Multi-modal wound healing

Abstract

There is provided a dressing, processing unit, system and methods for modulating a wound state of a tissue injury. The dressing comprises a plurality of electrodes configured to apply electrical stimulation to the tissue injury and an optical emitter configured to apply optical stimulation to the tissue injury. One or more of the electrical stimulation and the optical stimulation are applied according to a condition of the tissue injury. The electrical stimulation and the optical stimulation are applied simultaneously or sequentially.

Description

MULTI-MODAL WOUND HEALINGTECHNICAL FIELD

[0001] This invention relates to treating tissue injuries. In particular, the invention relates to a dressing, processor, system and method for modulating a wound state of a tissue injury.BACKGROUND

[0002] There are several types of tissue injuries that cannot easily or rapidly heal. These include chronic wounds such as diabetic foot lesions, venous leg and pressure ulcers; complex wounds such as burns; infected wounds; post-operative wounds; large or deep wounds; wounds in areas of poor blood supply; radiation-induced wounds; wounds in immunocompromised patients and wounds in older adults. These wounds may struggle to heal due to persistent infections which current anti-microbials struggle to treat; considerable wound complexity including the co-existence of different healing states, infection and bacterial biofilms combined with varying wound conditions; and often sufferers' lack of adherence to currently available home therapies.

[0003] Treating these injuries can therefore be painful and tedious for patients whilst also causing financial and time burdens on health services. Inadequate treatment can cause worsening of the condition, prolonged hospitalisation, expensive and extensive treatment and even lead to limb amputation or death.

[0004] It is in this context that the present invention is devised.BRIEF SUMMARY

[0005] In one aspect of the invention, there is a dressing for modulating the wound state of a tissue injury. The dressing comprises a plurality of electrodes configured to apply electrical stimulation to the tissue injury and an optical emitter configured to apply optical stimulation to the tissue injury. The optical stimulation and the electrical stimulation are applied simultaneously sequentially, or independently.

[0006] Advantageously, this provides a multifaceted approach for healing the tissue injury which results in a faster healing process and consequent reduced scarring. Both antimicrobial and accelerated healing properties can be provided in a single dressing. The dressing is also simple and convenient to use, which encourages patient compliance and reduces complications caused by incompliance or human error. The dressing can be adaptive or personalised for moreeffective treatment of the particular injury for the particular patient. The dressing is size-scalable to treat different wound sizes.

[0007] Modulating the wound state of a tissue injury encompasses the healing, infection control or treatment of the tissue injury. This can include antibacterial and anti-biofilm actions as well as the regrowth or healing of tissue.

[0008] The optical and electrical stimulation can each treat different aspects of a wound, resulting in a synergistic healing process. The optical and electrical stimulation can also work together to treat the same aspect of the wound to accelerate the healing of that aspect of the wound.

[0009] A range of parameters of non-pharmaceutical, electrical-optical treatment can be employed to achieve a multitude of outcomes. For example, optical stimulation can stress or kill bacteria, increase cell energy levels, fibroblast proliferation rates and reduce inflammation whereas electrical stimulation can disrupt biofilms and increase fibroblast proliferation rate and direct cellular migration, all which are key to tissue repair. Moreover, combining electrical and optical stimulation has an additive effect which is greater than the sum of the individual parts. That is, there is a synergistic interaction between optical and electrical stimulation which amplifies their combined effect.

[0010] As another example, exposing the tissue injury to wavelengths of red light and electrical stimulation can stabilise the environment of the tissue injury. The red light (ie 670 nm wavelength light) stimulates mitochondria to oxidise glucose faster, thus increasing metabolism, and can be used to decrease local glucose concentrations. This allows local blood glucose levels to be reduced when needed. This is particularly important for people with metabolic disease, as elevated blood glucose delays healing.

[0011] As a further example, red light stimulates fibroblasts to proliferate. Electrical stimulation also increases proliferation rate, but with a delay of 24 hours. Once the increased proliferation from electrical stimulation kicks in, there is an additive effect of light and electricity combined. Red light (670nm) and Electrical stimulation (AC monophasic pulse of 50pA with 250ms pulse width at 300mHz for 4 hours) both increase rate of wound closure separately in agreement with what has been reported elsewhere. Very importantly, a combination of the two modes has an additive effect, not reported elsewhere.

[0012] As another example, the electrical-optical stimulation can disrupt bacterial biofilms. Preliminary results have shown that the stimulation can release individual cells - planktonic bacteria. Planktonic bacteria are significantly more susceptible to current anti-microbials (i.e. antibiotics) in use, making the present dressing complimentary to current therapy pathways. Thestimulation employed by this invention can also directly kill these planktonic bacteria. Killing these planktonic bacteria removes infection to enable the wound to more effectively heal.

[0013] One or more of the electrical stimulation and the optical stimulation are applied according to a condition of the tissue injury.

[0014] Advantageously, this enables the stimulation strategy to be tailored according to a condition of the tissue injury, which can further improve the healing process (or wound state) of the wound. Certain types of electrical or optical stimulation may be beneficial for treating one type of wound, but detrimental to treating a different type of wound. Applying the electrical or the optical stimulation according to the condition of the wound can therefore minimise detrimental effects and maximise beneficial effects on the healing process.

[0015] Where some types of stimulation may have both positive and negative effects on the wound state, that type of stimulation may only be used for as long as necessary to achieve the positive effect. This enables the benefits of that stimulation to be utilised whilst minimising or controlling a negative impact. For example, 670nm light can be used to increase a wound healing rate by increasing fibroblast proliferation. However in the presence of infection the 670nm light would also increase bacterial proliferation rates. In addition, electrical stimuli of certain amplitude and waveform combinations can be beneficial to the wound treatment but also has the effect of activating neurons and subsequently muscle fibres in the vicinity, to levels that cause contractions and therefore pain. Combining stimuli modalities and parameters appropriately can achieve the positive outcomes for the healing process while avoiding the aforementioned or any other negative side effects.

[0016] The condition of the tissue injury may comprise two or more conditions. The electrical stimulation may be applied according to a first condition of the two or more conditions and the optical stimulation may be applied according to a second condition of the two or more conditions.

[0017] This enables the electrical and optical stimulation to target different types of wound or tissue injury within the overall tissue injury.

[0018] The plurality of electrodes may comprise a plurality of electrode pairs, and each electrode pair is configured to apply different electrical stimulation to the tissue injury based on the condition of the tissue injury across the electrode pair.

[0019] There may be a plurality of optical emitters. Each optical emitter may be configured to apply different optical stimulation to the tissue injury based on the condition of the tissue injury in an area surrounding the optical emitter.

[0020] Different regions of the tissue injury will have different characteristics, such as different states of healing and different levels of inflammation, infection, biofilm etc. Applying differentelectrical stimulation across different electrode pairs and different optical stimulation through different optical emitters enables the regions to be treated individually. The electrical and optical stimulation can each be tailored according to the different conditions of the tissue injury in the regions across the different electrode pairs, which can facilitate the overall healing of the tissue injury. That is, targeting different stimulation techniques to particular areas can result in a faster healing process than using the same stimulation technique across the entire tissue injury.

[0021] The plurality of electrodes may be further configured to periodically apply effectively non-modulating electrical signals to the tissue injury and to receive electrical signals indicative of the condition of the tissue injury. In addition, the electrodes may measure electrical signals, such as biosignals, corresponding to naturally occurring processes to acquire further information regarding the tissue injury. One or both of the electrical stimulation and the optical stimulation may be applied based on the received electrical signals.

[0022] The dressing may further comprise an optical sensor configured to periodically receive optical signals reflected from the tissue injury, wherein the optical signals are indicative of the condition of the tissue injury. One or both of the electrical stimulation and the optical stimulation may be applied based on the received optical signals.

[0023] Applying the electrical and optical stimulation according to periodically received electrical or optical data enables the electrical and optical stimulation techniques to adapt according to the healing process or current condition of the tissue injury. An electrical or optical stimulation technique that is appropriate when the dressing is first applied may become less appropriate after some time has passed. Frequent scanning of the affected region allows for the detection of changes associated with the improvement or deterioration or shifting of the affected regions thus allowing for the re-allocation of the nodes or combinations of nodes to be used and the stimulation parameters, modalities and combinations that need to be applied both optically and electrically.

