Wound dressing material

Abstract

Disclosed embodiments relate to a wound dressing capable of generating nitric oxide. The wound dressing includes a cover layer, an acid-providing layer, and a nitrite-providing layer. The acid-providing layer includes acidic groups and may be a hydrogel or xerogel. The nitrite-providing layer includes nitrite. The wound dressing may also include other layers, such as one or more water-absorbing / dispersing layers or masking layers. The masking layer may at least partially prevent the visibility of layers below the masking layer. Nitrite ions in the nitrite-providing layer may react with acidic groups in the acid-providing layer to generate nitric oxide. The acid-providing layer may further include one or more material layers to reduce the adhesiveness of the acid-providing layer. The acid-providing layer may also include perforations.

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 the delivery of nitric oxide (NO) and / or the delivery of other active agents.

Background Art

[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 potent 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 a decrease in the supply of nitric oxide in diabetic patients is a worsening factor in non-healing chronic ulcers. A decrease in the supply of nitric oxide can lead to vascular damage such as endothelial dysfunction and vascular inflammation. Vascular damage can also lead to a decrease 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 a wound. Under normal conditions, the free radical nitric oxide (NO) has a short lifespan and is converted to a more stable chemical species within seconds of its 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 be generated. 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. It will be understood by those skilled in the art that the applications of the materials, devices, methods, and systems described herein are not limited to a particular tissue, a particular location on the body, or a particular injury.

[0006] In some configurations, a wound dressing for treating a wound includes one or more nitric oxide generating layers and a moisture absorbing and dispersing layer configured to suck up fluid horizontally and / or vertically.

[0007] The wound dressing of the above paragraph may include one or more of the following features. The wound dressing may further include a cover layer configured to form a seal around the wound. The one or more nitric oxide generating layers may include a nitric oxide source layer. The one or more nitric oxide generating layers may include an activator layer. The water absorption and dispersion layer may be positioned directly below the activator layer. The water absorption and dispersion layer may be attached to the activator layer. The water absorption and dispersion layer may be attached to the acid providing layer by adhesion, suturing, or heat welding. The wound dressing may further include a second water absorption and dispersion layer, with the activator layer sandwiched between the two water absorption and dispersion layers. The activator layer may be completely surrounded within the two water absorption and dispersion layers. The water absorption and dispersion layer may include a plurality of fibers, and most of the plurality of fibers may extend horizontally or substantially horizontally. The water absorption and dispersion layer may include a plurality of fibers, and 80% to 90% of the plurality of fibers may extend horizontally or substantially horizontally. The cover layer may be moisture permeable. The cover layer may have an outer perimeter larger than the outer perimeter of the activator layer, thereby defining a boundary region between the outer perimeter of the cover layer and the outer perimeter of the activator layer. At least a portion of the boundary region of the cover layer may be configured to be sealed against the skin around the wound. The nitric oxide source layer may include an aqueous solution of nitrite. The nitric oxide source layer may include dry nitrite. The nitrite may be selected from the group consisting of ammonium nitrite, calcium nitrite, sodium nitrite, and potassium nitrate. The nitric oxide source layer may include a mesh. The activator layer may include a xerogel or a hydrogel. The activator layer may include a foam. The activator may include a plurality of perforations. The wound dressing may further include a concealment layer.

[0008] In some configurations, a wound dressing for treating a wound includes one or more nitric oxide generating layers and a masking element configured to at least partially prevent visualization of underlying layers.

[0009] The wound dressing of the above paragraph may include one or more of the following features. The wound dressing may further include a cover layer, and the masking element is positioned under the cover layer. The wound dressing may further include a cover layer, and the masking element is positioned above the cover layer. The wound dressing may further include a cover layer, and the cover layer is the masking element. The masking element may include one or more viewing windows. The wound dressing may further include a water-absorbing and dispersing layer. The water-absorbing and dispersing layer may include a plurality of fibers, and most of the plurality of fibers extend horizontally or substantially horizontally. The wound dressing may further include a cover layer, and the cover layer has an outer periphery larger than the outer periphery of the acid-providing layer, thereby defining a boundary region between the outer periphery of the cover layer and the outer periphery of the acid-providing layer. At least a portion of the boundary region of the cover layer may be configured to be sealed against the skin surrounding the wound. The nitric oxide generating layer may include a nitrite-providing layer containing nitrite. The nitrite-providing layer may include an aqueous solution of nitrite. The nitrite-providing layer may include dry nitrite. The nitrite may be selected from the group consisting of ammonium nitrite, calcium nitrite, sodium nitrite, and potassium nitrate. The nitrite-providing layer may include a mesh. The nitric oxide generating layer may include an acid-providing layer containing an acidic group. The acid-providing layer may include a xerogel or a hydrogel. The acid-providing layer may include a foam. The acid-providing layer may include a plurality of perforations. The wound dressing may include a display layer configured to change a display upon contact with nitric oxide. The masking element may include a material configured to change a display upon contact with nitric oxide.

[0010] In some configurations, a method for treating a wound includes applying a wound dressing agent to the wound. The wound dressing includes one or more nitric oxide generating layers and a masking layer configured to at least partially prevent visualization of the underlying layer.

[0011] The method of the above paragraph may include one or more of the following features. The method may further include generating nitric oxide. The method may further include enabling nitrite ions to contact an acid.

[0012] In some configurations, a wound dressing for treating a wound includes a cover layer, a nitrite-providing layer, and an acid-providing layer. The cover layer is configured to form a seal around the wound. The nitrite-providing layer contains nitrite. The acid-providing layer is positioned under the cover layer and contains acidic groups. Visualization of the acid-providing layer and / or the nitrite-providing layer is prevented from above the cover layer.

[0013] The wound dressing of the above paragraph may include one or more of the following features. The cover layer may be at least partially opaque such that the cover layer prevents visualization of the acid-providing layer and / or the nitrite-providing layer below the cover layer. The wound dressing may further include a water-absorbing and dispersing layer. The water-absorbing and dispersing layer may include a plurality of fibers, and most of the plurality of fibers extend horizontally or substantially horizontally. The cover layer may be moisture-permeable. The cover layer may have an outer perimeter larger than the outer perimeter of the acid-providing layer, thereby defining a boundary region between the outer perimeter of the cover layer and the outer perimeter of the acid-providing layer. At least a portion of the boundary region of the cover layer may be configured to be sealed against the skin around the wound. The nitrite-providing layer may contain an aqueous solution of nitrite. The nitrite-providing layer may contain dry nitrite. The nitrite may be selected from the group consisting of ammonium nitrite, calcium nitrite, sodium nitrite, and potassium nitrite. The nitrite-providing layer may include a mesh. The acid-providing layer may include a xerogel or a hydrogel. The acid-providing layer may include a foam. The acid-providing layer may include a plurality of perforations. The wound dressing may further include a display layer configured to change a display upon contact with nitric oxide. The cover layer may include a material that changes a display upon contact with nitric oxide.

[0014] In some configurations, a method for treating a wound includes applying a wound dressing agent to the wound. The wound dressing includes one or more nitric oxide generating layers and a water-absorbing and dispersing layer configured to suck up fluid horizontally and / or vertically.

[0015] The method of the above paragraph may include one or more of the following features. The method may further include generating nitric oxide. The method may further include enabling the nitric oxide source to contact the activator layer. The water-absorbing and dispersing layer may be pre-attached to one of the one or more nitric oxide generating layers before applying the wound dressing to the wound. The wound dressing may further include a cover layer, the cover layer having an outer perimeter larger than the outer perimeter of the acid-providing layer, thereby defining a boundary region between the outer perimeter of the cover layer and the outer perimeter of the acid-providing layer, and sealing at least a portion of the boundary region of the cover layer against the skin surrounding the wound. The wound dressing may further include a concealment layer positioned between the acid-providing layer and the cover layer.

[0016] In some configurations, a wound dressing for treating a wound includes a cover layer, a nitrite-providing layer, and an acid-providing 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 further includes one or more pores penetrating the thickness of the acid-verifying layer.

[0017] The wound dressing of the above paragraph may include one or more of the following features. The cover layer may be moisture-permeable. The cover layer may have an outer perimeter larger than the outer perimeter of the acid-providing layer, thereby defining a boundary region between the outer perimeter of the cover layer and the outer perimeter of the acid-providing layer. At least a portion of the boundary region of the cover layer may be configured to be sealed against the skin surrounding the wound. The nitrite-providing layer may contain an aqueous solution of nitrite. The nitrite-providing layer may contain dry nitrite. The nitrite may be selected from the group consisting of ammonium nitrite, calcium nitrite, sodium nitrite, and potassium nitrite. The nitrite-providing layer may include a mesh. The acid-providing layer may include a xerogel or a hydrogel. The acid-providing layer may include a foam. The wound dressing may include a concealment layer positioned between the acid-providing layer and the cover layer.

[0018] In some configurations, the wound dressing includes a nitric oxide source layer having a plurality of through-holes penetrating the thickness of the acid-verifying layer and a water-absorbing and dispersing layer.

[0019] The wound dressing of the above paragraph may include one or more of the following features. The wound dressing may further include a cover layer configured to form a seal around the wound. The cover layer may be moisture permeable. The nitric oxide source layer may include an aqueous solution of nitrite. The nitric oxide source layer may include dry nitrite. The nitrite may be selected from the group consisting of ammonium nitrite, calcium nitrite, sodium nitrite, and potassium nitrate. The nitric oxide source layer may include a mesh. The wound dressing may further include a concealment layer.

[0020] In some configurations, a method for generating a wound dressing includes generating an acid-providing gel layer. Generating the acid-providing gel layer includes positioning a template on a mold, adding a gel prepolymer on the template on the mold, enabling the gel prepolymer to be absent from a plurality of locations on the template and defining a plurality of perforations, and curing the gel prepolymer.

[0021] The method of the above paragraph may include one or more of the following features. The template may include a plurality of perforations. The template may have a higher surface energy than the mold. Generating the acid-providing gel layer may further include inverting the acid-providing gel layer after curing the gel prepolymer on the mold, positioning another template on the cured gel prepolymer, adding an additional portion of the gel prepolymer on the cured gel prepolymer, and curing the additional portion of the gel prepolymer. The template may include a plurality of pillars. The template may include a woven or non-woven material. The template may include polypropylene, polyethylene, or a combination thereof.

[0022] In some configurations, a method for generating a wound dressing agent includes generating an acid-providing gel layer. Generating the acid-providing gel layer includes positioning a material layer on a mold, adding a gel prepolymer on the material layer on the mold, and curing the gel prepolymer.

