Systems and methods for administering nitric oxide using negative pressure wound therapy

Abstract

A system including a delivery solution that, when administered to a wound of a patient, includes a nitric oxide gas component. A negative pressure device is configured to create subatmospheric pressure at an application site surrounding the wound and is configured to provide instillation of the delivery solution to the wound of the patient.

Description

SYSTEMS AND METHODS FOR ADMINISTERING NITRIC OXIDE USING NEGATIVE PRESSURE WOUND THERAPYCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This patent application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application Ser. No. 63 / 642,255, filed on May 3, 2024; U.S. Provisional Application Ser. No. 63 / 670,350, filed on July 12, 2024 and U.S. Provisional Application Ser. No. 63 / 696,943, filed on September 20, 2024. The disclosures of these prior applications are considered part of the disclosure of this application and are hereby incorporated by reference in their entireties.FIELD

[0002] The present disclosure relates generally to systems and methods for administering nitric oxide therapy, such as using negative pressure wound therapy, multi-chamber intravenous bag systems and methods, and the like.BACKGROUND

[0003] This section provides background information related to the present disclosure which is not necessarily prior art.

[0004] Negative pressure wound therapy (NPWT), sometimes referred to as vacuum-assisted closure (VAC), is a wound management system that uses sub-atmospheric pressure to help wounds heal. NPWT can be used to treat a variety of wounds, including acute or chronic wounds, second- degree and third-degree bums, pressure ulcers, diabetic ulcers, and other injuries. NPWT can also be used to treat closed wounds, such as surgical incisions and skin grafts.

[0005] Negative pressure wound therapy with instillation (NPWTi) is a treatment for wounds that combines negative pressure sealing and drainage with irrigation and / or topical solutions. Some NPWT systems include instillation capabilities. For example, NPWTi systems typically include a vacuum system in conjunction with a liquid pump connected to an intravenous (IV) bag, which contains the solution to be instilled to the wound. However, many traditional NPWT systems do not include instillation capabilities. These systems would benefit from being retrofitted with an adapter to enable the NPWT systems to have instillation capabilities.

[0006] One example of an instillation solution that can be administered using NPWTi is a Nitric Oxide (NO) containing solution. NO is a molecular compound that is naturally occurring in vascular systems of the body produced by an enzyme or site-specific isozyme called nitric oxide synthases (NOS), and when available in sufficient concentration, plays a key role in the dynamic molecular and cellular skin wound healing processes.

[0007] In the epithelial layers of all blood vessels, this endogenous molecule is primarily produced by endothelial Nitric Oxide Synthase (eNOS) and acts as a signaling molecule where it is dispensed by vascular flows. NO can motivate important cellular functions found in the vascular response cascade associated with wound healing including vasodilation, contraction and clotting, closure, and NO-guided inflammation management. When appropriately activated and sustained by a sufficient concentration, NO is a powerful promoter of improved oxygenation and nutrient delivery as well as an anti-pathogenic within the biosphere of wounded tissues.

[0008] Likewise, when stimulated by excessive inflammation, inducible Nitric Oxide Synthase (iNOS) actively produces NO, which can terminate inflammatory neutrophilic and macrophagic functions and actively target and dismantle pathogens associated with chronic wound development leading up to scar formation, renewed cellular growth, and epithelial healing requisite to wound contraction and wound scar remodeling.

[0009] In some situations, due to age and / or concomitant disease, the body lacks sufficient NO concentration to produce and deliver sufficient synthase-driven NO on its own to overcome the initial stages of increasing inflammation which lead to chronic wounding. In such cases, an alternative exogenous NO supplementation may be required to move the body / wound through inflammation to later stages in the healing process.

[0010] Even so, NO supplementation poses significant challenges primarily associated with its short half-life (often estimated to be less than three seconds), and its proclivity to instantaneously react with ambient oxygen to form Nitrogen Dioxide (NO2), which in turn can further complicate the storage, transportation, and topical wound site application of NO. Moreover, methods for motivating the diffusion of NO directly into the wound pose significant challenges.SUMMARY

[0011] This section provides a general summary of the means and methods associated with the invention and is not a comprehensive disclosure of its full scope or of all its features.

[0012] One aspect of the disclosure provides a system that includes a delivery solution that, when administered to a wound of a patient, includes a nitric oxide gas component. The system includes a negative pressure device configured to create subatmospheric pressure at an application site surrounding the wound and configured to provide instillation of the delivery solution to the wound of the patient.

[0013] This aspect may include one or more of the following optional features. In some implementations, the delivery solution includes a first solution and a second solution that mix with one another and react to produce the nitric oxide gas component. In further implementations, the first solution and the second solution turbulently mix with one another, such as at a Reynold’s Number of 2,000 or more. In other implementations, the first solution and the second solution are delivered to the application site as one selected from the group consisting of (i) laminar flow and(ii) transitional flow. In these implementations, the first solution and the second solution may at least partially mix with one another at a drape at the wound of the patient.

[0014] In some examples, the delivery solution mixes with a reactant to generate the nitric oxide gas component to provide a therapeutic effect, and the reactant is disposed at one selected from the group consisting of (i) the skin of the patient, (ii) a dressing at the application site and(iii) a drape at the wound of the patient.

[0015] In some aspects, the wound includes at least one selected from the group consisting of (i) a diabetic foot ulcer, (ii) a pressure ulcer, (iii) an arterial ulcer, (iv) a venous ulcer, (v) a surgical wound, (vi) an open fracture, (vii) a fasciotomy, (viii) a skin graft, (ix) a bum, (x) a deep tissue injury, (xi) an abrasion, (xii) a skin tear, (xiii) a tendon tear and (xiv) a wound at risk of not healing.

[0016] In some implementations, the delivery solution includes a multiphasic liquid. In further implementations, the multiphasic liquid contains suspended particulates to provide additional therapy to the application site. In other implementations, the delivery solution includes a biphasic liquid.

[0017] Another aspect of the disclosure provides a method that includes providing a negative pressure device configured to provide instillation of a delivery solution. The method includes creating, via the negative pressure device, subatmospheric pressure at an application sitesurrounding a wound of a patient. The method includes suspending, via the negative pressure device, creation of the subatmospheric pressure at the application site. The method includes delivering the delivery solution to the application site, the delivery solution including a nitric oxide gas component when delivered to the application site, and the method includes instilling the delivery solution into the wound. This aspect may include one or more of the following optional features.

[0018] In some implementations, the delivery solution is produced by simultaneously delivering a first solution and a second solution and mixing the first solution and the second solution, resulting in a chemical reaction that produces the nitric oxide gas component of the delivery solution. In further implementations, the chemical reaction includes an acidified nitrite reaction. In further implementations, the first solution and the second solution are stored separately from one another. In further implementations, the first solution and the second solution are delivered to the application site through separate channels. In even further implementations, the channels for delivering the first solution and the second solution are each configured to prevent the first solution, the second solution, and the delivery solution from reentering the respective channels. In some further implementations, the first solution and the second solution mix with one another at the application site. In other further implementations, the first solution and the second solution mix with one another before entering the application site. In further implementations, the negative pressure device includes a dressing at the application site that is configured to promote mixing of the first solution and the second solution. In some further implementations, the first solution and the second solution are each delivered to the application site in predetermined quantities. In some further implementations, the delivery solution is removed from the application site via an off-take gas / liquid separator to sequester liquid from gas. In some implementations, the first solution and the second solution turbulently mix with one another. In some implementations, the method further includes delivering at least a third solution to the application site.

[0019] The delivery solution may include a multiphasic liquid that may include suspended particulates to provide additional therapy to the application site. Optionally, the delivery solution includes a biphasic liquid.

[0020] Yet another aspect of the disclosure provides a system including a dressing configured to form an airtight seal on the skin of a patient at an application site surrounding a wound of thepatient. A device is in fluid communication with the application site. The device alternates between exerting a subatmospheric force on the application site and instilling a delivery solution in the application site. The delivery solution includes a nitric oxide gas component. This aspect may include one or more of the following optional features.

