:1.
5. The wound dressing of any one of claims 1 to 4, wherein the first and second electrodes (9, io) are interdigitated.
6. The wound dressing of claim i/any one of claims 1 to 5, wherein the first and second electrodes (9, lo) have the same dimensions.
7. The wound dressing of claim 1/any one of claims 1 to 5, wherein the first electrode (9) has different dimensions to the second electrode (w).
-17 - 8. The wound dressing of any one of claims i to 5, wherein the fingers (31, 36) of the first and second electrodes (9, io) have the same widths (wi, w2).
9. The wound dressing of any one of claims i to 5, wherein the widths (w0 of the fingers (31) of the first electrode (9) are different to the widths (w2) of the fingers (36) of the second electrode (1o).
10. The wound dressing of any one of claims i to 5, wherein the fingers (31, 36) of the first and second electrodes (9, io) have the same lengths (1,,12).in The wound dressing of any one of claims i to 5, wherein the lengths (1,) of the fingers (31) of the first electrode (9) are different to the lengths 02) of the fingers (36) of the second electrode (1o).12. The wound dressing of any one of claims i to 5, wherein the interstitial spaces (33, 38) of the first and second electrodes (9,10) have the same widths (s,, s2).13. The wound dressing of any one of claims 1 to 5, wherein the interstitial space widths (s1) of the first electrode (9) are different to the interstitial space widths (w2) of the second electrode (1o).14. The wound dressing of any one of Sims 1 to 13, wherein the first electrodes (9) has the same shape to the second electrode (1o).15. The wound dressing of claim 1/any one of claims 1 to 13, wherein the first electrode (9) has a different shape to the second electrode (1o).16. The wound dressing of claim 1/any one of claims i to 15, wherein the fingers (31, 36) of the first and second electrodes (9, 10) are arranged in a repeating configuration.17. The wound dressing of claim i/any one of claims i to 16, having a size of 2 cm x 4 cm.18. The wound dressing of claim 1/any one of claims i to 16, having a size of 5 cm x 10 cm.19. The wound dressing of claim i/any one of claims i to 16, having a size of 20 cm x 40 cm.20. The wound dressing of any one of claims i to 19 wherein a first /5 adhesion layer (5,) is disposed on the first face (3) of the substrate (2) and the first electrode (9) and a second adhesion layer (52) is disposed on the first face (3) of the substrate (2) and the second electrode (10); and the adhesion layer is electrically conductive.21. The wound dressing of any one of claims i to 19 wherein a first adhesion layer 5, is disposed on the first face (3) of the substrate (2) and the first electrode (9) and a second adhesion layer (52) is disposed on the first face (3) of the substrate (2) and the second electrode (10); and the adhesion layer is electrically insulating.22.The wound dressing of any one of claims i to 19 wherein an adhesion layer (5) is disposed on the first face (3) of the substrate 2 and the first and second electrodes (9, 10); and the adhesion layer is electrically insulating.-19 - 23.The wound dressing of any one of claims i to 22 wherein an edge (40) of the first electrode and an edge (41) of the second electrode are straight.24. The wound dressing of any one of claims i to 22 wherein an edge (40) of the first electrode and an edge (41) of the second electrode have a boustrophedonic shape and interlock each other.25.The wound dressing of any one of claims i to 22 wherein an edge (40) of the first electrode and an edge (41) of the second electrode have a zig-zag shape and /0 interlock each other.26. The wound dressing of any one of claims i to 22 wherein an edge (4o) of the first electrode and an edge (41) of the second electrode have a sinusoidal-like shape and interlock each other.27.The wound dressing of any one of claims t to 26 wherein the first and second electrodes (9, lo) have a generally circular shape.28. The wound dressing of any one of claims i to 27 further 20 comprises a power source (16); and a switch; wherein the power source is connectable to the first and second electrodes (9, io) using the switch.29. The wound dressing of any one of claims t to 28 wherein a hydrogel is disposed on top of the coating (15).3o. The wound dressing of any one of claims t to 29 wherein the conductive material is biocompatible.31. The wound dressing of any one of claims i to 3o, wherein the conductive material is a conjugated polymer.32.The wound dressing of any one of claims i to 31 wherein the conductive material is poly(3,4-ethylenedioxythiophene).33.The wound dressing of any one of claims i to 31 wherein the conductive material is poly(3,4-ethylenedioxythiophene):polystyrene sulfonate.io 34.The wound dressing of any one of claims i to 33, further comprising: a reference electrode (2i); and a potentiostat (20).-21 -