[0024] For example, light exposure has been shown to stress bacteria. Blue light (420nm -460nm) and electrical stimulation can reduce bacterial growth rate and kill bacteria with enough exposure but may also damage or impede the healing of underlying skin. Periodic scanning of a region affected by bacteria means that the optical-electrical stimulation technique required to kill the bacteria can be switched to a different technique once the data shows that the bacteria have been killed. This enables the bacteria to be killed in a way which reduces negative impacts on the underlying human cells.

[0025] The stimulation technique used by the dressing may be chosen to improve a long term outcome over a short term outcome. For example, exposure to red light has been shown toreduce inflammation whereas exposure to blue light can increase inflammation. Temporary exposure to blue wavelengths of light can give short bursts of increased inflammation, which leads to reduced inflammation in the long-term. The present invention may determine an amount of exposure to blue wavelength light which balances the long term positive benefits of some exposure and the negative short term impact of temporarily increased inflammation.

[0026] The dressing may further comprise a pressure sensor, which may be formed by the plurality of electrodes. At least one of the electrical stimulation and optical stimulation may be applied based on the received pressure data.

[0027] Pressure information can be advantageous when treating injuries such as diabetic foot wounds. Reducing a pressure of the wound can promote healing by encouraging blood flow to the wound site which then accelerates the healing of the wound.

[0028] The condition of the tissue injury may comprise one or more of a healing phase of the injury, a presence of inflammation, a presence of infection, a presence of a bacterial biofilm, and a presence of necrosis. The condition of the tissue injury may be referred to as the wound state. The wound state may refer to the current condition or stage of a wound, encompassing its characteristics, progression, and potential for healing. This includes factors like depth, presence of infection, and the overall healing phase.

[0029] These conditions can have different effects on the healing of the tissue injury so may require different stimulation techniques to treat.

[0030] The term healing phase (which may be used interchangeably with healing stage) covers a current state of damage to or healing of the injury, such as an amount, extent or severity of the injury and a degree to which the injury has healed. This term is intended to encompass the full range of terms which often vary according to the type or cause of the injury. For example, there are different medical classifications of burn injuries (first degree, second degree, etc) according to a depth of skin and tissue damage. There are also different grading systems of pressure injuries based on tissue loss and exposure of underlying structures. All systems and classifications relating to an amount, extent or severity of the injury are encompassed by the term healing phase.

[0031] In another aspect of the invention, there is a processing unit for modulating a wound state of a tissue injury. The processing unit is configured to receive data indicative of a condition of the tissue injury. The processing unit is configured to determine, based on the received data, one or more of an electrical stimulation technique and an optical stimulation technique for modulating the wound state of the tissue injury. The processing unit is further configured tooutput a signal indicative of the one or more determined electrical stimulation technique and optical stimulation technique.

[0032] This enables a stimulation technique to be determined according to a condition of a tissue injury. The electrical-optical stimulation technique employed by the dressing may be based on the signal output by the processing unit.

[0033] Where the data indicative of a condition of the tissue injury is received by sensors associated with the dressing, the processing unit can provide an intelligent wound treatment technique which adapts according to the progress of the condition of the tissue injury.

[0034] The processing unit may be configured to analyse the received data to obtain a map of the tissue injury and identify, using the map, one or more regions of the tissue injury according to a condition of the tissue injury in the one or more regions. The processing unit may be further configured to determine the one or more of the electrical stimulation technique and the optical stimulation technique for each region of the tissue injury.

[0035] This enables specific factors affecting the healing of the tissue injury to be addressed individually. The tissue injury is not treated as a whole, but divided into regions according to a condition of the tissue within the region, where the different regions can then be subjected to appropriate simulation techniques simultaneously. This enables areas of the tissue injury suffering from, for example, inflammation, to be subjected to a different stimulation technique compared to other areas of the tissue injury suffering from, for example, necrosis. T reating each aspect of the tissue injury in this manner facilitates a faster wound healing process.

[0036] A region of the tissue injury that is affected by two or more conditions may be treated with an electrical-optical stimulation technique which provides the best overall treatment for the particular combination of conditions. This may be a compromise of the stimulation techniques that would be most appropriate for the two conditions individually, or may be a bespoke stimulation technique particular to that particular combination of conditions.

[0037] The processing unit may be configured to determine the electrical stimulation technique and the optical stimulation technique that combine to facilitate a healing of the tissue injury.

[0038] The synergistic effect of the electrical stimulation and the optical stimulation is considered when determining an optimal or appropriate stimulation technique for treating the tissue injury of a region of the tissue injury. Facilitating the healing of the tissue injury can include accelerating the healing process or improvement of the wound state, reducing scarring formed as a result of the healing process, reducing a pain or discomfort felt by the patient during the healing process, reducing infection, and reducing potential complications during the healing process.

[0039] In another aspect of the invention, there is a system for modulating a wound state of a tissue injury. The system comprises a dressing and a processing unit.

[0040] In yet another aspect of the invention, there is a method for modulating a wound state of a tissue injury. The method comprises applying electrical stimulation and optical stimulation to the tissue injury.

[0041] This can improve the healing or condition of the tissue injury and facilitate a process of healing the wound.

[0042] In a further aspect of the invention there is another method for modulating a wound state of a tissue injury. The method comprises receiving data indicative of a condition of the tissue injury. The method further comprises determining, based on the received data, one or more of an electrical stimulation technique and an optical stimulation technique for modulating the wound state of the tissue injury. The method also comprises outputting a signal indicative of the one or more electrical stimulation technique and optical stimulation technique.

[0043] In yet a further aspect of the present disclosure, a dressing for modulating a wound state of a tissue injury is provided. The dressing comprises a flexible substrate supporting a multi-nodal array of bio-transceiver nodes, each node comprising an electrode pair and an optrode having an optical emitter and an optical detector, each node being selectively configurable as a sensing node and / or a stimulation node. The dressing further comprises a switching circuitry configured to operate the nodes in time-multiplexed sensing and / or stimulation modes and to drive different nodes concurrently; and a controller. The controller is configured to periodically acquire multimodal wound data by applying at least one nonmodulating test electrical signal via selected electrode pairs and by receiving at least one optical reflectance signal via the optrode. The controller is further configured to generate a depthsensitive spatial wound-state map from the multimodal wound data and segment the wound into a plurality of regions according to local condition; determine, for each region, an electrical stimulation technique and / or an optical stimulation technique including one or more of amplitude, waveform, frequency, phase, duty cycle and node selection; select electrode pairs, electrode spacing, carrier frequency and / or relative phase so as to position an electrical stimulation focus at a target depth estimated from the multimodal wound data; command different nodes to deliver different stimulation modalities or parameters in different regions simultaneously; select stimulation parameters that concurrently produce an antibacterial effect and a healingaccelerant effect without one effect detrimentally impacting the other by enforcing a conflictavoidance constraint derived from the wound-state map; apply a controller-defined stimulation sequence comprising at least a blue-light antibacterial phase of a predefined duration and a red-light metabolic phase with electrical stimulation applied after a delay corresponding to fibroblast response kinetics; and periodically update the spatial wound-state map and reallocate nodes between sensing and / or stimulation in response to changes in wound condition.

[0044] The controller may be configured to fuse bioimpedance data and multi-wavelength optical reflectance data and optionally one or more of temperature, pressure, hydration and pH data when generating the spatial wound-state map.

[0045] A segmentation-classified region of the plurality of regions may represent one or more of infection, inflammation, necrosis, granulation and healing stage.

[0046] The controller may be configured to provide blue-range optical stimulation between 420 nm and 460 nm to an infection-classified region of the plurality of regions.

[0047] The controller may be configured to apply electrical stimulation to disrupt a bacterial biofilm, then apply blue light optical stimulation to kill at least some, or all, of the bacteria in the biofilm.

[0048] The controller may be configured to provide red-range optical stimulation including about 670 nm in combination with electrical stimulation to a granulation-classified region of the plurality of regions.

[0049] The controller may be configured to apply short-burst blue-range optical stimulation to infection-classified regions of the plurality of regions until one or more infection indicators diminish.

[0050] The controller may be configured to apply electrical stimulation with a delay relative to red-range optical stimulation corresponding to fibroblast response kinetics.

[0051] The electrical stimulation may comprise one or more of monophasic, biphasic or multiphasic pulses at microcurrent amplitudes which may be within biocompatible limits.

