Control and activation of wound dressings

Abstract

Disclosed embodiments relate to a wound dressing capable of generating nitric oxide. The wound dressing may include a cover layer, an activator layer, such as an acid-providing layer, and a nitric oxide source layer, such as a nitrite-providing layer. The activator layer may include acidic groups and may be a hydrogel, xerogel, or other suitable material. The nitric oxide source layer may include nitrite. Nitrite ions in the nitric oxide source layer may react with the acidic groups in the activation layer to generate nitric oxide. The activation layer may include a central window, and a central absorbent material may be positioned in the window. Various separation layers may also be incorporated into the dressing to control the interaction between the activation layer and the nitric oxide source layer.

Description

Technical Field

[0001] Materials, devices, methods, and systems such as therapeutic compositions, wound care materials, their uses, and methods of treatment using the same are disclosed herein. In some examples, the materials, devices, and systems described herein include wound dressings configured for nitric oxide (NO) delivery and / or delivery of other active agents.

[0002] Description of Related Art Nitric oxide (NO) is a well-known molecule with multiple biological functions. For example, nitric oxide affects vasodilation of blood vessels, stimulates angiogenesis, affects the host immune response, and exhibits a strong broad-spectrum antibacterial activity and anti-biofilm activity. Due to these multiple roles, NO exhibits a strong effect on tissues, and an increase in the amount of NO can support the acceleration of healing in wounds, particularly chronic wounds.

[0003] In addition, diabetic patients often have lower levels of nitric oxide compared to healthy patients, and the reduction in nitric oxide supply in diabetic patients is a worsening factor in non-healing chronic ulcers. The reduction in nitric oxide supply can lead to vascular damage such as endothelial dysfunction and vascular inflammation. Vascular damage can also lead to a reduction in blood flow to the extremities, potentially causing an increased risk of neuropathy and non-healing ulcers in diabetic patients and a higher risk of limb amputation.

[0004] Therefore, there is a need for an improved mechanism for delivering an effective dose of nitric oxide to wounds. Under normal conditions, nitric oxide (NO), a free radical, has a short lifespan and is converted to a more stable chemical species within seconds of generation. Thus, for example, when gaseous nitric oxide comes into contact with air, the gaseous nitric oxide is rapidly oxidized to nitrogen dioxide (NO 2) will occur. Therefore, it may be difficult to maintain a high concentration of nitric oxide within a wound dressing or other similar structure over a long period of time. Therefore, a device or wound dressing having one or more layers containing a more stable composition can effectively generate nitric oxide over time upon activation for the stable and sustained delivery of nitric oxide to biological tissue. Of particular note is the mechanism for delivering nitric oxide in combination with the use of a wound dressing, particularly a negative pressure wound dressing, and / or while undergoing negative pressure wound therapy and / or other appropriate therapies.

Summary of the Invention

[0005] Embodiments of the present disclosure relate to materials, devices, methods, and systems for wound treatment. Some of the disclosed embodiments relate to materials, devices, methods, and systems for delivering nitric oxide to a wound. Those skilled in the art will understand that the applications of the materials, devices, methods, and systems described herein are not limited to specific tissues or specific injuries.

[0006] In some embodiments, a wound dressing for treating a wound can include a cover layer configured to form a seal around the wound, an active agent layer, a dry nitric oxide source layer, a dry nitric oxide source layer that contains little or relatively little liquid, and a water-absorbing distribution layer.

[0007] In certain embodiments, the wound dressing further comprises a masking layer configured to at least partially limit visualization of the wound. The dry nitric oxide source layer may comprise a nitrite. The nitrite may comprise sodium nitrite. The activator layer may be positioned over the dry nitric oxide source layer. In some embodiments, the dry nitric oxide source layer may be positioned over the activator layer. The moisture-absorbing dispersion layer may be positioned between the activator layer and the dry nitric oxide source layer. The activator layer may comprise a hydrogel or a xerogel. The wound dressing may comprise a second dry nitric oxide source layer. The wound dressing may be configured to generate nitric oxide when placed over the wound. In an embodiment, the wound dressing may be configured not to generate nitric oxide prior to placement on the wound.

[0008] In certain embodiments, a wound dressing for treating a wound may comprise a cover layer, an activator layer positioned under the cover layer, a nitric oxide source layer, and a separation layer positioned between the activator layer and the nitric oxide source layer, the separation layer being configured to prevent contact between the activator layer and the nitric oxide source layer. In some embodiments, the separation layer may comprise a tab configured to be removed from the wound dressing such that contact occurs between the activator layer and the nitric oxide source layer when the tab is removed. The separation layer may comprise a degradable material configured such that contact occurs between the activator layer and the nitric oxide source layer when the degradable material degrades.

[0009] In some embodiments, a wound treatment device may comprise an activator hydrogel comprising a plurality of capsules, each capsule comprising a separation layer encapsulating a nitric oxide source material, the separation layer being configured to prevent contact between the activator hydrogel and the nitric oxide source material. The separation layer may be configured to break upon application of mechanical pressure such that contact occurs between the activator hydrogel and the nitric oxide source material when the separation layer breaks.

[0010] In some embodiments, a wound dressing for treating a wound may comprise an active agent hydrogel and a nitric oxide source hydrogel, wherein the nitric oxide source hydrogel includes a surface facing the active agent hydrogel, and the surface facing the active agent hydrogel includes a layer of sodium nitrite. The active agent hydrogel may comprise a plurality of perforations. The nitric oxide source hydrogel may comprise a plurality of perforations.

[0011] In certain embodiments, a method of delivering an active ingredient to a wound may include placing an active ingredient platform over the wound, wherein the active ingredient platform comprises a dosing portion and an adhesive frame, and the dosing portion comprises the active ingredient; and adhering a reactive platform onto the active ingredient platform to form a seal, wherein the reactive platform comprises a reactive portion configured to activate the dosing portion such that the active ingredient is delivered to the wound. The active ingredient may include a therapeutic agent configured to promote wound healing. The dosing platform may be inactive until the reactive platform is adhered to the active ingredient platform.

[0012] In some configurations, a wound dressing for treating a wound may include a cover layer, a nitrite-providing layer, an acid-providing layer positioned under the cover layer, and a central absorbent material for absorbing wound exudate. The cover layer is configured to form a seal around the wound. The nitrite-providing layer contains nitrite. The acid-providing layer contains acidic groups and includes a window at the center of the acid-providing layer. The central absorbent material is positioned within the window of the acid-providing layer.

[0013] The wound dressing of the above paragraph may include one or more of the following features. The acid-providing layer may be configured to be positioned on the skin around the wound or on the edge of the wound when the wound dressing is applied to the wound. The central absorbent material may be configured to be positioned on the wound when the wound dressing is applied to the wound. The central absorbent material may be completely enclosed by the acid-providing layer. The wound dressing may include a water-absorbing dispersion layer configured to suck up fluid horizontally. The wound dressing may further include a frame layer positioned under the acid-providing layer, the frame layer defining a window at the center of the frame layer. The frame layer may be configured to be attached to the skin around the wound. The frame layer may be attached to the cover layer. The nitrite-providing layer may be positioned within the window of the frame layer. The acid-providing layer may include xerogel or hydrogel.

[0014] In some configurations, a method for treating a wound includes applying a wound dressing to the wound. The wound dressing includes a cover layer configured to form a seal around the wound, a nitrite-providing layer containing nitrite, an acid-providing layer positioned under the cover layer, and a central absorbent material for absorbing wound exudate. The acid-providing layer includes acidic groups and also includes a window at the center of the acid-providing layer. The central absorbent material is positioned within the window of the acid-providing layer.

[0015] The method of the above paragraph may include one or more of the following features. The method may further include generating nitric oxide such that the nitric oxide is delivered to the skin around the wound or the edge of the wound. The method may further include positioning a wound dressing such that an acid-providing layer is at least partially positioned over the skin around the wound or the edge of the wound. The method may further include positioning a wound dressing such that a central absorbent material is at least partially positioned over the wound. The central absorbent material may be completely encapsulated by the acid-providing layer. The wound dressing may further include a moisture-absorbing dispersion layer configured to draw fluid horizontally. The wound dressing may further include a frame layer positioned under the acid-providing layer, the frame layer defining a window at the center of the frame layer. The method may further include attaching the frame layer to the skin around the wound. The frame layer may be attached to a cover layer. The acid-providing layer may include a xerogel or a hydrogel.

[0016] In some configurations, a wound dressing for treating a wound includes a cover layer, a nitrite-providing layer, and an acid-providing layer positioned under the cover layer. The cover layer is configured to form a seal around the wound. The nitrite-providing layer contains nitrite. The acid-providing layer contains acidic groups and also includes a window at the center of the acid-providing layer.

[0017] The wound dressing of the above paragraph may include one or more of the following features. The acid-providing layer may be configured to be positioned over the skin around the wound or the edge of the wound when the wound dressing is applied to the wound. The wound dressing may include a moisture-absorbing dispersion layer configured to draw fluid horizontally. The wound dressing may further include a frame layer positioned under the acid-providing layer, the frame layer defining a window at the center of the frame layer. The frame layer is configured to be attached to the skin around the wound. The frame layer may be attached to the cover layer. The nitrite-providing layer may be positioned within the window of the frame layer. The acid-providing layer may include a xerogel or a hydrogel.

[0018] In an embodiment, a wound dressing for treating a wound may include a cover layer, an active agent layer positioned under the cover layer, a nitric oxide source layer, and a folded separation layer positioned between the active agent layer and the nitric oxide source layer, the folded separation layer configured to prevent contact between the active agent layer and the nitric oxide source layer, and an upper frame positioned above the separation layer and under the cover layer, the upper frame having an adhesive on an upper side of the frame.

[0019] Alternative or additional embodiments described herein provide a composition comprising one or more features of the above description or any description elsewhere in this specification.

[0020] Alternative or additional embodiments described herein provide a wound contact layer comprising one or more features of the above description or any description elsewhere in this specification.

[0021] Alternative or additional embodiments described herein provide a wound dressing comprising one or more features of the above description or any description elsewhere in this specification.

[0022] Alternative or additional embodiments described herein provide a wound treatment system comprising one or more features of the above description or any description elsewhere in this specification.

[0023] Alternative or additional embodiments described herein provide a method for treating a wound comprising one or more features of the above description or any description elsewhere in this specification.

Brief Description of the Drawings

[0024]

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DETAILED DESCRIPTION OF THE INVENTION

[0025] Overview The embodiments described herein relate to materials, devices, methods, and systems that incorporate, include, or utilize one or more compositions and / or materials that effectively generate a gas (e.g., nitric oxide) over time upon activation. Embodiments herein are directed to devices and / or wound dressings having one or more layers containing compositions and / or materials that effectively generate nitric oxide over time upon activation. For example, one or more nitric oxide generating layers may include a nitrate delivery layer that contains nitrates and can release nitrate ions, whereby the nitrate ions can generate nitric oxide upon reaction with an acid. In some embodiments, one or more nitric oxide generating layers may further include an acidic group providing layer in addition to the nitrate delivery layer. One or more nitric oxide generating layers can be utilized as stand-alone components for separate positioning at a wound site or can be incorporated into any number of multilayer wound dressings and wound treatment devices as described hereinafter with respect to FIGS. 1-11. Embodiments of the present disclosure are generally applicable for use in negative pressure or vacuum therapy systems, or compression therapy systems, under ambient conditions.

[0026] Some of the preferred embodiments described herein incorporate, include, or utilize one or more nitric oxide generating layers. Such one or more nitric oxide generating layers can possess one or more of the following functional characteristics: inflammation-related activity, blood flow-related activity, antibacterial, anti-plankton and anti-biofilm activity, ease of application and / or removal as one piece, cutability / tearability, conformity to the three-dimensional contour of the wound surface, abrasion resistance, compatibility with negative pressure wound therapy and / or compression wound therapy, exudate management, ability to facilitate autolytic debridement of the wound, ability to promote wound healing, and self-indication of compositional or functional changes. Antibacterial activity, such as antibacterial activity in vitro, can include one or more of broad-spectrum antibacterial activity, anti-biofilm activity, rapidity of killing of microorganisms, and persistent killing of microorganisms, and the microorganisms can include one or more of: gram-negative bacteria, gram-positive bacteria, fungi, yeast, viruses, algae, archaea, and protozoa.

[0027] The specific preferred embodiments described herein provide a wound treatment system. Such a wound treatment system may comprise a nitric oxide generating layer configured to be sized to be positioned over a wound and / or the area surrounding the wound. One of ordinary skill in the art will understand that when an apparatus / coating / layer is described as being disposed over or on a wound, such an apparatus / coating / layer may extend over and treat the area surrounding the wound. In some examples, stimulation of the area surrounding the wound and / or the wound edge may play a role in initiating the wound healing process, and the wound healing process may be activated through delivery of nitric oxide to the area surrounding the wound and / or the wound edge. Delivery of nitric oxide to the area surrounding the wound and / or the wound edge may target, for example, epithelial cell activity to promote movement of the epithelial tongue, vasodilation of the microcirculation of the skin surrounding the wound to promote richness by providing oxygen and nutrients, and angiogenesis to promote granulation tissue formation. The wound treatment system described herein may further comprise a secondary wound dressing configured to be positioned separately over the nitric oxide generating layer. The nitric oxide generating layer may have an adhesive adhered to the lower surface, and the adhesive may be configured such that the nitric oxide generating layer may be disposed in proximity to the wound. The secondary wound dressing, when used, may adhere to the skin surrounding the wound and may have the same size or may be larger than the nitric oxide generating layer, whereby the nitric oxide generating layer will contact or be disposed in proximity to the wound and / or the area surrounding the wound. The secondary wound dressing may alternatively or additionally be configured to form a seal against the skin surrounding the wound such that the nitric oxide generating layer will contact or be disposed in proximity to the wound. The wound treatment system may further comprise a negative pressure source configured to supply negative pressure through the secondary wound dressing and through a wound contact layer to the wound.

[0028] Certain other preferred embodiments described herein provide a multilayer wound dressing as described herein with respect to FIGS. 1-11. Such a multilayer wound dressing can incorporate one or more nitric oxide generating layers as its component layers, or can include a composite or laminate that includes one or more nitric oxide generating layers as part of one of its component layers. The multilayer wound dressing can comprise a nitric oxide generating layer as described above or elsewhere herein, a permeation layer and / or an absorption layer above / below the one or more nitric oxide generating layers, a wound contact layer below the one or more nitric oxide generating layers, and a cover layer above the permeation layer and / or absorption layer. The wound dressing can further comprise a negative pressure port positioned on or above the cover layer. The one or more nitric oxide generating layers can have an outer peripheral shape that is substantially the same as the outer peripheral shape of the cover layer. Alternatively, the one or more nitric oxide generating layers can have an outer peripheral shape that is smaller than the outer peripheral shape of the cover layer.

[0029] One of ordinary skill in the art will understand that a nitric oxide generating composition, such as any disclosed in this "Summary" section of this specification or elsewhere in this specification, can be loaded into one or more nitric oxide generating layers in any suitable form, such as through entanglement of adsorption, absorption, chemical and / or physical adhesion, and / or through powder form. One of ordinary skill in the art will further understand that a reaction composition, such as any disclosed in this section of this specification or elsewhere in this specification, can be incorporated into any suitable absorption layer disclosed in this section or elsewhere in this specification, and / or any suitable permeation layer disclosed in this section or elsewhere in this specification, and / or any suitable foam layer disclosed in this section or elsewhere in this specification by any suitable means.

[0030] In certain embodiments, the wound treatment systems and multilayer wound dressings disclosed above in this specification or elsewhere in this specification may incorporate or comprise a nitric oxide generating layer. As described in this section of the specification or elsewhere, particularly as described below, the nitric oxide generating layer may be configured to be activated to release nitric oxide. At least a portion of the released nitric oxide may be released, for example, by diffusion. To facilitate the release and diffusion of nitric oxide, the nitric oxide generating layer may be disposed in proximity to the wound.

[0031] Some preferred embodiments described herein provide a method of treating a wound, non-wounded tissue, or other suitable site. Such a method may include disposing a nitric oxide generating layer, separately or as part of a multilayer wound dressing having a nitric oxide generating layer, over the wound. The method may include adhering a separate nitric oxide generating layer and / or a multilayer wound dressing having a nitric oxide generating layer to healthy skin surrounding the wound. Such a method may further include one or more of the following steps. A further wound dressing may be disposed over a separate nitric oxide generating layer or a multilayer wound dressing having a nitric oxide generating layer disposed over the wound. A wound exudate, or any wet or aqueous medium other than a wound exudate, may be provided to reach and / or contact the nitric oxide generating layer. The wound exudate, or any wet or aqueous medium other than a wound exudate, may diffuse or be drawn into a wound dressing incorporating the nitric oxide generating layer or into a wound dressing provided over the nitric oxide generating layer. Negative pressure may be applied to a separate nitric oxide generating layer or a multilayer wound dressing having a nitric oxide generating layer, whereby wound exudate is drawn directly into the nitric oxide generating layer or into a wound dressing incorporating the nitric oxide generating layer or into a wound dressing provided over the nitric oxide generating layer.

[0032] Those skilled in the art will understand that the wound dressings, devices, and systems disclosed in this "Summary" section or elsewhere in this specification may include one or more layers, compositions, materials, or components that generate gases other than nitric oxide, in addition to, or instead of, a nitric oxide generating layer, composition, or material. For example, a wound dressing or device may include one or more layers that effectively generate a vasodilator, such as carbon monoxide or hydrogen sulfide, over time upon activation.

[0033] Those skilled in the art will further understand that carbon monoxide and / or hydrogen sulfide can, where appropriate, be used instead of, or in combination with, a nitric oxide delivery element (such as a layer). Further details regarding the generation and delivery of carbon monoxide and / or hydrogen sulfide can be found in Chapter 6 of the text Inorganic and Organometallic Transition Metal Complexes with Biological Molecules and Living Cells, ISBN 978-0-12-803814-7, which is incorporated herein by reference. For example, hydrogen sulfide can be generated from elements / layers containing cleavable / releasable hydrogen sulfide, diallyl thiosulfinate, GYY4137, S - mesalamine ATB - 429, S - naproxen ATB - 346, S - diclofenac ATB - 337 / ACS - 15. For example, carbon monoxide can be generated from elements / layers that provide complexes of carbon monoxide bound to suitable metals such as chromium, molybdenum, tungsten, manganese, rhenium, iron, ruthenium, cobalt, rhodium, and iridium. Such complexes can release carbon monoxide, be photo - cleavable, and / or be enzymatically triggered to induce the release of carbon monoxide in response to interaction with a suitable ligand.

[0034] Methods of treating a wound Some preferred embodiments described herein provide a method for treating a wound, non-injured tissue, or other suitable site. Such a method can include disposing one or more nitric oxide generating layers, separately or as a multilayer wound dressing having one or more nitric oxide generating layers, over the wound. The method can include adhering a separate one or more nitric oxide generating layers and / or a multilayer wound dressing having one or more nitric oxide generating layers to healthy skin surrounding the wound, such as the area surrounding the wound. The method can further include one or more of the following steps. A further wound dressing can be disposed over a separate one or more nitric oxide generating layers or a multilayer wound dressing having one or more nitric oxide generating layers disposed over the wound. A wound exudate, or any wet or aqueous medium other than the wound exudate, can be provided to reach and / or contact the one or more nitric oxide generating layers. The wound exudate, or any wet or aqueous medium other than the wound exudate, can diffuse or be drawn into a wound dressing incorporating the one or more nitric oxide generating layers or into a wound dressing provided over the one or more nitric oxide generating layers. Negative pressure can be applied to a separate one or more nitric oxide generating layers or a multilayer wound dressing having one or more nitric oxide generating layers as described in the "Negative Pressure Wound Therapy (NPWT) System" section below or elsewhere in this specification, whereby the wound exudate is suctioned directly into the one or more nitric oxide generating layers or into a wound dressing incorporating the one or more nitric oxide generating layers or into a wound dressing provided over the one or more nitric oxide generating layers.