[0021] In some implementations, the device includes a pump for exerting the subatmospheric force on the application site. In further implementations, the delivery solution includes a first solution and a second solution that mix with one another and react to produce the nitric oxide gas component. In even further implementations, the first solution and the second solution turbulently mix with one another to produce a biphasic flow of the delivery solution. In other further implementations, the first solution and the second solution are instilled in the application site via one or more pumps. In some further implementations, the first solution and the second solution are instilled in the application site in quantities sufficient to allow for full coverage of the application site without disrupting the airtight seal of the dressing. In some further implementations, the system includes a wound dressing, tubing, entry ports, a canister, an offtake valve, and a pump system that are non-reactive with the first solution, the second solution, and the nitric oxide gas component.

[0022] In some examples, the device alternates between exerting the subatmospheric force on the application site and instilling the delivery solution in the application site for a predetermined period of time. In other examples, the device alternates between exerting the subatmospheric force on the application site and instilling the delivery solution in the application site in a cyclical period. In some other examples, the device instills in the application site a steady amount of the delivery solution and outputs a steady amount of the delivery solution to provide a continuous flow of the solution while maintaining a predetermined constant pressure in the application site.

[0023] In some aspects, the device alternates between instilling in the application site a steady amount of the delivery solution maintained at a predetermined constant pressure and exerting the subatmospheric force on the application site without any of the delivery solution at the application site for a predetermined period of time. In some aspects, the device includes a release valve to release pressure in the dressing to maintain the airtight seal of the dressing while the nitric oxide gas component is produced in the application site.

[0024] Another aspect of the disclosure provides a system that includes a negative pressure wound therapy (NPWT) device capable of instillation of a delivery solution to an application sitesurrounding a wound of a patient. A lumen is in fluid communication with the NPWT device and a drape at the wound of the patient. A multi-compartment reservoir is in fluid communication with the NPWT device, and contains a first solution and a second solution to be used for instillation. A joining element is capable of introducing the first solution from a first compartment of the reservoir with a second solution from a second compartment of the reservoir in a manner to induce mixing of the delivery solution. This aspect may include one or more of the following optional features.

[0025] In some implementations, the first solution and the second solution, when introduced, create a reaction that produces a therapeutic gas. In some implementations, the therapeutic gas includes oxygen. In other implementations, the therapeutic gas includes nitric oxide. In further implementations, the first solution includes an acid and the second solution includes a nitrite salt. The nitric oxide may provide a therapeutic effect to the wound of at least one selected from the group consisting of (i) cleansing, (ii) debriding, (iii) aspirating, (iv) moistening, (v) vasodilating, (vi) removal of bioburden, (vii) reduce local edema and inflammatory exudate, (viii) promote tissue granulation, (ix) infection management, (x) antimicrobial effects, (xi) biofilm disruption, (xii) wound healing, and (xiii) cell signaling. The nitric oxide gas may be generated from a donor that includes at least one selected from the group consisting of (i) a nitrite salt, (ii) a nitrate, (iii) diazeniumdiolates, (iv) nitrosothiols, and (v) a nitric oxide-carrying polymer.

[0026] In some examples, back-flow preventers prevent the mixed delivery solution from entering the reservoirs. In some aspects, the pressure relief element is in fluid communication with the joining element to relieve pressure from mixing the delivery solution.

[0027] In some aspects, the first solution includes a concentrate and the second solution includes a diluent. In some examples, the drape is configured to be non-reactive with the delivery solution. In some implementations, the first solution and the second solution are dispensed in equal amounts. In some other implementations, the first solution and the second solution are dispensed in unequal amounts. Optionally, a cleansing solution is used to cleanse the lumen of residual mixed delivery solution between operations. In some implementations, the reservoir includes (i) a first compartment containing the first solution, (ii) a second compartment containing the second solution, and (iii) a third compartment containing the cleaning solution. The mixing may include turbulent mixing.

[0028] An additional aspect of the disclosure provides a method of providing instillation to a site on a patient. The method includes providing a negative pressure wound therapy (NPWT)device capable of instillation. An airtight barrier is created around a wound at the site of application using a non-reactive dressing. A multi-compartment reservoir is capable of dispensing a first solution and a second solution. The method includes mixing the first solution and the second solution and sending the mixed solution to the site of application for therapeutic effect. This aspect may include one or more of the following optional features.

[0029] In some implementations, the therapeutic effect includes at least one selected from the group consisting of (i) cleansing, (ii) debriding, (iii) aspirating, (iv) moistening, (v) vasodilating, (vi) removal of bioburden, (vii) reduce local edema and inflammatory exudate, (viii) promote tissue granulation, (ix) infection management, (x) antimicrobial effects, (xi) biofilm disruption, (xii) wound healing, and (xiii) cell signaling. In some aspects, the first solution includes a concentrate and the second solution includes a diluent. In some examples, the wound includes at least one selected from the group consisting of (i) a diabetic foot ulcer, (ii) a pressure ulcer, (iii) an arterial ulcer, (iv) a venous ulcer, (v) a surgical wound, (vi) an open fracture, (vii) a fasciotomy, (viii) a skin graft, (ix) a bum, (x) a deep tissue injury, (xi) an abrasion, (xii) a skin tear, (xiii) a tendon tear and (xiv) a wound at risk of not healing.

[0030] In some implementations, sending the mixed solution to the site of application delivers nitric oxide to the wound. In further implementations, the nitric oxide is produced from a donor, and wherein the donor includes one selected from the group consisting of (i) a nitrite salt, (ii) a nitrate, (iii) diazeniumdiolates, (iv) nitrosothiols, and (v) nitric oxide-carrying polymers. In other further implementations, the nitric oxide is produced from an acidified nitrite reaction.

[0031] Another aspect of the disclosure provides a method of providing mixed delivery solution to an application site on a patient using negative pressure wound therapy (NPWT). The method includes providing a NPWT system configured to instill a first solution to the application site. The method includes providing a drape configured to provide an airtight seal around the application site and further configured to provide an open-celled foam dressing over the application site under the drape. The method includes providing at least one channel in fluid communication between the drape and the NPWT system. The method includes providing an adapter configured to connect between the NPWT system and the channel. The adapter includes at least a second solution and at least one sensor. The adapter is configured to motivate the second solution to enter the channel to provide the second solution to the application site. The method includes receiving, by the adapter, a signal from the sensor indicating that the NPWT system isnot providing suction or providing less suction and operating the adapter to provide the second solution to the application site through the channel. This aspect may include one or more of the following optional features.

[0032] In some examples, the first solution is provided by the NPWT system and mixes with the second solution provided by the adapter to produce the mixed instill solution. In some aspects, the first solution and the second solution are provided to the application site in sequence. In some implementations, the adapter further provides a third solution to the application site to mix with the second solution.

[0033] In some examples, the first solution and the second solution mix with one another to produce a therapeutic agent for at least one selected from the group consisting of (i) cleansing, (ii) debriding, (iii) aspirating, (iv) moistening, (v) vasodilating, (vi) removal of bioburden, (vii) reduce local edema and inflammatory exudate, (viii) promote tissue granulation, (ix) infection management, (x) antimicrobial effects, (xi) biofilm disruption, (xii) wound healing, and (xiii) cell signaling. In further examples, the therapeutic agent includes the mixed delivery solution including at least one selected from the group consisting of (i) nitric oxide, (ii) oxygen, (iii) an antimicrobial agent, (iv) an antiseptic agent, and (v) a debriding agent.

[0034] In some aspects, the first solution and the second solution turbulently mix between the adapter and the application site. In some examples, the first solution and the second solution are stored separately from one another. In some implementations, the first solution includes a nitrite salt and the second solution includes an acid. In some examples, the first solution includes a therapeutic solution concentrate and the second solution includes a diluent. In some implementations, the second solution is a gas including nitric oxide. In some aspects, the adapter includes at least one fluid pump for generating a pressure head in the second solution to motivate the second solution to enter the channel. In some aspects, the second solution is motivated by gravity to enter the channel, and the adapter is configured to adjust between blocking the second solution from entering the channel and allowing the second solution to enter the channel.

[0035] Yet another aspect of the disclosure provides a method of providing delivery solution to a wound using negative pressure wound therapy (NPWT). The method includes providing a NPWT system and providing a drape configured to provide an airtight seal around an application site on a patient and further configured to provide an open-celled foam dressing over the site under the drape. The method includes providing a first channel in fluid communication between thedrape and the NPWT system. The method includes providing an adapter configured to connect between the NPWT system and the first channel. The adapter includes a solution and a method to motivate fluid flow. The method includes providing a connection to deliver the solution through a second channel to the first channel at a junction. The method includes closing off the first channel before the junction with the second channel. The method includes motivating flow of the solution in the first channel and delivering the solution to the application site through the first channel. This aspect may include one or more of the following optional features.