[0023] The method of the above paragraph may include one or more of the following features. Generating the acid-providing gel layer may further include floating a material layer on the gel prepolymer before curing the gel prepolymer. Generating the acid-providing gel layer may further include adding an additional portion of the gel prepolymer on the material layer and curing the additional portion of the gel prepolymer after curing the gel prepolymer. Generating the acid-providing gel layer may further include inverting the acid-providing gel layer, positioning another material layer on the cured gel prepolymer, adding an additional portion of the gel prepolymer on the cured gel prepolymer, and curing the additional portion of the gel prepolymer after curing the gel prepolymer on a mold. The material layer may include a woven or non-woven material. The material layer may include a mesh. The material layer may include polypropylene, polyethylene, or a combination thereof. The material layer may be pretreated with a wetting agent. The gel prepolymer may include a prepolymer for a hydrogel or a xerogel.

[0024] In some configurations, a method for treating a wound includes applying a wound dressing to the wound. The wound dressing 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 further includes one or more material layers.

[0025] The method of the above paragraph may include one or more of the following features. The method may further include generating nitric oxide. The method may further include enabling the nitrite ions of the nitrite to contact the acid-providing layer.

[0026] In some configurations, a wound dressing for treating a wound includes a cover layer, a nitrite-providing layer, and an acid-providing layer. The cover layer is configured to form a seal around the wound. The nitrite-providing layer contains nitrite. The acid-providing layer is positioned under the cover layer and contains acidic groups. The acid-providing layer includes one or more material layers fixed therein.

[0027] The wound dressing of the above paragraph may include one or more of the following features. One or more material layers may include a woven or non-woven material. One or more material layers may include a mesh. One or more material layers may include polypropylene, polyethylene, or a combination thereof. The acid-providing layer may include one material layer, and the material layer covers the side facing the wound on the lower side of the acid-providing layer. The acid-providing layer may include one material layer, and the material layer covers the upper side of the acid-providing layer opposite to the side facing the wound. The acid-providing layer may be sandwiched between one or more material layers. The acid-providing layer may be encapsulated by one or more material layers. One or more material layers may be embedded in the acid-providing layer. The acid-providing layer may include a xerogel or a hydrogel. The material layer may be fixed to the acid-providing layer without an adhesive. The acid-providing layer may include a plurality of perforations.

[0028] Alternative or additional embodiments described herein provide a composition comprising one or more of the features of the above description or any description elsewhere in this specification.

[0029] Alternative or additional embodiments described herein provide a wound contact layer comprising one or more of the features of the above description or any description elsewhere in this specification.

[0030] Alternative or additional embodiments described herein provide a wound dressing comprising one or more of the features of the above description or any description elsewhere in this specification.

[0031] Alternative or additional embodiments described herein provide a wound treatment system comprising one or more of the features of the above description or any description elsewhere in this specification.

[0032] Alternative or additional embodiments described herein provide a method of treating a wound comprising one or more of the features of the above description or any description elsewhere in this specification. BRIEF DESCRIPTION OF THE DRAWINGS

[0033]

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Mode for Carrying Out the Invention

[0034] 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 can include a nitrate delivery layer that contains nitrate 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 can 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 positioning separately at the wound site or can be incorporated into any number of multilayer wound dressings and wound treatment devices as described below 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.

[0035] 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 sustained 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.

[0036] Certain 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. Those skilled in the art will understand that when an apparatus / coating / layer is described as being disposed over or across 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 can 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.

[0037] 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 component layers thereof, or can include a composite or laminate including 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, one or more permeation layers and / or absorption layers 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 on 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.

[0038] One of ordinary skill in the art will understand that a nitric oxide generating composition, such as any disclosed in this "Summary" section of the present specification or elsewhere in the present specification, can be loaded into one or more nitric oxide generating layers in any suitable form, such as via adsorption, absorption, entanglement of chemical and / or physical adhesion, and / or in powder form. One of ordinary skill in the art will further understand that a reaction composition, such as any disclosed in this section of the present specification or elsewhere in the present specification, can be incorporated into any suitable absorption layer disclosed in this section or elsewhere in the present specification, and / or any suitable permeation layer disclosed in this section or elsewhere in the present specification, and / or any suitable foam layer disclosed in this section or elsewhere in the present specification, by any suitable means.

[0039] 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 positioned in proximity to the wound.

[0040] Some preferred embodiments described herein provide methods of treating a wound, non-wounded tissue, or other suitable site. Such methods may include placing a nitric oxide generating layer, either 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 methods may further include one or more of the following steps. A further wound dressing may be placed 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 other moist or aqueous medium other than a wound exudate, may be provided to reach and / or contact the nitric oxide generating layer. A wound exudate, or any other moist 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.

[0041] One of ordinary skill in the art will understand that the wound dressings, devices, and systems disclosed in this "Summary" section of the specification or elsewhere may include one or more layers, compositions, materials, or components that generate gases other than nitric oxide, in addition to or instead of the 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.

[0042] One of ordinary skill in the art will further understand that carbon monoxide and / or hydrogen sulfide can, where suitable, 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-methalamide 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.

[0043] Method for treating a wound Some preferred embodiments described herein provide methods for treating wounds, non-injured tissue, or other suitable locations. Such methods can include placing one or more nitric oxide generating layers, either separately or as part of 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 around the wound. The method can further include one or more of the following steps. Additional wound dressings can be placed 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 other moist 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 other moist 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 drawn 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.

[0044] As described above or elsewhere in this specification, a method of treating a wound, non-wounded tissue, or other suitable site may further comprise delivering a 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, a method of treating a wound, non-wounded 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 pressure, negative pressure, and compressive pressure to the wound through the wound contact layer in a programmable manner.

[0045] In embodiments, a method of treating a wound, non-wounded 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.

[0046] In some embodiments, a method of treating a wound, non-wounded 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 to 72 hours after positioning the wound dressing agent in contact with the microorganisms.

[0047] 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 helps close and heal many forms of “difficult to heal” wounds by reducing tissue edema, promoting blood flow and granulation tissue formation, removing excessive exudate, and reducing 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 fluid and stabilizing tissue at the parallel sites of closure. Further beneficial uses of TNP treatment can be found in grafts and flaps where removal of excess fluid is important and the graft is required to be in proximity to the tissue to ensure tissue viability.

[0048] As used herein, a negative pressure or negative pressure 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, in other words, 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.

[0049] Negative pressure ranges for some embodiments of the present disclosure can be about -80 mmHg, or between about -20 mmHg and -200 mmHg. It should be noted that these pressures are relative to 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 between about -40 mmHg and -150 mmHg. Alternatively, pressure ranges of -75 mmHg or less, -80 mmHg or less, or greater than 80 mmHg can be used. Also, in other embodiments, pressure ranges below -75 mmHg can be used. As an alternative, pressure ranges of approximately -100 mmHg or even above -150 mmHg can be supplied by a negative pressure device.

[0050] In some embodiments of the wound closure devices described herein, an increase in wound reduction can lead to an increase in tissue expansion in the surrounding wound tissue. This effect may, in some cases, be enhanced 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 varied over time using, for example, 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 patents are hereby incorporated by reference in their entirety.

[0051] The embodiments of the wound dressing, 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 on May 22, 2013 as International Application No. PCT / IB2013 / 001469 and published as International Publication No. 2013 / 175306 (A2) on November 28, 2013, and "WOUND DRESSING", filed on July 31, 2013 as International Application No. PCT / IB2013 / 002060 and published as WO2014 / 020440, the disclosures of which are hereby incorporated by reference in their entirety. The embodiments of the wound dressing, 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 U.S. Patent Application Publication No. 2016 / 0339158, published on November 24, 2016, entitled "FLUIDIC CONNECTOR FOR NEGATIVE PRESSURE WOUND THERAPY", each of their disclosures being hereby incorporated by reference in their entirety, including further details regarding the embodiments of the wound dressing, the components and principles of the wound dressing, and the materials used in the wound dressing.

[0052] 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 entirety 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.

[0053] Multilayer wound dressing for NPWT Figure 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 a 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.

[0054] One or more luminal tubes or conduits 740 connect the wound dressing 720 to a negative pressure device 750 configured to supply a 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 by 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.

[0055] 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.

[0056] 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 a pump as 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 a 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 suitably prepared wound, which in some cases may 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 a gap in the dressing 100 and sealed to the uppermost 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. Thereafter, the pump is activated, thereby supplying negative pressure to the wound. Application of the negative pressure may be applied until a desired level of wound healing is achieved.

[0057] 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 near or on the end or corner of the dressing 100, such as at or away from the 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 can be 30 mm in dimension 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.

[0058] 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 herein 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 backing layer 220 attached to the top layer or cover layer, or 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, and 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.

[0059] As used herein, the upper layer, top layer, or upper layer refers to the layer that is farthest from the surface of the skin or wound while the dressing 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 surface of the skin or wound while the dressing is in use and positioned over the wound.

[0060] As illustrated in FIG. 2C, the wound contact layer 222 may be a polyurethane layer, a polyethylene layer, or other 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 helps prevent tissue ingrowth into 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 help prevent tissue ingrowth into the wound dressing while allowing wound exudate to flow into the dressing. In some configurations, the wound contact layer 222 may help 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.

[0061] 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, hydrocolloid 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 surrounding 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.

[0062] The permeable layer 226 may be positioned 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 site. 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 absorbs 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.

[0063] 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 an entire component layer or as 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.

[0064] One or more nitric oxide generating layers can be constructed to be flexible yet rigid 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.

[0065] In some embodiments, the absorbent layer 221 is provided above the permeable layer 226. The absorbent, which can include a foam or nonwoven natural or synthetic material and optionally a superabsorbent, forms a reservoir for fluids, specifically liquids removed from the wound site. In some embodiments, layer 221 can also assist in drawing fluid towards the backing layer 220.

[0066] The material of the absorbent layer 221 can 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 distribute the fluid throughout the layer by a wicking action so as to draw the fluid from the wound site and store it throughout the absorbent layer. This thereby aids in preventing agglomeration over the area of the absorbent layer. The capacity of the absorbent material must be sufficient to manage the rate at which wound exudate flows when a negative pressure is applied. During 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 can typically be manufactured from Freudenberg 114 - 224 - 4 of ALLEVYN (trademark) foam or Chem-Posite (trademark) 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.

[0067] 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 throughout the layer. The use of cellulose fibers introduces a high-speed wicking element that helps to quickly and evenly distribute 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 assists in bringing the liquid into contact with the upper cover layer in order to help increase the evaporation rate of the dressing.

[0068] Preferably, a gap, hole, or orifice 227 is provided in the backing layer 220 so that a negative pressure can 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 the 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 drawn 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 can 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 can be made from a soft or conformable material.

[0069] Optionally, the absorbent layer 221 includes at least one through hole 228 disposed so as to be under the fluid connector 110. The through hole 228 may be the same size as the opening 227 of the backing layer in some embodiments, or may be larger or smaller. As illustrated in FIG. 2C, a single through hole can 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 a particular embodiment 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 certain embodiments of the present disclosure, using through holes in the superabsorbent layer may provide an unblocked fluid flow path, particularly when the absorbent layer is near saturation.