[0035] As described above or elsewhere in this specification, methods of treating a wound, intact tissue, or other suitable site may further comprise delivering negative pressure to the wound through a wound contact layer, as described in the following "Negative Pressure Wound Therapy (NPWT)" section or elsewhere in this specification. The wound contact layer may substantially maintain the negative pressure delivered for at least about 24 hours, or at least about 48 hours, or at least about 72 hours. Alternatively, methods of treating a wound, intact tissue, or other suitable site may comprise applying a compressive (positive) pressure to the wound through a wound contact layer. Alternatively, the method may comprise varying the atmospheric, negative, and compressive pressures to the wound through the wound contact layer in a programmable manner.

[0036] In embodiments, methods of treating a wound, intact tissue, or other suitable site may comprise using a wound contact layer, or a wound treatment system or wound dressing comprising a wound contact layer, under ambient conditions not associated with a negative pressure wound therapy system, as described above or elsewhere in this specification.

[0037] In some embodiments, methods of treating a wound, intact tissue, or other suitable site may reduce the wound bioburden, for example, by reducing the number of viable microorganisms (CFU / sample) within the first 4 hours after application of the wound contact layer, at least in vitro. In some examples, the number of viable microorganisms may be reduced by 4 logs or more 48 - 72 hours after positioning the wound dressing agent in contact with the microorganisms.

[0038] Negative Pressure Wound Therapy (NPWT) System Embodiments of the present disclosure are generally, but not necessarily, applicable for use in a topical negative pressure (TNP) therapy system. Briefly, negative pressure wound therapy assists in closing and healing many forms of "difficult to heal" wounds by reducing tissue edema, promoting blood flow and granulation tissue formation, and removing excessive exudate, and can reduce bacterial load (and thus the risk of infection). In addition, the therapy can reduce wound discomfort and lead to earlier healing. The TNP therapy system may also assist in the healing of surgically closed wounds by helping to remove fluids and stabilizing tissue at parallel positions of closure. Further beneficial uses of TNP therapy can be found in grafts and flaps where removal of excess fluid is important and the graft needs to be in close proximity to the tissue to ensure tissue viability.

[0039] As used herein, a negative pressure or vacuum level, such as -X mmHg, represents a pressure level relative to normal ambient pressure, which may correspond to 760 mmHg (or 1 atm, 29.93 inHg, 101.325 kPa, 14.696 psi, etc.). Thus, a negative pressure value of -X mmHg reflects an absolute pressure that is X mmHg lower than 760 mmHg, or, put another way, an absolute pressure of (760 - X) mmHg. Further, a negative pressure that is "lower" or "less" than X mmHg corresponds to a pressure closer to atmospheric pressure (e.g., -40 mmHg is lower than -60 mmHg). A negative pressure that is "higher" or "greater" than -X mmHg corresponds to a pressure further from atmospheric pressure (e.g., -80 mmHg is higher than -60 mmHg). In some embodiments, local ambient pressure is used as a reference point, and such local atmospheric pressure may not necessarily be, for example, 760 mmHg.

[0040] The negative pressure ranges related to some embodiments of the present disclosure can be about -80 mmHg, or about -20 mmHg to -200 mmHg. It should be noted that these pressures are relative to the normal ambient pressure, which can be 760 mmHg. Therefore, -200 mmHg would be substantially about 560 mmHg. In some embodiments, the pressure range can be about -40 mmHg to -150 mmHg. Alternatively, pressure ranges below -75 mmHg, below -80 mmHg, or exceeding 80 mmHg can be used. Also, in other embodiments, pressure ranges below -75 mmHg can be used. As an alternative, a pressure range of approximately -100 mmHg or even above -150 mmHg can be supplied by the negative pressure device.

[0041] In some embodiments of the wound closure device described herein, an increase in wound shrinkage can lead to an increase in tissue expansion in the surrounding wound tissue. This effect may, in some cases, be increased by changing the force applied to the tissue in conjunction with an increase in the tensile force applied to the wound by an embodiment of the wound closure device, for example, by changing the negative pressure applied to the wound over time. In some embodiments, the negative pressure can be changed over time, for example, using a sine wave, a square wave, or in synchronization with one or more physiological indicators of the patient (e.g., heart rate). Examples of such applications for which further disclosure can be found include U.S. Patent No. 8,235,955, entitled "Wound treatment apparatus and method," issued on August 7, 2012, and U.S. Patent No. 7,753,894, entitled "Wound cleansing apparatus with stress," issued on July 13, 2010. The disclosures of both of these patents are hereby incorporated by reference in their entirety.

[0042] Embodiments of the wound dressings, wound dressing components, wound treatment devices, and methods described herein may also be combined with or used in addition to those described in "APPARATUSES AND METHODS FOR NEGATIVE PRESSURE WOUND THERAPY," filed as International Application No. PCT / IB2013 / 001469 on May 22, 2013, and published as International Publication No. 2013 / 175306 (A2) on November 28, 2013; and in "WOUND DRESSING," filed as International Application No. PCT / IB2013 / 002060 on July 31, 2013, and published as WO2014 / 020440, the disclosures of which are hereby incorporated by reference in their entirety. Embodiments of the wound dressings, wound treatment devices, and methods described herein may also be combined with or used in addition to those described in U.S. Patent No. 9,061,095, issued on June 23, 2015, entitled "WOUND DRESSING AND METHOD OF USE"; and in U.S. Patent Application Publication No. 2016 / 0339158, published on November 24, 2016, entitled "FLUIDIC CONNECTOR FOR NEGATIVE PRESSURE WOUND THERAPY," the disclosures of each of which are hereby incorporated by reference in their entirety, including further details regarding embodiments of the wound dressings, components and principles of the wound dressings, and materials used in the wound dressings.

[0043] In addition, some embodiments related to TNP wound treatment involving a wound dressing, in combination with the pumps or associated electronics described herein, may also be combined with or used in addition to those described in "REDUCED PRESSURE APPARATUSES," published as International Publication No. 2016 / 174048 (A1) on November 3, 2016, the entire disclosure of which is hereby incorporated by reference. In some of these embodiments, the pump or associated electronics may be integrated within the wound dressing to provide a single article to be applied to the wound.

[0044] Multilayer wound dressing for NPWT FIG. 1 illustrates an example of a negative pressure wound therapy system 700. The system includes a wound cavity 710 covered by a wound dressing 720, which can be a dressing according to any of the examples described herein. The dressing 720 is positioned over, inside, throughout, or around the wound cavity 710 and can further seal the wound cavity so that negative pressure can be maintained within the wound cavity. For example, the film layer of the wound dressing 720 can provide a substantially fluid-impermeable seal over the wound cavity 710. In some embodiments, a wound filler, such as a foam or gauze layer, can be utilized to fill the wound. The wound filler can include one or more nitric oxide generating layers (e.g., a nitrite delivery layer, an acidic group providing layer), as described in this section or elsewhere in this specification. For example, in a conventional negative pressure wound therapy system that utilizes a foam or gauze, such as the Smith&Nephew RENASYS negative pressure wound therapy system that utilizes a foam (RENASYS-F) or gauze (RENASYS-G), the foam or gauze can be supplemented with a nitric oxide generating layer as described above. When supplementing a foam or gauze layer or other wound packing material, one or more nitric oxide generating layers can be inserted separately into the wound or pre-attached to the wound packing material for insertion into the wound.

[0045] One or more luminal tubes or conduits 740 connect the wound dressing 720 to a negative pressure device 750 configured to supply reduced pressure. The negative pressure device 750 includes a negative pressure source. The negative pressure device 750 can be a canisterless device (meaning that exudate is collected in the wound dressing and / or moved for collection to another location via the tube 740). In some embodiments, the negative pressure device 750 can be configured to include or support a canister. Additionally, in any of the embodiments disclosed herein, the negative pressure device 750 can be fully or partially embedded in, attached to, or supported by the wound dressing 720.

[0046] The conduit 740 can be any suitable article configured to provide at least a substantially sealed fluid flow path or passageway between the negative pressure device 750 and the wound cavity 710 so as to supply reduced pressure to the wound cavity. The conduit 740 can be formed from polyurethane, PVC, nylon, polyethylene, silicone, or any other suitable rigid or flexible material. In some embodiments, the wound dressing 720 can have a port configured to receive an end of the conduit 740. For example, the port can include a hole in a film layer. In some embodiments, the conduit 740 can pass through and / or otherwise through the film layer of the wound dressing 720 to supply reduced pressure to the wound cavity 710 so as to maintain a desired level of reduced pressure within the wound cavity. In some embodiments, at least a portion of the conduit 740 is integral with or attached to the wound dressing 720.

[0047] FIG. 2A illustrates one embodiment of a negative pressure wound therapy system 10 that uses a wound dressing 100 together with a fluid connector 110. Additional examples of negative pressure wound therapy involving a wound dressing in combination with the pumps described herein may also be used in combination with, or in addition to, those described in U.S. Patent No. 9,061,095, which is hereby incorporated by reference in its entirety. In the figure, the fluid connector 110 may comprise an elongated conduit, more preferably a bridge 120 having a proximal end 130 and a distal end 140, and an applicator 180 at the distal end 140 of the bridge 120. The system 10 may include a source of negative pressure, such as a pump or a negative pressure unit 150 capable of supplying negative pressure. The pump may comprise a canister or other container for storing wound exudate and other fluids that may be removed from the wound. The canister or container may also be provided separately from the pump. In some embodiments, the pump 150 may be a canisterless pump, such as the PICO™ pump sold by Smith & Nephew. The pump 150 may be connected to the bridge 120 via a tube, or the pump 150 may be directly connected to the bridge 120. In use, the dressing 100 is preferably placed over a wound that may, in some cases, be filled with a wound packing material, such as a foam or a gauze, as described above. The applicator 180 of the fluid connector 110 has a sealing surface that is placed over the gap in the dressing 100 and sealed to the top surface of the dressing 100. Prior to, during, or after connection of the fluid connector 110 to the dressing 100, the pump 150 is connected to a coupler 160 via a tube or directly to the bridge 120. The pump is then activated, thereby supplying negative pressure to the wound. Application of the negative pressure may be continued until a desired level of wound healing is achieved.

[0048] As shown in FIG. 2B, the fluid connector 110 preferably comprises an enlarged distal end or head 140 that is in fluid communication with the dressing 100, as will be described in further detail below. In one embodiment, the enlarged distal end has a round or circular shape. The head 140 is illustrated in the figure as being positioned near the end of the dressing 100, but may be positioned anywhere on the dressing. For example, some embodiments may be provided at a location that is not on or near the end or corner of the dressing 100, but rather at the center or off-center. In some embodiments, the dressing 10 may comprise two or more fluid connectors 110, each having one or more heads 140 in fluid communication therewith. In a preferred embodiment, the head 140 may be dimensioned 30 mm along its widest edge. The head 140 at least partially forms an applicator 180 that is configured to be sealed against the uppermost surface of the wound dressing as described above.

[0049] FIG. 2C illustrates a cross-section through a wound dressing 100 similar to the wound dressing 10 described in International Patent Application Publication No. 2013 / 175306 (A2), which is incorporated by reference in its entirety, together with the fluid connector 110. Alternatively, the wound dressing 100, which can be any of the wound dressing embodiments disclosed herein, or any combination of any number of features of the wound dressing embodiments disclosed herein, can be placed over the wound site to be treated. The dressing 100 can be arranged to form a cavity sealed over the wound site. In a preferred embodiment, the dressing 100 comprises a top layer or cover layer, or a backing layer 220 attached to any wound contact layer 222, both of which will be described in more detail below. These two layers 220, 222 are preferably joined or sealed together to define an internal space or chamber. This internal space or chamber may comprise additional structures adapted to distribute or transmit negative pressure and store wound exudate and other fluids removed from the wound, as well as other functions that will be described in more detail below. Examples of such structures described below include a permeable layer 226 and an absorbent layer 221.

[0050] As used herein, the upper layer, top layer, or upper layer refers to the layer that is farthest from the skin or the surface of the wound while the covering material is in use and positioned over the wound. Thus, the lower surface, lower layer, bottom layer, or lower layer refers to the layer that is closest to the skin or the surface of the wound while the covering material is in use and positioned over the wound.

[0051] As illustrated in FIG. 2C, the wound contact layer 222 may be a polyurethane layer, a polyethylene layer, or another flexible layer that has been perforated, for example, via a hot pin process, a laser ablation process, or an ultrasonic process, or in some other way, or otherwise made permeable to liquids and gases. The wound contact layer 222 has a lower surface 224 and an upper surface 223. The perforations 225 include through-holes in the wound contact layer 222, thereby preferably enabling fluid to flow through the layer 222. The wound contact layer 222 serves to prevent tissue ingrowth into the other materials of the wound dressing. Preferably, the perforations are small enough to meet this requirement while allowing fluid to flow therethrough. For example, perforations formed as slits or holes having dimensions in the range of 0.025 mm to 1.2 mm are considered small enough to enable wound exudate to flow into the dressing while preventing tissue ingrowth into the wound dressing. In some configurations, the wound contact layer 222 can serve to maintain the integrity of the entire dressing 100 while creating an airtight seal around the absorbent pad to maintain a negative pressure in the wound.

[0052] Some embodiments of the wound contact layer 222 may also act as a carrier for any upper and lower adhesive layers (not shown). For example, a lower pressure-sensitive adhesive may be provided on the lower surface 224 of the wound dressing 100, while an upper pressure-sensitive adhesive layer may be provided on the upper surface 223 of the wound contact layer. A pressure-sensitive adhesive that may be a silicone, hot melt, hydrophilic colloid or acrylic-based adhesive, or other such adhesive, may be formed on both sides of the wound contact layer, or optionally on a selected one of the sides, or may not be formed on either side of the wound contact layer. When a lower pressure-sensitive adhesive layer is utilized, it may help to adhere the wound dressing 100 to the skin around the wound site. In some embodiments, the wound contact layer may comprise a perforated polyurethane film. The lower surface of the film may be provided with a silicone pressure-sensitive adhesive, and the upper surface may be provided with an acrylic pressure-sensitive adhesive, which may help the dressing to maintain its integrity. In some embodiments, the polyurethane film layer may be provided with adhesive layers on both its upper and lower surfaces, and all three layers may be perforated together.

[0053] The permeable layer 226 may be located above the wound contact layer 222. In some embodiments, the permeable layer can be a porous material. As used herein, the permeable layer may be referred to as a spacer layer, and this term may be used interchangeably to refer to the same components described herein. This permeable layer 226 allows for the permeation of fluids, including liquids and gases, from the wound site into the upper layer of the wound dressing away from the wound. In particular, the permeable layer 226 preferably ensures that an open air channel can be maintained such that a negative pressure is transmitted over the wound area even when the absorbent layer has absorbed a significant amount of exudate. Layer 226 should preferably remain open under the normal pressures that will be applied during negative pressure wound therapy as described above, whereby the entire wound site receives an equal negative pressure. Layer 226 may be formed from a material having a three-dimensional structure. For example, a knitted or woven spacer fabric (e.g., a warp knitted polyester such as Baltex 7970), or a non-woven fabric may be used. The three-dimensional material may include a 3D spacer fabric material similar to the materials described in International Publication No. WO2013 / 175306 (A2) and International Publication No. WO2014 / 020440, the disclosures of which are incorporated by reference in their entirety.

[0054] In certain embodiments, the wound dressing 100 may incorporate or include one or more nitric oxide generating layers (e.g., a nitrite delivery layer, an acidic group providing layer), as described in this section or elsewhere in this specification. One of ordinary skill in the art will understand that the wound dressing 100 may incorporate any of the one or more nitric oxide generating layers disclosed in this section or elsewhere in this specification. One of ordinary skill in the art will also understand that one or more nitric oxide generating layers may be incorporated as all or part of a component layer. In some embodiments, one or more nitric oxide generating layers may be provided under the permeable layer 226. In some embodiments, one or more nitric oxide generating layers may be provided over the wound contact layer 222. In certain embodiments, one or more nitric oxide generating layers may replace the permeable layer 226 such that one or more nitric oxide generating layers are provided between the absorbent layer 221 (described further below) and the wound contact layer 222. In some embodiments, one or more nitric oxide generating layers may supplement or replace the absorbent layer 221. In some embodiments, the wound dressing 100 does not have a wound contact layer 222, and one or more nitric oxide generating layers may be the lowermost layer of the wound dressing 100. One or more nitric oxide generating layers may have the same or substantially the same size and shape as the permeable layer 226 and / or the absorbent layer 221.

[0055] One or more nitric oxide generating layers can be constructed to be flexible but stiff enough to withstand negative pressure so that when negative pressure is supplied to the wound dressing 100, the negative pressure is sufficiently transmitted to the wound without the one or more nitric oxide generating layers collapsing excessively. The one or more nitric oxide generating layers can be constructed to include pores in a number or size sufficient to allow transmission of negative pressure. The one or more nitric oxide generating layers can include, for example, a gap or hole under the port to transmit negative pressure and / or wound fluid. Further, the one or more nitric oxide generating layers can have a thickness suitable for transmitting a suitable negative pressure to the wound. For example, the one or more nitric oxide generating layers can have a thickness of about 1 mm to 10 mm, or 1 mm to 7 mm, or 1.5 mm to 7 mm, or 1.5 mm to 4 mm, or 2 mm to 3 mm. In some embodiments, the one or more nitric oxide generating layers can have a thickness of about 2 mm.

[0056] In some embodiments, the absorbent layer 221 is provided above the permeable layer 226. The absorbent, which can include a foam or non-woven natural or synthetic material and optionally a superabsorbent, forms a reservoir for fluid, specifically the liquid removed from the wound site. In some embodiments, layer 221 can also assist in drawing fluid towards the backing layer 220.

[0057] The material of the absorbent layer 221 may also prevent the liquid collected within the wound dressing 100 from freely flowing within the dressing and preferably acts to contain any collected liquid within the dressing. The absorbent layer 221 also helps to disperse the fluid throughout the layer by a wicking action so as to draw the fluid from the wound site and store it across the absorbent layer. This aids in preventing agglomeration across the area of the absorbent layer. The capacity of the absorbent must be sufficient to manage the rate at which wound exudate flows when a negative pressure is applied. In use, since the absorbent layer experiences a negative pressure, the material of the absorbent layer is chosen to absorb liquid under such circumstances. For example, there are several materials such as superabsorbent materials that can absorb liquid when under a negative pressure. The absorbent layer 221 may typically be manufactured from Freudenberg 114 - 224 - 4 of ALLEVYN™ foam or Chem-Posite™ 11C - 450. In some embodiments, the absorbent layer 221 may comprise a composite material including superabsorbent powder, fibrous materials such as cellulose, and binding fibers. In a preferred embodiment, the composite material is an air-laid, thermally bonded composite material.

[0058] In some embodiments, the absorbent layer 221 is a layer of non-woven cellulose fibers having a superabsorbent material in the form of dry particles dispersed across the layer. The use of cellulose fibers introduces a high-speed wicking element that helps to rapidly and evenly disperse the liquid absorbed by the dressing. Aligning a number of twist-like fibers leads to a strong capillary action of the fiber pad that serves to distribute the liquid. In this way, the liquid is efficiently supplied to the superabsorbent material. Also, the wicking action aids in bringing the liquid into contact with the upper cover layer in order to assist in increasing the evaporation rate of the dressing.

[0059] Preferably, a gap, hole, or orifice 227 is provided in the backing layer 220 to enable negative pressure to be applied to the covering material 100. The fluid connector 110 is preferably attached or sealed on top of the backing layer 220 over the orifice 227 made in the covering material 100 to transmit negative pressure through the orifice 227. A long pipe may be coupled to the fluid connector 110 at a first end and to a pump unit (not shown) at a second end to enable fluid to be pumped from the covering material. When the fluid connector adheres to the top layer of the wound covering material, the long pipe may be coupled at the first end of the fluid connector such that the pipe or conduit extends away from the fluid connector parallel to or substantially along the top surface of the covering material. The fluid connector 110 may be adhered and sealed to the backing layer 220 using an adhesive such as acrylic, cyanoacrylate, epoxy, UV curable, or hot melt adhesive. The fluid connector 110 may be formed from a soft polymer such as polyethylene, polyvinyl chloride, silicone, or polyurethane having a hardness of 30 to 90 on the Shore A scale. In some embodiments, the fluid connector 110 may be made from a soft or conformable material.