[0052] The optrodes may be configured to provide pulsed or continuous illumination in one or more of blue, red and infrared wavelength bands, and two or more optrodes within a region can be driven concurrently to shape an optical fluence profile.

[0053] The nodes may be configurable for bipolar, tripolar or tetrapolar bioimpedance sensing during sensing phases.

[0054] The controller may be configured to operate at least two spatially separated electrode pairs at respective carrier frequencies higher than an envelope frequency and with a controllable relative phase to synthesise a lower-frequency amplitude envelope at a selected target locus and depth, while maintaining per-electrode limits.

[0055] The controller may be configured to maintain per-electrode instantaneous charge and charge density below a configured maximum while producing the amplitude envelope at the target locus.

[0056] The controller may be configured to select electrode spacing, carrier frequency and relative phase to control depth of peak electrical field and in-plane focus width.

[0057] Optical stimulation from two or more optrodes in a region may be driven concurrently or in sequence to provide a target optical fluence pattern.

[0058] The controller may be configured to employ a simulation or optimisation module to evaluate candidate multi-site carrier assignments against an objective function that maximises envelope amplitude at the target locus subject to per-electrode limits and the conflict-avoidance constraint.

[0059] The dressing may further comprise a membrane layer arranged to improve electrical contact and an outer covering layer arranged to provide environmental protection.

[0060] The controller may be configured to update a depth setpoint per region based on at least one temporal trend in the multimodal wound data.

[0061] The controller may be configured to detect node integrity using sensing signals to identify connectivity issues that may affect performance, and when a broken contact is detected the controller is configured to select neighbouring nodes and drive parameters to achieve a similar localised stimulation outcome.

[0062] The controller may be configured to evaluate impedance to identify a high-impedance path associated with at least one air bubble, scar and / or necrotic tissue, or pus, and further configured to select at least one alternative electrode path and / or adjust electrical parameters including carrier frequency and amplitude to avoid or compensate such path.

[0063] The controller may be configured to limit at least one electrical parameter in an innervated region to avoid neuronal activation or painful muscle contraction.

[0064] The controller may be configured to store at least one historical wound-state map and adapt a stimulation parameter based on at least one temporal trend.

[0065] The dressing may further comprise a wireless communication interface arranged to transmit wound-state data and receive an updated stimulation policy.

[0066] In yet another aspect of the present disclosure, a controller for modulating a wound state is provided. The controller is configured to receive multimodal wound data comprising electrical bioimpedance data and optical reflectance data and optionally one or more of temperature, pressure, hydration, pH and oxygenation data, the controller being configured to:generate a depth-sensitive spatial wound-state map from the multimodal wound data; classify regions of the wound as one or more of infection, inflammation, necrosis, granulation and healing stage; select, for each region, an electrical stimulation technique and / or an optical stimulation technique including one or more of amplitude, waveform, frequency, phase, duty cycle and node selection; optimise combined electrical and optical stimulation so as to concurrently achieve antibacterial effects and healing-accelerant effects without mutual detriment, including by applying temporal sequencing, dose constraints and a conflict-avoidance rule; output node-level control signals to a multi-nodal array of bio-transceiver nodes to deliver simultaneous regionspecific stimulation across different regions, including multi-site carrier drives having controllable relative phase; select electrode pairs, electrode spacing, carrier frequency and / or relative phase to focus electrical stimulation at a target depth; and periodically re-map the wound state and reassign nodes between sensing and stimulation.

[0067] In this example, the spatial wound-state map may be generated by fusing bioimpedance spectra with multi-wavelength optical reflectance data and thermal gradient data.

[0068] The region classification may be performed using a trained model arranged to output infection, inflammation, necrosis and / or granulation labels.

[0069] Temporal sequencing may comprise a limited blue-light antibacterial phase followed by a red-light metabolic phase and electrical stimulation after a delay aligned to fibroblast proliferation kinetics.

[0070] Stimulation parameter selection may ensure compliance with pain-avoidance thresholds and exposure limits.

[0071] The controller may be further configured to store historical spatial wound-state maps and adapt a stimulation parameters based on at least one temporal trend.

[0072] The controller may be further configured to communicate wirelessly with a remote device to transmit wound-state data and receive an updated policy.

[0073] Node selection for sensing may use bipolar, tripolar or tetrapolar electrode configurations to vary interrogation depth and improve depth estimation of the target.

[0074] In yet another aspect of the present disclosure, a system comprising the dressing according to any of the examples herein and a controller according to any examples herein, the system being configured to deliver electrical and optical stimulation to different regions of a wound simultaneously based on the updated depth-sensitive spatial wound-state map.

[0075] The system may further comprise a wireless transceiver arranged to transmit woundstate data and stimulation logs to a remote device.

[0076] The controller may be external to the dressing and the dressing includes addressing circuitry arranged for time-multiplexed operation of the nodes.

[0077] The dressing may include a transceiver coil arranged for power reception and data communication.

[0078] The dressing may comprise a hermeticity layer and a main electronics unit including front-end sensing and stimulation circuitry and power management circuitry.

[0079] The system may be configured to detect transitions in wound state and automatically reclassify regions and update regional stimulation techniques.

[0080] In yet another aspect of the present disclosure, a bio-transceiver array for a wound dressing is provided. The bio-transceiver array comprises a plurality of nodes, each node including an electrode pair arranged for both electrical stimulation and bioimpedance sensing, an optrode arranged for both optical stimulation and optical sensing, and switching circuitry arranged to enable time-multiplexed operation between sensing and stimulation.

[0081] Neighbouring nodes may be arranged to form a two-dimensional lattice on a flexible substrate.

[0082] The optrode may be configured to provide multi-wavelength output including blue, red and infrared bands and includes a photodiode arranged to measure optical reflectance.

[0083] The electrode pair may be configurable as bipolar, tripolar or tetrapolar during sensing to adjust interrogation depth.

[0084] In any of the aspects, examples and embodiments described herein, the controller may be configured to concurrently drive at least two spatially distinct regions with the same and / or different stimuli, including the same and / or different carrier frequencies, phases or optical settings.

[0085] Local switching may support independent addressing of nodes while enabling simultaneous stimulation in at least two regions.

[0086] Electrode pair spacing and selectable phase difference may be configured to control depth of peak electrical field.

[0087] The present invention provides a wearable wound healing device appropriate for home and early stage use. Antibacterial and wound acceleration actions are advantageously applied in combination. Wound mapping and real-time localised stimulation enable the precise application of appropriate stimulation to address the localised needs of the tissue injury.BRIEF DESCRIPTION OF THE DRAWINGS

[0088] To easily identify the discussion of any particular element or act, the most significant digit or digits in a reference number refer to the figure number in which that element is first introduced.

[0089] Figure 1A is a block diagram of a dressing in accordance with an embodiment of the invention.

[0090] Figure 1 B is another block diagram of a dressing in accordance with an embodiment of the invention.

[0091] Figure 2 is a block diagram of a processing unit in accordance with an embodiment of the invention.

[0092] Figure 3 is a block diagram of a system in accordance with an embodiment of the invention.

[0093] Figure 4 is an exploded view diagram of a dressing in accordance with an embodiment of the invention.

[0094] Figure 5 is a flow chart showing a method of modulating a wound state in accordance with an embodiment of the invention.

[0095] Figure 6 illustrates results of biofilm disruption cell culture experiments.

[0096] Figure 7 illustrates results of fibroblast migration cell culture experiments.

[0097] Figure 8 illustrates results of fibroblast proliferation cell culture experiments.

[0098] Figure 9 illustrates FEM simulations indicating regional and depth selectivity.DETAILED DESCRIPTION

[0099] Figure 1A shows a block diagram of a dressing 100 for application to a tissue injury according to an embodiment. In this disclosure, a dressing is intended to encompass any material or wearable device that can be applied to a tissue injury. The dressing may be a flexible wound dressing, a wearable garment, the insole of a shoe or a sock, a plaster or a probe for application in tubular orifices that have incurred injury. The dressing may protect the tissue injury from external contaminants or trauma, promote healing, control bleeding, or absorb fluids leaked from the tissue injury.