[0070] 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 permeation layer 226. Thereby, the negative pressure applied to the fluid connector 110 can be transmitted to the permeation 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 the 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 permeation 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.

[0071] 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 serves to cover the wound and seal the wound cavity in which the wound dressing is placed. 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 adhesion 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 enables the movement of liquid from the wound exudate through the layer and evaporation from the outer surface of the film. The backing layer 220 preferably comprises two layers, namely, a polyurethane film and an adhesive pattern spread over 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.

[0072] The absorbent layer 221 may have an area larger than that of the permeable layer 226 such that the absorbent layer overlaps 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 is in direct contact with the wound contact layer 222 and aids in the more rapid absorption of exudate into the absorbent layer. Further, this outer channel ensures that liquid cannot accumulate at the outer periphery of the wound cavity, which otherwise could seep out from the seal around the dressing and lead to the formation of a leak. 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.

[0073] 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. During 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 diameter of the wound-facing portion of the fluid connector 11 or the orifice 227.

[0074] In particular, 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 this way, the fluid connector 110 and the filter 214 may be less likely to contact wound fluid that could prematurely occlude the filter 214 to prevent transmission of negative pressure to the wound site.

[0075] 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 that heads 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 of 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.

[0076] FIG. 2D illustrates one embodiment of a wound dressing similar to the wound dressings of FIGS. 2A-2C. Referring to FIG. 2D, the 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 windows or apertures. Examples of wound dressings having a concealment layer and a visual window are described in International Patent Publication No. WO2014 / 020440, which is 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.

[0077] 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 create an opening under the port 2150. In certain embodiments, the port may be replaced with or used in combination with a fluid connector as illustrated in FIG. 2C. It will be understood that multiple openings may be utilized as an alternative. 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 layer and the concealment layer 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, particularly when the absorbent layer 2110 is near saturation.

[0078] 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.

[0079] 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 minor change, the patient is unlikely to notice any aesthetic differences. Reducing or eliminating visual indicators of wound exudate from the patient's wound is likely to have a beneficial effect on the patient's health, for example, reducing stress.

[0080] In some embodiments, the concealment layer can be formed from a non-woven fabric (e.g., polypropylene) and can be thermally bonded using a diamond pattern having a bonding area of 19%. In various embodiments, the concealment layer can be hydrophobic or hydrophilic. Depending on the application, in some embodiments, the hydrophilic concealment layer can provide additional moisture permeability. However, in some embodiments, the hydrophobic concealment layer can still provide sufficient moisture permeability (i.e., through appropriate material selection, thickness of the concealment layer), while also allowing for better retention of dyes or colors in the concealment layer. Thus, the dyes or colors can be confined under the concealment layer. In some embodiments, this can allow the concealment layer to be colored in a bright color or white. In a preferred embodiment, the concealment layer is hydrophobic. In some embodiments, the concealment layer material can be sterilizable using ethylene oxide. Other embodiments can be sterilized using gamma irradiation, electron beam, steam, or other alternative sterilization methods. Additionally, in various embodiments, the concealment layer can be colored or tinted, for example, in a medical blue color. The concealment layer can also be constructed from multiple layers, including a colored layer laminated or fused to a stronger non-colored layer. Preferably, the concealment layer is odorless and exhibits minimal shedding of fibers.

[0081] Multilayer covering material 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 can 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 can 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 can include various layers positioned between the wound contact layer 505 and the cover layer 501. For example, the dressing can include one or more absorbent layers or one or more permeable layers, as described herein with reference to Figures 2A-2C.

[0082] As shown in Figures 3A-3E, the dressing 500 can 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 can be provided to enable odor control. An absorbent layer 502, such as a layer of superabsorbent wicking material containing cellulose fibers and superabsorbent polyacrylate particles, is provided over layer 504 and is slightly larger in dimension than layer 504 to allow for overlap of the superabsorbent material and act as a leak barrier. 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 top surface of the superabsorbent where colored exudate remains. In this embodiment, this is of a smaller dimension (plan view) than layer 502 and can be used by a clinician to visualize the edge of the absorbent layer to evaluate whether the dressing needs to be changed.

[0083] 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 of the specification or elsewhere in the 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.

[0084] 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.

[0085] Further details regarding wound dressings that can be combined with or used in addition to the embodiments described herein can be found in U.S. Patent No. 9,877,872, issued on January 30, 2018, entitled "WOUND DRESSING AND METHOD OF TREATMENT", the disclosure of which is hereby incorporated by reference in its entirety herein, including further details relating to embodiments of wound dressings, components and principles of wound dressings, and materials used in wound dressings.

[0086] Multilayer wound dressing with integrated negative pressure source In some embodiments, some or all of the other components of the TNP system, such as a negative pressure source (such as a pump) and 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. Further, some embodiments regarding wound treatment comprising the wound dressings described herein can be combined with or used in addition to those described in International Application No. WO2016 / 174048 and International Patent Application No. PCT / EP2017 / 055225, filed on March 6, 2017, entitled "WOUND TREATMENT APPARATUSES AND METHODS WITH NEGATIVE PRESSURE SOURCE INTEGRATED INTO THE WOUND DRESSING", the disclosures of which are hereby incorporated by reference in their entirety herein and include further details relating to embodiments of wound dressings, components and principles of wound dressings, and materials used in wound dressings and components of wound dressings.

[0087] 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.

[0088] 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 embodiment, 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.

[0089] 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 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 the 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 spread over 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 in this specification, 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 a cover layer 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 the nitric oxide to the tissue so that the nitric oxide can interact with the user's body. One of ordinary skill in the art will understand that the cover layer can be made to be vapor-permeable but nitric oxide-impermeable.

[0090] 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 produces nitric oxide at the wound site when activated or otherwise stimulated to produce 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 producing nitric oxide at the wound site can be reduced. For example, the nitric oxide source layer 12600 and / or elements 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 alkali metal nitrates and / or alkaline earth metal nitrates. 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 ) 2or may contain any other suitable nitrite. In some embodiments, a precursor of nitrite ions, such as nitrous acid, nitrate ions, nitroprusside ions, or any of their pharmacologically acceptable salts, can be used as a source of nitrite. In some embodiments, the nitric oxide releasing agent may contain a 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.

[0091] In some embodiments, the nitric oxide releasing agent of the nitric oxide source layer 12600 may include diazeniumdiolates, including O-alkylated diazeniumdiolates, O-derivatized diazeniumdiolates, and non-O-derivatized diazeniumdiolates. 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 diazeniumdiolates. 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.

[0092] 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.

[0093] 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 can be 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.

[0094] 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 so that the nitric oxide source layer 12600 does not substantially adhere to the skin or wound or 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.

[0095] 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 a proton in an aqueous environment, thereby reducing the pH at the site of application. In certain embodiments, the acidic group or acidic moiety is fixed 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 embodiments, the activator layer 12400 may be 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 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, body fluids 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.

[0096] 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 2, 3, 4, 5, 6, 7 or more nitric oxide source layers and / or activator layers.

[0097] In some embodiments, the activator layer 12400 includes a hydrogel so that the activator layer 12400 can absorb wound exudate. In a specific example, the activator layer 12400 may be constructed from 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 the 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.

[0098] In some embodiments, instead of being provided as an active agent layer, such as active agent layer 12400, the active agent material for the active agent layer is provided as a dispensable composition, for example, a prepolymer solution or otherwise in a 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 in close proximity 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 functionality. 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 ultimately result in polymer formation immediately prior to 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 a change 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 upon application to the skin from a dispenser or syringe. 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.

[0099] When the coating 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

[0100] 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 coating 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 coating 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 coating material 12000. When the coating material 12000 is activated, the nitrogen monoxide releasing agent from the nitrogen monoxide source layer 12600 can disperse within the coating 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 coating material, for example, by a selectively permeable membrane, whereby the nitrogen monoxide can prevent the growth of microorganisms within the coating material or kill the microorganisms.

[0101] 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 reducing agent may lead to increased production of nitric oxide, but very high levels of reducing agent may be toxic.

[0102] 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 nitric oxide generating layers.

[0103] Nitric Oxide Dressing Materials and Structures As will be appreciated 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, may include a plurality of suitable constructs and different types of materials. For example, the top layer furthest from the wound may be a top or cover film layer, such as a polyurethane material or a top or cover layer as disclosed herein. Such a top or cover film may be constructed from the material used for the cover layer of the RENASYS drape, sold by Smith+Nephew. Beneath the top or cover film layer may be a masking or cloth layer, which may be constructed from any suitable material disclosed as a masking or cloth layer in this specification. The masking layer may 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 may also be utilized. In certain embodiments, the masking layer may be a foam. Beneath 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 may be constructed from a hydrogel adhesive, optionally containing a central polyester support mesh and / or a support release liner. The activator layer may be constructed from any suitable hydrogel material disclosed herein, such as acrylic acid hydrogel and / or sulfonic acid hydrogel. Beneath the activator layer may be a water-absorbing dispersion layer, which may 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 may be constructed from a 3-D knit woven in a net pattern, 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 may 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 may use the same material and may 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 dressing. In certain embodiments, the ALLEVYN or PICO dressings disclosed in FIGS. 2 and 3 can be placed directly over the activator layer and 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.

[0104] Chemiluminescence FIG. 6 shows an exemplary configuration 600 for a chemiluminescence protocol for testing a nitric oxide delivery coating, 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 instrument using an air flow at atmospheric pressure, the sample box 602 and the nitrogen supply can be connected to the instrument. 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 embodiments, 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.

[0105] 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, the NO / NO 2 concentration can be checked in ppm units.

[0106] 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 NO 2 is desirable. Nitrogen dioxide (NO 2 ) can exhibit antibacterial properties, but NO 2has neither vasodilatory properties nor the ability to activate cell proliferation of NO. Therefore, by removing oxygen from the body of the hydrogel where nitrite acidification occurs, or by means such as reducing the oxidation of dissolved nitric oxide (NO), NO is reduced as much as possible during nitrite acidification. 2 The generation of is generally desirable. The nitric oxide delivery coating material disclosed herein can generate both NO and NO. 2 In some embodiments, the nitric oxide coating material disclosed herein has an NO / NO 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., and can generate NO and NO. 2 In some embodiments, the nitric oxide coating material disclosed herein has an NO / NO 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., and can generate NO and NO. 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.

[0107] Figures 7A-7B show examples of experimental configuration 700 and subsequent results 750 that demonstrate 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 relation to 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 described herein in FIGS. 2A-2D. The dressing is sealed over a chamber 706 that contains 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 of time 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.

[0108] 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.

[0109] Figures 8A to 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 experimental 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 experimental 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.