[0060] Optionally, the absorbent layer 221 includes at least one through-hole 228 disposed such that it is under the fluid connector 110. The through-hole 228 may be the same size as the opening 227 in the backing layer in some embodiments, or may be larger or smaller. As illustrated in FIG. 2C, a single through-hole may be used to provide an opening under the fluid connector 110. It will be understood that multiple openings may alternatively be utilized. Additionally, if one or more ports are to be utilized according to certain embodiments of the present disclosure, one or more openings may be made in the absorbent layer in alignment with each respective fluid connector. Although not essential to some embodiments of the present disclosure, using through-holes in the superabsorbent layer may provide an unobstructed fluid flow path, particularly when the absorbent layer is near saturation.

[0061] As illustrated in FIG. 2C, the gap or through-hole 228 is preferably provided in the absorption layer 221 below the orifice 227 such that the orifice is directly connected to the permeable layer 226. This allows the negative pressure applied to the fluid connector 110 to be transmitted to the permeable layer 226 without passing through the absorption layer 221. This ensures that the negative pressure applied to the wound site is not inhibited by the absorption layer even if the absorption layer absorbs wound exudate. In other embodiments, the gap may not be provided in the absorption layer 221, or alternatively, a plurality of gaps may be provided under the orifice 227. In a further alternative embodiment, an additional layer such as another permeable layer, or a concealment layer as described in International Patent Application Publication No. WO2014 / 020440, which is incorporated by reference in its entirety, may be provided above the absorption layer 221 and below the backing layer 220.

[0062] The backing layer 220 is preferably gas-impermeable but water-vapor permeable and may extend across the width of the wound dressing 100. For example, it may be a polyurethane film (e.g., Elastollan SP9109) having a pressure-sensitive adhesive on one side. The backing layer 220 is impermeable to gases and thus operates to cover the wound and seal the wound cavity in which the wound dressing is placed on top. In this way, an effective chamber is created between the backing layer 220 and the wound site where a negative pressure can be established. The backing layer 220 is preferably sealed to the wound contact layer 222 within the boundary region around the dressing via, for example, an adhesive technique or a welding technique to prevent air from being drawn into the boundary region. The backing layer 220 protects the wound from external bacterial contamination (bacterial barrier) and allows liquid from the wound exudate to move through the layer and evaporate from the outer surface of the film. The backing layer 220 preferably includes two layers, namely, a polyurethane film and an adhesive pattern spread on this film. The polyurethane film is preferably moisture-permeable and may be manufactured from a material whose water permeability increases when wet. In some embodiments, the moisture permeability of the backing layer increases when the backing layer is wet. The moisture permeability of the wet backing layer may be up to about 10 times that of the dry backing layer.

[0063] The absorbent layer 221 may have an area larger than that of the permeable layer 226 such that the absorbent layer overlaps with the edge of the permeable layer 226, thereby ensuring that the permeable layer does not contact the backing layer 220. This provides an outer channel of the absorbent layer 221 that directly contacts the wound contact layer 222 and aids in more rapid absorption of exudate into the absorbent layer. Further, this outer channel ensures that liquid cannot be retained at the outer periphery of the wound cavity, which, if otherwise, may seep out from the seal around the dressing material and lead to the formation of leakage. As illustrated in FIG. 2C, the absorbent layer 221 may define a perimeter smaller than that around the backing layer 220 such that a boundary line or boundary region is defined between the edge of the absorbent layer 221 and the edge of the backing layer 220.

[0064] As shown in FIG. 2C, one embodiment of the wound dressing 100 includes a gap 228 in the absorbent layer 221 disposed below the fluid connector 110. In use, for example, when negative pressure is applied to the dressing 100, the wound-facing portion of the fluid connector may contact the permeable layer 226 and, thus, may assist in transmitting negative pressure to the wound site even when the absorbent layer 221 is filled with wound fluid. Some embodiments may have a backing layer 220 that is at least partially adhered to the permeable layer 226. In some embodiments, the gap 228 is at least 1-2 mm larger than the wound-facing portion of the fluid connector 11 or the diameter of the orifice 227.

[0065] Particularly, in embodiments with a single fluid connector 110 and a through-hole, as illustrated in FIG. 2B, the fluid connector 110 and the through-hole may preferably be located at an off-center position. Such a location may allow the dressing 100 to be positioned on the patient such that the fluid connector 110 is lifted relative to the remainder of the dressing 100. When positioned in such a manner, the fluid connector 110 and the filter 214 may be less likely to contact wound fluid that can prematurely occlude the filter 214 to prevent transmission of negative pressure to the wound site.

[0066] Similar to the embodiments of the wound dressing described above, some wound dressings comprise a perforated wound contact layer with a silicone adhesive on the skin contact surface and an acrylic adhesive on the back surface. In some embodiments, the wound contact layer can be constructed from polyurethane, polyethylene, or polyester. Above this bounded layer is a permeable layer. Above the permeable layer is an absorbent layer. The absorbent layer can include a superabsorbent non-woven (NW) pad. The absorbent layer can contact the permeable layer by approximately 5 mm beyond the perimeter. The absorbent layer can have a gap or through-hole towards one end. The gap can be approximately 10 mm in diameter. Above the permeable layer and the absorbent layer is a backing layer. The backing layer can be a high moisture vapor transmission rate (MVTR) film that is a pattern coated with an acrylic adhesive. The high MVTR film and the wound contact layer enclose the permeable layer and the absorbent layer to create a perimeter boundary of approximately 20 mm. The backing layer can have a 10 mm gap that overlaps above the gap in the absorbent layer. Above the hole, a fluid connector can be coupled that comprises a liquid-impermeable, gas-permeable semi-permeable membrane (SPM) or filter that overlaps above the gap described above.

[0067] Figure 2D illustrates one embodiment of a wound dressing similar to the wound dressings of FIGS. 2A - 2C. Referring to FIG. 2D, a masking or concealment layer 2107 may be positioned under at least a portion of the backing layer 2140. In some embodiments, the concealment layer 2107 may have any of the same features, materials, or other details of any of the other embodiments of the concealment layers disclosed herein, including but not limited to having any visual window or aperture. Examples of wound dressings having a concealment layer and a visual window are described in International Patent Publication No. WO2014 / 020440, which is hereby incorporated by reference in its entirety. Additionally, the concealment layer 2107 may be positioned adjacent to the backing layer or adjacent to any other desired dressing layer. In some embodiments, the concealment layer 2107 may be adhered to the backing layer or formed integrally with the backing layer. Preferably, the concealment layer 2107 has substantially the same size and shape as the absorbent layer 2110 and is configured to overlay it. Thus, in these embodiments, the concealment layer 2107 has a smaller area than the backing layer 2140.

[0068] Preferably, the absorbent layer 2110 and the concealment layer 2107 include at least one through - hole 2145 positioned such that it is under the port 2150. Of course, the respective holes through these various layers 2107, 2140, and 2110 may be of different sizes relative to each other. As illustrated in FIG. 2D, a single through - hole may be used to provide an opening under the port 2150. In certain embodiments, the ports may be interchanged with or used in combination with fluid connectors such as those illustrated in FIG. 2C. It will be understood that multiple openings may alternatively be utilized. Additionally, if one or more ports are to be utilized according to a particular embodiment of the present disclosure, one or more openings may be made in the absorbent and concealment layers in alignment with each respective port. Although not essential to some embodiments of the present disclosure, using through - holes in the superabsorbent layer may provide an unobstructed fluid flow path, especially when the absorbent layer 2110 is near saturation.

[0069] The gap or through-hole 2144 may be provided in the absorption layer 2110 and the shielding layer 2107 below the orifice 2144 such that the orifice is directly connected to the permeable layer 2105. This enables the negative pressure applied to the port 2150 to be transmitted to the permeable layer 2105 without passing through the absorption layer 2110. This ensures that the negative pressure applied to the wound site is not inhibited by the absorption layer even if the absorption layer absorbs wound exudate. In other embodiments, the gap may not be provided in the absorption layer 2110 and / or the shielding layer 2107, or alternatively, a plurality of gaps may be provided under the orifice 2144.

[0070] In some embodiments, the shielding layer 1404 may help reduce the unsightliness of the dressing during use by using a material that provides partial concealment or masking of the dressing surface. The shielding layer 1404 of one embodiment only partially conceals the dressing such that a clinician can access the necessary information by observing the spread of exudate across the dressing surface. This partial masking property of the shielding layer enables the clinician to perceive different colors caused by exudate, blood, by-products, etc. in the dressing and enables visual evaluation and monitoring of the extent of spread across the dressing. However, since the change in the color of the dressing from its clean state to a state containing exudate is only a slight change, the patient is less likely to notice any aesthetic differences. Reducing or eliminating visual indicators of wound exudate from the patient's wound can have a positive impact on the patient's health, for example, is likely to reduce stress.

[0071] In some embodiments, the backing layer may be formed from a non-woven fabric (e.g., polypropylene) and may be heat-bonded using a diamond pattern having a 19% bonding area. In various embodiments, the backing layer may be hydrophobic or hydrophilic. Depending on the application, in some embodiments, a hydrophilic backing layer may provide additional moisture permeability. However, in some embodiments, a hydrophobic backing layer may still provide sufficient moisture permeability (i.e., through appropriate material selection, backing layer thickness), while also allowing for better retention of dyes or colors in the backing layer. Thus, the dyes or colors may be confined under the backing layer. In some embodiments, this may allow the backing layer to be colored in a bright color or white. In a preferred embodiment, the backing layer is hydrophobic. In some embodiments, the backing layer material may be sterilizable using ethylene oxide. Other embodiments may be sterilized using gamma irradiation, electron beam, steam, or other alternative sterilization methods. Additionally, in various embodiments, the backing layer may be colored or tinted, for example, in a medical blue color. The backing layer may also be constructed from multiple layers, including a colored layer laminated or fused to a stronger non-colored layer. Preferably, the backing layer is odorless and exhibits minimal shedding of fibers.

[0072] Multilayer dressing for use without negative pressure Figures 3A - 3D illustrate various embodiments of a wound dressing 500 that can be used to heal a wound without negative pressure. Figure 3E illustrates a cross-section of the wound dressings of Figures 3A - 3D. As shown in the dressings of Figures 3A - 3E, the wound dressing may have a plurality of layers similar to the dressings described with reference to Figures 2A - 2D, except that the dressings of Figures 3A - 3E do not include a port or fluid connector. The wound dressings of Figures 3A - 3E may include a cover layer 501 and a wound contact layer 505, as described herein. In some embodiments, the cover layer 501 may be permeable to moisture and / or air. The wound dressing may include various layers positioned between the wound contact layer 505 and the cover layer 501. For example, the dressing may include one or more absorbent layers or one or more permeable layers, as described herein with reference to Figures 2A - 2C.

[0073] As shown in FIGS. 3A - 3E, the dressing 500 may include a perforated wound contact layer 505 and a top film 501. Further components of the wound dressing 500 include a foam layer 504, such as a layer of polyurethane hydrocellular foam sized to cover the recommended dimensions of the wound corresponding to a selected specific dressing size. An optional layer of activated charcoal cloth (not shown) of the same or slightly smaller dimensions as layer 504 may be provided to enable odor control. An absorption layer 502, such as a layer of superabsorbent eolian material containing cellulose fibers and superabsorbent polyacrylate particles, is provided over layer 504 and is slightly larger in dimension than layer 504, allowing for overlap of the superabsorbent material and acting as a leak prevention. Over layer 502, a masking or concealment layer 503, such as a layer of three - dimensional knitted spacer fabric, is provided to provide protection from pressure while allowing partial masking of the uppermost surface of the superabsorbent where colored exudate remains. In this embodiment, this is of a smaller dimension (plan view) than layer 502 and enables visualization of the edge of the absorption layer, which can be used by a clinician to evaluate whether the dressing needs to be changed.

[0074] The wound dressing 500 may incorporate or include one or more nitric oxide generating layers (e.g., a nitrite delivery layer, an acidic group providing layer), as described in this section or elsewhere. Those skilled in the art will understand that the wound dressing 500 may incorporate any of the one or more nitric oxide generating layers disclosed in this section or elsewhere in this specification. Those skilled in the art will also understand that one or more nitric oxide generating layers may be incorporated as all or part of the component layers. In some embodiments, the nitric oxide generating layer may be provided under the cover layer 501. In some embodiments, the nitric oxide generating layer may be provided over the wound contact layer 505. In certain embodiments, the dressing 500 may not include the wound contact layer 505 such that one of the nitric oxide generating layers is the bottom layer and is configured to contact the wound surface. In some embodiments, the nitric oxide generating layer may be provided under the foam layer 504. In an embodiment, the nitric oxide generating layer may replace the foam layer 504. In some embodiments, the dressing 500 may include only the cover layer 501 and one or more nitric oxide generating layers.

[0075] As described above, one or more nitric oxide generating layers may be incorporated into or used with commercially available dressings such as ALLEVYN (trademark) foam, ALLEVYN (trademark) Life, ALLEVYN (trademark) Adhesive, ALLEVYN (trademark) Gentle Border, ALLEVYN (trademark) Gentle, ALLEVYN (trademark) Ag Gentle Border, ALLEVYN (trademark) Ag Gentle, Opsite Post-Op Visible. In some embodiments, the wound dressing 500 may include a cover layer 501, a wound contact layer 505, and a nitric oxide generating layer sandwiched therebetween. In some embodiments, the wound dressing 500 may include a cover layer 501, an absorption layer 502, a nitric oxide generating layer under the absorption layer 502, and a wound contact layer 505.

[0076] Further details regarding wound dressings that may be combined with or used in addition to the embodiments described herein can be found in U.S. Patent No. 9,877,872, issued January 30, 2018, entitled "WOUND DRESSING AND METHOD OF TREATMENT," which disclosure is hereby incorporated by reference in its entirety herein, including further details regarding embodiments of wound dressings, components and principles of wound dressings, and materials used in wound dressings.

[0077] Multilayer wound dressing with integrated negative pressure source In some embodiments, the negative pressure source (such as a pump) and some or all of the other components of the TNP system, such as a power source, sensors, connectors, user interface components (buttons, switches, speakers, screens, etc.), can be integrated with a wound dressing such as the dressing described above in connection with FIGS. 1-3D. Additionally, some embodiments regarding wound treatment with the wound dressings described herein may also be combined with and used in addition to the embodiments described in International Application No. WO2016 / 174048 and International Patent Application No. PCT / EP2017 / 055225, filed March 6, 2017, entitled "WOUND TREATMENT APPARATUSES AND METHODS WITH NEGATIVE PRESSURE SOURCE INTEGRATED INTO WOUND DRESSING," the disclosures of which are hereby incorporated by reference in their entirety herein and include further details regarding embodiments of wound dressings, components and principles of wound dressings, and materials used in wound dressings and wound dressing components.

[0078] In some embodiments, the pump and / or other electronic components may be configured to be adjacent to or positioned next to the absorber and / or permeable layer of the wound dressing such that the pump and / or other electronic components are part of a single device that will still be applied to the patient with the pump and / or other electronic components positioned away from the wound site.

[0079] Nitric oxide generating layer Figures 4 and 5 illustrate a wound dressing 12000 that includes a nitric oxide generating layer, according to some embodiments. In the illustrated embodiments, the wound dressing 12000 may include a cover layer 12200, an active agent layer 12400, and a nitric oxide source layer 12600. In some embodiments, the wound dressing 12000 may include additional layers, as further described herein. Those skilled in the art will understand that the various sections of the dressing may be referred to as "layers," although such sections may be other suitable shapes or configurations.

[0080] The cover layer 12200 is gas-impermeable but may be moisture-permeable and may extend across the width of the wound dressing 12000. For example, it may be a polyurethane film having a pressure-sensitive adhesive on one side (e.g., Elastollan SP9109 or Elastollan SP806). The cover layer 12200 may be impermeable to gases and, therefore, this layer may operate to cover the wound and seal the wound cavity in which the wound dressing is disposed thereon. Therefore, a chamber or a sealed wound space is created between the cover layer 12200 and the wound site. In some embodiments, a negative pressure may be established within the chamber or the sealed wound space created between the cover layer 12200 and the wound site. The cover layer 12200 protects the wound from external bacterial contamination (bacterial barrier) and allows liquid from the wound exudate to move through the layer and evaporate from the outer surface of the film. The cover layer 12200 may include two or more layers, for example, a polyurethane film and an adhesive pattern spreading on the film. In a particular example, the polyurethane film may be moisture-permeable and may be manufactured from a material whose water permeability increases when wet. In some embodiments, the moisture permeability of the cover layer is higher when the cover layer is wet. The moisture permeability of the wet cover layer may be up to about 10 times that of the dry cover layer. In some embodiments, the cover layer 12200 may be replaced or supplemented with an additional wound dressing described elsewhere herein, whereby the additional wound dressing is positioned over the nitric oxide generating layer. The cover layer may also be waterproof so that dressings incorporating such cover layers can be used in the shower. The cover layer may be configured so that nitric oxide does not leak out immediately through the cover layer, which means that the cover layer is nitric oxide-impermeable or semi-permeable, thereby confining nitric oxide to the tissue so that nitric oxide can interact with the user's body. Those skilled in the art will understand that the cover layer can be made to be vapor-permeable but nitric oxide-impermeable.

[0081] The nitric oxide source layer 12600 can provide one or more nitric oxide releasing agents to the wound site. The nitric oxide releasing agent can include any chemical entity that generates nitric oxide at the wound site when activated or otherwise stimulated to generate nitric oxide at the wound site. In some embodiments, the nitric oxide releasing agent can include nitrite ions, nitrates, organic and inorganic nitrates, or any pharmacologically acceptable source of nitrous acid, whereby the nitrite ions for generating nitric oxide at the wound site can be reduced. For example, the nitric oxide source layer 12600 and / or the element can include one or more of ammonium nitrite, lithium nitrite, calcium nitrite, sodium nitrite, potassium nitrite. In some embodiments, the nitric oxide source layer can be a suitable material layer or element that includes an alkali metal nitrate and / or an alkaline earth metal nitrate. In certain embodiments, the nitrate is LiNO 2 , NaNO 2 , KNO 2 , RbNO 2 , CsNO 2 , FrNO 2 , Be(NO 2 ) 2 , Mg(NO 2 ) 2 , Ca(NO 2 ) 2 , Sr(NO 2 ) 2 , Ba(NO 2 ) 2 , Ra(NO 2 ) 2may contain nitrite or any other suitable nitrite. In some embodiments, a precursor of nitrite ions, such as nitrous acid, nitrate ions, nitroprusside ions, or any pharmaceutically acceptable salts thereof, can be used as a source of nitrite. In some embodiments, the nitric oxide releasing agent may contain nitrite such as a nitro-functionalized compound. For example, the nitric oxide releasing agent may include nitroglycerin, isoamyl nitrite, isosorbide mononitrate, N-(ethoxycarbonyl)-3-(4-morpholinyl) sydnonimine, 3-morpholinosydnonimine, 1,2,3,4-oxatriazolium, 5-amino-3-(3,4-di-chlorophenyl)-chloride, 1,2,3,4-oxatriazolium, 5-amino-3-(chloro-2-methyl-phenyl) chloride, 1,2,3,4-oxatriazolium, 3-(3-chloro-2-methylphenyl)-5-[[[cyanomethylamino]carbonyl]amino]-hydroxide inner salt, S-nitroso-N-acetyl-(D,L)-penicillamine, l-[(4’,5’-bis(carboxymethoxy)-2l-nitrophenyl)methoxy]-2-oxo-3,3,diethyl-l-triazenedipotassium salt, and [l-(4’,5’-bis(carbomethoxy)-2’-nitrophenyl)methoxy]-2-oxo-3,3-diethyl-1-triazenediacetoxymethyl ester.