[0100] The tissue injury may be any type of wound or damage to, on or under the skin of a patient and onto which a dressing may be applied. Tissue injuries may comprise one or more lacerations, burns, inflammation areas, ulcers, infections, regions of necrosis, biofilms, or surgical wounds. These may be referred to as types of tissue injury. A condition of the tissueinjury may comprise one or more of these types of tissue injuries. The condition of the tissue injury may consider an extent, size or severity of each type of tissue injury as well as an extent or state of healing of the tissue injury. The condition of the tissue injury may be referred to as a wound state.

[0101] The dressing 100 comprises a plurality of electrodes 102 and an optical emitter 104 incorporated into a substrate. The plurality of electrodes 102 includes at least a pair of electrodes. Each electrode among the plurality of electrodes may be configured to apply electrical stimulation (a current) to the tissue of the patient. The electrical stimulation may be applied according to the type of the tissue injury.

[0102] The optical emitter 104 is configured to output optical stimulation to the tissue of the patient. The optical stimulation may comprise electromagnetic waves, and the electromagnetic waves may have wavelengths falling within the optical wavelength range. The optical emitter 104 may be configured to output electromagnetic waves of a single wavelength, or two or more wavelengths. The optical stimulation may be applied according to the type of the tissue injury.

[0103] The electrodes 102 and optical emitter 104 may be configured to output respective electrical and optical stimulation based on the type of the tissue injury. In an embodiment, the outputs of one or more of the electrodes 102 and optical emitter 104 may be predetermined based on the type of the tissue injury. For example, a dressing 100 for a burn injury may have a first configuration of electrical and optical stimulation, whereas a dressing for a surgical injury may have a second configuration of electrical and optical stimulation, where the first configuration and second configuration are different.

[0104] In another embodiment, the outputs of one or more of the electrodes 102 and optical emitter 104 may adapt according to the healing of the tissue injury. In this embodiment, which will be described in more detail with reference to Figure 1B, one or more sensing means may obtain data indicative of a condition of the tissue injury. The electrodes 102 and optical emitter 104 may output respective electrical and optical stimulation based on the data obtained by the sensing means.

[0105] Figure 1B shows a block diagram of a dressing 100 for application to a tissue injury according to an embodiment.

[0106] The dressing 100 further comprises one or more sensing means 106. The sensing means 106 may be referred to as sensors. The sensing means may comprise a plurality of electrodes for measuring local biopotentials or carrying out bioimpedance measurements. The plurality of electrodes used as the sensing means 106 may be the same electrodes 102 asdiscussed in relation to Figure 1A. That is, the plurality of electrodes 102 may perform both sensing and stimulation of the tissue of the patient.

[0107] The sensing means 106 may comprise one or more optical sensors or photodiodes for performing optical tissue interrogation at different wavelengths. The sensing means may comprise one or more optocouples (combined LED and photodiode) or optrodes (here the term “optrode” describes any combination of an optical emitter - e.g. LED or optical fibre or other -and an optical detector) for combined optical sensing and optical stimulation of the tissue of the patient. That is, the optical emitter 104 described in relation to Figure 1A may be provided by the optocouple or optrode of the sensing means 106. This reduces the number of electronic components required to be incorporated into the dressing 100.

[0108] The sensing means 106 may comprise both electrodes 102 and optrodes so that both electrical and optical measurements of the tissue injury can be obtained. The electrodes 102 and optrodes may be referred to as bio-transceivers because they act as transceivers for use with biological material. In this way, the same nodes can be used for both sensing and stimulation. The use of electrodes and optrodes as sensors and the methods required to do so would be known to the skilled person.

[0109] Acting in the sensing mode the bio-transceivers act as sensors. The bio-transceivers be sequentially accessed to scan the affected region acquiring electrical data such as bioimpedance readings; electrodermal response; skin bio-potential readings.

[0110] In certain embodiments, such as in the case of diabetic foot injury applications, a pressure sensing means for obtaining pressure data may be incorporated into the dressing. The plurality of electrodes 102 may be configured to obtain pressure data. For example, the shape of the electrodes can be made such that pressure readings are also obtained (such as in the case of diabetic foot applications). The manner in which the electrodes 102 can be configured to obtain pressure readings would be known to the skilled person.

[0111] The plurality of electrodes 102 or optrodes can also be used to obtain hydration readings. Furthermore electrochemical readings can also be incorporated for acidity / pH levels, such as through electrode coatings or through the use of ion-sensitive field effect transistors (ISFETs).

[0112] The optrodes can obtain optical reflection readings at different wavelengths, including in green and red light wavelengths as well as infrared wavelengths to determine circulatory aspects, perfusion, infection as well as temperature I thermal variations. Temperature or thermal variations could also be measured using other types of temperature sensorsincorporated into the dressing 100. In some embodiments the combination of two wavelengths allow for the extraction of blood oxygenation information.

[0113] The combination of these sensing arrays can be used to acquire multi-parametric data regarding the affected area. This data can be combined, either offline, or remotely, or in a data processing stage on or in the vicinity of the dressing 100 to obtain the electrical-optical stimulation technique appropriate for the particular characteristics of the tissue injury.

[0114] The dressing 100 may further include a battery and associated electronics.

[0115] Figure 2 shows a block diagram of a controller 200 (or processing unit) for controlling a dressing 100. More particularly, the controller 200 may control one or more of the electrical and optical stimulation output by the electrodes 102 and optical emitter 104 of the dressing. The controller 200 and the dressing 100 may form an integrated device or be separate devices. Where the controller 200 is separate from the dressing 100, the controller 200 may control the electrical and optical stimulations output by a plurality of dressings 100.

[0116] The controller 200 comprises an input 202, a processor 204, and an output 206. The input 202 receives data indicative of a condition of a tissue injury. The input 202 may receive data obtained by the sensing means 106 for a particular tissue injury. In this case, the controller may provide bespoke electrical-optical stimulation techniques for that particular tissue injury. This may be referred to as Wound Intelligent Treatment (WIT).

[0117] The input 202 may receive generic data relating to general classes, conditions, categories or types of tissue injury (such as infected tissue injuries, burn injuries, surgical wound injuries etc). In this case, the controller 200 may be used to pre-program a plurality of dressings 100 according to the general type of tissue injury such that, for example, a dressing 100 for surgical wounds has a different stimulation technique to a dressing 100 for diabetic foot wounds.

[0118] The processor 204 processes the received data to determine, based on the received data, one or more of an electrical stimulation technique and an optical stimulation technique for modulating the wound state of the tissue injury.

[0119] In the WIT embodiment, appropriate algorithms can be used to generate a planar image or map of the affected area, segregating it in regions of interest according to the localised conditions. Artificial intelligence may be utilised for this purpose. This mapping of different tissue types may include wounded areas of different healing stages, bacteria, inflammation, necrosis , temperature, pressure, pH levels, hydration levels, and oxygenation. Appropriate front-end electronics can be used to interface with the sensing means 106 while being appropriately miniaturised and used in a safe and power efficient fashion. These include current injection circuitry that can be used both for bipolar, tripolar and tetrapolar bioimpedance sensing and forapplication of electrical stimulation and - if needed - to supply accurate current to light emitting nodes like LEDs. Appropriate algorithms can be used to classify these regions according to their properties in relation to wound progression, infection or inflammation or scarring.

[0120] The extraction of a wound map or affected area map can allow for several actions. Firstly, the algorithms allow for the determination of the array nodes (electrodes, optrodes, other types of bio-transceivers) that are placed appropriately in the vicinity of transitional regions to offer refined measurements. Repeating the scanning of these regions through different combinations or pairings of electrodes or optocouples will allow for more refined spatial and depth measurements offering a better level of detail without consuming the resources that would be needed if refined measurements were to be provided over the overall affected area. In both electrical impedance I bioimpedance and in optical reflectance measurements, the distance and topology and geometry of electrodes or light emitter-detector combinations involved in the measurement offer variations in the tissue area and depth interrogated, thus allowing for appropriate combinations that can be used to refine measurements locally.

[0121] Next, the algorithms can determine the optimum combination, geometry, topology and location of the nodes that can be used to stimulate an area to offer biomodulation I actuation that affects biological function, including all of the effects mentioned area (e.g. fibroblast migration and proliferation, endothelial cell transdifferentiation, bacterial biofilm disruption, bacteriostatic and bactericidal effects, anti-inflammatory effects, systemic effects etc). Following the determination of the most appropriate nodes for effecting biomodulation through electrical-optical, electromagnetic or bimodal or multimodal stimulation the embodiment will have the option to be used for simultaneous or sequential stimulation of different regions with different stimuli according to the effect that needs to be achieved towards treatment. Algorithms can determine the appropriate stimulus or combination of stimuli parameters to be used depending on the effect that needs to be achieved locally and globally over the affected area and using a database formed by the data that has been extracted from experimentation and simulations.