[0110] Figure 8B shows the experimental results when testing a full coating design using a pull tab and a self-sealing boundary. The pull tab is initially used to separate the nitric oxide source layer from the activator layer. Therefore, when the tab is removed and the coating gets wet, the interaction between the nitric oxide source layer and the activator layer generates nitric oxide. In this experimental execution, after DI water was added, the full coating design with a pull 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.

[0111] Figure 8C shows an example of the experimental results for a coating containing a degradable film. Here, the degradable film is disposed between the activator layer and the nitric oxide source layer, such that once the degradable layer decomposes, nitric oxide is generated. In this experimental 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 at its first peak at the 80-minute mark, and 66 ppm of NO and 5 ppm of NO 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 at the 160-minute mark. 2 and released 66 ppm of NO and 5 ppm of NO at its second and maximum peak at the 110-minute mark, 2 and gradually decreased to approximately 45 ppm of NO and 2 ppm of NO at the 160-minute mark. 2 The concentration gradually decreased.

[0112] Figure 9 shows an example of the relative peak output in ppm for activator hydrogels (acid-providing) with or without a water-absorbing dispersion layer, including polypropylene, polypropylene ethylene, 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, but 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 increased fluid transport and an improved 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 NO2 The concentrations were approximately 30 ppm and 2 ppm, respectively. Polypropylene 40 g / m 2 In the hardened water-absorbed dispersion layer, peaks NO and NO 2 The concentrations were approximately 38 ppm and 5 ppm, respectively. Polypropylethylene 30 g / m 2 According to the pressure absorption dispersion layer, the peaks of NO and NO 2 The concentrations were approximately 35 ppm and 3 ppm, respectively. Polypropylethylene 30 g / m 2 In the hardened water-absorbed dispersion layer, peaks NO and NO 2 The concentrations were about 35 ppm and 3 ppm, respectively. The elastic polyester press-type water-absorbent dispersion layer showed peaks of NO and NO 2 The concentrations were approximately 35 ppm and 3 ppm, respectively. The FLEX pressurized water-absorption dispersion layer showed peaks of NO and NO 2 The concentrations were approximately 55 ppm and 8 ppm, respectively.

[0113] 10A-10D show NO and NO over time for several embodiments incorporating an active agent layer and a nitric oxide providing layer. 2 Examples of concentrations of sodium isoascorbate are shown. As shown in Figures 10A-10B, activator layers containing about 2-3% sodium isoascorbate were tested with or without different water absorption / dispersion layers pressed or cured. The gel without the water absorption / dispersion layer produced pNO = 785 ppm and pNO2 = 78 ppm (p indicates peak). The activator layer with stretchable polyester pressed into the gel produced pNO = 506 ppm and pNO2 = 24 ppm. For the stretchable polyester cured on the activator layer, pNO = 625 ppm, pNO2 = 50 ppm. For the polypropylene pressed into the gel, pNO = 508 ppm and pNO2 = 26 ppm. For the polypropylene cured into the gel, pNO = 624 ppm and pNO2 = 26 ppm.

[0114] Figures 10C and 10D show the NO and NO 2 concentration over time for an activator layer containing about 1-2% sodium isoascorbate with or without different water-absorbing and dispersing layers that are pressed or cured. The activator layer without an ADL produced pNO = 334 ppm and pNO2 = 40 ppm. For the stretchable polyester water-absorbing and dispersing layer pressed into the activator layer, pNO = 211 ppm and pNO2 = 10 ppm. For the stretchable polyester water-absorbing and dispersing layer cured in the activator layer, pNO = 247 ppm and pNO2 = 14 ppm. For the polypropylene water-absorbing and dispersing layer pressed into the activator layer, pNO = 112 ppm and pNO2 = 5 ppm. For the polypropylene water-absorbing and dispersing layer cured in the activator layer, pNO = 184 ppm and pNO2 = 8 ppm. As described elsewhere herein, curing the water-absorbing and dispersing layer in the activator layer can improve fluid treatment and nitric oxide production compared to nitrogen dioxide production.

[0115] Xerogel and hydrogel constructs Reference may be made herein 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 having 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.

[0116] 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 solution of sodium 2-acrylamido-2-methyl-1-propanesulfonate can be present in the xerogel. The hydrogel and xerogel can be prepared by dissolving acrylamido-2-methyl-1-propanesulfonic acid (SA) stabilized with supplied MEHQ 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 minimal amount of light in the 2-hydroxy-2-methylpropiophenone photoinitiator in PEG diacrylate, 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 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS acid) and glycerol for 10 to 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 the mold to form a gel three times as thick.

[0117] Layer of nitric oxide generating coating material Figures 11 and 12 illustrate a wound dressing 14000 having a nitric oxide generating layer. The wound dressing 14000 can be similar to the wound dressing 12000. The wound dressing 14000 can include a cover layer 14200, an activator layer or acid providing layer 14400, and a nitric oxide source layer or nitrite providing layer 14600, each of which can 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.

[0118] The cover layer 14200 may be similar to the cover layer 12200. The cover layer 14200 may have a greater length and width than 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 so that wound exudate can be contained within the wound dressing 14000 and form a seal.

[0119] In the illustrated embodiment, the wound dressing 14000 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 14000. 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 faster 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 1 to 220 grams per square meter (gsm) (or about 1 to about 220 gsm), 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 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 0.07 mm to 7.0 mm, 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.

[0120] 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 having 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.

[0121] 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 14800 that is greater than the thickness of the water-absorbing and dispersing layer 14800. 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 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.

[0122] In some embodiments, at least a portion of the fiber volume of the water absorption dispersion layer 14800 can extend vertically (i.e., perpendicular to the planes of the top and bottom surfaces of the material), or substantially or approximately perpendicular. 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 can extend vertically, or substantially, or approximately vertically. Such fiber orientation can facilitate the vertical suction of fluid through the water absorption dispersion layer 14800. In some embodiments, the ratio of the amount of fluid suctioned vertically across the water absorption dispersion layer 14800 to the amount of fluid suctioned laterally through the water absorption dispersion 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.

[0123] In some embodiments, the water absorption dispersion layer 14800 can be positioned under the acid-providing layer 14400, as shown in FIGS. 11 and 12. In some embodiments, the water absorption dispersion layer 14800 can be positioned above the acid-providing layer 14400.

[0124] In some embodiments, a wound dressing having a nitric oxide generating layer can include two or more water absorption dispersion layers. FIGS. 13 and 14 illustrate a wound dressing 16000 having a first water absorption dispersion layer 16820 and a second water absorption dispersion layer 16840, which are two water absorption dispersion layers. The wound dressing 16000 further includes a cover layer 16200, an acid-providing layer 16400, and a nitrite-providing layer 16600, which are similar to the cover layer 14200, the acid-providing layer 14400, and the nitrite-providing layer 14600, respectively. The first water absorption dispersion layer 16820 and the second water absorption dispersion layer 16840 are similar to the water absorption dispersion layer 14800 of the wound dressing 14000.

[0125] As illustrated in FIGS. 13 and 14, the acid-providing layer 16400 can be sandwiched between a first fluid dispersion layer 16820 and a second fluid dispersion layer 16840. In some embodiments, both the first and second dispersion layers can be positioned above or below the acid-providing layer 16400.

[0126] In some embodiments, one or more layers of the nitric oxide-generating wound dressing can be transparent. For example, the cover layers such as cover layer 12200, cover layer 14200, and cover layer 16200 can be transparent. Further, acid-providing layers such as acid-providing layer 12400, acid-providing layer 14400, and acid-providing layer 16400 can be translucent when wet because the hydrogel material contacts, for example, wound exudate. In some embodiments, the masking layer can be positioned within the wound dressing to prevent visualization of the wound or wound exudate through the cover layer or acid-providing layer.

[0127] FIGS. 15 and 16 illustrate a wound dressing 18000 that includes a cover layer 18200, an acid-providing layer 18400, a nitrite-providing layer 18600, and a water-absorbing dispersion layer 18800. The wound dressing 18000 can be similar to dressings 14000, 16000, and the layers of the wound dressing 18000 can be similar to the corresponding layers of the wound dressings 14000 and 16000, except as described herein.

[0128] The wound dressing 18000 may include a masking or concealing layer 18900 to prevent visualization of the wound or wound exudate through the cover layer 18200 or the acid-providing layer 18400. The masking or concealing layer 18900 may be positioned under at least a portion of the cover layer 18200. In some embodiments, the concealing layer 18900 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 a visual window are described in International Patent Publications WO2013 / 007973 and WO2014 / 020440, which are incorporated herein by reference in their entirety. Additionally, the concealing layer 18900 may be positioned directly under the cover layer 18200 or adjacent to any other desired dressing layer. In the illustrated embodiment, the concealing layer 18900 is positioned between the cover layer 18200 and the acid-providing layer 18400. In some embodiments, the concealing layer 18900 may be adhered to the cover layer or formed integrally with the cover layer 18200. The concealing layer 18900 may have substantially the same size and shape as the acid-providing layer 18400 and may be configured to overlay it. Thus, in these embodiments, the concealing layer 18900 has a smaller area than the cover layer 18200. In some embodiments, a water-absorbing and dispersing layer, such as the water-absorbing and dispersing layer described elsewhere herein, may be opaque and function as a masking or concealing layer.

[0129] Construction of the nitric oxide generating dressing In some embodiments, at least a portion of the layers of wound dressings 12000, 14000, 16000, 18000 can be attached to each other to prevent peeling of the layers. In some embodiments, one or more layers of wound dressings 12000, 14000, 16000, 18000 can include an adhesive coating for attachment. In some embodiments, one or more layers of wound dressings 12000, 14000, 16000, 18000 can be sticky or adhesive even when they do not have an additional adhesive coating so that they can be attached to adjacent layers. For example, layers 12400, 14400, 16400, 18400 have adhesive properties and can be attached to other layers. However, when the layers absorb moisture or wound exudate, the adhesive properties of the layers may be lost or weakened, which can result in peeling of the layers. Therefore, additional means for securing the layers of the wound dressing are desirable.