[0036] In some implementations, the adapter includes a negative pressure channel for delivering negative pressure to the application site. In some examples, the solution from the adapter is configured to contact and react with a reactant to provide a therapeutic effect, and the reactant is disposed at one or more of the group consisting of (i) skin of the patient, (ii) the drape, and (iii) the dressing. In further examples, the reaction produces at least one selected from the group consisting of (i) nitric oxide and (ii) oxygen. In other further examples, the solution includes one selected from the group consisting of (i) an acid and (ii) a nitrite salt, and the reactant includes the other from the group consisting of (i) the acid and (ii) the nitrite salt. In other further examples, the reactant is disposed at one selected from the group consisting of (i) the drape and (ii) the dressing, and the reactant does not touch the patient and reacts in contact with the solution as it flows through the one selected from the group consisting of (i) the drape and (ii) the dressing to provide the therapeutic effect.

[0037] In some aspects, the solution includes a first solution and a second solution that mix with one another to produce the solution including a therapeutic agent for at least one selected from the group consisting of (i) cleansing, (ii) debriding, (iii) aspirating, (iv) moistening, (v) vasodilating, (vi) removal of bioburden, (vii) reduce local edema and inflammatory exudate, (viii) promote tissue granulation, (ix) infection management, (x) antimicrobial effects, (xi) biofilm disruption, (xii) wound healing, and (xiii) cell signaling. In further aspects, the solution includes one selected from the group consisting of (i) nitric oxide and (ii) oxygen. In even further aspects, the solution is a mixture of two or more solutions. In other even further aspects, one of the two or more solutions includes a nitrite salt and another of the two or more solutions includes an acid. The two or more solutions may be stored separately from one another. Further, one of the two or more solutions may include a therapeutic solution concentrate and another of the two or more solutions may include a diluent.

[0038] In some aspects, the adapter includes a mixing element to promote mixing of the two or more solutions. In further aspects, the mixing element includes a shear inducing element, and wherein the shear inducing element includes at least one selected from the group consisting of (i) studs, (ii) channels, (iii) ribs, (iv) screens, (v) helix agitators, (vi) inline static mixers, (vii) T- junctions, (viii) Y-junctions, and (ix) impellers.

[0039] Optionally, the method further includes providing a reactive agent surrounded by the seal that reacts with at least one selected from the group consisting of (i) the first solution, (ii) the second solution, and (iii) the mixed solution.

[0040] Additionally, an aspect of the disclosure provides a computer-implemented method that when executed on data processing hardware causes the data processing hardware to perform operations. The operations include delivering a delivery solution to an application site covering a wound of a patient. The delivery solution includes a nitric oxide gas component when delivered to the application site. The application site is in fluid communication with a negative pressure wound therapy (NPWT) system. The operations include operating the NPWT system to create subatmospheric pressure at the application site. This aspect may include one or more of the following optional features.

[0041] In some implementations, delivering the delivery solution includes causing a first solution to mix with a second solution. Mixing of the first solution and the second solution causes a reaction that produces the nitric oxide gas component. In further implementations, the first solution and the second solution are stored separate from one another. In other further implementations, mixing of the first solution and the second solution occurs within a conduit upstream of the application site. In other further implementations, mixing of the first solution and the second solution occurs at the application site. In other further implementations, the first solution and the second solution turbulently mix with one another, such as at a Reynold’s Number of 2,000 or more.

[0042] In some aspects, operating the NPWT system to create subatmospheric pressure at the application site occurs prior to delivering the delivery solution. In further aspects, operating the NPWT system to create subatmospheric pressure at the application site occurs after delivering the delivery solution. In even further aspects, operating the NPWT system to create subatmospheric pressure at the application site is paused while delivering the delivery solution. In other evenfurther aspects, operating the NPWT system to create subatmospheric pressure at the application site occurs while delivering the delivery solution.

[0043] In some examples, a reactant is disposed at the application site, and delivering the delivery solution to the application site causes the delivery solution and reactant to react and produce the nitric oxide component. In further examples, the reactant is disposed at one or more of the group consisting of (i) the skin of the patient, (ii) a dressing at the application site and (iii) a drape at the wound of the patient.

[0044] In some implementations, delivering the delivery solution includes operating a pump to motivate the delivery solution to the application site. In further implementations, the delivery solution includes a first solution and a second solution. The first solution and the second solution mix to react and produce the nitric oxide gas component upstream of the pump and the application site.

[0045] In some aspects, delivering the delivery solution includes operating a first pump to motivate a first solution to the application site and operating a second pump to motivate a second solution to the application site. The first solution and the second solution mix to react and produce the nitric oxide gas component at the application site.

[0046] In some examples, a flow rate of the delivery solution to the application site is based at least in part on a volume of the application site.

[0047] In some implementations, the delivery solution is delivered to the application site via a conduit. The operations further include transmitting light along the conduit to at least partially illuminate the application site, the light including one selected from the group consisting of (i) near infrared light and (ii) far infrared light. In further implementations, transmitting light along the conduit occurs while delivering the delivery solution to the application site. In other further implementations, transmitting light along the conduit occurs while operating the NPWT system to create subatmospheric pressure at the application site. In some implementations, a drape at least partially covers the wound of the patient and the conduit is disposed at or near an opening in the drape to at least partially illuminate the wound of the patient through the opening in the drape.

[0048] In some aspects, the delivery solution includes a biphasic solution. In some examples, the delivery solution includes a multiphasic solution. In further examples, the multiphasic solution includes solid particulates. The solid particulates may include collagen.

[0049] Another aspect of the disclosure provides a system. The system includes memory hardware storing instructions that, when executed on data processing hardware in communication with the memory hardware, cause the data processing hardware to perform operations. The operations include delivering a delivery solution to an application site covering a wound of a patient. The delivery solution includes a nitric oxide gas component when delivered to the application site. The application site is in fluid communication with a negative pressure wound therapy (NPWT) system. The operations include operating the NPWT system to create subatmospheric pressure at the application site. This aspect may include one or more of the following optional features.

[0050] In some implementations, delivering the delivery solution includes causing a first solution to mix with a second solution. Mixing of the first solution and the second solution causes a reaction that produces the nitric oxide gas component. In further implementations, the first solution and the second solution are stored separate from one another. In other further implementations, mixing of the first solution and the second solution occurs within a conduit upstream of the application site. In other further implementations, mixing of the first solution and the second solution occurs at the application site. In other further implementations, the first solution and the second solution turbulently mix with one another, such as at a Reynold’s Number of 2,000 or more.

[0051] In some aspects, operating the NPWT system to create subatmospheric pressure at the application site occurs prior to delivering the delivery solution. In further aspects, operating the NPWT system to create subatmospheric pressure at the application site occurs after delivering the delivery solution. In even further aspects, operating the NPWT system to create subatmospheric pressure at the application site is paused while delivering the delivery solution. In other even further aspects, operating the NPWT system to create subatmospheric pressure at the application site occurs while delivering the delivery solution.

[0052] In some examples, a reactant is disposed at the application site, and delivering the delivery solution to the application site causes the delivery solution and reactant to react and produce the nitric oxide component. In further examples, the reactant is disposed at one or more of the group consisting of (i) the skin of the patient, (ii) a dressing at the application site, and (iii) a drape at the wound of the patient.

[0053] In some implementations, delivering the delivery solution includes operating a pump to motivate the delivery solution to the application site. In further implementations, the delivery solution includes a first solution and a second solution. The first solution and the second solution mix to react and produce the nitric oxide gas component upstream of the pump and the application site.

[0054] In some aspects, delivering the delivery solution includes operating a first pump to motivate a first solution to the application site and operating a second pump to motivate a second solution to the application site. The first solution and the second solution mix to react and produce the nitric oxide gas component at the application site.

[0055] In some examples, a flow rate of the delivery solution to the application site is based at least in part on a volume of the application site.

[0056] In some implementations, the delivery solution is delivered to the application site via a conduit. The operations further include transmitting light along the conduit to at least partially illuminate the application site, the light including one selected from the group consisting of (i) near infrared light and (ii) far infrared light. In further implementations, transmitting light along the conduit occurs while delivering the delivery solution to the application site. In other further implementations, transmitting light along the conduit occurs while operating the NPWT system to create subatmospheric pressure at the application site. In some implementations, a drape at least partially covers the wound of the patient and the conduit is disposed at or near an opening in the drape to at least partially illuminate the wound of the patient through the opening in the drape.