[0122] The electrical stimuli used can range from low (mHz) to high frequency (MHz), low to high amplitude (voltage, current or electric field) within bio-compatible ranges and a range of monophasicor biphasic or multiphasic wave-shapes and waveforms with the bouts of stimulation lasting for appropriate durations (seconds, minutes or hours) and repeated when needed. The optical stimuli can be continuous or pulsed applied at different wavelengths in the regions of blue, red and infrared for appropriate durations (seconds to hours) depending on the effect that needs to be achieved.

[0123] Our data uniquely allow us to combine parameters of uni-modal as well as multi-modal stimuli to achieve better outcomes in terms of wound healing and antibacterial effects, often combined and without these actions being detrimental to each other. For example, we have achieved bacterial biofilm disruption using similar electrical stimuli that we used in fibroblast migration I proliferation. This is a unique advantage of this method and it can also be used to tackle bacteria in affected areas of different types of biology (human, animal, plant) or materials (e.g. in water, surfaces) without the need for pharmaceutical interventions that bring about antimicrobial resistance. Moreover these stimuli can be combined to reduce antimicrobial resistance in bacteria that have developed it, for example through their forming resistant biofilms.

[0124] The intelligent, closed loop aspect of the WIT method can involve frequent iterations of sensing, localising and stimulation with adjustable modalities and parameters to offer a personalised, tailored treatment and to adjust the treatment in real-time as the needs of the affected area vary. There is no need for the patient to intervene or to change settings or dressings, making it ideal for home use.

[0125] Moreover, the sensed data can be stored in a memory. The stored data can then be used to provide progression historical data or be transmitted to a healthcare professional to monitor the progression of the patient’s condition and advise or intervene accordingly.

[0126] The output 206 may output an electrical signal indicative of the determined stimulation technique to the dressing 100. The electrodes 102 and optical emitters 104 of the dressing 100 can be controlled according to the determined stimulation technique output to the dressing 100.

[0127] Figure 3 is a block diagram of a system 300 for facilitating a wound state of a tissue injury. The system 300 comprises a dressing 100 and a controller 200.

[0128] The dressing 100 and controller 200 may be provided together in the same product. For example, the dressing 100 and the 200 may both be physically located within one or more end products that are applied to the tissue injury of the patient. In this embodiment, the output 206 of the controller 200 may output an electrical signal which causes one or both of the plurality of electrodes 102 and the optical emitter 104 to modulate their stimulations. The controller 200 may modulate one or both of the electrical and optical stimulations based on sensor data received by the controller 200 from a sensing means included in the dressing 100. The dressing 100 and the controller 200 may have a wired or wireless connection.

[0129] Alternatively, the dressing 100 and controller 200 may be separate entities. In this embodiment, the controller 200 may not be incorporated into the product that is applied to the tissue injury of the patient. The controller 200 may be used to pre-program the dressing 100 sothat the plurality of electrodes 102 and the optical emitter 104 output predetermined stimulations. There may be a range of predetermined stimulation configurations to suit a variety of different types of tissue injury.

[0130] Figure 4 shows an exploded view diagram of a dressing 400 according to an embodiment of the invention. This embodiment may be the WIT embodiment described above.

[0131] The dressing 400 comprises a membrane 402, an electrode layer 404, optical emitter layer 406, a hermeticity layer 408, a transceiver coil 410, a main electronics unit 412, and an outer covering layer 414.

[0132] The membrane 402 improves the electrical contact of the electrodes from the electrode layer 404 with the tissue of the patient. The membrane 402 may be a disposable transparent perforated biocompatible membrane, such as a polymer hydrogel.

[0133] The electrode layer 404 is a flexible substrate comprising the plurality of electrodes 102. The electrode layer 404 may be disposable.

[0134] The electrodes 102 may form an array of electrode nodes. The array of electrodes may be configured for both sensing and stimulation of the tissue injury.

[0135] The optical emitter layer 406 comprises a flexible substrate supporting a plurality of optical emitters 104. Optrodes or optocouples may be used as the optical emitters 104 to enable both the emission and the detection of optical waves to be provided by a single component. The electrode layer 404 and the optical emitter layer 406 may be provided on the same layer such that the electrodes 102 and optical emitters 104 form a multi-nodal array.

[0136] The hermeticity layer 408 is a flexible membrane for protecting the transceiver coil 410 and main electronics unit 412 from fluid secreted by the tissue wound.

[0137] The transceiver coil 410 is used for power reception and signal transmission and reception. The transceiver coil 410 can instead be incorporated inside the outer covering layer 414, attached to the outer covering layer 414, or be a secondary unit placed near and electrically connected to the dressing 400.

[0138] The main electronics unit 412 contains the front-end electronics for the sensing and stimulatory electrical and optical nodes including amplification, and signal preprocessing as well as signal conditioning and sourcing from a miniaturised Voltage-Controlled Voltage Source (VCVS) I Voltage-Controlled Current Source (VCCS) stage. Back end electronics can include data conversion (ADC) for transmission and further processing externally; data conversion (DAC) of received external commands for appropriate signal forming, as well as switching and multiplexing for combining nodes as needed. The main electronics unit 412 may include arechargeable battery and appropriate power control. Biocompatibility I safety and circuit protection circuitry can be included. The unit may be located at the inside of the outer covering layer 414, or inside a secondary unit placed near and electrically connected to the dressing 400.

[0139] The outer covering layer 414 protects the dressing 400 from the external environment.

[0140] Figure 5 is a flow chart showing a method of modulating a wound state according to an embodiment. The method may be performed by a system 300.

[0141] In step 502, an input 202 of a controller 200 receives data indicative of a condition of a tissue injury. The data may be obtained by one or more sensing means 106 incorporated into a dressing 100 applied to the tissue injury. The data may be obtained through prior experiments performed on a variety of conditions of tissue injuries.

[0142] In step 504, the received data is processed by the processor 204 of the controller 200 to determine a stimulation technique suitable for modulating the wound state of the tissue injury. The stimulation technique comprises an electrical stimulation technique and an optical stimulation technique to be performed by the emitters (such as electrodes and optrodes) of the dressing. The data may be processed according to the methods described in relation to Figure 2.

[0143] In step 506, the determined stimulation technique is output by the output 206 of the controller 200. The stimulation technique may be output to one or more emitters of the dressing.

[0144] In step 508, the electrodes 102 and optical emitters 104 of the dressing 100 apply respective electrical and optical stimulation based on the output stimulation technique.

[0145] In the case of the smart WIT dressing, where sensing means 106 are incorporated into the dressing 100, the method may repeat. That is, the sensing means 106 may continuously or periodically receive data indicative of a condition of the tissue injury, and transmit this data to a controller 200 so that the stimulation technique may be adapted according to changes in the condition of the tissue injury.

[0146] Further examples of dressings, controllers, bio-transceiver arrays and systems according to the present disclosure will now be described. It should be appreciated that features described in relation to figures 1 to 5 may be implemented in the examples described below.

[0147] In one example, a dressing for modulating a wound state of a tissue injury is provided. The dressing may be that of figures 1A, 1 B, 3 and 4. The dressing comprises a flexible substrate supporting a multi-nodal array of bio-transceiver nodes, each node comprising an electrode pair and an optrode having an optical emitter and an optical detector, each node being selectively configurable as a sensing node and / or a stimulation node. The dressing further comprises aswitching circuitry configured to operate the nodes in time-multiplexed sensing and / or stimulation modes and to drive different nodes concurrently; and a controller. The controller may be that of figure 2 and 3. The controller is configured to periodically acquire multimodal wound data by applying at least one non-modulating test electrical signal via selected electrode pairs and by receiving at least one optical reflectance signal via the optrode. The controller is further configured to generate a depth-sensitive spatial wound-state map from the multimodal wound data and segment the wound into a plurality of regions according to local condition; determine, for each region, an electrical stimulation technique and / or an optical stimulation technique including one or more of amplitude, waveform, frequency, phase, duty cycle and node selection; select electrode pairs, electrode spacing, carrier frequency and / or relative phase so as to position an electrical stimulation focus at a target depth estimated from the multimodal wound data; command different nodes to deliver different stimulation modalities or parameters in different regions simultaneously; select stimulation parameters that concurrently produce an antibacterial effect and a healing-accelerant effect without one effect detrimentally impacting the other by enforcing a conflict-avoidance constraint derived from the wound-state map;apply a controller-defined stimulation sequence comprising at least a blue-light antibacterial phase of a predefined duration and a red-light metabolic phase with electrical stimulation applied after a delay corresponding to fibroblast response kinetics; and periodically update the spatial wound-state map and reallocate nodes between sensing and / or stimulation in response to changes in wound condition.