[0130] Figures 17 and 18 illustrate the wound dressing 20000. The wound dressing 20000 is similar to the wound dressing 16000 and includes a cover layer 16200, a first water-absorbing and dispersing layer 16820, an acid-providing layer 16400, a second water-absorbing and dispersing layer 16840, and a nitrite-providing layer 16600. The layers of the wound dressing 20000 can be similar to the corresponding layers of the wound dressing 16000 except as described herein. The wound dressing 20000 further includes a frame layer 20100. The frame layer 20100 is positioned on the side facing the wound or the bottom side of the dressing 20000 and can cover at least the boundary region of the wound dressing 20000. The frame layer 20100 can be a polyurethane layer or a polyethylene layer, or another flexible layer. The frame layer 20100 has a lower surface and an upper surface. In some embodiments, at least a portion of the upper surface of the frame layer 20100 is attached to the cover layer 20200. In some embodiments, at least a portion of the lower surface of the frame layer 20100 can be attached to the skin around the wound. In some embodiments, the frame layer 20100 includes a window 20110 such that fluid communication is enabled between the nitrite-providing layer 20600 and the other layers of the wound dressing 20000. In some embodiments, the window 20110 has the same or a larger size as the nitrite-providing layer 20600 such that the nitrite-providing layer 20600 is positioned within the window 20110. In some embodiments, the frame layer 20100 is positioned under the second water-absorbing and dispersing layer 20840 and / or the acid-providing layer 20400. In some embodiments, the water-absorbing and dispersing layers 20820 and 20840, and / or the acid-providing layer 20400 are completely surrounded by the cover layer 20200 and the frame layer 20100 except for the window 20110. In some configurations, the frame layer 20100 can help maintain the integrity of the entire dressing 20000 while forming a liquid-tight seal around the wound. As shown in Figures 19 and 20, in some embodiments, the frame layer 20100 can be a wound contact layer 20900, such as the wound contact layer described elsewhere herein, and may not include the window 20110.The wound contact layer 20900 can be shaped and / or sized to enable fluid communication from the nitrite-providing layer 20600 to other layers such as the water-absorbing dispersion layers 20820 and 20840 or the acid-providing layer 20400. The wound contact layer 20900 can include perforations to facilitate fluid communication through the wound contact layer 20900. One or both sides of the wound contact layer 20900 can be coated with an adhesive.

[0131] In some embodiments, delamination of the layers of the wound dressing can be prevented by physically joining the layers, such as by adhesive, welding, or suturing. FIG. 21 illustrates a cross-sectional view of a hydrogel layer 22400 encapsulated within a first water-absorbing dispersion layer 22820 and a second water-absorbing dispersion layer 22840. As illustrated in FIG. 21, the outer edges of the first and second water-absorbing layers 22820 and 22840 can be attached around the hydrogel layer 22400 such that the first and second water-absorbing layers 22820 and 22840 and the hydrogel layer 22400 are assembled as a single piece. The first and second water-absorbing layers 22820 and 22840 can be attached to each other at their outer edges by adhesive, heat welding, suturing, or any other suitable means. In some embodiments, the first and second water-absorbing dispersion layers 22820 and 22840 are formed as a single layer, and the hydrogel layer 22400 can be wrapped and / or encapsulated by the single layer of the water-absorbing dispersion layer. In some embodiments, the first water-absorbing dispersion layer 22820 and / or the second water-absorbing dispersion layer 22840 can be a concealment layer, such as the concealment layer 18900 or any other layer described elsewhere in this specification.

[0132] FIG. 22 illustrates a cross-sectional view of a hydrogel layer 23400 sandwiched between a first water-absorbent dispersion layer 23820 and a second water-absorbent dispersion layer 23840. As illustrated in FIG. 25, the first water-absorbent dispersion layer 23820 and the second water-absorbent dispersion layer 23840 are joined to each other and to the hydrogel layer 23400 by stitching (23900) through the hydrogel layer 23400 at one or more points. In some embodiments, the first and second water-absorbent dispersion layers 23820 and 23840 may be spot-welded at multiple points through the hydrogel layer 23400. As described elsewhere herein, the hydrogel layer 23400 may be perforated, and the first and second dispersion layers 23820 and 23840 may be joined through the perforations of the hydrogel layer 23400. In some embodiments, the first water-absorbent dispersion layer 22820 and / or the second water-absorbent dispersion layer 22840 may be a concealing layer, such as the concealing layer 18900 or any other layer described elsewhere herein.

[0133] As shown in FIGS. 23 and 24, the wound dressing 14001 may further include a masking element, masking layer, or concealing layer 14901 to prevent visualization of the wound or wound exudate through the cover layer 14201 or the acid-providing layer 14401. The masking layer or concealing layer 14901 may be positioned under at least a portion of the cover layer 14201. In some embodiments, the masking or concealing layer 14901 may be positioned on top of the cover layer 14201. In some embodiments, the concealing layer 14901 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 incorporated herein by reference in their entirety. Additionally, the concealing layer 14901 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 14901 is positioned between the cover layer 14201 and the acid-providing layer 14401. In some embodiments, the concealing layer 14901 may be adhered to or integrally formed with the cover layer 14201. The concealing layer 14901 may have substantially the same size and shape as the acid-providing layer 14401 and may be configured to overlay it. Thus, in these embodiments, the concealing layer 14901 has an area that is the same as or smaller than the cover layer 14201. In some embodiments, the masking or concealing layer 14901 may be able to draw fluid horizontally and / or vertically and may similarly function as a moisture-absorbing and dispersing layer. In some embodiments, the cover layer 14201 may be partially or completely opaque or colored such that the cover layer 14201 functions as a masking or concealing layer and can prevent visualization of the wound or wound exudate through the cover layer 14201 and / or prevent visualization of the layer under the cover layer 14201.

[0134] The masking layer or the concealment layer 14901 can be constructed from one or more polymers such as polypropylene, polyester, polyurethane, polyvinyl chloride, polyamide, viscose, polyester, polypropylene, cellulose, or any copolymer thereof. In some embodiments, the masking layer or the concealment layer 14901 can include a foam, a mesh, or any other suitable type of material. In some embodiments, the masking layer or the concealment layer 14901 can be at least partially coated with a hydrophobic coating so as to prevent excessive immersion by wound exudate. The hydrophobic coating can be applied to the lower side facing the wound of the masking layer 14901, the opposite upper side, or either or both sides. In some embodiments, the masking layer or the concealment layer 14901 can include a hydrophilic coating to facilitate the transport of wound exudate towards the evaporative cover layer 14201. The hydrophilic coating can be applied to the lower side facing the wound of the masking layer 14901, the opposite upper side, or either or both sides. In some embodiments, the masking layer 14901 can contain a reducing agent that facilitates the reduction of nitrite ions to nitric oxide. For example, the masking layer 14901 can contain hydroquinone, ascorbic acid, potassium iodide, erythorbic acid or sodium erythorbate, or sodium D-isoascorbate monohydrate, tocopherol, butylated hydroxyanisole, butylated hydroxytoluene, butylated hydroxyquinone, beta-carotene, lipoic acid, and / or uric acid. Further examples of reducing agents are described in International Patent Publication No. WO2009 / 019498, which is incorporated herein by reference in its entirety.

[0135] In some embodiments, the masking layer 14901 can be colored such that visualization of wound fluid in the underlying layer is prevented even when the layer is saturated with wound fluid. For example, the masking layer 14901 can be blue, pink, red, orange, or green. In some embodiments, the masking layer 14901 can be white such that wound exudate can be visible when the layer underlying the masking layer 14901 is saturated. In such embodiments, clinical determination of the spread of the exudate can be made by observing the spread of the exudate through the masking layer 14901.

[0136] In some embodiments, the masking layer 14901 has a size that is the same as or larger than the size of the acid-providing layer 14401, the water-absorbing dispersion layer 14801, the nitrite-providing layer 14601, and / or any other fluid-absorbing layer such that visualization of the wound exudate or layer underlying the masking layer 14901 can be completely blocked. In some embodiments, the masking layer 14901 has a size that is smaller than the size of the acid-providing layer 14401, the water-absorbing dispersion layer 14801, the nitrite-providing layer 14601, and / or any other fluid-absorbing layer such that one or more layers underlying the masking layer 14901 are visible around the edge of the masking layer 14901. For example, the acid-providing layer 14901 can be constructed from a hydrogel, and when the acid-providing layer 14401 is saturated and becomes transparent or changes color, such a change becomes visible from above and around the edge of the masking layer 14901 such that a clinician or patient is informed of a change in the wound condition, thereby triggering a change in the wound dressing or other suitable action. The masking layer 14901 may cover about 50% or more, 60% or more, 70% or more, 80% or more, 90% or more of the area of the layer directly beneath the masking layer 14901 (e.g., the acid-providing layer 14401).

[0137] In some embodiments, the masking layer 14901 may include one or more viewing windows that may enable visualization through the layers below the masking layer 14901. For example, the masking layer 14901 may include holes that extend through the thickness of the masking layer 14901. The holes may have any suitable shape, such as a circle, crescent, star, triangle, square, diamond, or any other suitable shape. The holes or viewing windows may constitute 5% or more, 10% or more, 20% or more, 30% or more, 50% or more, 70% or more, 90% or more of the area of the masking layer 14901. In some embodiments, the holes or viewing windows are evenly or substantially evenly spaced in the masking layer 14901.

[0138] In some embodiments, the wound dressing 14001 may include a display layer for indicating the therapeutic delivery of nitric oxide. For example, the display layer may include a polyurethane that changes color upon contact with nitric oxide or nitrogen dioxide. Such a color change may be used to indicate that nitric oxide is being generated and delivered to the wound. In some embodiments, the display layer may include any other polymer having a chemical group (e.g., an aromatic group) that exhibits a color change when exposed to nitric oxide. In some embodiments, other layers described elsewhere in this specification, such as the masking layer 14901 and / or the water-absorbing dispersion layer 14801, may include a material that changes color upon contact with nitric oxide or nitrogen dioxide such that the masking layer 14901 or the water-absorbing dispersion layer 14801 may indicate that nitric oxide is being generated and delivered to the wound. The display layer may be visible from above the wound dressing through the cover layer 14200 or any other layer.

[0139] In some embodiments, the wound dressing 14001 may include one or more layers having a color-changing indicator that changes color when exposed to nitrite. The color-changing indicator may be a Griess reagent. Such a color-changing indicator may indicate the presence of nitrite ions in the wound dressing 14001.

[0140] Material layer having a hydrogel layer As described elsewhere in this specification, the acid-providing layers 12400 and 14401 can be constructed from a gel such as a hydrogel. In embodiments, the hydrogel can have a tacky 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.

[0141] Continuing with FIGS. 23 and 24, in some embodiments, the acid-providing hydrogel layer 14401 can include one or more material layers 14421 as a shielding layer to mask at least a portion of the adhesive properties of the hydrogel. The material layer(s) 14421 can be applied to at least a portion of the lower side of the acid-providing hydrogel layer 14401 facing the wound and / or the side of the hydrogel layer 14401 that does not face the upper side of the wound. 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 side of the hydrogel layer. In some embodiments, the material layer can at least partially cover the upper and / or lower side 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 side 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.

[0142] In some embodiments, the material layer can be constructed from a suitable net, mesh, knitted, woven, or non-woven 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.

[0143] The hydrogel has adhesive properties, but 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.