[0057] In some aspects, the delivery solution includes a biphasic solution. In some examples, the delivery solution includes a multiphasic solution. In further examples, the multiphasic solution includes solid particulates. The solid particulates may include collagen.

[0058] Another aspect of the disclosure provides a system. The system includes a negative pressure wound therapy (NPWT) device configured to (i) deliver a delivery solution to an application site surrounding a wound of a patient and (ii) create subatmospheric pressure at the application site. A conduit is in fluid communication with the NPWT device and a drape at the wound of the patient. The delivery solution is delivered to the application site via the conduit during operation of the NPWT device. A light emitter is configured to transmit light along the conduit to at least partially illuminate the application site. The light includes at least one selectedfrom the group consisting of (i) near infrared light and (ii) far infrared light. This aspect may include one or more of the following optional features.

[0059] In some implementations, the light emitter is configured to transmit light along the conduit while the conduit delivers the delivery solution to the application site. In some aspects, the light emitter is configured to transmit light along the conduit while the NPWT device creates subatmospheric pressure at the application site. In some examples, the drape at least partially covers the wound of the patient and the conduit is disposed at or near an opening in the drape to at least partially illuminate the wound of the patient through the opening in the drape. In some implementations, the delivery solution includes a nitric oxide gas component when delivered to the application site.

[0060] A method of treating a wound in a patient in need of such treatment may include administering nitric oxide to the patient using the systems and methods described herein. The wound may include at least one selected from the group consisting of (i) a diabetic foot ulcer, (ii) a pressure ulcer, (iii) an arterial ulcer, (iv) a venous ulcer, (v) a surgical wound, (vi) an open fracture, (vii) a fasciotomy, (viii) a skin graft, (ix) a bum, (x) a deep tissue injury, (xi) an abrasion, (xii) a skin tear, (xiii) a tendon tear, and (xiv) a wound at risk of not healing. The nitric oxide may provide a therapeutic effect to the wound of at least one selected from the group consisting of (i) cleansing, (ii) debriding, (iii) aspirating, (iv) moistening, (v) vasodilating, (vi) removal of bioburden, (vii) reduce local edema and inflammatory exudate, (viii) promote tissue granulation, (ix) infection management, (x) antimicrobial effects, (xi) biofilm disruption, (xii) wound healing, and (xiii) cell signaling.

[0061] Further areas of applicability will become apparent from the description provided herein. The description and specific examples in this summary are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure.DRAWINGS

[0062] The drawings described herein are for illustrative purposes only of selected configurations and not all possible implementations and are not intended to limit the scope of the present disclosure.

[0063] FIG. 1A is a schematic view of an exemplary device for administering nitric oxide using negative pressure wound therapy in accordance with implementations of the present disclosure;

[0064] FIG. IB is a schematic view of another exemplary device for administering nitric oxide using negative pressure wound therapy in accordance with implementations of the present disclosure;

[0065] FIG. 1C is a schematic view of another exemplary device for administering nitric oxide using negative pressure wound therapy in accordance with implementations of the present disclosure;

[0066] FIG. ID is a flowchart of an exemplary method for administering nitric oxide using the devices of FIGS. 1A-1C, in accordance with principles of the present disclosure;

[0067] FIG. 2A is a schematic view of an exemplary nitric oxide multi chamber intravenous bag system in accordance with the principles of the present disclosure;

[0068] FIG. 2B is a schematic view of another exemplary nitric oxide multi chamber intravenous bag system in accordance with the principles of the present disclosure;

[0069] FIG. 2C is a schematic view of another exemplary nitric oxide multi chamber intravenous bag system in accordance with the principles of the present disclosure;

[0070] FIG. 2D is a schematic view of another exemplary nitric oxide multi chamber intravenous bag system in accordance with the principles of the present disclosure;

[0071] FIG. 2E is a flowchart of an exemplary method for administering nitric oxide using the devices of FIGS. 2A-2D, in accordance with principles of the present disclosure;

[0072] FIG. 3A is a schematic view of an exemplary device for administering nitric oxide using negative pressure wound therapy in accordance with implementations of the present disclosure;

[0073] FIG. 3B is a schematic view of another exemplary device for administering nitric oxide using negative pressure wound therapy in accordance with implementations of the present disclosure;

[0074] FIG. 3C is a wound area that can be used in connection with the devices in FIGS. 3A and 3B; and

[0075] FIG. 3D is a flowchart of an exemplary method for administering nitric oxide using the devices of FIGS. 3 A and 3B, in accordance with principles of the present disclosure.

[0076] Corresponding reference numerals indicate corresponding parts throughout the drawings.DETAILED DESCRIPTION

[0077] Example configurations will now be described more fully with reference to the accompanying drawings. Example configurations are provided so that this disclosure will be thorough and will fully convey the scope of the disclosure to those of ordinary skill in the art. Specific details are set forth such as examples of specific components, devices, and methods, to provide a thorough understanding of configurations of the present disclosure. It will be apparent to those of ordinary skill in the art that specific details need not be employed, that example configurations may be embodied in many different forms, and that the specific details and the example configurations should not be constmed to limit the scope of the disclosure.

[0078] Negative Pressure Wound Therapy (NPWT) aids healing by applying sub-atmospheric “negative pressure” (NP) through a vacuum line to a wound to reduce local edema and inflammatory exudate and promote tissue granulation. Some NPWT devices feature a liquid “instill” capability that washes and irrigates the wound to aid healing without disrupting the airtight pad and drape which cover the wound bed. For instill, NP is paused, and fluids like saline or antimicrobial washes are delivered through a second line or lumen to dwell on the wound bed, controlled by the NPWT system settings. Afterward, NP resumes and the instill liquids are suctioned off.

[0079] Nitric oxide (NO) is an endogenous cell signaling molecule vital to the molecular healing cascade. NO drives inflammation reduction, cell proliferation, collagen deposition, angiogenic production of granulation tissues, wound closure, and scar formation. It is a natural vasodilator and broad-spectrum antimicrobial with no known resistance. Despite its advantageous wound healing properties, the use of NO in wound healing has been limited given its reactive nature and very short half-life, making topical application challenging.

[0080] The mechanical benefits of NPWT may be combined with the healing properties of NO gas to promote both perfusion and granulation, while also accelerating wound healing at the molecular level. NO instill solution may promote vasodilation, disrupt and eradicate biofilm, and trigger cellular and molecular responses that drive healing. In contrast, normal saline only irrigates the wound, and antimicrobial washes lack the many cellular healing benefits NO provides.

[0081] As discussed further below, aspects of the disclosure are directed to systems and methods for delivering instillation solutions, and more particularly instillation solutions containing NO, to a wound site of a patient. The NO may be the result of a chemical reaction that occurs at or near the wound site, such as within a sealed chamber or cell at the wound site or at a portion of the system shortly before delivery of the NO to the wound site. The chemical reaction may occur due to the mixing or turbulent mixing of two or more solutions or fluids, where the solutions may respectively include liquid solutions, biphasic solutions (e.g., containing liquid and gas portions), multiphasic solutions (e.g., containing liquid, gas, and solid particulate portions), and the like. Embodiments described further below include a system having pumps configured to apply a vacuum or negative pressure to a sealed application site surrounding a wound of a patient and configured to deliver two solutions to the application site, where the solutions mix (e.g., turbulently mix) to react and cause NO gas to interact with the wound. Additional embodiments described further below include a system that delivers the first solution and the second solution to the application site via a single pump, such as a peristaltic pump, where mixing (e.g., turbulent mixing) of the solutions to react occurs as the solutions travel within conduits to the pump and application site so that NO gas may interact with the wound at the application site. In these embodiments, pressure relief may be provided via valves in communication with the conduits and / or in communication with the containers or reservoirs holding the solutions. Moreover, embodiments described further below include an adapter that connects with a negative pressure (NP) monitor (with or without instill capabilities) that applies negative pressure to the application site. In these embodiments, the adapter delivers the first solution and the second solution to one or more lines or conduits of the NP monitor and causes the solutions to mix (e.g., turbulently mix) so that NO gas may interact with the wound at the application site. Further, in these embodiments, the adapter may include an electromagnetic light source, such as a near infrared (NIR) light source or far infrared (FIR) light source, that directs NIR light and / or FIR light toward the application site to provide additional therapeutic benefits. Optionally, these embodiments may deliver one solution to the application site, where the solution reacts with a substance present at the application site (e.g., in a wound dressing) to cause NO gas to interact with the wound.