[0082] In some embodiments, the nitric oxide releasing agent of the nitric oxide source layer 12600 may include diazeniumdiolate, including O-alkylated diazeniumdiolate, O-derivatized diazeniumdiolate, and non-O-derivatized diazeniumdiolate. For example, the nitric oxide releasing agent may include diethylamine / NO, V-PYRRO / NO, and / or spermine / NO. In some embodiments, the nitric oxide releasing agent of the nitric oxide source layer 12600 may include S-nitrosothiols such as S-nitro-glutathione, S-nitroso-N-acetylcysteine, S-nitroso-acetylpenicillamine. In some embodiments, the nitric oxide releasing agent of the nitric oxide source layer 12600 may include silica or silica nanoparticles modified with nitric oxide. In some embodiments, the nitric oxide releasing agent may be a polymer modified with nitric oxide to contain nitric oxide. For example, polyethyleneimine, polypropyleneimine, polybutyleneimine, polyurethane, or polyamide may be modified with nitric oxide to form diazeniumdiolate. In some embodiments, the nitric oxide source layer 12600 may be constructed from such polymers modified with nitric oxide. Further examples of nitric oxide releasing agents are provided in International Publication No. WO2006 / 058318, and Liang et al., “Nitric oxide generating / releasing materials”, Future Science OA, 1(1)(2015), which are hereby incorporated by reference in their entirety.

[0083] In some embodiments, the nitric oxide source layer 12600 may contain a nitric oxide releasing agent (e.g., sodium nitrite) in an aqueous solution. For example, the nitric oxide source layer 12600 may include a material soaked in a solution of a nitric oxide releasing agent (e.g., sodium nitrite). In some embodiments, the nitric oxide source layer 12600 may contain a dry nitric oxide releasing agent (e.g., sodium nitrite) in solid form.

[0084] The nitric oxide source layer 12600 may include a mesh, foam, gel, or any other material suitable for containing a nitric oxide releasing agent. For example, the nitric oxide source layer 12600 may include a mesh soaked in a nitric oxide releasing agent (e.g., sodium nitrite) solution. The mesh may be knitted, woven, or non-woven. The mesh may be made from a polymeric material, such as viscose, polyamide, polyester, polypropylene, or combinations thereof. In some embodiments, the nitric oxide source layer 12600 may include polypropylene, polyester, polyurethane, polyvinyl chloride, polyamide, viscose, polyester, polypropylene, and / or cellulose. As described herein, the nitric oxide source layer 12600 may be constructed from one or more polymers modified with nitric oxide. The nitric oxide source layer 12600 may also be made of a hydrogel without acidic groups to prevent reaction with nitrite ions that release nitric oxide. In some embodiments, the nitric oxide source layer 12600 may be constructed from a coloring material so that the nitric oxide source layer 12600 is visible to assist in positioning the wound dressing 12000 during application to the wound and to reduce the risk of incomplete removal of the nitric oxide source layer 12600 from the wound after treatment. The nitric oxide source layer 12600 may be fully or semi-permeable to the diffusion of nitric oxide.

[0085] In some embodiments, the nitric oxide source layer 12600 is the lowermost layer of the dressing 12000 such that the nitric oxide source layer 12600 can contact the wound. In some embodiments, the nitric oxide source layer 12600 may be positioned within and / or on the wound. The nitric oxide source layer may be constructed such that the nitric oxide source layer 12600 does not substantially adhere to the skin or wound, or does not cause damage to the wound when in contact with the wound. In some embodiments, the dressing 12000 may include one or more layers, such as a wound contact layer, beneath the nitric oxide source layer 12600. In some embodiments, the dressing 12000 may include two or more nitric oxide source layers. For example, the wound dressing 12000 may include 2, 3, 4, 5, 6, 7 or more nitric oxide source layers.

[0086] The activator layer 12400 may contain a chemical agent, functional group, or functional moiety that can activate and / or facilitate the release of nitric oxide from a nitric oxide-releasing agent. For example, a proton or acidic environment promotes the reduction of nitrite to nitric oxide, and the activator layer 12400 may include an acidic group or acidic moiety that can provide protons in an aqueous environment, thereby lowering the pH at the site of application. In certain embodiments, the acidic group or acidic moiety is immobilized in the activator layer 12400, for example, on the surface of the activator layer 12400. The acidic group or acidic moiety may be covalently bonded in the activator layer 12400. In some embodiments, the activator layer 12400 may contain an acidic solution. The activator layer 12400 may include a mesh, foam, gel, or any other material suitable for containing an acidic group or acidic moiety. In an embodiment, the activator layer 12400 is positioned on top of the nitric oxide source layer 12600, or the activator layer 12400 may be positioned under the nitric oxide source layer 12600. In some embodiments, the activator layer 12400 may include a proton source such as water, methanol, ethanol, propanol, butanol, pentanol, hexanol, phenol, naphthol, or a polyol, phosphoric acid, succinate, carbonate, acetate, format, propionic acid, butyrate, fatty acid, amino acid, or ascorbic acid, or any suitable enzymatic or catalytic compound. In some embodiments, a body fluid such as blood, lymph, bile, or wound exudate may function as an activator and assist the activator layer 12400. In some embodiments, the wound dressing 12000 may not include the activator layer 12400, and the wound fluid or wound exudate may function as an activator. Further examples of activators for nitric oxide-releasing agents are provided in International Publication No. WO2006 / 058318 and Liang et al., “Nitric oxide generating / releasing materials”, Future Science OA, 1(1)(2015), which are hereby incorporated by reference in their entirety.

[0087] In some embodiments, the wound dressing 12000 may include two or more nitric oxide source layers and / or two or more activator layers. For example, the wound dressing 12000 may include two, three, four, five, six, seven or more nitric oxide source layers and / or activator layers.

[0088] In some embodiments, the activator layer 12400 includes a hydrogel such that the activator layer 12400 can absorb wound exudate. In certain examples, the activator layer 12400 may be constructed from a xerogel. The activator layer 12400 may be constructed from any suitable material disclosed herein. The gel of the activator layer 12400 may be presented in different physical formats. For example, the activator layer 12400 may be foamed during curing. The hydrogel may be poured into a foam and then cured within the foam. In some embodiments, the activator layer 12400 may be perforated through its thickness. The perforations may be sized to allow fluid absorption and to release a desired therapeutic dose of nitric oxide from the wound dressing. For example, the perforations may have a diameter of approximately 0.1 mm to 10 mm, 0.15 mm to 7 mm, 0.2 mm to 5 mm, 0.5 mm to 4 mm, or 0.7 mm to 3 mm. The perforations may have a circular, square, triangular, or any other suitable shape. The foamed construct and / or the perforations may contribute to the fluid handling ability of the activator layer.

[0089] In some embodiments, rather than being provided as an active agent layer, such as active agent layer 12400, the active agent material for the active agent layer may be provided as a dispensable composition, for example, as a prepolymer solution or in another form that can be shaped, so that it can be more freely applied by and around the wound. For example, the active agent material may be provided as a gel prepolymer solution so that it can be applied by a clinician close to or around a wound having an irregular shape and size. In some embodiments, the active agent material, such as a gel prepolymer solution, may be provided in a syringe and / or applied using a syringe, and the gel prepolymer solution may have a viscosity suitable for dispensing from the syringe. The active agent material may also be formulated so that it can be rapidly cured and once applied to or around the wound, it no longer flows. The active agent material may include an evaporative solvent such as isopropanol. The active agent material may have a suitable secondary curing mechanism, such as a photoinitiating acrylate functional group. In some embodiments, the active agent material may be provided as a reactive two-part system. For example, the first part and the second part may be provided to be mixed so as to result in polymer formation immediately before dispensing. In some embodiments, the first part and the second part may be oppositely charged fluid gels, whereby they interact upon mixing to provide a gel that substantially does not flow. In some embodiments, the active agent material may include a material such as a gel that changes in response to changes in the environment. For example, the active agent material may include a material such as a specific pluronic so that it can be cured when the temperature changes when applied from a dispenser or syringe to the skin. The active agent material may be applied so that it can interact with nitrite from the nitric oxide source layer 12600 (which may provide nitrite) to generate nitric oxide. Once the active agent material is applied and cured or otherwise no longer flows, the cover layer 18200 may be applied.

[0090] When the covering material 12000 is activated, for example, by arranging the activator layer 12400 in contact with the nitrogen monoxide source layer 12600, the nitrogen monoxide releasing agent from the nitrogen monoxide source layer 12600 releases nitrogen monoxide. For example, in some embodiments, nitrite can be reduced to nitrogen monoxide in the presence of the acidic environment provided by the activator layer 12400 as shown below.

Number

[0091] The activator layer 12400 and the nitrogen monoxide source layer 12600 can be positioned such that the nitrogen monoxide releasing agent reacts to provide nitrogen monoxide. For example, the activator layer 12400 and the nitrogen monoxide source layer 12600 may be in contact with each other within the covering material 12000 during use. In some embodiments, one or more additional layers can be positioned between the activator layer 12400 and the nitrogen monoxide source layer 12600. In some embodiments, the activator layer 12400 and the nitrogen monoxide source layer 12600 can be fluidly separated from each other before the covering material 12000 is applied to the patient to prevent premature release of nitrogen monoxide. For example, the nitrogen monoxide source layer 12600 can be provided in a separate package from the rest of the covering material 12000. When the covering material 12000 is activated, the nitrogen monoxide releasing agent from the nitrogen monoxide source layer 12600 can disperse within the covering material 12000. In some embodiments, the nitrogen monoxide releasing agent can be dissolved in the wound exudate, and the wound exudate can facilitate the dispersion of the nitrogen monoxide releasing agent. At least a portion of the nitrogen monoxide releasing agent will react to release nitrogen monoxide in the presence of the activator of the activator layer 12400. The generated nitrogen monoxide can diffuse into the wound or be delivered to the wound by any suitable mechanism. In some embodiments, the generated nitrogen monoxide is not delivered immediately or at all, but instead is retained within the covering material, for example, by a selectively permeable membrane, whereby the nitrogen monoxide can prevent the growth of microorganisms within the covering material or kill the microorganisms.

[0092] In some embodiments, the wound dressing 12000 may include a reducing agent that facilitates the reduction of a nitric oxide releasing agent (e.g., nitrite ions) to nitric oxide. Physiologically acceptable examples of such reducing agents include, but are not limited to, iodide anions, ascorbic acid, ascorbic acid (e.g., sodium ascorbate), isoascorbic acid (e.g., sodium isoascorbate), hydroquinone, butylquinone, and tocopherol. The reducing agent may be included in one or more layers of the wound dressing 12000. For example, the reducing agent may be included in the cover layer 12200, the activator layer 12400, the nitric oxide source layer 12600, the wound contact layer 12800, and / or any suitable layer of the nitric oxide generating wound dressing described herein. The reducing agent may be incorporated into one or more layers by, for example, physical confinement, physical mixing, coating, covalent bonding, or any other suitable method. The reducing agent may be incorporated into the dressing within a suitable layer, such as a hydrogel activation layer, at about 0.01 - 5.0%, 0.1 - 4.5%, 1.0 - 3.0%, 1.0 - 1.5%, and / or 1.5 - 2.5% w / w. For example, the w / w% may be about 0.03%, 1.2%, 1.4%, or 2.43%. Higher levels of the reducing agent may lead to an increase in nitric oxide production, but very high levels of the reducing agent may be toxic.

[0093] As described herein, the nitric oxide source layer may include nitrite and may be referred to herein as a nitrite delivery layer or a nitrite providing layer. As described herein, the activator layer may include an acid and may be referred to herein as an acid providing layer or an acid delivery layer. The nitric oxide source layer / nitrite delivery layer / nitrite providing layer and the activator layer / acid providing layer may be collectively or individually referred to herein as the nitric oxide generating layer.

[0094] Nitric Oxide Dressing Materials and Structures As will be understood by those skilled in the art, the materials and coating constructs described above in connection with the nitric oxide delivery coating 1200 of FIGS. 4 and 5, and elsewhere in this specification, can include a plurality of suitable constructs and different types of materials. For example, the top layer furthest from the wound can be a top or cover film layer, such as a top or cover layer disclosed herein, such as a polyurethane material. Such a top or cover film can be constructed from the material used for the cover layer of the RENASYS drape, sold by Smith+Nephew. Under the top or cover film layer can be a masking or cloth layer, which can be constructed from any suitable material disclosed herein as a masking or cloth layer. The masking layer can be constructed from stretchable and non-stretchable polyesters, polyethylene, polypropylene, polypropylethylene, and non-woven fabrics, and suitable mixtures thereof. Further suitable non-woven fabrics and mixtures can also be utilized. In certain embodiments, the masking layer can be a foam. Under the masking layer or cloth layer is an activator layer similar to the activator layers described throughout this specification and this entire document. Such an activator layer can be constructed from a hydrogel adhesive, optionally containing a central polyester support mesh and / or a support release liner. The activator layer can be constructed from any suitable hydrogel material disclosed herein, such as acrylic acid hydrogel and / or sulfonic acid hydrogel. Under the activator layer can be a water-absorbing dispersion layer, which can be constructed from any suitable water-absorbing dispersion layer material disclosed herein, such as in connection with FIG. 2. For example, the water-absorbing dispersion layer can be constructed from a 3D knit woven in a net form, gauze, and / or stretchable polyester fibers, similar to the material used in Acticoat Flex by Smith+Nephew, although silver is optional. In some embodiments, the water-absorbing dispersion layer can be constructed from a prepolymer solution having a mixture of water, surfactant, and polyethylene glycol, such as the foam used in the Allevyn foam by Smith+Nephew. The masking layer and the water-absorbing dispersion layer can use the same material and can be interchangeable.In certain embodiments, the water-absorbing dispersion layer can be pushed into and / or cured within the activator layer. Curing the water-absorbing dispersion layer within the activator layer can improve the rate of nitric oxide formation due to more rapid transport. Beneath the water-absorbing dispersion layer, there can be a contact layer constructed from any suitable material disclosed herein, such as in relation to FIG. 2. For example, the wound contact layer can include a silicone adhesive and a perforated polyurethane film. The wound contact layer can include an acrylic adhesive. A nitric oxide source layer, such as a nitrite layer constructed from any suitable material disclosed herein, can be positioned beneath the wound contact layer such that the nitric oxide source layer is direct with respect to the wound or other tissue. In some embodiments, the nitric oxide source layer can be in other locations, such as above the activator layer and / or elsewhere within the coating. In certain embodiments, the ALLEVYN or PICO coating disclosed in FIGS. 2 and 3 can be placed directly over the activator layer and the underlying nitric oxide source layer. Placing the nitric oxide source layer directly against the wound, the area surrounding the wound, and / or other tissue can allow for an increase in the direct release of nitric oxide into the tissue.

[0095] Chemiluminescence Figure 6 shows an exemplary configuration 600 for a chemiluminescence protocol for testing a nitric oxide delivery coating material, such as those disclosed above in connection with FIGS. 4 and 5. The protocol can include a sample 602, a desiccant 604, an air source 606, a chemiluminescence detector 608, a nitrogen supply 610, an air pump 612, a mass flow meter 614, and a T-piece connector 616. In certain embodiments, a ThermoFisher 42i-HL detector can be used as the chemiluminescence detector 608. After warming the device using an air flow at atmospheric pressure, the sample box 602 and the nitrogen supply can be connected to the device. The nitrogen flow through the mass flow controller can be set to a suitable value, such as about 1-100, 10-90, 25-75, 40-60, or about 50 mL / min. After flushing the system (e.g., for about 1-60, 10-50, 20-40, or about 30 minutes), a nitric oxide source layer (such as a nitrate mesh) and an activator layer (such as an acid-providing hydrogel) can be placed within the sample chamber 602. In an embodiment, the nitrate mesh has a smaller total area than the activator layer. In certain embodiments, the nitric oxide source layer and / or the activator layer can have a length and / or width of about 0.5-20, 1-10, 2-8, or about 4-6 centimeters. In certain embodiments, the nitric oxide source layer can be 2.5 cm × 2.5 cm, while the activator layer can be 3 cm × 3 cm.

[0096] NO / NO 2 The release concentration can be measured at an appropriate rate by the chemiluminescence detector, checking the concentration in ppb or ppm units, and monitoring periodically, such as every about 1, 2, 5, 10, 30, 60, or 90 seconds. In certain embodiments, NO / NO 2 concentration can be checked in ppm units.

[0097] As will be understood by those skilled in the art, for the coatings disclosed herein, such as the coatings described in connection with FIGS. 4 and 5, maximizing NO beyond 2 NO is desirable. Nitrogen dioxide (NO 2 ) can exhibit antibacterial properties, but NO 2does not have the vasodilatory properties or the ability of NO to activate cell proliferation. Therefore, it is recommended to reduce NO as much as possible in the acidification of nitrite, such as by removing oxygen from the body of the hydrogel in which the acidification of nitrite occurs, thereby reducing the oxidation of dissolved nitric oxide (NO). 2 It is generally desirable to reduce the occurrence of NO and NO. 2 In some embodiments, the nitric oxide coatings disclosed herein can produce both NO / NO in a ratio of about 0.5:1 to 500:1, 1:1 to 400:1, 10:1 to 300:1, 20:1 to 200:1, 50:1 to 100:1, etc. 2 NO and NO in the ratio 2 For example, the ratio can be about or at least about 0.5:1, 1.01:1, 1.1:1, 1:1, 2:1, 5:1, 10:1, 20:1, 30:1, 50:1, 100:1, 200:1, or 500:1.

[0098] Figures 7A-7B show an example of experimental configuration 700 and subsequent results 750 demonstrating nitric oxide delivery from a combination of an activator layer and a nitric oxide source layer while under negative pressure, similar to the dressing described in connection with FIGS. 4 and 5. As shown in FIG. 7A, a negative pressure wound therapy pump 702 is connected to a negative pressure wound therapy dressing 704, such as those described herein in FIGS. 2A-2D. The dressing is sealed over a chamber 706 containing a nitrite test solution 708 that changes color in the presence of NO. FIG. 7B shows an example of the results of the negative pressure nitric oxide experiment shown in FIG. 7A. Prior to applying negative pressure, the test solution did not change color (750). After running negative pressure for a period to ensure no change in background color as shown at 760, an activator layer 710 (such as an acid-providing hydrogel) as described herein was placed in the chamber and negative pressure was applied. Again, no color change occurred (770). Finally, a nitric oxide source layer 712 (such as a sodium nitrite mesh) as described herein was placed on top of the activator layer 780 without contacting the nitric oxide source layer to the nitrite test solution, and negative pressure was applied. After 15 minutes of negative pressure, the indicator solution changed color (790), thereby demonstrating that the interaction between the activator layer and the nitric oxide layer can produce nitric oxide even under negative pressure.

[0099] As will be understood by those skilled in the art, negative pressure can be applied to any of the nitric oxide delivery dressings disclosed herein, such as the dressings described in FIGS. 4 and 5 and elsewhere in this specification. Dressings such as those described in FIGS. 2A-2D can be placed over an activator layer and a nitric oxide source layer disposed within a wound, thereby delivering nitric oxide to the wound while simultaneously applying negative pressure wound therapy.

[0100] Figures 8A - 8C show examples of the execution of chemiluminescence experiments using the same protocol as described above. As will be understood by those skilled in the art, these measured values obtained in these experiment executions are merely illustrative, and the disclosure herein is not limited to such values. Figure 8A shows the experimental results when testing a dry sodium nitrite mesh with the arrangement shown in Figure 8A, which includes a polyurethane cover layer overlapping on a stretchable polyester ADL layer positioned on a hydrogel activator layer sandwiched between another stretchable polyester ADL layer on a dry sodium nitrate mesh. In this experiment execution, after DI water was added, the dry sodium nitrite mesh released NO at about 550 ppm and NO 2 at about 75 ppm at its peak at the 25 - minute mark, and gradually decreased in concentration to about 80 ppm of NO and 10 ppm of NO 2 at the 50 - minute mark.