[0144] 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. 25 illustrates a process of physically implanting or adhering a material layer inside or on the hydrogel layer during the formation of the hydrogel layer, according to some embodiments. As illustrated in FIG. 25, the material layer 16201 can be positioned in the mold 16401, for example, at the bottom of the mold 16401, to cure the hydrogel layer. Before being positioned in the mold 16401, the material layer 16201 can be pretreated to be hydrophilic using a wetting agent, for example, to improve its affinity with the hydrogel prepolymer.

[0145] After the material layer 16201 is positioned at the bottom of the mold 16401, 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 16201 can be substantially wetted with the first portion of the hydrogel prepolymer. The pre-treated material layer 16201 positioned at the bottom of the mold 16401 further facilitates the lateral spread of the hydrogel prepolymer, and the bottom of the mold 16401 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 16201 can rise from the bottom of the mold 16401 to the top of the hydrogel prepolymer. In some embodiments, the material layer 16201 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 16201 has risen, the first portion of the hydrogel prepolymer can be cured to form a first hydrogel layer 16501, and the material layer 16201 can be fixed to the top of the first hydrogel layer 16501, 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.

[0146] In some embodiments, after the first hydrogel layer 16501 is formed, a second portion of the hydrogel prepolymer can be added to the mold over the first hydrogel layer 16501 and the material layer 16201. After the second portion of the hydrogel prepolymer is added, the material layer 16201 can be encapsulated by the second portion of the hydrogel prepolymer and the first hydrogel layer 16501. Since the material layer 16201 is fixed to the first hydrogel layer 16501, it may not rise or float. The second portion of the hydrogel prepolymer can then be cured to form a second hydrogel layer 16701, and the material layer 16201 can be encapsulated by the hydrogel layers 16501 and 16701 that can be integrated within a single layer. The material layer 16201 implanted and embedded within the integrated hydrogel layer formed by the hydrogel layers 16501 and 16701 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 carried out in any suitable order and can involve the addition or removal of certain steps. FIG. 26 illustrates a process of physically implanting a material layer on both the upper and lower sides of a hydrogel layer during the formation of the hydrogel layer, according to some embodiments. However, those skilled in the art will understand that the material layer may be added to only one side. As illustrated in FIG. 26, after the first hydrogel layer 16501 having the material layer 16201 is formed as described in connection with FIG. 25, it is removed from the mold 16401, inverted, and returned into the mold 16401, whereby the side of the hydrogel layer 16501 having the material layer 16201 faces the bottom of the mold 16401.Next, another material layer 16801 is positioned on top of the hydrogel layer 16501, and then a second portion of the hydrogel prepolymer is added on top of the hydrogel layer 16501 and the material layer 16801. The material layer 16801 can float and rise to the top of the second portion of the hydrogel prepolymer in a manner similar to the material layer 16201 that floats during the formation of the hydrogel layer 16501, as described in connection with FIG. 25. After the material layer 16801 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 16901 together with the hydrogel layer 16501, and the material layer 16801 can be fixed to the top of the hydrogel layer 16901, thereby masking the upper side of the hydrogel layer 16901. The second portion of the hydrogel prepolymer can be cured by UV from the upper side, the lower side, or both sides, or by any other suitable method known in the art. As a result, the hydrogel layer 16901 can be sandwiched between the material layers 16201 and 16801, which are fixed to the hydrogel layer 16901.

[0147] Perforated hydrogel layer The acid-providing layer (e.g., a 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 the acid-providing layer can be transported to one or more additional absorbent layers and / or evaporation 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.

[0148] 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.

[0149] 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 surface 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 top of 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.

[0150] 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.

[0151] 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. Next, 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. Next, 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.

[0152] In some embodiments, shielding layers, such as shielding layers 16200 and 16800, may be perforated and may function as a mold plate 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. 25 and 26.

[0153] In some embodiments, the mold plate for the hydrogel layer can include a plurality of posts, and the hydrogel prepolymer can be poured around the posts 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 electrospump 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.

[0154] Nitric Oxide - Generating Wound Dressing for Treating the Area around a Wound In some cases, irritation of the area around 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 area around and / or at the wound edge. Delivery of nitric oxide to the area around and / or at the wound edge can target, for example, epithelial cell activity to promote movement of the epithelial tongue, vasodilation of the microcirculation of the skin around the wound to promote perfusion by providing oxygen and nutrients, and angiogenesis to promote granulation tissue formation.

[0155] Figures 27 and 28 illustrate a wound dressing 18001 for delivery of nitric oxide to the area around and / or at the wound edge, according to some embodiments. The wound dressing 18001 is similar to the wound dressing 14001 of FIG. 25 and can include a cover layer 18201, an acid - providing layer 18401, a water - absorbing dispersion layer 18801, and a nitrite - providing layer 18601. The layers of the wound dressing 18001 can be similar to the corresponding layers of the wound dressing 14001.

[0156] In the illustrated embodiment, the acid - providing layer 18401 is provided in a boundary region that includes a central absorbent 18451. The acid - providing layer 18401 and the central absorbent 18451 may or may not be attached to each other. In some embodiments, the acid - providing layer 18401 and the central absorbent 18451 may be provided as an integral component. The acid - providing layer 18401 can define a window at the center, and the central absorbent 18451 can be shaped and / or sized to fit within the window of the acid - providing layer 18401.

[0157] The acid-providing layer 18401 can be constructed from materials similar to the acid-providing layers 12400 and 14400. For example, the acid-providing layer 18401 can be constructed from a hydrogel or a xerogel and can contain acidic groups or acidic moieties. In some embodiments, the acid-providing layer 18401 can be constructed from a mesh, foam, gel, or any other material suitable for containing acidic groups or acidic moieties. The acid-providing layer 18401 can provide an acidic environment in the boundary region of the wound dressing 18001, thereby generating nitric oxide from the boundary region of the wound dressing 18001 for delivery around or at the wound boundary. As illustrated in FIG. 28, the acid-providing layer 18401 can be sized and / or positioned such that the acid-providing layer 18401 is at least partially positioned over the wound perimeter 18921. The acid-providing layer 18401 can include a plurality of perforations, or one or more material layers such as the material layers 16201 and 16801 described elsewhere in this specification.

[0158] In the illustrated embodiment, the acid-providing layer 18401 is in a frame shape. However, the acid-providing layer 18401 may have any other suitable shape or configuration. In some embodiments, the acid-providing layer 18401 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 boundary regions close to the immediate wound perimeter area. Each of the acid-providing strips can be positioned on the sides of the wound to create an acid-providing layer 18401 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 layers described herein.

[0159] The central absorbent 18451 can be positioned over the wound to absorb wound exudate. For example, as illustrated in FIG. 28, the central absorbent 18451 can be sized and / or positioned such that the central absorbent 18451 is at least partially positioned over the wound 18911. In some embodiments, the central absorbent 18451 may be the same size as the wound or larger than the wound such that the central absorbent 18451 completely covers the wound. In some embodiments, the central absorbent 18451 may be smaller than the wound such that the acid-providing layer 18401 can be positioned near the wound edge.

[0160] The central absorbent 18451 may comprise a foam or a non-woven natural or synthetic material, and optionally may include a superabsorbent, and may form a reservoir for fluids, specifically the liquid removed from the wound site. In some embodiments, the central absorbent 18451 may also assist in drawing fluid towards the cover layer 18200. The material of the central absorbent 18451 may also prevent the liquid collected within the wound dressing 18001 from freely flowing within the dressing, and preferably acts to contain any liquid collected within the dressing. The capacity of the absorbent material may be sufficient to manage the rate at which wound exudate flows when a negative pressure is applied. In some embodiments, the central absorbent 18451 may 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 18451 may be manufactured from Freudenberg 114-224-4 of ALLEVYN (trademark) foam or Chem-Posite (trademark) 11C-450. In some embodiments, the central absorbent 18451 may include a superabsorbent powder, a fibrous material such as cellulose, and binding fibers. In some embodiments, the composite is an aeolian, thermally bonded composite. In some embodiments, the central absorbent 18451 is a layer of non-woven cellulose fibers having superabsorbent in the form of dry particles dispersed throughout. The use of cellulose fibers may 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 may lead to a strong capillary action of the fiber pad that helps to disperse the liquid. Thus, the superabsorbent may be more efficiently supplied with liquid. In certain embodiments, the suction action may also assist in bringing the liquid into contact with the upper cover layer so as to assist in increasing the transpiration rate of the dressing.

[0161] The wound dressing 18001 further includes a frame layer 18101 that can further support the acid-providing layer 18401. The frame layer 18101 is positioned on the side facing the wound or the bottom side of the dressing 18001 and can cover at least the boundary region of the wound dressing 18001. The frame layer 18101 may be a polyurethane layer, a polyethylene layer, or another suitable flexible layer. The frame layer 18101 has a lower surface and an upper surface. In some embodiments, at least a portion of the upper surface of the frame layer 18101 is attached to the cover layer 18201. In some embodiments, at least a portion of the lower surface of the frame layer 18101 can be attached to the skin around the wound. In some embodiments, the frame layer 18101 includes a window 18111 to enable fluid communication between the nitrite-providing layer 18601 and the other layers of the wound dressing 18001. In some embodiments, the window 18111 has the same or a larger size as the nitrite-providing layer 18601 such that the nitrite-providing layer 18601 is positioned within the window 18111. In some embodiments, the frame layer 18101 is positioned under the water-absorbing dispersion layer 18801 and / or the acid-providing layer 18401. In some embodiments, the water-absorbing dispersion layer 18801 and / or the acid-providing layer 18401 are completely surrounded by the cover layer 18201 and the frame layer 18101 except for the window 18111. In some configurations, the frame layer 18101 can help maintain the integrity of the entire dressing 18001 while also forming a liquid-tight seal around the wound.

[0162] In some embodiments, instead of being provided as the acid-providing layer 18401, the acid-providing material may be provided as a dispensable composition, e.g., a prepolymer solution or otherwise 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 as to be applicable by a clinician in proximity around 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 such 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 in contact with a wound fluid or moisture such as, e.g., 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 may 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 specific pluronic so as to be curable when the temperature changes upon application from a dispenser or syringe to the skin. The acid-providing material may be applied so as to interact with nitrite from the nitrite-providing layer 18601 to generate nitric oxide. Once the acid-providing material is applied and cured or otherwise made non-flowing, the cover layer 18200 may be applied.

[0163] 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 18601. 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 cooperatively, 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 contacted 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 polyol may be provided to be mixed immediately before 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 does not substantially flow. In some embodiments, the first and / or second parts may include materials such as gels that change in response to changes in the environment. For example, the first and / or second parts may include a material such as a specific pluronic such that it can be cured when the temperature changes upon application to the skin from a dispenser or syringe.Once the first and second portions are mixed, applied, cured, or otherwise rendered non - flowing, the cover layer 18200 can be applied.