[0082] It is noted hereinafter that “mix” or “mixing” or “turbulence” or “turbulent mixing” connotes a confluence of multiple flows. It is noted hereinafter that “complete turbulent mixing” connotes a confluence of multiple flows having a combined Reynold’s Number (Re) in excess of2,000 or greater than 2,100, where the Re may be defined by the dimensionless formulation Re = (mean fluid density x combined flow speed x conduit internal diameter) / (fluid dynamic viscosity) as is common to the fields of Fluid Mechanics / Dynamics. In some examples, characteristics of the two or more flows (e.g., mean fluid density, fluid dynamic viscosity, and flow speed) and / or characteristics of the conduits carrying the flows to the application site (e.g., conduit internal diameter) may achieve turbulent mixing at a sufficient Re (e.g., at a Re of 2,000 or greater). In some examples, mixing may be achieved by one or more of the non-limiting list of increasing the flow speed, increasing the conduit internal diameter, dynamic mixing, static mixing, or a shear inducing element like a T-joint, Y-joint, linear mixer, stud, channel, rib, screen, helix agitator, inline static mixer, impeller, and the like. That is, turbulent mixing may be crucial for the generation of the NO from the two solutions. For complete mixing to occur in flows in pipes or conduits, the Re must be greater than or equal to 2,000.

[0083] In other examples, one or more solutions may be delivered to the application site as a laminar flow or transitional flow (e.g., having a Re less than 2,000). When one solution is delivered to the application site, the solution may mix or interact with a reactant at the application site in a manner sufficient to generate NO gas. When two solutions are delivered to the application site with laminar flow, the two solutions may mix within or due to engagement with the drape or dressing at the application site in a manner sufficient to generate Nitric Oxide.

[0084] Referring to FIG. 1A, aNitric Oxide (NO) formulation delivery system 100 is generally shown. The NO delivery system 100 may be used and configured to deliver NO as set forth herein. As will become apparent, the NO delivery system 100 is configured to deliver and administer NO to a wound 12 of a patient using negative pressure wound therapy. For example, the NO delivery system 100 and negative pressure wound therapy may be utilized in the context of the non-limiting list of installation, irrigation, aspirating, cleansing, debriding, infection management, promoting healthy blood flow, biofilm disruption and / or removal, inflammation management, wound healing, wound bed preparation, reducing local edema and inflammatory exudate, promote tissue granulation, provide antimicrobial effects, cell signaling, and the like. Example wounds 12 of the patient that may be treated by the NO delivery system 100 and negative wound therapy include the non-limiting list of diabetic foot ulcers, pressure ulcers, arterial ulcers, venous ulcers, surgical wounds, open fractures, fasciotomies, skin grafts, burns, deep tissue injuries, abrasions, skin tears, tendon tears, wounds at risk of not healing, and the like.

[0085] The NO delivery system 100 may include a negative pressure device 102 in fluid communication with a dressing 104 configured to form an airtight seal on skin 10 of a patient at a chamber or application site 14 surrounding the wound 12. In some implementations, the negative pressure device 102 includes one or more of a positive displacement pump (peristaltic, gear, piston, syringe, etc.) or any other suitable pump, as well as a single pump with multiple pump heads (syringes, etc.). The negative pressure device 102 may be generally handheld or portable for ease of transportation, or the negative pressure device 102 may be wearable and mounted to the patient. Further, the negative pressure device 102 may include other electronics and circuitry not shown, such as a power source (e.g., battery), input components (e.g., buttons), display screen, speaker, processor(s) to automate the operation of the device, transportable and / or interchangeable reservoir packets, microfluidic chambers, and the like. The wound dressing 104 may be formed of a thin film and may cooperate with other components, adhesives, etc., to ensure the application site 14 maintains an airtight seal against the skin 10 of the patient. In some implementations, a gauze, bandage, or other liquid permeable or open-celled wound dressing or drape 103 (e.g., FIG. 3C) (i.e., a dressing that permits fluid to move through it) may be applied to the wound 12 in the application site 14. The dressing 103 may be configured to promote mixing of the first solution and the second solution delivered to the application site 14 and the wound dressing 103 is non- reactive with the first solution, the second solution, and NO that is the result of the first solution mixing and reacting with the second solution, as described in greater detail below. In some implementations, the non-reactive wound dressing 103 may contain reactive elements to react with one or more of the instillation solutions to produce the NO.

[0086] The negative pressure device 102 includes a first pump 106 configured to exert a subatmospheric force (e.g., between 25 and 200 mmHg, or between 50 and 125 mmHg) on the application site 14 to create a subatmospheric (or negative gauge) pressure or vacuum within the application site 14. The first pump 106 exerts the subatmospheric force on the application site 14 via a conduit 108 in fluid communication with an inlet port 110 connected to the dressing 104. The negative pressure device 102 includes an exhaust port or release valve 124 in fluid communication with the first pump 106 via a conduit 126. That is, the first pump 106 may be in fluid communication with the conduit 108 and the conduit 126 and is disposed between the inlet port 110 and the exhaust port 124. In some implementations, the exhaust port 124 may be connected directly to the dressing 104 or to the conduit 108 between the inlet port 110 and the firstpump 106. When the first pump 106 exerts the subatmospheric force on the application site 14, the first pump 106 may draw out fluids or other material from the wound 12 and application site 14, and, in some implementations, may discharge such fluids through the exhaust port 124. In other implementations, the negative pressure device 102 may include a separate container for containing these fluids, which can be discharged through other means, including manually.

[0087] The negative pressure device 102 includes a second pump 112 that contains the first solution or is in communication with a reservoir that contains the first solution. In some implementations, the first solution may comprise water and nitrite salt, such as to produce an acidified nitrite reaction when mixed with an acid. The second pump 112 is configured to periodically deliver or instill predetermined quantities of the first solution to the application site 14 through a conduit 114. The conduit 114 is in fluid communication with an inlet port 116 connected to the dressing 104. In some implementations, the inlet port 116 includes an off-take gas / liquid separator to sequester liquid from gas. In some implementations, the inlet port 116 may prevent fluids from entering or reentering the conduit 114 after delivery to the application site 14.

[0088] The negative pressure device 102 includes a third pump 118 that contains the second solution or is in communication with a reservoir that contains the second solution. In some implementations, the second pump 112 and the third pump 118 are integrated into a single pump with two separate containers or reservoirs for containing the first and second solutions, respectively. In other implementations, the first pump 106, the second pump 112, and the third pump 118 are all integrated into a single pump with multiple pump heads. In some implementations, the second solution may comprise water and acid, such as to produce the acidified nitrite reaction when mixed with the nitrite salt of the first solution. The third pump 118 is configured to periodically deliver or instill predetermined quantities of the second solution to the application site 14 through a conduit 120. The conduit 120 is in fluid communication with an inlet port 122 connected to the dressing 104. In some embodiments, the inlet port 116 and the inlet port 122 are adjacent to one another. In some embodiments, the inlet port 116 and the inlet port 122 are in fluid communication with one another. In some implementations, the inlet port 122 includes an off-take gas / liquid separator to sequester liquid from gas. In some implementations, the inlet port 122 may prevent fluids from entering or reentering the conduit 120 after delivery to the application site 14. In some implementations, the inlet port 116 and / or the inlet port 122delivering the first and second solutions, respectively, can extend into the dressing 104 and surround the wound 12, including the wound dressing 103, such as via an annular pad.

[0089] The negative pressure device 102 includes a controller 128 including data processing hardware 128a in communication with memory storage hardware 128b. The data processing hardware 128a can process instructions for execution by the controller 128 to control the negative pressure device 102, including instructions stored in the memory 128b to, for example, activate and deactivate the first pump 106, deliver and stop delivery of the first solution from the second pump 112, and deliver and stop delivery of the second solution from the third pump 118. In other implementations, multiple processors may be used, as appropriate, along with multiple memories and types of memory.