[0101] Figure 8B shows the experimental results when testing a full - coating design using a pull - out tab and a self - sealing boundary. The pull - out tab is initially used to separate the nitric oxide source layer from the activator layer. Therefore, when the tab is removed and the coating becomes wet, the interaction between the nitric oxide source layer and the activator layer generates nitric oxide. In this experiment execution, after DI water was added, the full - coating design with a pull - out tab and a self - sealing boundary released NO at about 84 ppm and NO 2 at about 15 ppm at its peak at the 17 - minute mark, and gradually decreased in concentration to about 25 ppm of NO and 5 ppm of NO 2 at the 50 - minute mark.

[0102] Figure 8C shows an example of the experimental results for a coating containing a degradable film. Here, the degradable film is placed between the activator layer and the nitric oxide source layer, such that once the degradable layer decomposes, nitric oxide is generated. In this experiment execution, after DI water was added, the coating containing the degradable film released NO at about 1000 ppm and NO 2 at about 45 ppm at its peak at the 25 - minute mark, and gradually decreased in concentration to about 225 ppm of NO and 20 ppm of NO 2The concentration gradually decreased. The experimental protocol was also used to test the activator layer containing sodium isoascorbate. In this experimental run, after DI water was added, the activator layer containing sodium isoascorbate released approximately 52 ppm of NO and 4 ppm of NO 2 at its first peak at the 80-minute mark, and 66 ppm of NO and 5 ppm of NO 2 at its second and maximum peak at the 110-minute mark, and gradually decreased to approximately 45 ppm of NO and 2 ppm of NO 2 at the 160-minute mark.

[0103] Figure 9 shows an example of the relative peak output in ppm for an activator hydrogel (acid-providing) with or without a water-absorbing dispersion layer, including polypropylene, polypropylethylene, or stretch polyester water-absorbing dispersion layers having various gsm (g / m 2 ). In the absence of a water-absorbing dispersion layer, the peak NO and NO 2 concentrations were approximately 55 ppm and 10 ppm, respectively. Those skilled in the art will understand that the water-absorbing dispersion layer can enable improved fluid dispersion and handling throughout a larger area such as a coating material. According to a 17 gsm polypropylene pressed water-absorbing dispersion layer, the peak NO and NO 2 concentrations were approximately 20 ppm and 2 ppm, respectively. According to a 17 gsm polypropylene cured water-absorbing dispersion layer, the peak NO and NO 2 concentrations were approximately 40 ppm and 5 ppm, respectively. As explained above, curing the water-absorbing dispersion layer can enable an increase in fluid transport and an improvement in the rate of nitric oxide formation. According to a 30 g / m 2 polypropylene pressed water-absorbing dispersion layer, the peak NO and NO 2 concentrations were approximately 40 ppm and 5 ppm, respectively. According to a 30 g / m 2 polypropylene water-absorbing dispersion layer, the peak NO and NO 2 concentrations were approximately 40 ppm and 5 ppm, respectively. According to a 40 g / m 2 polypropylene pressed water-absorbing dispersion layer, the peak NO and NO 2The concentrations were approximately 30 ppm and 2 ppm, respectively. 40 g / m of polypropylene 2 In the cured water-absorbing dispersion layer of, peak NO and NO 2 The concentrations were approximately 38 ppm and 5 ppm, respectively. 30 g / m of polypropylene ethylene 2 According to the pressing water-absorbing dispersion layer of, peak NO and NO 2 The concentrations were approximately 35 ppm and 3 ppm, respectively. 30 g / m of polypropylene ethylene 2 In the cured water-absorbing dispersion layer of, peak NO and NO 2 The concentrations were approximately 35 ppm and 3 ppm, respectively. According to the stretchable polyester pressing water-absorbing dispersion layer, peak NO and NO 2 The concentrations were approximately 35 ppm and 3 ppm, respectively. According to the FLEX pressing water-absorbing dispersion layer, peak NO and NO 2 The concentrations were approximately 55 ppm and 8 ppm, respectively.

[0104] Figures 10A to 10D show examples of the concentrations of NO and NO over time for several embodiments incorporating an activator layer and a nitric oxide providing layer 2 As shown in Figures 10A to 10B, activator layers containing approximately 2 - 3% sodium isoascorbate were tested with or without different water-absorbing dispersion layers that were pressed or cured. Gels without a water-absorbing dispersion layer produced pNO = 785 ppm and pNO2 = 78 ppm (p indicates peak). An activator layer with stretchable polyester pressed into the gel produced pNO = 506 ppm and pNO2 = 24 ppm. For stretchable polyester cured on the activator layer, pNO = 625 ppm and pNO2 = 50 ppm. For polypropylene pressed into the gel, pNO = 508 ppm and pNO2 = 26 ppm. For polypropylene cured in the gel, pNO = 624 ppm and pNO2 = 26 ppm.

[0105] Figures 10C and 10D show the NO and NO over time for activator layers containing approximately 1 - 2% sodium isoascorbate with or without different water-absorbing dispersion layers that were pressed or cured2 Examples of the concentrations are shown. The activator layer without ADL produced pNO = 334 ppm and pNO2 = 40 ppm. For the stretchable polyester water-absorbing dispersion layer pressed into the activator layer, it was pNO = 211 ppm and pNO2 = 10 ppm. For the stretchable polyester water-absorbing dispersion layer cured in the activator layer, it was pNO = 247 ppm and pNO2 = 14 ppm. For the polypropylene water-absorbing dispersion layer pressed into the activator layer, it was pNO = 112 ppm and pNO2 = 5 ppm. For the polypropylene water-absorbing dispersion layer cured in the activator layer, it was pNO = 184 ppm and pNO2 = 8 ppm. As described elsewhere herein, curing the water-absorbing dispersion layer in the activator layer can improve fluid treatment and nitric oxide generation compared to nitrogen dioxide generation.

[0106] Xerogel and hydrogel constructs In this specification, reference may be made to xerogels. Xerogels can be formed from gels by drying in an unhindered state of contraction. As will be understood by those skilled in the art, a xerogel is a gel that has a very low water content, a water content so low that the minimal reaction to form nitric oxide occurs without the addition of further water and / or liquid. For example, a xerogel may be substantially free of water in the dry state. Drying can be accomplished by any suitable means known in the art.

[0107] In certain examples, a hydrogel (which can become a xerogel after drying) can be generated with or without glycerol and can contain, if desired, a standard amount, or twice, three times, four times the required amount of the crosslinking agent PEG diacrylate. A sodium 2-acrylamido-2-methyl-1-propanesulfonate solution can be present in the xerogel. The hydrogel and xerogel can be prepared by dissolving the supplied MEHQ-stabilized acrylamido-2-methyl-1-propanesulfonic acid (SA) in water to convert it to the sodium salt and then neutralizing it to pH 7.0 with 50% NaOH while cooling from a 10 °C water bath to form a solution of the neutralized acid (NaAMPS). The hydrogel prepolymer can be prepared by pre-dispersing a 2-hydroxy-2-methylpropiophenone photoinitiator in PEG diacrylate with minimal light and then mixing it with a 58% aqueous solution of sodium 2-acrylamido-2-methyl-1-propanesulfonate (NaAMPS), a mixture of sodium isoascorbate, pre-ground acrylamido-2-methyl-1-propanesulfonic acid (AMPS acid) and glycerol for 10 - 20 minutes. The AMPS acid can be completely dissolved in the stirred NaAMPS solution before gradually adding glycerol, and then the photoinitiator / diacrylate mixture can be completely dissolved in a water bath. In certain embodiments, the hydrogel can also be prepared using twice the normal amount of photoinitiator / crosslinking agent and / or omission of glycerol and / or using three times the amount of prepolymer mixture in a mold to form a gel three times as thick.

[0108] Nitric oxide generating coating material using dry sodium nitrite Figures 11A - 11D illustrate embodiments of a nitric oxide generating wound dressing having various layer arrangements. Those skilled in the art will understand that the various layers illustrated in Figures 11A - 11D may be ordered in any suitable order, and the order illustrated in the figures is merely exemplary. In some embodiments, the top layer may be a cover layer 13002 having any of the same characteristics, materials, or other details of the cover layers disclosed herein, such as being constructed from a film. The cover layer 13002 may be suitable for sealing the dressing over the wound, for connecting to a negative pressure source, and / or for maintaining negative pressure at the wound site. In certain embodiments, the border region of the cover layer 13002 may be attached to the skin surrounding the wound to form a seal such that wound exudate can be contained within the wound dressing 13000. Beneath the cover layer, there may be a masking or concealment layer 13004 (referred to herein as the "masking layer") to prevent or limit visualization of the wound or wound exudate through the cover layer 13002. The masking layer 13004 may be positioned beneath at least a portion of the cover layer 13002. In some embodiments, the masking layer 13004 may have any of the same characteristics, materials, or other details of other embodiments of the masking layers disclosed herein, including but not limited to having any visual windows or apertures. Examples of wound dressings having a concealment layer and visual windows are described in International Patent Publications WO2013 / 007973 and WO2014 / 020440, which are hereby incorporated by reference in their entirety. Additionally, the masking layer 13004 may be positioned adjacent to the cover layer or adjacent to any other dressing layer as desired. In the illustrated embodiment, the masking layer 13004 is positioned between the cover layer 13002 and the acid providing layer 13006. As described elsewhere herein and as understood by those skilled in the art, the active agent layer may be an acid providing layer or other suitable layer. In certain embodiments, the masking layer 13004 may be adhered to or integrally formed with the cover layer 13002. The masking layer 13004 may have substantially the same size and shape as the active agent layer 13006 and may be configured to overlay it.The masking layer 13004 may have an area smaller than that of the cover layer 13002. In certain embodiments, the masking layer 13004 can draw fluid horizontally and, similarly, can function as a moisture-absorbing dispersion layer.

[0109] In certain embodiments, the activator layer 13006 can have any of the same characteristics, materials, or other details of any of the other embodiments of the activator layer disclosed herein. For example, the activator layer 13006 can be an adhesive and can be constructed from a hydrogel or xerogel configured to have a plurality of acidic groups or acidic moieties that can provide protons in an aqueous environment. As described elsewhere herein, under such acidic conditions, nitrite ions from the nitric oxide source layer 13010 can be reduced to nitric oxide for delivery to wounded or intact skin. As described elsewhere herein and as will be understood by those skilled in the art, the activator layer can be a nitrite-providing layer or other suitable layer. The activator layer 13006 (e.g., a hydrogel layer) can include a plurality of perforations that extend through the thickness of the activator layer, as described elsewhere herein. The plurality of perforations can allow or facilitate the passage of wound exudate through the activator layer such that wound exudate below the activator layer 13004 can be transported to one or more additional absorption layers and / or evaporation layer(s) (e.g., the cover layer) above the activator layer, thereby preventing excessive accumulation of wound exudate below the activator layer 13004. Additionally, the plurality of perforations can provide an increased surface area of the activator layer, thereby increasing the absorption rate of the activator layer.

[0110] As shown in FIG. 11A, in an embodiment, the moisture-absorbing dispersion layer 13008 can be disposed between the active agent layer 13006 and the nitrite-providing layer 13010. In certain embodiments, the moisture-absorbing dispersion layer 13008 can be constructed to preferably draw fluid, such as wound exudate, horizontally when it is absorbed through the layers of the covering material 13000. Such lateral draw of the fluid can allow for maximum dispersion of the fluid through the active agent layer 13006, enabling the active agent layer 13006 to reach its full holding capacity. Further, since nitrite ions dissolved in the liquid can spread faster across the surface of the active agent layer 13006, the moisture-absorbing dispersion layer 13008 can facilitate the production of nitric oxide. Some embodiments of the moisture-absorbing dispersion layer 13008 can include viscose, polyester, polypropylene, cellulose, or a combination of some or all of these, and the material can be needle-punched. Some embodiments of the moisture-absorbing dispersion layer 13008 can include cellulose in the range of 40 to 160 gsm (or about 40 to about 160 gsm), for example, 80 (or about 80) gsm. Some embodiments of the moisture-absorbing dispersion layer 14800 can include polyethylene within the range of 40 to 150 grams per square meter (gsm). In some embodiments, the moisture-absorbing dispersion layer 13008 may have a thickness of 1.2 mm or about 1.2 mm, or may have a thickness in the range of about 0.5 mm to 3.0 mm, about 0.5 mm to about 3.0 mm, 0.7 mm to 2.5 mm, 0.9 mm to 2.1 mm, or 1.1 mm to 1.5 mm. In certain embodiments, the moisture-absorbing dispersion layer 13008 can be constructed from a material that withstands compression at levels of negative pressure commonly applied during negative pressure therapy.

[0111] The water-absorbent dispersion layer 13004 may include a plurality of loosely wrapped fibers that can be disposed within a substantially horizontal fibrous network. In some embodiments, the water-absorbent dispersion layer 13004 may consist of a mixture of two fiber types. One may be flat fibers that can have a width of 20 μm to 50 μm, or about 20 μm to about 50 μm, and may include a cellulosic material. The other fibers may be bicomponent fibers having a core with a diameter of 8 μm to 10 μm, about 8 μm to about 10 μm, 7 μm to 11 μm, 6 μm to 12 μm, or 5 μm to 13 μm, and an outer layer with a thickness of 1 μm to 2 μm, about 1 μm to about 2 μm, 1 μm to 2.3 μm, 0.8 μm to 2.5 μm, or 0.5 μm to 3 μm. The bicomponent fibers may be a mixture of a polyethylene (PE) type material and polyethylene terephthalate (PET). In some embodiments, the core of the bicomponent fiber may be PET, and the outer layer may be PE. The PE / PET fibers may have a smooth surface morphology, while the cellulose fibers may have a relatively rough surface morphology. In some embodiments, the ADL material may include about 60% to about 90% cellulose fibers, for example, approximately 75% cellulose fibers, and about 10% to about 40% PE / PET fibers, for example, about 25% PE / PET fibers. In some embodiments, the water-absorbent dispersion layer 13004 may include split microfibers.

[0112] Most of the fiber volume can extend horizontally (i.e., parallel to the planes of the top and bottom surfaces of the material), or substantially or approximately horizontally. In another embodiment, 80% to 90% (or about 80% to about 90%) or more of the fiber volume can extend horizontally, or substantially or approximately horizontally. In another embodiment, all or substantially all of the fiber volume can extend horizontally, or substantially or approximately horizontally. In some embodiments, most of the fibers, 80% to 90% (or about 80% to about 90%) or more, or even all or substantially all of the fibers span a distance (horizontal or lateral distance) perpendicular to the thickness of the water-absorbing and dispersing layer 13004 that is greater than the thickness of the water-absorbing and dispersing layer 13004. In some embodiments, the horizontal or lateral distance spanned by such fibers is 2 times (or about 2 times) or more, 3 times (or about 3 times) or more, 4 times (or about 4 times) or more, 5 times (or about 5 times) or more, or 10 times (or about 10 times) or more the thickness of the water-absorbing and dispersing layer 13004. Such fiber orientation can facilitate the lateral uptake of fluid through the water-absorbing and dispersing layer 113004. This can more evenly disperse fluids such as wound exudate throughout the water-absorbing and dispersing layer 13004. In some embodiments, the ratio of the amount of fluid taken up laterally across the water-absorbing and dispersing layer 13004 to the amount of fluid taken up vertically through the water-absorbing and dispersing layer 13004 under negative pressure can be 2:1 or more, or about 2:1 or more, or in some embodiments, up to 10:1 or more, or about 10:1 or more.

[0113] Continuing with FIG. 11A, in embodiments, the nitric oxide source layer 13010 can be provided under the water-absorbing dispersion layer 13004. Such a nitric oxide source layer 13010 can have any of the same features, materials, or other details of any of the other embodiments of the nitric oxide source layers disclosed herein. For example, the nitric oxide source layer 13010 can be a nitrite-providing layer. For example, the nitric oxide source layer can be a wet mesh impregnated with a sodium nitrite solution. In some embodiments, the nitric oxide source layer 13010 can be dry and can include a dry nitrate source such as dry sodium nitrite. Such dry sodium nitrite can be loaded into a material layer, which is constructed from a suitable material such as any of the materials disclosed herein. As will be understood by those skilled in the art, dry materials and / or substances do not contain or relatively contain liquids. For example, polypropylene, polyethylene, or melt-extrudable fibers can be suitable materials for such layers. In embodiments, such a nitric oxide source layer 13010 layer may need to be first separated from the activator layer 13006 when the activator layer is a hydrogel in order to avoid reactions and nitric oxide generation prior to application to the wound and / or skin. As illustrated in FIG. 14A, the dry fluid-absorbing layer 13008 can serve to separate the nitric oxide source layer 13010 and the hydrogel activator layer 13004 prior to application. However, such a dry sodium nitrite-providing layer can be adjacent to the xerogel activator layer 13006 since the xerogel will not become wet. In the case of xerogel, activation can occur upon contact with a fluid such as wound exudate when the wound exudate is drawn through the dressing. In the case of hydrogel, when a fluid such as wound exudate contacts the water-absorbing dispersion layer 13008, nitrite ions can then contact the acidic environment created by the activator layer, thereby generating nitric oxide that can then migrate into the wound and / or skin. In some embodiments, each of the layers, such as the nitric oxide source layer, the activator layer, and any other suitable layers, can be stored dry prior to use. Prior to application to the skin or wound, the layers can be moistened with a suitable liquid such as physiological saline.

[0114] As shown in FIG. 11B, to maintain nitric oxide release, there may be several layers containing dry sodium nitrite, such as a first nitric oxide source layer 13010 and a second nitric oxide source layer 13012 that will be "activated" when wound fluid reaches the layer and wets it. The sodium nitrite can contact the acidic groups of the hydrogel or xerogel of the activator layer 13006, thereby generating nitric oxide. In certain embodiments, there may be 2, 3, 4, 5, 6 or more layers containing dry sodium nitrite. As shown in FIG. 14B, the masking layer 13004 can serve to prevent contact between the second nitric oxide source layer 13012 and the activator layer 13004. In certain embodiments, additional moisture-absorbing and / or masking layers can be sandwiched by the activator layer to provide additional nitric oxide sources.

[0115] As shown in FIGS. 11C and 11D, in an embodiment, the activator layer 13006 can be positioned under the nitric oxide source layer, thereby depending on the coating material that wets (from wound exudate) and activates the nitrite-providing layer 13010.

[0116] FIG. 12 illustrates one embodiment of a wound dressing 14000 similar to the dressings of FIGS. 4, 5, and 11A-11D. However, here, a nitric oxide source layer 14002, such as those disclosed herein, can be attached to the dressing 14000 by a tether 14004 such that the nitric oxide source component or layer 14002 (hereinafter, "layer") can be kept separate from an activator layer 14006, such as those disclosed herein. In certain embodiments, the tether can be constructed from any suitable material, such as a screw. The nitric oxide source layer (dry or wet) can be kept separate from the remainder of the dressing on a foldable tether 14004, such that the nitric oxide source layer can be folded into a position under the dressing when the dressing is applied to a wound and / or skin and needs to be activated to deliver nitric oxide (as shown in FIG. 12). In some embodiments, a moisture-absorbing dispersion layer 14008, such as those disclosed herein, can be disposed under the activator layer 14006. However, one of ordinary skill in the art will understand that such a moisture-absorbing dispersion layer 14008 can be optional and that the nitric oxide source layer 14002 can be disposed in direct contact with the activator layer. In certain embodiments, the nitric oxide source layer 14002 may need to be packaged in a separate pouch so that it cannot contact the remainder of the dressing before activation is required. Also, as will be understood by one of ordinary skill in the art, such a dressing 14000 can include a cover layer 14010, such as those disclosed herein, to seal the dressing. In certain embodiments, the nitric oxide source can be directly tethered to a standard wound dressing, such as those disclosed herein. Such a nitric oxide source can be folded under a standard wound dressing such that nitric oxide is delivered to the wound and / or uninjured tissue.