[0164] The term The above - mentioned patents, specifications, and other references, including any that may be listed in the attached application documents, are hereby incorporated by reference into this specification. Aspects of the present disclosure can be further modified, as necessary, to provide further embodiments using the systems, functions, and concepts of the various references described herein.

[0165] It should be understood that features, materials, properties, 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 claims, abstract, and drawings), or all steps of any method or process similarly disclosed, can 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 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.

[0166] Although certain embodiments are described, these embodiments are presented by way of example only and are not intended to limit the scope of the subject matter protected. In fact, the novel methods and systems described herein can be embodied in various other forms. Further, various omissions, substitutions, and changes can 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 implemented 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, or others may be added. For example, the actual steps or the order of steps implemented in the disclosed process may differ from those shown in the drawings. Depending on the embodiment, certain steps described above may be excluded, or others may be added. Further, the features and characteristics of the specific embodiments disclosed above can be combined in different ways to form additional embodiments, all of which fall within the scope of this disclosure.

[0167] This disclosure includes certain embodiments, examples, and applications, 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, including 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 can be defined by the claims presented herein or hereafter presented.

[0168] 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 interpreted otherwise within the context in which it is used. Thus, such conditional language is generally not intended to suggest 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 should be performed in any particular embodiment, is necessarily included in one or more embodiments, regardless of user input or the presence of instructions. Terms such as "comprising," "including," and "having" 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 (and 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" encompasses all of the following interpretations of the words with respect to the listing of two or more items: 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, can 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, when used in this application, mean the entire present specification and not a particular part of the present specification.

[0169] Conjunctive phrases such as the phrase "at least one of X, Y, and Z" are to be construed differently depending on the context in which they are generally used to suggest that an item, term, etc. can be any of X, Y, or Z, unless specifically described otherwise. Thus, such conjunctive phrases are generally 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.

[0170] Terms of degree as used herein, such as 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 yields the desired result. 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.

[0171] 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.

[0172] 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 is 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.

[0173] Various modifications to the embodiments described in this disclosure may be 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.

[0174] Certain embodiments of the present disclosure are subsumed in the claims presented at the end of this specification or in other claims presented later. [Additional Item 1] A wound dressing for treating wounds, comprising: one or more nitric oxide generating layers; and a water-absorbing and dispersing layer configured to suck up fluid horizontally and / or vertically. [Additional Item 2] The wound dressing according to Additional Item 1, further comprising a cover layer configured to form a seal around the wound. [Additional Item 3] The wound dressing according to Additional Item 1 or 2, wherein the one or more nitric oxide generating layers include a nitric oxide source layer. [Additional Item 4] The wound dressing according to any one of Additional Items 1 to 3, wherein the one or more nitric oxide generating layers include an activator layer. [Additional Item 5] The wound dressing according to Additional Item 4, wherein the water-absorbing and dispersing layer is positioned directly below the activator layer. [Additional Item 6] The wound dressing according to Additional Item 4 or 5, wherein the water-absorbing and dispersing layer is attached to the activator layer. [Additional Item 7] The wound dressing according to Additional Item 6, wherein the water-absorbing and dispersing layer is attached to the acid-providing layer by adhesion, suturing, or heat welding. [Additional Item 8] The wound dressing according to any one of Additional Items 4 to 7, further comprising a second water-absorbing and dispersing layer, wherein the activator layer is sandwiched between the two water-absorbing and dispersing layers. [Additional Item 9] The wound dressing according to Additional Item 8, wherein the activator layer is completely surrounded within the two water-absorbing and dispersing layers. [Additional Item 10] The wound dressing according to any one of Additional Items 1 to 9, wherein the water-absorbing and dispersing layer includes a plurality of fibers, and most of the plurality of fibers extend horizontally or substantially horizontally. [Additional Item 11] The wound dressing according to any one of Additional Items 1 to 10, wherein the water-absorbing and dispersing layer includes a plurality of fibers, and 80% to 90% of the plurality of fibers extend horizontally or substantially horizontally. [Additional Item 12] The wound dressing according to any one of Additional Items 2 to 11, wherein the cover layer is moisture-permeable. [Additional Item 13] The wound dressing according to any one of claims 2 to 12, wherein the cover layer has an outer circumference larger than the outer circumference of the activator layer, thereby defining a boundary region between the outer circumference of the cover layer and the outer circumference of the activator layer. [Claim 14] The wound dressing according to claim 13, wherein at least a part of the boundary region of the cover layer is configured to be sealed against the skin around the wound. [Claim 15] The wound dressing according to any one of claims 3 to 14, wherein the nitric oxide source layer contains an aqueous solution of the nitrite. [Claim 16] The wound dressing according to any one of claims 3 to 14, wherein the nitric oxide source layer contains dry nitrite. [Claim 17] The wound dressing according to claim 15 or 16, wherein the nitrite is selected from the group consisting of ammonium nitrite, calcium nitrite, sodium nitrite, and potassium nitrate. [Claim 18] The wound dressing according to any one of claims 3 to 17, wherein the nitric oxide source layer contains a mesh. [Claim 19] The wound dressing according to any one of claims 4 to 18, wherein the activator layer contains xerogel or hydrogel. [Claim 20] The wound dressing according to any one of claims 4 to 19, wherein the activator layer contains a foam. [Claim 21] The wound dressing according to any one of claims 4 to 19, wherein the activator layer has a plurality of perforations. [Claim 22] The wound dressing according to any one of claims 1 to 21, further comprising a concealment layer. [Claim 23] A method for treating a wound, comprising applying a wound dressing to the wound, the wound dressing comprising one or more nitric oxide generating layers, and a water-absorbing and dispersing layer configured to suck up fluid horizontally and / or vertically. [Claim 24] The method according to claim 23, further comprising generating nitric oxide. [Claim 25] The method according to claim 23 or 24, further comprising enabling the nitric oxide source to contact the activator layer. [Claim 26] The method according to any one of claims 23 to 25, wherein the water-absorbing and dispersing layer is pre-attached to one of the one or more nitric oxide generating layers before applying the wound dressing to the wound. [Claim 27] The method according to any one of appended claims 23 to 26, wherein the wound dressing further comprises a cover layer, the cover layer has an outer periphery larger than the outer periphery of the acid-providing layer, whereby a boundary region is defined between the outer periphery of the cover layer and the outer periphery of the acid-providing layer, and at least a part of the boundary region of the cover layer seals against the skin surrounding the wound. [Appended claim 28] The method according to any one of appended claims 23 to 27, wherein the wound dressing further comprises a concealment layer positioned between the acid-providing layer and the cover layer. [Appended claim 29] 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, the acid-providing layer further comprising one or more pores penetrating through the thickness of the acid-verifying layer. [Appended claim 30] The wound dressing according to appended claim 29, wherein the cover layer is moisture-permeable. [Appended claim 31] The wound dressing according to appended claim 29 or 30, wherein the cover layer has an outer periphery larger than the outer periphery of the acid-providing layer, thereby defining a boundary region between the outer periphery of the cover layer and the outer periphery of the acid-providing layer. [Appended claim 32] The wound dressing according to appended claim 31, wherein at least a part of the boundary region of the cover layer is configured to seal against the skin surrounding the wound. [Appended claim 33] The wound dressing according to any one of appended claims 29 to 32, wherein the nitrite-providing layer contains an aqueous solution of the nitrite. [Appended claim 34] The wound dressing according to any one of appended claims 29 to 32, wherein the nitrite-providing layer contains dry nitrite. [Appended claim 35] The wound dressing according to any one of appended claims 29 to 34, wherein the nitrite is selected from the group consisting of ammonium nitrite, calcium nitrite, sodium nitrite, and potassium nitrite. [Appended claim 36] The wound dressing according to any one of appended claims 29 to 35, wherein the nitrite-providing layer contains a mesh. [Appended claim 37] The wound dressing according to any one of appended claims 29 to 36, wherein the acid-providing layer contains xerogel or hydrogel. [Appended claim 38] The wound dressing according to any one of appended claims 29 to 37, wherein the acid-providing layer contains a foam. [Appended claim 39] The wound dressing according to any one of claims 29 to 38, further comprising a shielding layer positioned between the acid-providing layer and the cover layer. [Claim 40] A wound dressing comprising: A nitric oxide source layer having a plurality of through holes penetrating the thickness of the acid verification layer; A water-absorbing dispersion layer. [Claim 41] The wound dressing according to claim 40, further comprising a cover layer configured to form a seal around the wound. [Claim 42] The wound dressing according to claim 41, wherein the cover layer is moisture-permeable. [Claim 43] The wound dressing according to any one of claims 40 to 42, wherein the nitric oxide source layer contains an aqueous solution of the nitrite. [Claim 44] The wound dressing according to any one of claims 40 to 43, wherein the nitric oxide source layer contains dry nitrite. [Claim 45] The wound dressing according to claim 43 or 44, wherein the nitrite is selected from the group consisting of ammonium nitrite, calcium nitrite, sodium nitrite, and potassium nitrate. [Claim 46] The wound dressing according to any one of claims 40 to 45, wherein the nitric oxide source layer contains a mesh. [Claim 47] The wound dressing according to any one of claims 40 to 46, further comprising a shielding layer. [Claim 48] A wound dressing for treating a wound, comprising: One or more nitric oxide generation layers; A masking element configured to at least partially prevent visualization of the underlying layer. [Claim 49] The wound dressing according to claim 48, wherein the wound dressing further comprises a cover layer, and the masking element is positioned under the cover layer. [Claim 50] The wound dressing according to claim 48, wherein the wound dressing further comprises a cover layer, and the masking element is positioned on the cover layer. [Claim 51] The wound dressing according to claim 48, wherein the wound dressing further comprises a cover layer, and the cover layer is the masking element. [Claim 52] The wound dressing according to any one of claims 48 to 51, wherein the masking element comprises one or more viewing windows. [Claim 53] The wound dressing according to any one of claims 48 to 52, further comprising a water-absorbing dispersion layer. [Claim 54] The wound dressing according to claim 53, wherein the water-absorbing dispersion layer contains a plurality of fibers, and most of the plurality of fibers extend horizontally or substantially horizontally. [Claim 55] The wound dressing further comprises a cover layer, the cover layer having an outer periphery larger than the outer periphery of the acid-providing layer, thereby defining a boundary region between the outer periphery of the cover layer and the outer periphery of the acid-providing layer. The wound dressing according to any one of claims 48 to 54. [Claim 56] The wound dressing according to claim 55, wherein at least a part of the boundary region of the cover layer is configured to be sealed against the skin surrounding the wound. [Claim 57] The wound dressing according to any one of claims 48 to 56, wherein the nitric oxide generating layer comprises a nitrite-providing layer containing nitrite. [Claim 58] The wound dressing according to any one of claims 48 to 57, wherein the nitrite-providing layer contains an aqueous solution of the nitrite. [Claim 59] The wound dressing according to any one of claims 48 to 58, wherein the nitrite-providing layer contains dry nitrite. [Claim 60] The wound dressing according to any one of claims 57 to 59, wherein the nitrite is selected from the group consisting of ammonium nitrite, calcium nitrite, sodium nitrite, and potassium nitrite. [Claim 61] The wound dressing according to any one of claims 57 to 60, wherein the nitrite-providing layer comprises a mesh. [Claim 62] The wound dressing according to any one of claims 48 to 61, wherein the nitric oxide generating layer comprises an acid-providing layer containing an acidic group. [Claim 63] The wound dressing according to claim 62, wherein the acid-providing layer contains xerogel or hydrogel. [Claim 64] The wound dressing according to claim 62 or 63, wherein the acid-providing layer contains a foam. [Claim 65] The wound dressing according to any one of claims 62 to 64, wherein the acid-providing layer is provided with a plurality of perforations. [Claim 66] The wound dressing according to any one of claims 48 to 65, further comprising a display layer configured to change a display upon contact with nitric oxide. [Claim 67] The wound dressing according to any one of claims 48 to 66, wherein the masking element contains a material that changes a display upon contact with nitric oxide. [Claim 68] A method for treating a wound, comprising applying a wound dressing to the wound, the wound dressing comprising one or more nitric oxide generating layers, and a masking layer configured to at least partially prevent visualization of the underlying layer. [Claim 69] The method according to claim 68, further comprising generating nitric oxide. [Additional item 70] The method according to item 68 or 69, further comprising enabling nitrite ions to come into contact with an acid. [Additional item 71] 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; and A wound dressing in which visualization of the acid-providing layer and / or the nitrite-providing layer is prevented from above the cover layer. [Additional item 72] The wound dressing according to item 71, wherein the cover layer is at least partially opaque so as to prevent visualization of the acid-providing layer and / or the nitrite-providing layer under the cover layer. [Additional item 73] The wound dressing according to item 71 or 72, further comprising a water-absorbing and dispersing layer. [Additional item 74] The wound dressing according to item 73, wherein the water-absorbing and dispersing layer contains a plurality of fibers, and most of the plurality of fibers extend horizontally or substantially horizontally. [Additional item 75] The wound dressing according to any one of items 71 to 74, wherein the cover layer is moisture-permeable. [Additional item 76] The wound dressing according to any one of items 71 to 75, wherein the cover layer has an outer periphery larger than the outer periphery of the acid-providing layer, thereby defining a boundary region between the outer periphery of the cover layer and the outer periphery of the acid-providing layer. [Additional item 77] The wound dressing according to item 76, wherein at least a part of the boundary region of the cover layer is configured to be sealed against the skin around the wound. [Additional item 78] The wound dressing according to any one of items 71 to 77, wherein the nitrite-providing layer contains an aqueous solution of the nitrite. [Additional item 79] The wound dressing according to any one of items 71 to 77, wherein the nitrite-providing layer contains dry nitrite. [Additional item 80] The wound dressing according to any one of items 71 to 79, wherein the nitrite is selected from the group consisting of ammonium nitrite, calcium nitrite, sodium nitrite, and potassium nitrate. [Additional item 81] The wound dressing according to any one of items 71 to 80, wherein the nitrite-providing layer contains a mesh. [Additional item 82] The wound dressing according to any one of items 71 to 81, wherein the acid-providing layer contains xerogel or hydrogel. [Additional item 83] The wound dressing according to any one of appended claims 71 to 82, wherein the acid-providing layer contains a foam. [Appended claim 84] The wound dressing according to any one of appended claims 71 to 83, wherein the acid-providing layer has a plurality of perforations. [Appended claim 85] The wound dressing according to any one of appended claims 71 to 84, further comprising a display layer configured to change a display upon contact with nitric oxide. [Appended claim 86] The wound dressing according to any one of appended claims 71 to 84, wherein the cover layer contains a material that changes a display upon contact with nitric oxide. [Appended claim 87] 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, the acid-providing layer containing one or more material layers fixed therein. [Appended claim 88] The wound dressing according to claim 87, wherein the one or more material layers contain a woven or non-woven material. [Appended claim 89] The wound dressing according to claim 87 or 88, wherein the one or more material layers contain a mesh. [Appended claim 90] The wound dressing according to any one of appended claims 87 to 89, wherein the one or more material layers contain polypropylene, polyethylene, or a combination thereof. [Appended claim 91] The wound dressing according to any one of appended claims 87 to 90, wherein the acid-providing layer contains one material layer, and the material layer covers the side facing the wound on the lower side of the acid-providing layer. [Appended claim 92] The wound dressing according to any one of appended claims 87 to 91, wherein the acid-providing layer contains one material layer, and the material layer covers the upper side of the acid-providing layer opposite to the side facing the wound. [Appended claim 93] The wound dressing according to any one of appended claims 87 to 92, wherein the acid-providing layer is sandwiched between the one or more material layers. [Appended claim 94] The wound dressing according to any one of appended claims 87 to 93, wherein the acid-providing layer is encapsulated by the one or more material layers. [Appended claim 95] The wound dressing according to any one of appended claims 87 to 94, wherein the one or more material layers are embedded in the acid-providing layer. [Appended claim 96] The wound dressing according to any one of appended claims 87 to 95, wherein the acid-providing layer contains xerogel or hydrogel. [Appended claim 97] The wound dressing according to any one of claims 87 to 96, wherein the material layer is fixed to the acid-providing layer without an adhesive. [Claim 98] The wound dressing according to any one of claims 87 to 97, wherein the acid-providing layer comprises a plurality of perforations. [Claim 99] 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 nitrite-providing layer containing nitrite; an acid-providing layer positioned under the cover layer and containing an acidic group, the acid-providing layer comprising one or more material layers fixed therein. [Claim 100] The method according to claim 99, further comprising generating nitric oxide. [Claim 101] The wound dressing according to claim 99 or 100, further comprising enabling contact between nitrite ions of the nitrite and the acid-providing layer. [Claim 102] A method for producing a wound dressing, the method comprising: generating an acid-providing gel layer, positioning a material layer on a mold, adding a gel prepolymer on the material layer on the mold, and curing the gel prepolymer. [Claim 103] The method according to claim 102, wherein generating the acid-providing gel layer further comprises floating the material layer on the gel prepolymer before curing the gel prepolymer. [Claim 104] Generating the acid-providing gel layer comprises: after curing the gel prepolymer, adding an additional portion of the gel prepolymer on the material layer, and curing the additional portion of the gel prepolymer. [Claim 105] Generating the acid-providing gel layer comprises: after curing the gel prepolymer on the mold, inverting the acid-providing gel layer, positioning another material layer on the cured gel prepolymer, adding an additional portion of the gel prepolymer on the cured gel prepolymer, and curing the additional portion of the gel prepolymer. [Claim 106] The method according to any one of claims 102 to 105, wherein the material layer comprises a woven or non-woven fabric material. [Claim 107] The method according to any one of appended claims 102 to 106, wherein the material layer includes a mesh. [Appended claim 108] The method according to any one of appended claims 102 to 107, wherein the material layer includes polypropylene, polyethylene, or a combination thereof. [Appended claim 109] The method according to any one of appended claims 102 to 108, wherein the material layer is pretreated with a wetting agent. [Appended claim 110] The method according to any one of appended claims 102 to 109, wherein the gel prepolymer includes a prepolymer for a hydrogel or a xerogel. [Appended claim 111] A method for producing a wound dressing material, the method comprising: generating an acid-providing gel layer, positioning a template on a mold, adding a gel prepolymer on the template on the mold, the gel prepolymer not being present at a plurality of locations on the template and enabling the definition of a plurality of perforations, curing the gel prepolymer, and including generating. [Appended claim 112] The method according to claim 111, wherein the template includes a plurality of perforations. [Appended claim 113] The method according to claim 112, wherein the template has a higher surface energy than the mold. [Appended claim 114] Generating the acid-providing gel layer includes: inverting the acid-providing gel layer after curing the gel prepolymer on the mold, positioning another template on the cured gel prepolymer, adding an additional portion of the gel prepolymer on the cured gel prepolymer, and further curing the additional portion of the gel prepolymer. The method according to any one of claims 111 to 113. [Appended claim 115] The method according to any one of claims 111 to 114, wherein the template includes a plurality of columns. [Appended claim 116] The method according to any one of claims 111 to 115, wherein the template includes a woven or non-woven fabric material. [Appended claim 117] The method according to any one of claims 111 to 116, wherein the template includes polypropylene, polyethylene, or a combination thereof.