[0148] The controller may be configured to fuse bioimpedance data and multi-wavelength optical reflectance data and optionally one or more of temperature, pressure, hydration and pH data when generating the spatial wound-state map.

[0149] A segmentation-classified region of the plurality of regions may represent one or more of infection, inflammation, necrosis, granulation and healing stage.

[0150] The controller may be configured to provide blue-range optical stimulation between 420 nm and 460 nm to an infection-classified region of the plurality of regions.

[0151] The controller may be configured to operate the nodes so that electrical stimulation is applied to disrupt a bacterial biofilm to individual bacteria, followed by blue light being applied to singular individual bacteria, at a lower light intensity level or for a shorter illumination length of time, than is required without the disruption of the biofilm by electrical stimulation. This is to minimise the damage to human tissue usually associated with antimicrobial blue light stimulation of wounds.

[0152] The controller may be configured to apply electrical stimulation to disrupt a bacterial biofilm that has been formed on the wound, then apply blue light optical stimulation to kill at least some of the bacteria in the biofilm. By applying electrical stimulation to disrupt the biofilm, a lower intensity of blue light and / or a shorter period of blue light stimulation is required than if the biofilm is not disrupted. Thus, minimizing damage to surrounding healthy human tissue.

[0153] The controller may be configured to provide red-range optical stimulation including about 670 nm in combination with electrical stimulation to a granulation-classified region of the plurality of regions.

[0154] The controller may be configured to apply short-burst blue-range optical stimulation to infection-classified regions of the plurality of regions until one or more infection indicators diminish.

[0155] The controller may be configured to apply electrical stimulation with a delay relative to red-range optical stimulation corresponding to fibroblast response kinetics.

[0156] The electrical stimulation may comprise one or more of monophasic, biphasic or multiphasic pulses at microcurrent amplitudes which may be within biocompatible limits.

[0157] The optrodes may be configured to provide pulsed or continuous illumination in one or more of blue, red and infrared wavelength bands, and two or more optrodes within a region can be driven concurrently to shape an optical fluence profile.

[0158] The nodes may be configurable for bipolar, tripolar or tetrapolar bioimpedance sensing during sensing phases.

[0159] The controller may be configured to operate at least two spatially separated electrode pairs at respective carrier frequencies higher than an envelope frequency and with a controllable relative phase to synthesise a lower-frequency amplitude envelope at a selected target locus and depth, while maintaining per-electrode limits.

[0160] The controller may be configured to maintain per-electrode instantaneous charge and charge density below a configured maximum while producing the amplitude envelope at the target locus.

[0161] The controller may be configured to select electrode spacing, carrier frequency and relative phase to control depth of peak electrical field and in-plane focus width.

[0162] Optical stimulation from two or more optrodes in a region may be driven concurrently or in sequence to provide a target optical fluence pattern.

[0163] The controller may be configured to employ a simulation or optimisation module to evaluate candidate multi-site carrier assignments against an objective function that maximisesenvelope amplitude at the target locus subject to per-electrode limits and the conflict-avoidance constraint.

[0164] The dressing may further comprise a membrane layer arranged to improve electrical contact and an outer covering layer arranged to provide environmental protection.

[0165] The controller may be configured to update a depth setpoint per region based on at least one temporal trend in the multimodal wound data.

[0166] The controller may be configured to detect node integrity using sensing signals to identify connectivity issues that may affect performance, and when a broken contact is detected the controller is configured to select neighbouring nodes and drive parameters to achieve a similar localised stimulation outcome.

[0167] The controller may be configured to evaluate impedance to identify a high-impedance path associated with at least one air bubble, scar and / or necrotic tissue, or pus, and further configured to select at least one alternative electrode path and / or adjust electrical parameters including carrier frequency and amplitude to avoid or compensate such path.

[0168] The controller may be configured to limit at least one electrical parameter in an innervated region to avoid neuronal activation or painful muscle contraction.

[0169] The controller may be configured to store at least one historical wound-state map and adapt a stimulation parameter based on at least one temporal trend.

[0170] The dressing may further comprise a wireless communication interface arranged to transmit wound-state data and receive an updated stimulation policy.

[0171] In another example, a controller for modulating a wound state is provided. The controller is configured to receive multimodal wound data comprising electrical bioimpedance data and optical reflectance data and optionally one or more of temperature, pressure, hydration, pH and oxygenation data, the controller being configured to:generate a depth-sensitive spatial wound-state map from the multimodal wound data; classify regions of the wound as one or more of infection, inflammation, necrosis, granulation and healing stage; select, for each region, an electrical stimulation technique and / or an optical stimulation technique including one or more of amplitude, waveform, frequency, phase, duty cycle and node selection; optimise combined electrical and optical stimulation so as to concurrently achieve antibacterial effects and healing-accelerant effects without mutual detriment, including by applying temporal sequencing, dose constraints and a conflict-avoidance rule; output node-level control signals to a multi-nodal array of bio-transceiver nodes to deliver simultaneous regionspecific stimulation across different regions, including multi-site carrier drives havingcontrollable relative phase; select electrode pairs, electrode spacing, carrier frequency and / or relative phase to focus electrical stimulation at a target depth; and periodically re-map the wound state and reassign nodes between sensing and stimulation.

[0172] In this example, the spatial wound-state map may be generated by fusing bioimpedance spectra with multi-wavelength optical reflectance data and thermal gradient data.

[0173] The region classification may be performed using a trained model arranged to output infection, inflammation, necrosis and / or granulation labels.

[0174] Temporal sequencing may comprise a limited blue-light antibacterial phase followed by a red-light metabolic phase and electrical stimulation after a delay aligned to fibroblast proliferation kinetics.

[0175] Stimulation parameter selection may ensure compliance with pain-avoidance thresholds and exposure limits.

[0176] The controller may be further configured to store historical spatial wound-state maps and adapt a stimulation parameters based on at least one temporal trend.

[0177] The controller may be further configured to communicate wirelessly with a remote device to transmit wound-state data and receive an updated policy.

[0178] Node selection for sensing may use bipolar, tripolar or tetrapolar electrode configurations to vary interrogation depth and improve depth estimation of the target.

[0179] In yet another example, a system comprising the dressing according to any of the examples herein and a controller according to any examples herein, the system being configured to deliver electrical and optical stimulation to different regions of a wound simultaneously based on the updated depth-sensitive spatial wound-state map.

[0180] The system may further comprise a wireless transceiver arranged to transmit woundstate data and stimulation logs to a remote device.

[0181] The controller may be external to the dressing and the dressing includes addressing circuitry arranged for time-multiplexed operation of the nodes.

[0182] The dressing may include a transceiver coil arranged for power reception and data communication.

[0183] The dressing may comprise a hermeticity layer and a main electronics unit including front-end sensing and stimulation circuitry and power management circuitry.

[0184] The system may be configured to detect transitions in wound state and automatically reclassify regions and update regional stimulation techniques.

[0185] In yet another example, a bio-transceiver array for a wound dressing is provided. The bio-transceiver array comprises a plurality of nodes, each node including an electrode pair arranged for both electrical stimulation and bioimpedance sensing, an optrode arranged for both optical stimulation and optical sensing, and switching circuitry arranged to enable time-multiplexed operation between sensing and stimulation.

[0186] Neighbouring nodes may be arranged to form a two-dimensional lattice on a flexible substrate.

[0187] The optrode may be configured to provide multi-wavelength output including blue, red and infrared bands and includes a photodiode arranged to measure optical reflectance.

[0188] The electrode pair may be configurable as bipolar, tripolar or tetrapolar during sensing to adjust interrogation depth.

[0189] The controller of any example herein may be configured to concurrently drive at least two spatially distinct regions with the same and / or different stimuli, including the same and / or different carrier frequencies, phases or optical settings.