[0117] Figures 13A - 13F illustrate embodiments of a wound dressing 15000 similar to the dressings of FIGS. 4, 5, and 11A - 11D, including a cover layer 15002 as disclosed herein, an active agent layer 15004 as disclosed herein, and a nitric oxide source layer 15008 as disclosed herein. In certain embodiments, the separation layer 15006 can be positioned between the nitric oxide source layer 15008 and the active agent layer 15004, thereby preventing contact between the nitric oxide source layer 15008 and the active agent layer 15004 while the separation layer 15004 is in place. The separation layer 15004 can be constructed from any suitable material disclosed herein, such as a film, that can prevent interaction between the active agent layer 15004 and the nitric oxide source layer 15008. When the separation layer 15006 is removed, the active agent layer and the nitric oxide source layer can then contact each other, thereby generating nitric oxide as described elsewhere herein. One of ordinary skill in the art will understand that such an arrangement can be similar to a removable tab of an electronic or battery-operated device.

[0118] One of ordinary skill in the art will understand that the separation layers, such as those described above in connection with FIGS. 13A - 13F, and any separation layer described herein, can be varied in a variety of suitable ways to allow for interaction between the nitric oxide source layer and the activator layer, in addition to simply being removed. For example, the separation layer can generally be biodegradable and / or degradable such that when the separation layer is degraded, the activator layer and the nitric oxide layer can interact. The separation layer can be disrupted via interaction with an acid or an enzyme. The separation layer can be a temperature - reversing gel such that it melts more, thereby allowing for interaction between the activator layer and the nitric oxide source layer. The separation layer can be soluble such that the layer dissolves upon interaction with wound exudate. In certain embodiments, the separation layer can be bioabsorbable. The separation layer can be inactivated in a suitable manner such that the activator layer and the nitric oxide layer can interact. The separation layer can be thermally decomposed / melted. Finally, one of ordinary skill in the art will understand that the separation layer can be removed in any suitable manner, such as in part or in whole at once. Further, one of ordinary skill in the art will understand that such a separation layer can incorporate some of all of these options into a single separation layer, for example, the separation layer can be partially removable by mechanical means but also be degradable.

[0119] In certain embodiments, the dressing can be in the form of a sheath having an adhesive wound - contact layer, such as those disclosed herein, and a cover layer having one edge with a pull tab that extends outside of the dressing. Inside the sheath, a nitric oxide source layer (such as sodium nitrite) can be adhered to the wound - contact layer, covered by a pull tab having an activator layer on top of a film layer. In use, the pull tab can be removed and the sheath adheres to the wound and / or skin surface using a sealing strip to cover the location where the pull tab was removed. When the pull tab is removed, then the activator layer and the nitric oxide source layer can interact, thereby generating nitric oxide for delivery to the wound and / or skin.

[0120] In some embodiments, the nitric oxide generation reaction can be pressure-activated through the use of a capsule configuration. For example, a nitric oxide source (such as those disclosed herein) can be encapsulated by a separation layer that prevents interaction between the nitric oxide supply source and an activator source (such as those disclosed herein) and can be disposed within an activator source such as a hydrogel. Applying pressure to the combination can cause the capsules to rupture and, therefore, initiate the generation of nitric oxide. In certain embodiments, the activator source can be encapsulated and surrounded by the nitric oxide source. Alternatively, the capsule material can be degraded by a fluid such as wound exudate, and such degradable materials can degrade rapidly or slowly on an appropriate time scale. When the capsules are sufficiently degraded, the nitric oxide source and the activator source can then interact to generate nitric oxide. One of ordinary skill in the art will understand that such an approach can be applied to a plurality of configurations within a wound dressing material, such as a nitric oxide supply or activator material, an area (s) surrounded by walls of multiple capsules / beads, or other suitable configurations.

[0121] FIG. 13B illustrates an embodiment of a wound dressing 15100 similar to the dressing 15101 after removal of the covering material 15000 and the separation layer 15106 of FIG. 13A. The wound dressings 15100, 15101 include a top film or cover layer 1502 over the top of the dressing, similar to the cover layers disclosed herein. A wound contact layer 15110, similar to other wound contact layers disclosed herein, may be positioned under the dressing and may include a handle (not shown) that can be removed prior to placement of the dressing. Similar to the cover layers disclosed herein, the underside of the cover layer may be covered with a pattern spread pressure sensitive adhesive or any suitable adhesive disclosed herein. The pattern spread adhesive allows for breathability even after the separation layer 15106 has been removed as in 15101. In certain embodiments, the separation layer 15106 may be positioned between a nitric oxide source layer 15108 and an activator layer 15104, thereby preventing contact between the nitric oxide source layer 15108 and the activator layer 15104 while the separation layer 15004 is in place. The activator layer 15104 may be further surrounded by a stretchable polyester wrap 15103, such as described elsewhere herein. The separation layer 15106 may be constructed from any suitable material disclosed herein, such as a film, that can prevent interaction between the activator layer 15104 and the nitric oxide source layer 15108. In certain embodiments, the separation layer may be folded once, twice, three times, four times, or more. The separation layer also includes a tab 15107 that can be pulled to remove the separation layer. Above the separation layer may be an upper frame layer 15112, which may be a film material, such as the materials used for the cover layers disclosed herein, and may include adhesive only on the upper side, such that the adhesive is not adhered to the top of the separation layer 15106, allowing the separation layer to be removed more easily. The upper frame 15114 further provides a window 15116 to allow interaction between the activator layer 15104 and the nitric oxide source layer 15108. The lower frame 15114 may have adhesive only on the bottom surface, thereby presenting a non-adhesive upper surface to the separation layer 15106 and allowing for ease of removal of the separation layer.The lower frame 15114 may also include a window 15116 to enable interaction between the activator layer 15104 and the nitric oxide source layer 15108 after removal of the separation layer. When the separation layer 15106 is removed, the activator layer and the nitric oxide source layer may then contact as shown at 15101, thereby generating nitric oxide as described elsewhere herein. Also, when the separation film is removed, the top film or cover layer 15102 then seals the coating material as shown at 15101 (15118). One of ordinary skill in the art will understand that such an arrangement may be similar to a removable tab of an electronic or battery-operated device. The embodiment of FIG. 13B was used to generate the exemplary data in FIG. 8B above.

[0122] FIG. 13C is an enlarged version of the coating material 5100 of FIG. 13B showing the positioning of adhesives 15118, 15120 to facilitate removal of the folded separation layer 5106. FIG. 13D shows a top view of the coating material of FIGS. 13B and 13C showing the separation layer 15106, cover film 15102, and upper frame 15112.

[0123] FIG. 13E illustrates embodiments of wound dressing materials 15200, 15201 similar to the dressing material 15100 of FIGS. 15B - 15D. Here, the nitric oxide source layer 5208 (which may be a dry sodium nitrate mesh or sodium nitrate powder) may be included in a layer of one, two, three, four, or more water-soluble films having a gap 15212 thereunder beneath the wound contact layer 15210 and may be surrounded by a water-soluble film outer skin 5214 (such as a polyvinyl alcohol film or any suitable material disclosed herein). In certain embodiments, the water-soluble film outer skin may be sealed with a cover layer film. In some embodiments, the gap is about 0.1 - 5, 0.5 - 3, 1 - 2, or 1 cm 2It may have an area. When the fluid enters the coating material, the water-soluble material dissolves and can optionally pass through the gap, thereby enabling the nitric oxide layer to interact with the activator layer 15204. As shown in 15201, the water-soluble film 15216 can be a layer that separates the activator layer from the nitric oxide source layer. When the fluid enters the coating material, the film layer can dissolve, thereby enabling the activator layer to interact with the nitric oxide source layer to generate nitric oxide. The embodiment of FIG. 13E was used to generate the exemplary data of FIG. 8C shown above.

[0124] FIG. 13F illustrates an embodiment of a wound dressing 15300 similar to the dressings of FIGS. 13B - 13D. Here, a nitric oxide source (such as a sodium nitrate solution) 15308 can be encapsulated in a bubble wrap structure. Manual pressure on the bubble wrap (such as by pressing with a finger or a suitable tool) ruptures the bubbles, releasing the nitric oxide source, thereby enabling the nitric oxide source to interact with the activator layer 15304 to release nitric oxide.

[0125] Hydrogel nitric oxide source layer As described in WO / 2014 / 188174, which is hereby incorporated by reference in its entirety, the dressing utilized a mesh soaked in an aqueous solution of sodium nitrite. Such a wet mesh, when placed in contact with an acid-containing hydrogel as described above, can cause the release of nitric oxide through the interaction of sodium nitrite with protons from the acid. However, precise dosage control of the sodium nitrite delivered to the hydrogel can be difficult due to potential loss of the sodium nitrite solution into the packaging containing the mesh and loss during transport to the hydrogel.

[0126] FIG. 14 illustrates a wound dressing 16000 similar to the wound dressings of FIGS. 4, 5, 11A-11D, and 12-13, where the cover layer and certain other layers are not shown. However, one of ordinary skill in the art will understand that any suitable layer disclosed herein, such as a cover layer, a wound contact layer, a masking layer, or a moisture-absorbing dispersion layer, can be incorporated into the wound dressing 16000. As will be understood by one of ordinary skill in the art, within a wound dressing such as the wound dressing 16000, nitrite administration can be controlled to generate a specific dose of nitric oxide.

[0127] In an embodiment, the wound dressing 16000 can include a hydrogel activator layer 16002 as disclosed herein adjacent to a hydrogel nitric oxide source layer 16004, where the hydrogel nitric oxide source layer includes a non-acidic or weakly acidic hydrogel containing sodium nitrite or another suitable molecule. In certain embodiments, the two hydrogels can be initially separated and held and then placed together upon application. In some embodiments, the two hydrogels can be separated by a separation layer as disclosed herein to prevent interaction between the two hydrogels. One of ordinary skill in the art will understand that by contacting the nitric oxide source hydrogel 16004 with the activator hydrogel, the concentration of sodium nitrite from the nitric oxide source hydrogel and the protons from the activator hydrogel will equalize in the two hydrogels, causing the sodium nitrite to interact with the protons of the activator hydrogel and tend to generate nitric oxide for delivery to the wound and / or skin. One of ordinary skill in the art will understand that such hydrogels can be oriented in any suitable arrangement, such as a nitric oxide source hydrogel under the activator hydrogel or an activator hydrogel under the nitric oxide source hydrogel. In some examples, the two hydrogels can be arranged side by side, or one hydrogel can be surrounded by the other.

[0128] In some embodiments, to facilitate the delivery of nitric oxide to the wound, the wound-side hydrogel or both hydrogels can be perforated with pores or other suitable structures to increase the surface area and facilitate the interaction between the two hydrogels. For example, grooves on the surface of the hydrogel that contact the other hydrogel can be used to release nitric oxide.

[0129] In certain embodiments, instead of forming the nitric oxide source hydrogel as a non-acidic hydrogel with sodium nitrite incorporated therein, powdered sodium nitrite can be evenly scattered across the surface of the non-acidic hydrogel that will interact with the activator hydrogel (such as the acid that provides the hydrogel). The high adhesiveness of the non-acidic hydrogel surface can retain the total dose when a relatively even distribution is achieved. The even distribution can avoid overloading excessive portions of the adhesive gel surface, but in embodiments, the sodium nitrite can be unevenly scattered across the surface of the non-acidic hydrogel. By controlling the available amount of sodium nitrite per unit area of the coating material, a precise dose of the released nitric oxide can be controlled. In some embodiments, controlling the available amount of sodium nitrite per unit area can ensure the desired delivery of nitric oxide at therapeutic levels to all parts of the wound. For example, sodium nitrate can be incorporated in an amount of about 0 - 100 mg / cm 2 , about 20 - 80 mg / cm 2 , 40 - 60 mg / cm 2 , or about 50 mg / cm 2 .

[0130] Coating material for multiple parts Figures 15A and 15B illustrate an embodiment of an active ingredient delivery dressing 17000 configured to deliver an active ingredient to a wound and / or the skin surface, similar to the wound dressings of FIGS. 4, 5, 11A-11D, and 12-14. Those skilled in the art will understand that the ingredient delivery device 17000 of FIGS. 15A and 15B can be configured to deliver nitric oxide to a wound and / or the skin surface, but that the embodiments of FIGS. 15A and 15B can deliver any suitable type of active ingredient and are not limited to the delivery of nitric oxide. In particular, the ingredient delivery dressing 17000 of FIGS. 15A and 15B is suitable for the delivery of active ingredients that require a reaction to facilitate the production and / or delivery of the active ingredient. For example, the active ingredient may be a molecule having a healing effect or some other positive physiological effect on the wound and / or the skin.

[0131] In an embodiment, an active ingredient platform 17002 can be configured to contact a wound and / or the skin surface. The active ingredient platform 17002 can include an adhesive frame 17004 configured to adhere the active ingredient platform 17002 to a wound and / or the skin surface and / or to another platform such as a reactive platform 17008. The adhesive frame can be constructed from any suitable material disclosed herein, such as the material from which the wound contact layer disclosed herein is constructed. The dosing portion 17006 of the active ingredient platform 17002 can be rectangular, elliptical, square, polygonal, or any suitable shape. In an embodiment, the dosing portion can include a hydrophilic material to which the active ingredient is administered. The dosing portion can be solid or liquid.

[0132] In some embodiments, the active ingredient delivery coating 17000 may include a reactive platform 17008 that may include an adhesive frame 17010 and may be constructed from any suitable material disclosed herein, such as the materials from which the cover layers disclosed herein are constructed. The reactive portion 17012 of the reactive platform 17008 may include substances such as active absorbents, such as gels, that activate the active ingredient so that it can be delivered to the wound and / or skin surface when combined with the administration portion 17006 of the active ingredient platform. The reactive portion may be solid or liquid.

[0133] As shown in FIG. 15B, in an embodiment, when delivery to a wound and / or the skin is desired, the active ingredient platform may be adhered to the wound and / or skin surface, and the reactive platform may be placed on the active ingredient platform and sealed together to facilitate the reaction between the reactive portion and the active ingredient portion and generate the active ingredient for delivery to the wound. As will be understood by those skilled in the art, in an embodiment, the active ingredient of the administration portion 17006 may not be activated for delivery to the wound until after interaction with the active portion 17012. However, in some embodiments, the administration portion 17006 may deliver a certain amount of the active ingredient prior to activation by the reactive portion.

[0134] In some embodiments, the reactive platform may be removed from the active ingredient platform, for example, by peeling, and reapplied for re-administration to the wound and / or skin without damaging the wound and / or skin. The active ingredient delivery coating may also enable a physician to access the wound area without complete removal of the coating, such as via a swabbing test and / or via the administration portion.

[0135] Layer of nitric oxide generating coating Figures 16 and 17 illustrate a wound dressing 14100 having a nitric oxide generating layer. The wound dressing 14100 may be similar to the wound dressings of FIGS. 4, 5, and 11A-13A, such as the dressing 12000. The wound dressing 14000 may include a cover layer 14200, an acid providing layer 14400, and a nitrite providing layer 14600, each of which may be similar to the cover layer 12200, the activator layer or acid providing layer 12400, and the nitric oxide source layer or nitrite providing layer 12600, respectively.

[0136] The cover layer 14200 may be similar to the cover layer 12200. The cover layer 14200 may have a length and width greater than those of the other layers 14400, 14600, 14800 such that the cover layer 14200 defines a boundary region that extends between the outer periphery of the other layers and the outer periphery of the cover layer 14200. The boundary region of the cover layer 14200 may be attached to the skin surrounding the wound to form a seal such that wound exudate can be contained within the wound dressing 14100.

[0137] In the illustrated embodiment, the wound dressing 14100 further includes a water-absorbing and dispersing layer 14800. The water-absorbing and dispersing layer 14800 can be constructed to advantageously draw fluid, such as wound exudate, horizontally as it is absorbed through the layers of the dressing 14100. Such lateral draw of the fluid can allow for maximum dispersion of the fluid through the acid-providing layer 14400, enabling the acid-providing layer 14400 to reach its full holding capacity. Further, since nitrite ions dissolved in the liquid can spread more quickly across the surface of the acid-providing layer 14400, the water-absorbing and dispersing layer 14800 can facilitate the production of nitric oxide. Some embodiments of the water-absorbing and dispersing layer 14800 can include viscose, polyester, polypropylene, cellulose, or combinations of some or all thereof, and the material can be needle-punched. Some embodiments of the water-absorbing and dispersing layer 14800 can include cellulose in the range of 3 to 200 grams per square meter (gsm) (or about 3 to about 200 gsm), 5 to 190 gsm (or about 5 to about 190 gsm), 10 to 180 gsm (or about 10 to about 180 gsm), 20 to 170 gsm (or about 20 to about 170 gsm), or 40 to 160 gsm (or about 40 to about 160 gsm), for example, 80 (or about 80) gsm. Some embodiments of the water-absorbing and dispersing layer 14800 can include polyethylene in the range of 3 to 200 gsm (or about 3 to about 200 gsm), 5 to 190 gsm (or about 5 to about 190 gsm), 10 to 180 gsm (or about 10 to about 180 gsm), 20 to 170 gsm (or about 20 to about 170 gsm), or 40 to 150 gsm. In some embodiments, the water-absorbing and dispersing layer 14800 can have a thickness of 1.2 mm or about 1.2 mm, or can have a thickness in the range of 0.1 mm to 5.0 mm, 0.5 mm to 3.0 mm, 0.7 mm to 2.5 mm, 0.9 mm to 2.1 mm, or 1.1 mm to 1.5 mm. The water-absorbing and dispersing layer 14800 can be constructed from a material that withstands compression at levels of negative pressure commonly applied during negative pressure therapy.

[0138] The water-absorbing and dispersing layer 14800 may include a plurality of loosely wrapped fibers that can be disposed within a substantially horizontal fibrous network. In some embodiments, the water-absorbing and dispersing layer 14800 may consist of a mixture of two fiber types. One may be flat fibers that can have a width of 20 μm to 50 μm, or about 20 μm to about 50 μm, and may include a cellulosic material. The other fibers may be bicomponent fibers having a core with a diameter of 8 μm to 10 μm, about 8 μm to about 10 μm, 7 μm to 11 μm, 6 μm to 12 μm, or 5 μm to 13 μm, and an outer layer with a thickness of 1 μm to 2 μm, about 1 μm to about 2 μm, 1 μm to 2.3 μm, 0.8 μm to 2.5 μm, or 0.5 μm to 3 μm. The bicomponent fibers may be a mixture of a polyethylene (PE) type material and polyethylene terephthalate (PET). In some embodiments, the core of the bicomponent fibers may be PET, and the outer layer may be PE. The PE / PET fibers may have a smooth surface morphology, while the cellulose fibers may have a relatively rough surface morphology. In some embodiments, the ADL material may include about 60% to about 90% cellulose fibers, for example, approximately 75% cellulose fibers, and about 10% to about 40% PE / PET fibers, for example, about 25% PE / PET fibers. In some embodiments, the water-absorbing and dispersing layer 14800 may include split microfibers.

[0139] Most of the fiber volume can extend horizontally (i.e., parallel to the planes of the top and bottom surfaces of the material), or substantially or approximately horizontally. In another embodiment, 80% to 90% (or about 80% to about 90%) or more of the fiber volume can extend horizontally, or substantially or approximately horizontally. In another embodiment, all or substantially all of the fiber volume can extend horizontally, or substantially or approximately horizontally. In some embodiments, most of the fibers, 80% to 90% (or about 80% to about 90%) or more, or even all or substantially all of the fibers, extend over a distance (horizontal or lateral distance) perpendicular to the thickness of the water-absorbing and dispersing layer 14800 that is greater than the thickness of the water-absorbing and dispersing layer 14800. In some embodiments, the horizontal or lateral distance that such fibers extend over is 2 times (or about 2 times) or more, 3 times (or about 3 times) or more, 4 times (or about 4 times) or more, 5 times (or about 5 times) or more, or 10 times (or about 10 times) or more the thickness of the water-absorbing and dispersing layer 14800. Such fiber orientation can facilitate the lateral uptake of fluid through the water-absorbing and dispersing layer 14800. This can more evenly disperse fluids such as wound exudate throughout the water-absorbing and dispersing layer 14800. In some embodiments, the ratio of the amount of fluid taken up laterally across the water-absorbing and dispersing layer 14800 to the amount of fluid taken up vertically through the water-absorbing and dispersing layer 14800 under negative pressure can be 2:1 or more, or about 2:1 or more, or in some embodiments, up to 10:1 or more, or about 10:1 or more.