Claims

1. A wound dressing for treating a wound, comprising: one or more nitric oxide generating layers; and a masking element configured to at least partially prevent visualization of the underlying layer, wherein the wound dressing further comprises a water-absorbing and dispersing layer.

2. The wound dressing according to claim 1, wherein the wound dressing further comprises a cover layer, and the masking element is positioned under the cover layer.

3. The wound dressing according to claim 1, wherein the wound dressing further comprises a cover layer, and the masking element is positioned on the cover layer.

4. The wound dressing according to any one of claims 1 to 3, wherein the nitric oxide generating layer comprises a nitrite-providing layer containing nitrite.

5. 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; and an acid-providing layer positioned under the cover layer and containing an acidic group, the acid-providing layer comprising one or more material layers fixed therein, wherein the acid-providing layer comprises one material layer, and the material layer covers the side of the acid-providing layer facing the lower wound.

6. The wound dressing according to claim 5, wherein one or more of the material layers comprise a woven or non-woven material.

7. The wound dressing according to claim 5 or 6, wherein one or more of the material layers comprise a mesh.

8. The wound dressing according to any one of claims 5 to 7, wherein one or more of the material layers comprise polypropylene, polyethylene, or a combination thereof.

9. 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; and an acid-providing layer positioned under the cover layer and containing an acidic group, the acid-providing layer comprising one or more material layers fixed therein, wherein the acid-providing layer comprises one material layer, and the material layer covers the upper side opposite to the side of the acid-providing layer facing the wound.

10. 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 located under the cover layer and containing an acidic group, the acid-providing layer comprising one or more material layers fixed therein, and an acid-providing layer. A wound dressing in which the acid-providing layer is sandwiched between one or more of the material layers. **Claim 11**: 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 located under the cover layer and containing an acidic group, the acid-providing layer comprising one or more material layers fixed therein, and an acid-providing layer. A wound dressing in which the acid-providing layer is encapsulated by one or more of the material layers. **Claim 12**: The wound dressing according to any one of claims 5 to 11, wherein the acid-providing layer contains xerogel or hydrogel. **Claim 13**: The wound dressing according to any one of claims 5 to 12, wherein the material layer is fixed to the acid-providing layer without an adhesive. **Claim 14**: The wound dressing according to any one of claims 5 to 13, wherein the acid-providing layer has a plurality of perforations.

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