[0190] Local switching may support independent addressing of nodes while enabling simultaneous stimulation in at least two regions.

[0191] Electrode pair spacing and selectable phase difference may be configured to control depth of peak electrical field.

[0192] Further examples of the present disclosure will now be set out in the following numbered clauses.

[0193] Clause 1. A dressing for modulating a wound state of a tissue injury, the dressing comprising: a plurality of electrodes configured to apply electrical stimulation to the tissue injury; and an optical emitter configured to apply optical stimulation to the tissue injury; wherein one or more of the electrical stimulation and the optical stimulation are applied according to a condition of the tissue injury; and wherein the electrical stimulation and the optical stimulation are applied simultaneously or sequentially.

[0194] Clause 2. The dressing of clause 1, wherein the condition of the tissue injury comprises two or more conditions, and wherein the electrical stimulation is applied according to a first condition and the optical stimulation is applied according to a second condition, wherein the first condition and the second condition are different.

[0195] Clause 3. The dressing of clause 1 or 2, wherein: the plurality of electrodes comprises a plurality of electrode pairs; and each electrode pair is configured to apply different electricalstimulation to the tissue injury based on the condition of the tissue injury across the electrode pair.

[0196] Clause 4. The dressing of any one of clauses 1 to 3, wherein: the optical emitter comprises a plurality of optical emitters; and each optical emitter is configured to apply different optical stimulation to the tissue injury based on the condition of the tissue injury in an area surrounding the optical emitter.

[0197] Clause 5. The dressing of any one of clauses 1 to 4, wherein the plurality of electrodes are further configured to periodically apply electrical signals to the tissue injury and to receive electrical signals indicative of the condition of the tissue injury; and wherein one or both of the electrical stimulation and the optical stimulation are applied based on the received electrical signals.

[0198] Clause 6. The dressing of any one of clauses 1 to 5, further comprising an optical sensor configured to periodically receive optical signals reflected from the tissue injury, wherein the optical signals are indicative of the condition of the tissue injury; and wherein one or both of the electrical stimulation and the optical stimulation is applied based on the received optical signals.

[0199] Clause 7. The dressing of any one of clauses 1 to 6, further comprising a pressure sensor configured to receive pressure data, and wherein at least one of the electrical stimulation and optical stimulation are applied based on the received pressure data, optionally wherein the plurality of electrodes form the pressure sensor.

[0200] Clause 8. The dressing of any one of clauses 1 to 7, wherein the condition of the tissue injury comprises one or more of a healing phase of the injury, a presence of inflammation, a presence of infection, a presence of a biofilm, and a presence of necrosis.

[0201] Clause 9. A controller for modulating a wound state of a tissue injury, the controller configured to: receive data indicative of a condition of the tissue injury; determine, based on the received data, one or more of an electrical stimulation technique and an optical stimulation technique for modulating the wound state of the tissue injury; and output a signal indicative of the one or more determined electrical stimulation technique and optical stimulation technique.

[0202] Clause 10. The controller of clause 9, wherein the controller is further configured to: analyse the received data to obtain a map of the tissue injury; identify, using the map, one or more regions of the tissue injury according to a condition of the tissue injury in the one or more regions; and determine the one or more of the electrical stimulation technique and the optical stimulation technique for each region of the tissue injury.

[0203] Clause 11. The controller of clause 9 or 10, wherein the controller is configured to determine the electrical stimulation technique and the optical stimulation technique that combine to facilitate a healing of the tissue injury.

[0204] Clause 12. A system for modulating a wound state of a tissue injury, the system comprising: a dressing according to any of clauses 1 to 8; and a processing unit according to any of clauses 9 to 11.

[0205] Clause 13. A method for modulating a wound state of a tissue injury, the method performed by a dressing comprising a plurality of electrodes and an optical emitter, the method comprising: applying, by the plurality of electrodes, electrical stimulation to the tissue injury; and applying, by the optical emitter, optical stimulation to the tissue injury; wherein one or more of the electrical stimulation and the optical stimulation are applied according to a condition of the tissue injury; and wherein the electrical stimulation and the optical stimulation are applied simultaneously or sequentially

[0206] Clause 14. A method, performed by a processing unit, for modulating a wound state of a tissue injury, the method comprising: receiving data indicative of a condition of the tissue injury; determining, based on the received data, one or more of an electrical stimulation technique and an optical stimulation technique for modulating the wound state of the tissue injury; and outputting a signal indicative of the one or more determined electrical stimulation technique and optical stimulation technique.

[0207] Clause 15. The method of clause 14, wherein the method further comprises: analysing the received data to obtain a map of the tissue injury; identifying, based on the map, one or more regions of the tissue injury according to a condition of the tissue injury in the one or more regions; determining the one or more of the electrical stimulation technique and the optical stimulation technique for each region of the tissue injury; optionally wherein the method further comprises determining the electrical stimulation technique and the optical stimulation technique that combine to facilitate a healing of the tissue injury.

[0208] FURTHER EXAMPLES

[0209] Aspects of the present disclosure will now be illustrated by way of example only and with reference to the following experimentation.

[0210] In example 1, biofilm disruption cell culture experiments were performed, the results are illustrated in figure 6. Staphylococcus epidermidis biofilms were electrically stimulated (ES) and optic density of broth media assessed immediately following stimulation, as a metric of dispersion. Statistical significance determined by t-test: **=p<0.01. Error bars are standard deviations from the mean.

[0211] In example 2, fibroblast migration cell culture experiments were performed, the results are illustrated in figure 7. A standard scratch wound assay was carried out on a human dermal fibroblast cell line. Experiments were carried out under serum free conditions. The scratch wound was followed over 16 hours post scratch, and the rate of wound closure compared between the four conditions. Error bars are standard deviations from the mean.

[0212] In example 3, fibroblast proliferation cell culture experiments were performed, the results are illustrated in figure 8. A human dermal fibroblast cell line was used. Live cell counts were carried out 24 hours after stimulation intervention. Statistical significance determined by ANOVA and post hoc Tukey: **=p<0.01, ***=p<0.005. Error bars are standard deviations from the mean.

[0213] In example 4, finite element method (FEM) simulations were performed indicating regional and depth selectivity, the results are illustrated in figure 9. Depending on the connectivity of a number of electrodes used we are able to select a focused region to stimulate, with two cases shown in red.

[0214] It will be understood that the disclosure contemplates and includes, in addition to the above-disclosed embodiments, embodiments based on combinations of any two or more of the above-disclosed embodiments and embodiments including any combination of the above features. That is, the absence of explicit indication that two features may be combined or two embodiments may be combined does not mean that such combinations are not contemplated, but such combinations should be regarded as included herein.

Claims

CLAIMS1. A dressing for modulating a wound state of a tissue injury, the dressing comprising: a flexible substrate supporting a multi-nodal array of bio-transceiver nodes, each node comprising an electrode pair and an optrode having an optical emitter and an optical detector, each node being selectively configurable as a sensing node and / or a stimulation node;a switching circuitry configured to operate the nodes in time-multiplexed sensing and / or stimulation modes and to drive different nodes concurrently; anda controller configured to:periodically acquire multimodal wound data by applying at least one nonmodulating test electrical signal via selected electrode pairs and by receiving at least one optical reflectance signal via the optrode;generate a depth-sensitive spatial wound-state map from the multimodal wound data and segment the wound into a plurality of regions according to local condition;determine, for each region, an electrical stimulation technique and / or an optical stimulation technique including one or more of amplitude, waveform, frequency, phase, duty cycle and node selection;select electrode pairs, electrode spacing, carrier frequency and / or relative phase so as to position an electrical stimulation focus at a target depth estimated from the multimodal wound data;command different nodes to deliver different stimulation modalities or parameters in different regions simultaneously;select stimulation parameters that concurrently produce an antibacterial effect and a healing-accelerant effect without one effect detrimentally impacting the other by enforcing a conflict-avoidance constraint derived from the wound-state map;apply a controller-defined stimulation sequence comprising at least a bluelight antibacterial phase of a predefined duration and a red-light metabolic phase with electrical stimulation applied after a delay corresponding to fibroblast response kinetics; andperiodically update the spatial wound-state map and reallocate nodes between sensing and / or stimulation in response to changes in wound condition.