[0140] In some embodiments, at least a portion of the fiber volume of the water absorption dispersion layer 14800 may extend vertically (i.e., perpendicular to the planes of the top and bottom surfaces of the material), or substantially or approximately vertically. In some embodiments, more than 10%, more than 20%, more than 30%, more than 40%, more than 50%, more than 60%, more than 70%, more than 80%, or more than 90% of the fiber volume may extend vertically, or substantially or approximately vertically. Such fiber orientation may facilitate the vertical uptake of fluid through the water absorption dispersion layer 14800. In some embodiments, the ratio of the amount of fluid vertically taken up across the water absorption dispersion layer 14800 to the amount of fluid laterally taken up through the water absorption dispersion layer 14800 under negative pressure may be 2:1 or more, or about 2:1 or more, or in some embodiments, up to 10:1 or more, or about 10:1 or more.

[0141] In some embodiments, the water absorption dispersion layer 14800 may be positioned under the acid-providing layer 14400, as shown in FIGS. 16 and 17. In some embodiments, the water absorption dispersion layer 14800 may be positioned above the acid-providing layer 14400.

[0142] The wound dressing 14100 may further include a masking or concealing layer 14900 to prevent visualization of the wound or wound exudate through the cover layer 14200 or the acid-providing layer 14400. The masking or concealing layer 14900 may be positioned under at least a portion of the cover layer 14200. In some embodiments, the masking or concealing layer 14900 may be positioned on top of the cover layer 14200. In some embodiments, the concealing layer 14900 may have any of the same features, materials, or other details of any of the other embodiments of the concealing layers disclosed herein, including, but not limited to, having any visual windows or apertures. Examples of wound dressings having a concealing layer and visual windows are described in International Patent Publications WO2013 / 007973 and WO2014 / 020440, which are hereby incorporated by reference in their entirety. Additionally, the concealing layer 14900 may be positioned directly under or on top of the cover layer, or adjacent to any other desired dressing layer. In the illustrated embodiment, the concealing layer 14900 is positioned between the cover layer 14200 and the acid-providing layer 14400. In some embodiments, the concealing layer 14900 may be adhered to the cover layer or formed integrally with the cover layer 14200. The concealing layer 14900 may have substantially the same size and shape as the acid-providing layer 14400 and may be configured to overlay it. Thus, in these embodiments, the concealing layer 14900 has an area that is the same as or smaller than the cover layer 14200. In some embodiments, the masking or concealing layer 14900 may be able to draw fluid horizontally and / or vertically and may likewise function as a moisture-absorbing and dispersing layer. In some embodiments, the cover layer 14200 may be partially or completely opaque or colored such that the cover layer 14200 functions as a masking or concealing layer and can prevent visualization of the wound or wound exudate through the cover layer 14200 and / or prevent visualization of the layer under the cover layer 14200.

[0143] Material layer having a hydrogel layer As described elsewhere in this specification, the acid-providing layers 12400 and 14400 can be constructed from a gel such as a hydrogel. In embodiments, the hydrogel can have a sticky surface with adhesive properties, and in some configurations, it may be desirable to reduce the adhesion of the hydrogel of the acid-providing layer, such as the acid-providing layers described above and further herein, to improve the acid-providing hydrogel layer and facilitate handling.

[0144] In some embodiments, the acid-providing hydrogel layer 14400 can include one or more material layers 14420 as a shielding layer to mask at least a portion of the adhesive properties of the hydrogel. The material layer(s) 14420 can be applied to at least a portion of the lower side of the acid-providing hydrogel layer 14400 facing the wound and / or the side of the hydrogel layer 14400 that does not face the wound on the upper side. In some embodiments, the hydrogel layer can be completely encapsulated by the material layer. In some embodiments, the material layer can cover the entire upper and / or lower sides of the hydrogel layer. In some embodiments, the material layer can at least partially cover the upper and / or lower sides of the hydrogel layer. For example, the material layer can cover about 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more of the area of the upper and / or lower sides of the hydrogel layer. The partial covering of the hydrogel layer by the material layer can allow for a limited level of adhesion by partial masking.

[0145] In some embodiments, the material layer can be constructed from a suitable net, mesh, knitted fabric, woven fabric, or non-woven fabric material. In some embodiments, the material layer can be constructed from polypropylene, polyester, or a combination / copolymer thereof. The material layer may be permeable to fluids such as water or wound exudate, whereby the acid-supplying hydrogel layer can absorb the wound exudate and / or the acidic groups of the acid-supplying hydrogel layer can react with nitrite ions to produce nitric oxide.

[0146] The hydrogel has adhesive properties. However, in embodiments, the material layer may not simply be attached to the hydrogel layer by virtue of its adhesive properties. In the case of certain hydrogels, the adhesiveness of the hydrogel can be reduced or lost when the hydrogel absorbs a fluid such as wound exudate. Thus, the material layer may need to be fixed to the hydrogel layer via additional suitable means. For example, the material layer can be fixed to the hydrogel layer through the use of a flexible string, staples, or by suturing the material layer to the hydrogel. In some embodiments, the hydrogel layer can be encapsulated within a bag formed by the material layer.

[0147] In some embodiments, the material layer can be physically implanted or fixed to the hydrogel layer during the formation and / or curing of the hydrogel layer. FIG. 18 illustrates a process of physically implanting or adhering a material layer inside or on top of a hydrogel layer during the formation of the hydrogel layer, according to some embodiments. As illustrated in FIG. 18, the material layer 16200 can be positioned in a mold 16400, for example, at the bottom of the mold 16400, to cure the hydrogel layer. Before being positioned in the mold 16400, the material layer 16200 can be pretreated to be hydrophilic using a wetting agent, for example, to improve its affinity with the hydrogel prepolymer.

[0148] After the material layer 16200 is positioned at the bottom of the mold 16400, a first portion of the hydrogel prepolymer can be added. When the first portion of the hydrogel prepolymer is added, the pre-treated material layer 16200 can be substantially wetted with the first portion of the hydrogel prepolymer. The pre-treated material layer 16200 positioned at the bottom of the mold 16400 further facilitates the lateral spread of the hydrogel prepolymer, and the bottom of the mold 16400 can also be substantially wetted with a continuous layer of the first portion of the hydrogel prepolymer. After the first portion of the hydrogel prepolymer is added, the material layer 16200 can rise from the bottom of the mold 16400 to the top of the hydrogel prepolymer. In some embodiments, the material layer 16200 can rise to the top of the hydrogel prepolymer within 10 minutes, within 7 minutes, within 5 minutes, within 4 minutes, within 3 minutes, within 2 minutes, within 1 minute, or more than 10 minutes. After the material layer 16200 has risen, the first portion of the hydrogel prepolymer can be cured to form the first hydrogel layer 16500, and the material layer 16200 can be fixed to the top of the first hydrogel layer 16500, thereby masking the upper side of the cured hydrogel. The first portion of the hydrogel prepolymer can be UV from the upper side, lower side, or both sides, or any other suitable method known in the art, or any other suitable method known in the art.

[0149] In some embodiments, after the first hydrogel layer 16500 is formed, a second portion of the hydrogel prepolymer can be added to the mold over the first hydrogel layer 16500 and the material layer 16200. After the second portion of the hydrogel prepolymer is added, the material layer 16200 can be encapsulated by the second portion of the hydrogel prepolymer and the first hydrogel layer 16500. Since the material layer 16200 is fixed to the first hydrogel layer 16500, it may not rise or float. The second portion of the hydrogel prepolymer can then be cured to form the second hydrogel layer 16700, and the material layer 16200 can be encapsulated by the hydrogel layers 16500 and 16700 that can be integrated within a single layer. The material layer 16200 implanted and embedded within the integrated hydrogel layer formed by the hydrogel layers 16500 and 16700 can improve the structural integrity of the hydrogel layer. For example, when the hydrogel layer absorbs water, the hydrogel expands and the material layer can act as a reinforcing layer to prevent the hydrogel from stretching and falling off. In some embodiments, the refractive indices of the material layer and the hydrogel layer can be similar such that the material layer is completely invisible and the hydrogel layer appears as a single sheet of clear / transparent material. As will be understood by those skilled in the art, and as repeated later in this specification, the above description of the method for adding the material layer to the hydrogel is not limiting and can be performed in any suitable order and can involve the addition or removal of specific steps. FIG. 19 illustrates, according to some embodiments, the process of physically implanting a material layer over both the upper and lower sides of a hydrogel layer during the formation of the hydrogel layer. However, those skilled in the art will understand that the material layer may be added to only one side. As illustrated in FIG. 19, after the first hydrogel layer 16500 having the material layer 16200 is formed as described in connection with FIG. 18, it is removed from the mold 16400, inverted, and returned into the mold 16400, whereby the side of the hydrogel layer 16500 having the material layer 16200 faces the bottom of the mold 16400.Next, another material layer 16800 is positioned over the hydrogel layer 16500, and then a second portion of the hydrogel prepolymer is added over the hydrogel layer 16500 and the material layer 16800. The material layer 16800 can float and rise to the top of the second portion of the hydrogel prepolymer in a manner similar to the material layer 16200 that floats during the formation of the hydrogel layer 16500, as described in connection with FIG. 18. After the material layer 16800 has risen to the top of the second portion of the hydrogel prepolymer, the second portion of the hydrogel prepolymer can be cured to form a hydrogel layer 16900 together with the hydrogel layer 16500, and the material layer 16800 can be fixed to the top of the hydrogel layer 16900, thereby masking the upper side of the hydrogel layer 16900. The second portion of the hydrogel prepolymer can be cured by UV from the upper side, lower side, or both sides, or by any other suitable method known in the art. As a result, the hydrogel layer 16900 can be sandwiched between the material layers 16200 and 16800, which is fixed to the hydrogel layer 16900.

[0150] Perforated hydrogel layer The acid-providing layer (e.g., the hydrogel layer) can include a plurality of perforations that extend through the thickness of the acid-providing layer, as described elsewhere herein. The plurality of perforations can allow or facilitate the passage of wound exudate through the acid-providing layer such that wound exudate below or around the acid-providing layer can be transported to one or more additional absorbent and / or evaporative layer(s) (e.g., a cover layer) above the acid-providing layer, thereby preventing excessive accumulation of wound exudate below the acid-providing layer. Additionally, the plurality of perforations can provide an increased surface area of the acid-providing layer, thereby increasing the absorption rate of the acid-providing layer.

[0151] In some embodiments, the plurality of perforations can be formed after the acid-providing layer has been cured. For example, the perforations can be formed by punching holes from the acid-providing layer via ultrasonic perforation, via flame perforation, or via any other suitable method.

[0152] In some embodiments, the plurality of perforations can be formed during the formation of the acid-providing layer. For example, the plurality of perforations can be formed during the curing of the acid-providing gel layer. The perforations can be formed by guiding the location of the hydrogel prepolymer solution applied on the mold bottom or the release sheet such that there are small portions where the hydrogel prepolymer solution is not applied. In some embodiments, a mold plate having a high surface energy (i.e., wettability) can be used in combination with a lower energy surface such as the mold bottom or the release sheet. The mold plate can be perforated, and the hydrogel prepolymer solution can preferentially wet the mold plate except for the perforations, and the hydrogel prepolymer solution may not be positioned on the perforations of the mold plate. Such a dispersed hydrogel prepolymer solution, when cured, can form a perforated hydrogel layer. The hydrogel prepolymer can be cured by UV or any other suitable method known in the art.

[0153] In some embodiments, the mold plate can be hydrophilic or pretreated with a wetting agent to be hydrophilic. In certain embodiments, the mold plate can also be constructed to be hydrophobic. The mold plate can be constructed from polypropylene or polyethylene, or any other suitable material. The mold plate can be constructed from a woven or non-woven material, or any other suitable material. In some embodiments, the mold plate can be constructed from a spunbond material. The perforations of the mold plate can have a diameter of approximately 0.1 mm to 10 mm, 0.15 mm to 7 mm, 0.2 mm to 5 mm, 0.5 mm to 4 mm, or 0.7 mm to 3 mm.

[0154] In some embodiments, the mold plate can rise from the bottom of the mold to the top of the hydrogel prepolymer before curing. After the mold plate has risen, the hydrogel prepolymer can be cured to form a perforated hydrogel layer, and the mold plate can be fixed to the top of the perforated hydrogel layer. Then, a second portion of the hydrogel prepolymer can be added to the mold on top of the perforated hydrogel layer and the mold plate. After the second portion of the hydrogel prepolymer has been added, the mold plate can be encapsulated by the second portion of the hydrogel prepolymer and the perforated hydrogel layer. Since the mold plate is fixed to the perforated hydrogel layer, it may not rise or float. Then, the second portion of the hydrogel prepolymer can be cured to form a second perforated hydrogel layer, and the mold plate can be encapsulated within the perforated hydrogel layer and the second perforated hydrogel layer. In some embodiments, the hydrogel layer can be formed from two or more hydrogel layers.

[0155] In some embodiments, shielding layers such as shielding layers 16200 and 16800 may be perforated and may function as mold plates for the perforated hydrogel layer. Such perforated hydrogel layers can be prepared according to a method similar to the method described with respect to FIGS. 18 and 19.

[0156] In some embodiments, the mold plate for the hydrogel layer can include a plurality of pillars, and the hydrogel prepolymer can be poured around the pillars and cured to form a hydrogel layer having perforations. In some embodiments, the perforations or other patterns can be formed in the hydrogel layer by screen printing or by laying down "fibers" of hydrogel using a die, spinneret or electrospray process and then curing. The hydrogel prepolymer for these processes can include a viscosity modifier (e.g., a thixotropic agent) and / or can be positioned on a hydrophobic release paper to limit the diffusion of the prepolymer laid down before curing.

[0157] Nitric Oxide Generating Wound Dressing for Treating the Area around a Wound In some cases, stimulation of the tissue surrounding the wound (the skin surrounding the wound) and the wound edge can play a role in initiating the wound healing process. In certain embodiments, the wound healing process can be activated through delivery of nitric oxide to the tissue surrounding and / or at the wound edge. Delivery of nitric oxide to the tissue surrounding and / or at the wound edge can target, for example, epithelial cell activity to promote movement of epithelial tongues, vasodilation of the microcirculation of the skin surrounding the wound to promote perfusion by providing oxygen and nutrients, and angiogenesis to promote granulation tissue formation.

[0158] Figures 20 and 21 illustrate a wound dressing 18000 for delivery of nitric oxide to the tissue surrounding and / or at the wound edge, according to some embodiments. The wound dressing 18000 is similar to the wound dressing 14100 of FIG. 16 and can include a cover layer 18200, an acid providing layer 18400, a moisture absorbing dispersion layer 18800, and a nitrite providing layer 18600. The layers of the wound dressing 18000 can be similar to the corresponding layers of the wound dressing 14000 and / or 14100.

[0159] In the illustrated embodiment, the acid providing layer 18400 is provided in a boundary region that includes a central absorbent material 18450. The acid providing layer 18400 and the central absorbent material 18450 may or may not be attached to each other. In some embodiments, the acid providing layer 18400 and the central absorbent material 18450 may be provided as an integral component. The acid providing layer 18400 can define a window at the center, and the central absorbent material 18450 can be shaped and / or sized to fit within the window of the acid providing layer 18400.

[0160] The acid-providing layer 18400 can be constructed from materials similar to those of the acid-providing layers 12400 and 14400. For example, the acid-providing layer 18400 can be constructed from a hydrogel or a xerogel and can contain acidic groups or acidic moieties. In some embodiments, the acid-providing layer 18400 can be constructed from a mesh, foam, gel, or any other material suitable for containing acidic groups or acidic moieties. The acid-providing layer 18400 can provide an acidic environment in the boundary region of the wound dressing 18000, thereby generating nitric oxide from the boundary region of the wound dressing 18000 for delivery to the area around or at the boundary of the wound. As illustrated in FIG. 21, the acid-providing layer 18400 can be sized and / or positioned such that the acid-providing layer 18400 is at least partially positioned over the wound perimeter 18920. The acid-providing layer 18400 can include a plurality of perforations or one or more material layers such as the material layers 16200 and 16800 described elsewhere herein.

[0161] In the illustrated embodiment, the acid-providing layer 18400 is in a frame shape. However, the acid-providing layer 18400 may have any other suitable shape or configuration. In some embodiments, the acid-providing layer 18400 can be provided as a plurality of acid-providing strips rather than as a frame-shaped layer, such that the acid-providing strips can be separately applied to the boundary region close to the immediate wound perimeter area. Each of the acid-providing strips can be positioned on the side of the wound to create an acid-providing layer 18400 that fits closely around the wound. For example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more acid supply strips may be provided and / or applied around the wound. The acid-providing strips can be constructed from the same materials as the acid-providing layer described herein.

[0162] The central absorbent material 18450 can be positioned over the wound to absorb wound exudate. For example, as illustrated in FIG. 21, the central absorbent material 18450 can be sized and / or positioned such that the central absorbent 18450 is at least partially positioned over the wound 18910. In some embodiments, the central absorbent material 18450 may be the same size as the wound or larger than the wound such that the central absorbent material 18450 completely covers the wound. In some embodiments, the central absorbent material 18450 may be smaller than the wound such that the acid-providing layer 18400 can be positioned near the wound edge.

[0163] The central absorbent material 18450 can include a foam or non-woven natural or synthetic material, and optionally can include a superabsorbent material, and can form a reservoir for fluids, specifically the liquid removed from the wound site. In some embodiments, the central absorbent material 18450 can also assist in drawing fluid towards the cover layer 18200. The material of the central absorbent material 18450 can also prevent the liquid collected within the wound dressing 18000 from freely flowing within the dressing, and preferably acts to contain any liquid collected within the dressing. The capacity of the absorbent material can be sufficient to manage the rate at which wound exudate flows when negative pressure is applied. In some embodiments, the central absorbent material 18450 can be selected to absorb liquid under negative pressure. For example, there are some materials, such as superabsorbent materials, that can absorb liquid when under negative pressure. The central absorbent material 18450 can be manufactured from Freudenberg 114-224-4 of ALLEVYN (trademark) foam or Chem-Posite (trademark) 11C-450. In some embodiments, the central absorbent material 18450 can include superabsorbent powder, fibrous materials such as cellulose, and binding fibers. In some embodiments, the composite is an aeolian, thermally bonded composite. In some embodiments, the central absorbent material 18450 is a layer of non-woven cellulose fibers having superabsorbent material in the form of dry particles dispersed throughout. The use of cellulose fibers can introduce a high-speed suction element that helps to rapidly and evenly disperse the liquid absorbed by the dressing. Placing a plurality of twist-like fibers in parallel can lead to a strong capillary action of the fiber pad that helps to disperse the liquid. In this way, the superabsorbent material can be more efficiently supplied with liquid. In certain embodiments, the suction action can also assist in bringing the liquid into contact with the upper cover layer so as to assist in increasing the evaporation rate of the dressing.

[0164] The wound dressing 18000 further includes a frame layer 18100 that can further support the acid-providing layer 18400. The frame layer 18100 is positioned on the side facing the wound or the bottom side of the dressing 18000 and can cover at least the boundary region of the wound dressing 18000. The frame layer 18100 may be a polyurethane layer, a polyethylene layer, or another suitable flexible layer. The frame layer 18100 has a lower surface and an upper surface. In some embodiments, at least a portion of the upper surface of the frame layer 18100 is attached to the cover layer 18200. In some embodiments, at least a portion of the lower surface of the frame layer 18100 can be attached to the skin around the wound. In some embodiments, the frame layer 18100 includes a window 18110 to enable fluid communication between the nitrite-providing layer 18600 and the other layers of the wound dressing 18000. In some embodiments, the window 18110 has the same or a larger size as the nitrite-providing layer 18600 such that the nitrite-providing layer 18600 is positioned within the window 18110. In some embodiments, the frame layer 18100 is positioned under the water-absorbing dispersion layer 18800 and / or the acid-providing layer 18400. In some embodiments, the water-absorbing dispersion layer 18800 and / or the acid-providing layer 18400 are completely surrounded by the cover layer 18200 and the frame layer 18100, except for the window 18110. In some configurations, the frame layer 18100 can help maintain the integrity of the entire dressing 18000 while also forming a liquid-tight seal around the wound.