[0090] Upon delivery to the application site 14, the first solution and the second solution may mix with one another and create a chemical reaction that produces a delivery solution or mixture or fluid or liquid, such as a biphasic liquid or multiphasic liquid, containing NO gas, which is overall a compressible fluid. In some implementations, the mixing of the first and second solutions is highly turbulent, thereby ensuring adequate mixing. In some implementations, as shown in FIG. IB, the negative pressure device 102 may include a mixing chamber 130 where the first solution mixes with the second solution prior to entering the application site 14. In such an implementation, after the NO has been produced in the mixing chamber 130, the NO is delivered to the application site 14 through the inlet port 122.

[0091] The first pump 106 may exert the subatmospheric force on the application site 14 either continuously or intermittently, but preferably continuously, for a predetermined period of time (e.g., 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 14 hours, 17 hours, 18 hours, 23 hours, 24 hours, 35 hours, 36 hours, 47 hours, 48 hours, and the like) until it ceases exerting the subatmospheric force, or reduces the subatmospheric force, on the application site 14. Upon the first pump 106 ceasing to exert, or reducing, the subatmospheric force on the application site 14, the second and third pumps 112, 118 are configured to deliver or instill the first and second solutions, respectively, into the application site 14 in quantities sufficient to allow for full coverage of the application site 14 without generating pressure from the production of NO to disrupt the airtight seal of the dressing 104. The second and third pumps 112, 118 are configured to deliver or instill the first and second solutions, respectively, for a predetermined period from once every hour to once every other day. Theduration of delivery of the first and second solutions can range from 30 seconds to 2 hours (e.g., 30 seconds, 1 minute, 5 minutes, 10 minutes. 30 minutes, 60 minutes, 120 minutes). A double, back-to-back instillation of the solution may be administered for the first instillation. It may be configured such that the delivery or instillation of the first and second solutions are continuous or intermittent. For example, the second and third pumps 112, 118 may instill in the application site 14 a steady amount or continuous flow rate of the first and second solutions and the first pump 106 may output a steady amount or continuous flow rate of fluid in the application site 14 via the exhaust port 124 to provide a continuous flow of the first and second solutions while maintaining a predetermined constant pressure in the application site 14. The negative pressure device 102 may alternate between exerting the subatmospheric force on the application site 14 and delivering the first and second solutions to the application site 14.

[0092] Referring to FIG. 1C, in some implementations, the negative pressure device 102 includes a negative pressure device 102a that is connected to a nitric oxide device 102b. The negative pressure device 102a includes the first pump 106, exhaust port 124, and controller 128 as described above. The nitric oxide device 102b includes the second pump 112 and the third pump 118 as described above. In some implementations, the second pump 112 and the third pump 118 are integrated into a single pump with two separate containers or reservoirs for containing the first and second solutions, respectively. The nitric oxide device 102b may include a controller 132 including data processing hardware 132a in communication with memory storage hardware 132b. The controller 132 of the nitric oxide device 102b may be in communication with the controller 128 of the negative pressure device 102a to control the components of the negative pressure device 102. In this implementation, the nitric oxide device 102b may be used to retrofit preexisting negative pressure devices 102a to enable them to deliver NO.

[0093] Referring to FIG. ID, a method 1000 for administering NO to the wound 12 is generally shown. The method 1000 may be performed at least partially based on processing at the data processing hardware 128a instructions stored in the memory 128b of the controller 128. As step 1002, the first pump 106 creates subatmospheric pressure at the application site 14 by exerting a subatmospheric or negative pressure on the application site 14. At step 1004, the first pump 106 stops exerting a subatmospheric or negative pressure on the application site 14 or reduces the subatmospheric force applied to the application site 14. At step 1006, the second pump 112 delivers the first solution to the application site 14. At step 1008, the third pump 118 delivers thesecond solution to the application site 14. In some implementations, steps 1006 and 1008 may occur simultaneously, such that the first solution and the second solution may be delivered to the application site 14 at the same time. At step 1010, the first and second solution mix with one another prior to and / or within the application site 14, resulting in a chemical reaction that produces NO gas within the fluid at the application site 14. At step 1012, the NO confined to the application site 14 by the dressing 104 is instilled to the wound 12. After step 1012, the process may return to step 1002 as the negative pressure device 102 may cyclically alternate between creating a negative pressure in the application site 14 and administering the first and second solutions to the application site 14.

[0094] In some implementations, the first pump 106 may exert a subatmospheric force on the application site 14 at a force that permits the second pump 112 to still deliver the first solution to the application site 14 and the third pump 118 to deliver the second solution to the application site 14 while at least some subatmospheric force is applied to the application site 14. As the second and third pumps 112, 118 deliver the first and second solutions, respectively, the first and second solutions may trickle into the application site 14 and over the wound 12 and be drawn off through the first pump 106 and out through the exhaust port 124. This allows a constant flow of reactants to meet and produce NO over the wound 12.

[0095] In some examples, the first solution and the second solution may mix prior to being motivated, or as the two solutions are motivated, toward the application site 14 at the patient. For example, and referring to FIGS. 2A-2D, a Nitric Oxide multi bag system 210 is generally shown. The system 210 is an innovative multi-chamber intravenous (IV) bag system that uses two liquid reactants (one activator reactant and one NO donor reactant) to generate NO. The system 210 creates micro-turbulence in the instill line to entirely mix the reactant solutions, thereby creating an NO gas-carrying liquid in situ. As the resultant solution would comprise both liquid (instill) and gas (NO), the system 210 includes pressure relief mechanisms and volume flow controls to mediate over-pressurization and ensure the correct NO dose for the wound size and volume.

[0096] The system 210 represents an elegant and cost-effective system of enhancing the utility of NPWT with the active healing benefits of NO which exceed the capabilities of existing instill solutions. This innovation also overcomes the challenges of generating and delivering NO as an instill solution without disrupting normal clinical operations of NPWT, risking NPWT equipment damage, or risking patient safety.

[0097] The system 210 includes a first bag 212a and a second bag 212b. In some implementations, the bags 212a, 212b may be two distinct chambers of the same, unitary bag. The first bag 212a contains a first solution (e.g., one of an activator reactant or a NO donor reactant). The second bag 212b contains a second solution (e.g., the other of the activator reactant or the NO donor reactant). In some implementations, the first bag 212a contains the first solution discussed above (e.g., including water and a nitrite salt like sodium nitrite or potassium nitrite) and the second bag 212b contains the second solution discussed above (e.g., including water and acid). The bags 212a, 212b each optionally include an IV pole hook 214a, 214b and a pressure-relief valve 216a, 216b (e.g., a button or any other suitable valve) to relieve the pressure within the bags 212a, 212b. Although the system 210 includes IV bags that contain the first solution and the second solution, it should be understood that the first bag 212a and the second bag 212b may be representative of any suitable reservoir or container, such as a vial, a chamber, and the like.

[0098] The system 210 may include a pressure relief pipe 218 including a standpipe sponge. The pressure relief pipe 218 connects to a mixer or joining element 224 which receives the solutions from the first and second bags 212a, 212b through connections 220a, 220b respectively attached to each bag 212a, 212b. The pressure relief pipe 218 releases any excess pressure in the mixer 224 as a result of the reaction between the activator and NO donor that occurs in the mixer 224. As shown in FIG. 2B, the system 210 may include a first pressure relief pipe 218a connected directly to the first bag 212a and a second pressure relief pipe 218b connected directly to the second bag 212b.

[0099] The lines connecting the bags 212a, 212b to the mixer 224 may include backflow preventers 222a, 222b to prevent the solutions from flowing back into the bags 212a, 212b. In some implementations, the mixer or joining element 224 may include any suitable number of internal components or features to ensure adequate mixing (e.g., turbulent mixing) of the first solution and the second solution.

[0100] The mixer 224 connects with a conventional connector 226 of a NPWT device 228, which, in some implementations, may include a peristaltic pump or any other suitable device. By connecting to the conventional NPWT device 228 (with or without instill capability), the system 210 enables a conventional NPWT system to instill a solution containing NO, where it otherwise would not be able to do so.

[0101] Referring to FIG. 2C, the system 210 may include a third bag 212c, which may contain a saline wash, cleansing solution, or second therapeutic treatment. Similar to the first bag 212a and the second bag 212b, the third bag 212c may include a pole hook 214c, a pressure-relief valve 216c, and a connection 220c that fluidly connects the bag 212c to the NPWT device 228. A backflow preventer 222c may prevent the second therapeutic treatment from flowing back into the bag 212c when the second therapeutic treatment is flowing to the NPWT device 228.