2. The dressing of claim 1, wherein the controller is configured to fuse bioimpedance data and multi-wavelength optical reflectance data and optionally one or more of temperature, pressure, hydration and pH data when generating the spatial wound-state map.

3. The dressing of any preceding claim, wherein a segmentation-classified region represents one or more of infection, inflammation, necrosis, granulation and healing stage.

4. The dressing of any preceding claim, wherein the controller is configured to provide bluerange optical stimulation between 420 nm and 460 nm to an infection-classified region.

5. The dressing of any preceding claim, wherein the controller is configured to apply electrical stimulation to disrupt a bacterial biofilm, then apply blue light optical stimulation to kill at least some of the bacteria in the biofilm.

6. The dressing of any preceding claim, wherein the controller is configured to provide red-range optical stimulation including about 670 nm in combination with electrical stimulation to a granulation-classified region.

7. The dressing of any preceding claim, wherein the controller is configured to apply shortburst blue-range optical stimulation to infection-classified regions until one or more infection indicators diminish.

8. The dressing of any preceding claim, wherein the controller is configured to apply electrical stimulation with a delay relative to red-range optical stimulation corresponding to fibroblast response kinetics.

9. The dressing of any preceding claim, wherein electrical stimulation comprises one or more of monophasic, biphasic or multiphasic pulses at microcurrent amplitudes.

10. The dressing of any preceding claim, wherein optrodes are configured to provide pulsed or continuous illumination in one or more of blue, red and infrared wavelength bands, and two or more optrodes within a region can be driven concurrently to shape an optical fluence profile.

11. The dressing of any preceding claim, wherein nodes are configurable for bipolar, tripolar ortetrapolar bioimpedance sensing during sensing phases.

12. The dressing of any preceding claim, wherein the controller is configured to operate at least two spatially separated electrode pairs at respective carrier frequencies higher than an envelope frequency and with a controllable relative phase to synthesise a lower-frequency amplitude envelope at a selected target locus and depth, while maintaining per-electrode limits.

13. The dressing of any preceding claim, wherein the controller is configured to maintain per-electrode instantaneous charge and charge density below a configured maximum while producing the amplitude envelope at the target locus.

14. The dressing of any preceding claim, wherein the controller is configured to select electrode spacing, carrier frequency and relative phase to control depth of peak electrical field and in-plane focus width.

15. The dressing of any preceding claim, wherein optical stimulation from two or more optrodes in a region is driven concurrently or in sequence to provide a target optical fluence pattern.

16. The dressing of any preceding claim, wherein the controller is configured to employ a simulation or optimisation module to evaluate candidate multi-site carrier assignments against an objective function that maximises envelope amplitude at the target locus subject to per-electrode limits and the conflict-avoidance constraint.

17. The dressing of any preceding claim, further comprising a membrane layer arranged to improve electrical contact and an outer covering layer arranged to provide environmental protection.

18. The dressing of any preceding claim, wherein the controller is configured to update a depth setpoint per region based on at least one temporal trend in the multimodal wound data.

19. The dressing of any preceding claim, wherein the controller is configured to detect node integrity using sensing signals to identify connectivity issues that may affect performance, and when a broken contact is detected the controller is configured to selectneighbouring nodes and drive parameters to achieve a similar localised stimulation outcome.

20. The dressing of any preceding claim, wherein the controller is configured to evaluate impedance to identify a high-impedance path associated with at least one air bubble, scar and / or necrotic tissue, or pus, and further configured to select at least one alternative electrode path and / or adjust electrical parameters including carrier frequency and amplitude to avoid or compensate such path.

21. The dressing of any preceding claim, wherein the controller is configured to limit at least one electrical parameter in an innervated region to avoid neuronal activation or painful muscle contraction.

22. The dressing of any preceding claim, wherein the controller is configured to store at least one historical wound-state map and adapt a stimulation parameter based on at least one temporal trend.

23. The dressing of any preceding claim, wherein the dressing further comprises a wireless communication interface arranged to transmit wound-state data and receive an updated stimulation policy.

24. A controller for modulating a wound state, configured to receive multimodal wound data comprising electrical bioimpedance data and optical reflectance data and optionally one or more of temperature, pressure, hydration, pH and oxygenation data, the controller being configured to:generate a depth-sensitive spatial wound-state map from the multimodal wound data;classify regions of the wound as one or more of infection, inflammation, necrosis, granulation and healing stage;select, for each region, an electrical stimulation technique and / or an optical stimulation technique including one or more of amplitude, waveform, frequency, phase, duty cycle and node selection;optimise combined electrical and optical stimulation so as to concurrently achieve antibacterial effects and healing-accelerant effects without mutual detriment, including byapplying temporal sequencing, dose constraints and a conflict-avoidance rule; output node-level control signals to a multi-nodal array of bio-transceiver nodes to deliver simultaneous region-specific stimulation across different regions, including multi-site carrier drives having controllable relative phase;select electrode pairs, electrode spacing, carrier frequency and / or relative phase to focus electrical stimulation at a target depth; andperiodically re-map the wound state and reassign nodes between sensing and stimulation.

25. The controller of claim 24, wherein the spatial wound-state map is generated by fusing bioimpedance spectra with multi-wavelength optical reflectance data and thermal gradient data.

26. The controller of claim 24 or 25, wherein region classification is performed using a trained model arranged to output infection, inflammation, necrosis and / or granulation labels.

27. The controller of any of claims 24 to 26, wherein temporal sequencing comprises a limited blue-light antibacterial phase followed by a red-light metabolic phase and electrical stimulation after a delay aligned to fibroblast proliferation kinetics.

28. The controller of any of claims 24 to 26, wherein stimulation parameter selection ensures compliance with pain-avoidance thresholds and exposure limits.

29. The controller of any of claims 24 to 28, wherein the controller is configured to store historical spatial wound-state maps and adapt a stimulation parameters based on at least one temporal trend.

30. The controller of any of claims 24 to 29, wherein the controller is configured to communicate wirelessly with a remote device to transmit wound-state data and receive an updated policy.

31. The controller of any of claims 24 to 30, wherein node selection for sensing uses bipolar, tripolar or tetrapolar electrode configurations to vary interrogation depth and improve depth estimation of the target.

32. A system comprising the dressing of any of claims 1 to 23 and the controller of any of claims 24 to 31, the system being configured to deliver electrical and optical stimulation to different regions of a wound simultaneously based on the updated depth-sensitive spatial wound-state map.

33. The system of claim 32, further comprising a wireless transceiver arranged to transmit wound-state data and stimulation logs to a remote device.

34. The system of claim 32 or 33, wherein the controller is external to the dressing and the dressing includes addressing circuitry arranged for time-multiplexed operation of the nodes.

35. The system of any of claims 32 to 34, wherein the dressing includes a transceiver coil arranged for power reception and data communication.

36. The system of any of claims 32 to 35, wherein the dressing comprises a hermeticity layer and a main electronics unit including front-end sensing and stimulation circuitry and power management circuitry.

37. The system of any of claims 33 to 37, configured to detect transitions in wound state and automatically reclassify regions and update regional stimulation techniques.

38. A bio-transceiver array for a wound dressing, comprising a plurality of nodes, each node including an electrode pair arranged for both electrical stimulation and bioimpedance sensing, an optrode arranged for both optical stimulation and optical sensing, and switching circuitry arranged to enable time-multiplexed operation between sensing and stimulation.

39. The bio-transceiver array of claim 38, wherein neighbouring nodes are arranged to form a two-dimensional lattice on a flexible substrate.

40. The bio-transceiver array of claim 38 or 39, wherein the optrode is configured to provide multi-wavelength output including blue, red and infrared bands and includes a photodiode arranged to measure optical reflectance.

41. The bio-transceiver array of any of claims 38 to 40, wherein the electrode pair is configurable as bipolar, tripolar or tetrapolar during sensing to adjust interrogation depth.

42. The dressing, controller or system of any preceding claim, wherein the controller is configured to concurrently drive at least two spatially distinct regions with the same and / or different stimuli, including the same and / or different carrier frequencies, phases or optical settings.

43. The bio-transceiver array of any of claims 38 to 41 , wherein local switching supports independent addressing of nodes while enabling simultaneous stimulation in at least two regions.

44. The bio-transceiver array of any of claims 38 to 43, wherein electrode pair spacing and selectable phase difference are configured to control depth of peak electrical field.

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