[0165] In some embodiments, instead of being provided as the acid-providing layer 18400, the acid-providing material may be provided as a dispensable composition, e.g., a prepolymer solution or otherwise in a moldable form, so as to be more freely applicable around the wound. For example, the acid-providing material may be provided as a gel prepolymer solution so that it can be applied by a clinician in proximity to a wound having an irregular shape and size. In some embodiments, the acid-providing material, such as a gel prepolymer solution, may be provided in a syringe and / or applied using a syringe, and the gel prepolymer solution may have a viscosity suitable for dispensing from the syringe. The acid-providing material may also be formulated so that it can be rapidly cured and, when applied around the wound, will no longer flow. The acid-providing material may include an evaporative solvent such as isopropanol. The acid-providing material may have a suitable secondary curing mechanism, such as a photoinitiating acrylate functionality. In some embodiments, the acid-providing material may include a material that can swell and bond together when contacted with a wound fluid or moisture, such as, for example, methacrylate. In some embodiments, the acid-providing material may be provided as a reactive two-part system. For example, a first part containing isocyanate and a second part containing water or a polyol may be provided to be mixed immediately prior to dispensing so as to ultimately result in urethane formation. In some embodiments, the first part and the second part may be oppositely charged fluid gels, whereby they interact upon mixing to provide a gel that is substantially non-flowing. In some embodiments, the acid-providing material may include a material such as a gel that changes in response to a change in the environment. For example, the acid-providing material may include a material such as a particular pluronic so that it can be cured when the temperature changes upon application to the skin from a dispenser or syringe. The acid-providing material may be applied so as to interact with nitrite from the nitrite-providing layer 18600 to generate nitric oxide. Once the acid-providing material is applied and cured or otherwise rendered non-flowing, the cover layer 18200 may be applied.

[0166] In some embodiments, nitrite ions or nitrates may be provided as a dispensable composition in a manner similar to the acid delivery materials described herein, instead of or in addition to the nitrate-providing layer 18600. In some embodiments, both the acid delivery material and the nitrite ions or nitrates may be provided as one or more dispensable compositions such that they can be more freely applied around the wound. For example, in a two-part system, the first part may include an acid delivery material such as a gel prepolymer solution, the second part may include nitrite ions or nitrates, and the first and second parts may be mixed around the wound and dispensed collaboratively, thereby generating nitric oxide. In some embodiments, a static mixer such as a dual-barrel syringe having a mixing head may be used. The first and second parts may have viscosities suitable for dispensing from the syringe. The first and second parts may also be formulated such that it can be rapidly cured and will no longer flow when applied around the wound. Either or both of the first and second parts may include an evaporative solvent such as isopropanol. Either or both of the first and second parts may have a suitable secondary curing mechanism such as a photoinitiating acrylate functionality. In some embodiments, the acid delivery material may include materials that can swell and bond together when in contact with wound fluid or moisture, such as methacrylate. In some embodiments, the first and second parts may be provided as a reactive two-part system. For example, a first part containing isocyanate and a second part containing water or a polyol may be provided to be mixed immediately prior to dispensing to result in urethane formation. In some embodiments, the first part and the second part may be oppositely charged fluid gels, whereby they can interact upon mixing to provide a gel that substantially does not flow. In some embodiments, the first and / or second parts may include materials such as gels that change in response to a change in the environment. For example, the first and / or second parts may include a material such as a specific Pluronic that can be cured when the temperature changes upon application from a dispenser or syringe to the skin.Once the first and second portions are mixed, applied, cured, or otherwise rendered non - flowing, the cover layer 18200 can be applied.

[0167] The term The above - mentioned patents, specifications, and other references, including any that may be listed in the attached application documents, are incorporated herein by reference. Aspects of the present disclosure may be modified, as necessary, to provide further embodiments using the various reference systems, functions, and concepts described herein.

[0168] It should be understood that features, materials, characteristics, or groups described in connection with a particular aspect, embodiment, or example are applicable to other aspects, embodiments, or examples described herein, provided they do not conflict therewith. All features disclosed in this specification (including any attached patent claims, abstract, and drawings), or all steps of any method or process similarly disclosed, may be combined in any combination, except combinations where at least some of such features or steps are mutually exclusive. The subject matter of the protection is not limited to the details of any of the foregoing embodiments. The subject matter of the protection extends to any novel one of the features disclosed in this specification (including any attached patent claims, abstract, and drawings), or any novel combination thereof, or any novel one of the steps of any method or process similarly disclosed, or any novel combination thereof.

[0169] Although certain embodiments are described, these embodiments are presented merely as examples and are not intended to limit the scope of the subject matter. In fact, the novel methods and systems described herein may be embodied in a variety of other forms. Further, various omissions, substitutions, and changes may be made in the forms of the methods and systems described herein. Those skilled in the art will understand that in some embodiments, the actual steps performed in the illustrated or disclosed processes may differ from those shown in the drawings. Depending on the embodiment, certain steps described above may be excluded, while others may be added. For example, the actual steps or the order of steps performed in the disclosed process may differ from those shown in the drawings. Depending on the embodiment, certain steps described above may be excluded, while others may be added. Further, the features and characteristics of the specific embodiments disclosed above may be combined in different ways to form additional embodiments, all of which fall within the scope of this disclosure.

[0170] This disclosure includes certain embodiments, examples, and uses, but those skilled in the art will understand that this disclosure extends beyond the specifically disclosed embodiments to other alternative embodiments or uses and their obvious modifications and equivalents, and includes embodiments that do not necessarily provide all of the features and advantages described herein. Accordingly, the scope of this disclosure is not intended to be limited by the described embodiments and may be defined by the claims presented herein or presented hereafter.

[0171] Conditional language such as "can", "could", "might", or "may" typically conveys that a particular embodiment includes a particular feature, element, or step while other embodiments do not, unless specifically stated otherwise or otherwise interpreted within the context in which it is used. Thus, such conditional language generally does not imply that a feature, element, or step is necessarily required in one or more embodiments, or that logic for determining whether these features, elements, or steps are included in any particular embodiment, or are to be performed in any particular embodiment, regardless of user input or instructions, is necessarily included in one or more embodiments. Terms such as "comprises," "includes," and "has" are synonyms and are used in an inclusive, open-ended fashion and do not exclude additional elements, features, acts, operations, etc. Also, the term "or" is used in an inclusive sense (not an exclusive sense), so that, for example, when used to connect a list of elements, the term "or" means one, some, or all of the elements in the list. Similarly, the term "and / or" with respect to the listing of two or more items encompasses all of the following interpretations of the words: any one of the items in the listing, all of the items in the listing, and any combination of the items in the listing. Additionally, the term "each" as used herein, in addition to having its ordinary meaning, may also mean any subset of a series of elements to which the term "each" applies. Further, as used herein, the terms "herein," "above," "below," and similar words mean the entire present application when used in this application and do not refer to a particular part of the present specification.

[0172] Conjunctive phrases such as the phrase "at least one of X, Y, and Z" are to be construed otherwise only where specifically recited otherwise, depending on the context in which they are generally used to suggest that an item or term can be any of X, Y, or Z. Thus, such conjunctive phrases generally are not intended to suggest that a particular embodiment requires the presence of at least one X, at least one Y, and at least one Z.

[0173] Terms of degree used herein, for example, the terms "about," "approximately," "generally," and "substantially" as used herein, still represent a value, amount, or property that approximates a given value, amount, or property that performs the desired function or results in the desired outcome. For example, the terms "about," "approximately," "generally," and "substantially" can refer to amounts that are within less than 10%, less than 5%, less than 1%, less than 0.1%, and less than 0.01% of a given amount. As another example, in certain embodiments, the terms "generally parallel" and "substantially parallel" refer to a value, amount, or property that deviates from being exactly parallel by 15 degrees or less, 10 degrees, 5 degrees, 3 degrees, 1 degree, or 0.1 degree.

[0174] Any of the embodiments described herein can be used with or without a canister. Any of the coating material embodiments described herein can absorb and store wound exudate.

[0175] The scope of the present disclosure is not intended to be limited by the description of particular embodiments, and may be defined by the claims. The language of the claims should be interpreted broadly based on the language used in the claims and not limited to the examples described herein or the examples described during the prosecution of this application, and those examples should be construed as non-exclusive.

[0176] Various modifications to the embodiments described in this disclosure may become readily apparent to those skilled in the art, and the general principles defined herein may be applied to other embodiments without departing from the spirit or scope of the disclosure. Therefore, the disclosure is not intended to be limited to the embodiments shown herein, but should be accorded the widest scope consistent with the principles and features disclosed herein. Certain embodiments of the disclosure are subsumed in the claims set forth below or in other claims presented later.

[0177] Certain specific embodiments of the disclosure are subsumed in the claims presented at the end of this specification or in other claims presented later. [Additional Note 1] A wound dressing for treating wounds, comprising: a cover layer configured to form a seal around the wound; an active agent layer; a dry nitric oxide source layer that contains little or no liquid; and a moisture-absorbing dispersion layer. [Additional Note 2] The wound dressing according to Additional Note 1, further comprising a masking layer configured to at least partially limit the visualization of the wound. [Additional Note 3] The wound dressing according to Additional Note 1, wherein the dry nitric oxide source layer contains nitrite. [Additional Note 4] The wound dressing according to Additional Note 3, wherein the nitrite contains sodium nitrite. [Additional Note 5] The wound dressing according to any one of the preceding additional notes, wherein the active agent layer is positioned above the nitric oxide source layer. [Additional Note 6] The wound dressing according to any one of Additional Notes 1 to 4, wherein the nitric oxide source layer is positioned above the active agent layer. [Additional Note 7] The wound dressing according to any one of the preceding additional notes, wherein the moisture-absorbing dispersion layer is positioned between the active agent layer and the dry nitric oxide source layer. [Additional Note 8] The wound dressing according to any one of the preceding additional notes, wherein the active agent layer contains a hydrogel. [Additional Note 9] The wound dressing according to any one of Additional Notes 1 to 7, wherein the active agent layer contains a xerogel. [Additional Note 10] The wound dressing according to any one of the preceding additional notes, further comprising a second dry nitric oxide source layer. [Additional Note 11] The wound dressing according to any one of the preceding additional notes, configured to generate nitric oxide when the wound dressing is placed on the wound. [Additional Note 12] The wound dressing according to Additional Note 11, configured not to generate nitric oxide before being placed on the wound. [Additional Note 13] A wound dressing for treating a wound, comprising: a cover layer; an activator layer positioned under the cover layer; a nitric oxide source layer; a separation layer positioned between the activator layer and the nitric oxide source layer, the separation layer being configured to prevent contact between the activator layer and the nitric oxide source layer. [Appended Claim 14] The wound dressing according to appended claim 13, wherein the separation layer comprises a tab configured to be removed from the wound dressing, such that when the tab is removed, contact then occurs between the activator layer and the nitric oxide source layer. [Appended Claim 15] The wound dressing according to appended claim 13, wherein the separation layer comprises a degradable material configured such that when the degradable material degrades, contact occurs between the activator layer and the nitric oxide source layer. [Appended Claim 16] A wound treatment device, comprising: an activator hydrogel comprising a plurality of capsules, each capsule comprising a separation layer encapsulating a nitric oxide source material, the separation layer being configured to prevent contact between the activator hydrogel and the nitric oxide source material. [Appended Claim 17] The wound treatment device according to appended claim 16, wherein the separation layer is configured to be broken when mechanical pressure is applied, such that when the separation layer is broken, contact occurs between the activator hydrogel and the nitric oxide source material. [Appended Claim 18] A wound dressing for treating a wound, comprising: an activator hydrogel; a nitric oxide source hydrogel having a surface facing the activator hydrogel, the surface facing the activator hydrogel comprising a layer of sodium nitrite. [Appended Claim 19] The wound dressing according to appended claim 16, wherein the activator hydrogel comprises a plurality of perforations. [Appended Claim 20] The wound dressing according to appended claim 16 or 17, wherein the nitric oxide source hydrogel comprises a plurality of perforations. [Appended Claim 21] A method of delivering an active ingredient to a wound, comprising: placing an active ingredient platform on the wound, the active ingredient platform comprising a dosing portion and an adhesive frame, the dosing portion comprising the active ingredient. Adhering a reactive platform onto the active ingredient platform to form a seal, wherein the reactive platform comprises a reactive portion configured to activate the administration portion such that the active ingredient is delivered to the wound. The method includes forming the seal. [Appended Claim 22] The method according to appended claim 19, wherein the active ingredient comprises a therapeutic agent configured to promote wound healing. [Appended Claim 23] The method according to appended claim 21 or 22, wherein the administration platform is inactive until the reactive platform is adhered to the active ingredient platform. [Appended Claim 24] A wound dressing for treating a wound, comprising: A cover layer configured to form a seal around the wound; A nitrite-providing layer containing nitrite; An acid-providing layer positioned under the cover layer and containing an acidic group, wherein the acid-providing layer includes a window at the center of the acid-providing layer; A central absorption material for absorbing wound exudate, wherein the central absorption material is positioned within the window of the acid-providing layer. The wound dressing comprises the central absorption material. [Appended Claim 25] The wound dressing according to appended claim 24, wherein the acid-providing layer is configured to be positioned on the skin around the wound or on the edge of the wound when the wound dressing is applied to the wound. [Appended Claim 26] The wound dressing according to appended claim 24 or 25, wherein the central absorption material is configured to be positioned on the wound when the wound dressing is applied to the wound. [Appended Claim 27] The wound dressing according to any one of appended claims 24 to 26, wherein the central absorption layer is completely enclosed by the acid-providing layer. [Appended Claim 28] The wound dressing according to any one of appended claims 24 to 27, further comprising a water-absorbing and dispersing layer configured to suck up fluid horizontally. [Appended Claim 29] The wound dressing according to any one of appended claims 24 to 28, further comprising a frame layer positioned under the acid-providing layer, wherein the frame layer defines a window at the center of the frame layer. [Appended Claim 30] The wound dressing according to appended claim 29, wherein the frame layer is configured to be attached to the skin around the wound. [Appended Claim 31] The wound dressing according to appended claim 29 or 30, wherein the frame layer is attached to the cover layer. [Appended Claim 32] The wound dressing according to any one of appended claims 29 to 31, wherein the nitrate-providing layer is positioned within the window of the frame layer. [Appended claim 33] The wound dressing according to any one of appended claims 24 to 32, wherein the acid-providing layer contains xerogel or hydrogel. [Appended claim 34] A method for treating a wound, comprising: applying a wound dressing to the wound, the wound dressing comprising: a cover layer configured to form a seal around the wound; a nitrate-providing layer containing nitrate; an acid-providing layer positioned under the cover layer and containing an acidic group, the acid-providing layer including a window at the center of the acid-providing layer; a central absorbent material for absorbing wound exudate, the central absorbent material being positioned within the window of the acid-providing layer. [Appended claim 35] The method according to appended claim 34, further comprising generating nitric oxide such that the nitric oxide is delivered to the skin around the wound or the edge of the wound. [Appended claim 36] The method according to appended claim 34 or 35, further comprising positioning the wound dressing such that the acid-providing layer is at least partially positioned over the skin around the wound or the edge of the wound. [Appended claim 37] The method according to any one of appended claims 34 to 36, further comprising positioning the wound dressing such that the central absorbent material is at least partially positioned over the wound. [Appended claim 38] The method according to any one of appended claims 34 to 37, wherein the central absorbent layer is completely enclosed by the acid-providing layer. [Appended claim 39] The method according to any one of appended claims 34 to 38, wherein the wound dressing further comprises a water-absorbing and dispersing layer configured to suck up fluid horizontally. [Appended claim 40] The method according to any one of appended claims 34 to 39, wherein the wound dressing further comprises a frame layer positioned under the acid-providing layer, the frame layer defining a window at the center of the frame layer. [Appended claim 41] The method according to appended claim 40, further comprising attaching the frame layer to the skin around the wound. [Appended claim 42] The method according to appended claim 40 or 41, wherein the frame layer is attached to the cover layer. [Appended claim 43] The method according to any one of appended claims 34 to 42, wherein the acid-providing layer contains xerogel or hydrogel. [Appended claim 44] A wound dressing for treating a wound, a cover layer configured to form a seal around the wound, a nitrite-providing layer containing nitrite, an acid-providing layer positioned under the cover layer and containing an acidic group, wherein the acid-providing layer includes a window at the center of the acid-providing layer, the wound dressing comprising the acid-providing layer. [Appended Claim 45] The wound dressing according to appended claim 44, wherein the acid-providing layer is configured to be positioned on the skin around the wound or on the edge of the wound when the wound dressing is applied to the wound. [Appended Claim 46] The wound dressing according to appended claim 44 or 45, further comprising a water-absorbing and dispersing layer configured to suck up fluid horizontally. [Appended Claim 47] The wound dressing according to any one of appended claims 44 to 46, further comprising a frame layer positioned under the acid-providing layer, wherein the frame layer defines a window at the center of the frame layer. [Appended Claim 48] The wound dressing according to appended claim 47, wherein the frame layer is configured to be attached to the skin around the wound. [Appended Claim 49] The wound dressing according to appended claim 47 or 48, wherein the frame layer is attached to the cover layer. [Appended Claim 50] The wound dressing according to any one of appended claims 47 to 49, wherein the nitrite-providing layer is positioned within the window of the frame layer. [Appended Claim 51] The wound dressing according to any one of appended claims 44 to 50, wherein the acid-providing layer includes xerogel or hydrogel. [Appended Claim 52] A wound dressing for treating a wound, a cover layer, an activator layer positioned under the cover layer, a nitric oxide source layer, a folded separation layer positioned between the activator layer and the nitric oxide source layer, wherein the separation layer is configured to prevent contact between the activator layer and the nitric oxide source layer, the folded separation layer, an upper frame positioned on the separation layer and under the cover layer, wherein the upper frame has an adhesive on the upper side of the frame, the wound dressing comprising the upper frame.

Claims

1. A wound dressing for treating a wound, comprising: a cover layer; an activator layer positioned under the cover layer; a nitric oxide source layer; and a separation layer positioned between the activator layer and the nitric oxide source layer, the separation layer being configured to prevent contact between the activator layer and the nitric oxide source layer.

2. The wound dressing according to claim 1, wherein the separation layer comprises a tab configured to be removed from the wound dressing, such that when the tab is removed, contact then occurs between the activator layer and the nitric oxide source layer.

3. The wound dressing according to claim 1, wherein the separation layer comprises a degradable material configured such that when the degradable material degrades, contact occurs between the activator layer and the nitric oxide source layer.

4. A wound dressing for treating a wound, comprising: a cover layer configured to form a seal around the wound; a nitrite providing layer containing nitrite; an acid providing layer positioned under the cover layer and containing an acidic group, the acid providing layer including a window at the center thereof; and a central absorbent material for absorbing wound exudate, the central absorbent material being positioned within the window of the acid providing layer.

5. The wound dressing according to claim 4, wherein the central absorbent material is completely enclosed by the acid providing layer.

6. The wound dressing according to claim 4 or 5, further comprising a water absorption dispersion layer configured to suck up fluid horizontally.

7. The wound dressing according to any one of claims 4 to 6, further comprising a frame layer positioned under the acid providing layer, the frame layer defining a window at the center thereof.

8. The wound dressing according to claim 7, wherein the frame layer is configured to be attached to the skin around the wound.

9. The wound dressing according to claim 7 or 8, wherein the frame layer is attached to the cover layer.

10. The wound dressing according to any one of claims 7 to 9, wherein the nitrite providing layer is positioned within the window of the frame layer.

11. The wound dressing according to any one of claims 4 to 10, wherein the acid providing layer comprises xerogel or hydrogel. Claim 12 A wound dressing for treating a wound, comprising: a cover layer configured to form a seal around the wound; a nitrite-providing layer containing nitrite; an acid-providing layer containing an acidic group and positioned under the cover layer, the acid-providing layer including a window at the center of the acid-providing layer; A wound dressing comprising the above.

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