[0102] The system 210 may include a first valve 230 between the mixer 224 and the connector 226 of the NPWT device 228 for selectively permitting the instill solution (i.e., the first solution and the second solution mixed with each other) to flow to the NPWT device 228. The system 210 may include a second valve 232 between the connector 220c of the third bag 212c and the connector 226 of the NPWT device 228 for selectively permitting the cleansing solution to flow to the NPWT device 228. The valves may be manually operated or battery powered and / or automatically operated based on timing or feedback from one or more sensors. Thus, the NPWT device 228 may be operated to deliver the instill solution containing NO gas to the application site 14 with the first valve 230 in an opened position and the second valve 232 in a closed position and the NPWT device 228 may be operated to deliver the second therapeutic treatment to the application site 14 with the first valve 230 in a closed position and the second valve 232 in an opened position.

[0103] During operation, the first valve 230 may be closed and the second valve may be opened for a brief period (e g., 10 seconds). During this time, the cleansing solution may flow through the instill line to cleanse the instill line.

[0104] Optionally, and such as shown in FIG. 2D, the system 210 may be formed without pressure relief valves in communication with the bags 212a, 212b or mixer 224. In this example, the backflow preventers 222a, 222b may prevent gas bubbles from flowing into the bags 212a, 212b. Optionally, the backflow preventers 222a, 222b may be pressure-activated to allow pressure to flow into the bags 212a, 212b and the volume of gas may replace the volume of solution flowing from the bags 212a, 212b. The buttons 216a, 216b may be used to intermittingly relieve pressure from the bags 212a, 212b.

[0105] Although described herein as utilizing the NPWT device 228 to motivate the mixed solution containing NO gas to the application site 14 of the patient, it should be understood that the flow of mixed solution may be motivated in other suitable manners. For example, other typesof pumps or mechanical motivation may be implemented. Optionally, with the bags 212a, 212b suitably elevated, gravity may motivate the mixed solution containing NO gas to the application site 14.

[0106] FIG. 2E shows an example method 2000 of operating the system 210, which may be performed at least partially based on processing at data processing hardware instructions stored in the memory of a controller (e.g., controller 128). At operation 2002, the method 2000 includes providing a negative pressure device 228 configured to provide instillation of an instill solution. At operation 2004, the method 2000 includes creating subatmospheric pressure at the application site 14 surrounding the wound 12 of a patient via the negative pressure device 228. At operation 2006, the method 2000 includes suspending the subatmospheric pressure. At operation 2008, the method 2000 includes delivering the instill solution to the application site 14 where the instill solution includes the NO gas component when delivered to the application site 14. At operation 2010, the method 2000 includes instilling the instill solution into the wound 12.

[0107] In some examples, the first solution and the second solution may be mixed and delivered to one or more lines of a NP monitor by a specialized adapter. For example, and referring to FIG. 3A, an instillation solution adapter 400 is generally shown. The adapter 400 may be used and configured to connect with a NP monitor and reservoir 310 to deliver the instillation solution to the wound or application site 14 of a patient using NPWT techniques as set forth herein. In some implementations, the instillation solution includes NO.

[0108] The adapter 400 is configured to connect to the NP monitor 310, which may be any traditional NP monitor 310. For example, the NP monitor 310 may include a pump configured to exert a subatmospheric force on the application site 14 to create a subatmospheric (or negative gauge) pressure within the application site 14. The NP monitor 310 may include other components (reservoirs, circuitry, processors, hardware, display screen, pump, buttons, etc.) that are not shown. The NP monitor 310 includes a connector 312 configured to receive a NP connector 436 of a NP line 426 and an instill connector 438 of an instill line 428. In some implementations, the adapter 400 is configured to connect to a variety of different NP monitors 310 based on standard connections between the connectors 436, 438 and the connector 312. In this way, the adapter 400 may function as a universal adapter to enable traditional NP monitors to deliver NO to application sites.

[0109] In one example, the adapter 400 may connect to a NP monitor 310 which includes negative pressure capabilities and instill capabilities, via the NP line 426 and instill line 428, respectively, as shown in FIG. 3A. In another example, the adapter 400 may connect to a NP monitor 310 which only includes negative pressure capabilities via the NP line 426, and the adapter 400 modifies the functionality of the NP monitor 310 to enable it to instill liquid through the NP line 426, as shown in FIG. 3B.

[0110] The adapter 400 includes a body portion 402 and a reservoir portion 404. The body portion 402 includes a series of switches and pumps as will be described in greater detail below. The reservoir portion 404 includes a first reservoir 406 that contains the first solution, which may comprise water and nitrite salt. The reservoir portion 404 may include a second reservoir 408 that contains the second solution, which may comprise water and acid. In some implementations, the NP monitor 310 may include the second reservoir 408 that contains the second solution. In some implementations, the first solution and the second solution may mix with one another and create a chemical reaction that produces a liquid or fluid or solution containing NO gas, which is overall a compressible fluid. In another implementation, the reaction that produces the solution containing NO gas is an acidified nitrite reaction. In another implementation, the first and second solution may turbulently mix with one another. In other implementations, the first solution and the second solution may be any suitable solutions, compositions, and the like. For example, one of the first solution or the second solution may be formed of, or include, an antibacterial, an antimicrobial, metal-based antimicrobials, quaternary ammonium compounds, oxidizing agents, biguanides, a dilutant, a reactive agent, and the like. In some implementations, the first solution may be a concentrate of a therapeutic fluid and the second solution may be a diluent, which may result in a better shelf stability for the higher concentration therapeutic fluid and reduce storage and transportation costs. In some implementations, the first solution may be a liquid solution and the second solution may be a mixture of a liquid with suspended particles of ingredients to provide therapeutic effects. In other words, the liquid may include a biphasic liquid, a multiphasic liquid (e.g., including liquid, NO gas, and suspended particulates), or any suitable solution or fluid. The adapter 400 optionally includes a control panel and display that a user can use to adjust or view one or more of: dwell time, pump speed, amount of liquid, time for instill pumping / dosing period, pressure, level of fluid remaining in reservoirs 406 and 408, current operation (stall, pumping first solution, pumping second solution, etc.), and the like.

[0111] The body portion 402 may include a mixer or joining element 412 configured to create a turbulent flow. In some implementations, the mixer 412 may be disposed at any location along the NP line 426 or the instill line 428 at a mixing point. In some implementations, there may be multiple mixers 412 disposed at various locations, e.g., in the body portion 402, in theNP line 426, in the instill line 428, and / or within the application site 14 (e.g., in a seal or drape 104 or a wound dressing 103). The mixer 412 may include studs, channels, ribs, screens, helix agitators, impellers, or any other suitable devices. The mixer 412 is configured to disrupt the flow of the first solution and the second solution to ensure complete turbulent or micro-turbulent mixing of the two solutions into a combined turbulent solution with a Re of at least 2,100 while traversing the instill line 428.

[0112] The reservoir portion 404 includes a first reservoir switch 410 that is configured to selectively activate / deactivate the flow of the first solution out of the first reservoir 406. The reservoir portion 404 includes a second reservoir switch 412 that is configured to selectively activate / deactivate the flow of the second solution out of the second reservoir 408.

[0113] The body portion 402 includes a first pump 414 in fluid communication with the first reservoir 406 and a second pump 416 in fluid communication with the second reservoir 408. The pumps 414, 416 may be positive displacement pumps (e.g., peristaltic, gear, piston, syringe, etc.) or any other suitable pumps. The body portion 402 includes a first pump instill switch 418 and a first pump NP switch 420. The first pump instill switch 418 is configured to selectively activate / deactivate the flow of the first solution out of the first pump 414 and to the instill line 428. The first pump NP switch 420 is configured to selectively activate / deactivate the flow of the first solution out of the first pump 414 and to the NP line 426. The body portion 402 includes a second pump instill switch 422 and a second pump NP switch 424. The second pump instill switch 422 is configured to selectively activate / deactivate the flow of the second solution out of the second pump 416 and to the instill line 428. The second pump NP switch 424 is configured to selectively activate / deactivate the flow of the second solution out of the second pump 416 and to the NP line 426.

[0114] The adapter 400 includes a connector 430 configured to receive a NP connector 432 of the NP line 426 and an instill connector 434 of the instill line 428. As set forth above, the standardization of connectors enables the adapter 400 to function as a universal adapter to connect NP monitors 310 to common application sites 14. As shown in FIGS. 3A and 3B, the NP line 426may include a first portion extending between the application site 14 and the NP connector 432 and a second portion extending between the connector 430 (which receives the NP connector 432) and the NP connector 436, and the instill line 428 may include a first portion extending between the application site 14 and the instill connector 434 and a second portion extending between the connector 430 (which receives the instill connector 434) and the instill connector 438.

[0115] The body portion 402 includes an NP line switch 440 and an instill line switch 442. The NP line switch 440 is configured to selectively activate / deactivate the NP or vacuum forces transmitted from the NP monitor 310 through the NP line 426. The instill line switch 442 is configured to selectively activate / deactivate the flow of the liquid instill through the instill line 428. The adapter 400 includes a first line clamp 446 configured to prevent backflow to the NP monitor 310 and a second line clamp 448 configured to prevent backflow to the adapter 400. In some implementations, the adapter 400 may include one or more clamps or backflow preventors at the pumps 414, 416 to prevent liquid from pressurizing the pumps 414, 416.

[0116] The adapter 400 may include a near-infrared radiation (NIR) or far infrared (FIR) laser diode 450 configured to use the NP line 426 and / or the instill line 428 as light pipes conducting NIR / FIR light to the wound at the application site 14. That is, the diode 450 may be capable of illuminating the translucent line 426, 428 to use it as a form of light pipe and flood the application site 14 with NIR radiation (e.g., having wavelengths between about 780 nm to 1,000 nm) and / or FIR radiation (e.g., having wavelengths between about 3 pm to 100 pm). For example, one or both of the lines 426, 428 may be disposed at or near or aligned with an opening or window or channel or passageway formed in the wound dressing 103 at the application site 104 so that light emitted by the laser diode 450 travels along the line 426, 428 and at least partially illuminates the wound 12 through the opening in the wound dressing 103.

[0117] NIR or FIR light from the laser diode 450 may aid in the wound-healing process because of its ability to stimulate cell proliferation, vasodilation, and increase tissue regeneration in vitro, as well as provide thermal, photodynamic, and photobiomodulation potential. In some implementations, the laser diode 450 may transmit NIR light and / or FIR light to the application site 14 during instillation or during vacuum.

[0118] Put another way, NIR radiation, and particularly around wavelengths of about 800 nm to 830 nm, is effective in promoting wound healing. It has been found to amplify the effects of NO in wound healing and studies have shown that light having wavelengths between about 800nm to 830 nm may be the most effective for wound repair and regeneration. FIR radiation has also been shown to improve wound healing. Thus, the effects of NIR and FIR radiation may benefit the processes of NO supplementation.

[0119] The application site 14 includes a seal or dressing 104 and a drape or wound dressing 103. The seal 104 is configured to form an airtight seal on the skin of a patient and may be formed of a thin film or any other suitable material. The seal 104 may cooperate with adhesives or other materials to maintain the airtight seal on the patient’s skin, thereby creating a chamber surrounding the wound. The adhesive may be non-reactive with the solution and / or NO gas delivered to the application site 14. The wound dressing 103 may include a gauze, bandage, or other liquid permeable or open-celled wound dressing (i.e., a dressing that permits fluid to move through it) that may be applied to the wound at the application site 14. In some implementations, the seal 104 may include a valve 105 (e.g., a check valve, one-way valve underneath the drape 104, or any other suitable valve) that dispels any excess liquid or air within the application site 14 to ensure that the seal 104 does not burst or exceed a predetermined pressure or volume. In some embodiments, the valve 105 may be fluidly connected to the adapter by means of a tube.

[0120] As set forth above, the adapter 400 may connect to a NP monitor 310 that either does or does not have instill capabilities, i.e., does have an instill line 428 (as shown in FIG. 3A) or does not have an instill line (as shown in FIG. 3B). Referring to FIG. 3A, the first pump instill switch 418 and the second pump instill switch 422 are open or on, while the first pump NP switch 420 and the second pump NP switch 424 are closed or off. This configuration allows the first solution and second solution to flow from the first pump 414 and the second pump 416, respectively, to the instill line 428 where the two solutions can be mixed at the mixer 412 and are instilled to the application site 14. The switches 418, 420 may also both be open so that the adapter 400 delivers the first solution to the NP line 426 and the instill line 428. Similarly, the switches 422, 424 may also both be open so that the adapter 400 delivers the second solution to the NP line 426 and the instill line 428.

[0121] In implementations where the second reservoir 408 containing the second solution is disposed in the NP monitor 310, the NP monitor 310 functions as programmed with the second solution being instilled to the application site 14 through the instill line 428, and the adapter 400 cyclically closes off the instill line switch 442 to temporarily suspend instillation of the second solution from the NP monitor 310 through the instill line 428 and turns on the first reservoir switch410 and the first pump instill switch 418 to deliver the first solution through the instill line 428 so that the first solution and the second solution mix (e.g., turbulently mix) within the application site 14.

[0122] In some implementations, the adapter 400 may “hijack” or take over control of the NP line 426 and / or the instill line 428 from the NP monitor 310 by closing the switches 440, 442. In some implementations, the switch 440 may be closed and the switch 442 may be open, with the NP monitor 426 delivering an instill solution from the reservoir 408 through the instill line 428. In this implementation, the adapter 400 may then deliver one or more instill solutions through the NP line 426 while the switch 440 is closed.

[0123] In other implementations, the adapter 400 may keep the switches 440, 442 open to allow the NP monitor 310 to operate in its traditional manner by delivering a vacuum force through the NP line 426 and instill fluid through the instill line 428. After a period of time, the adapter 400 may close off the valve 442 and pump one or more of the first solution or second solution to the instill line 428 to interact with the fluid already in the instill line 428 via the NP monitor 310. This solution from the adapter 400 to the instill line 428 may result in a reaction or mixing (e.g., in the mixer 412, in the instill line 428, or at the application site 14) with the solution already in this instill line 428 via the NP monitor 310, or the solution from the adapter 400 may function as a clean-out to dispel the leftover liquid in the instill line 428 out of the instill line 428.

[0124] It should be understood that the various switches, valves, clamps, pumps, and other components, may function in a variety of different ways to achieve different results through various configurations. It will be apparent to those of ordinary skill in the art that the specific details of these additional configurations and implementations need not be described, but are still covered by the scope of this disclosure.

[0125] Referring to FIG. 3B, the NP monitor 310 cyclically activates and deactivates application of negative pressure to the application site 14. The periods when negative pressure is applied and suspended from application may be seconds or minutes. The adapter 400 may include one or more sensors 444 to determine whether the NP monitor 310 is applying a negative pressure through the NP line 426. In some implementations, the sensors 444 may include a pressure sensor, a photosensor, an ultrasonic sensor, a flow meter sensor, a density sensor, a motion sensor, and / or any other suitable sensor. In some implementations, the adapter 400 may stop instill when a predetermined pressure is reached in response to data received from one of the sensors 444 (e.g.,the sensor 444 adjacent the connector 430) to ensure that the drape 104 does not become overpressurized. In some implementations, the adapter 400 may include a microprocessor and circuitry that connects to the NP monitor 310 to control when the NP monitor 310 applies a negative pressure. When the NP monitor 310 is not applying a negative pressure through the NP line 426, the first pump instill switch 418 and the second pump instill switch 422 are closed or off, while the first pump NP switch 420 and the second pump NP switch 424 are open or on. This configuration allows the first solution and second solution to flow from the first pump 414 and the second pump 416, respectively, to the NP line 426 where the two solutions can mix at the mixer 412 and are instilled to the application site 14. In some implementations, the switch 440 may be configured (e.g., via a valve or other suitable mechanism) to permit the NP monitor 310 to draw a vacuum through the NP line 426 upstream from the switch 440. In this manner, the NP monitor 310 still operates as if it is properly creating a vacuum and does not detect any changes caused by the adapter 400.

[0126] After a predetermined amount of time applying the first solution and the second solution to the application site 14 through the NP line 426, the first pump NP switch 420 and the second pump NP switch 424 are switched to closed or off and the NP monitor 310 resumes applying a negative pressure to the application site 14 through the NP line 426. In this manner, the adapter 400 enables the NP monitor 310 to have instill capabilities that it otherwise would not have.

[0127] Referring to FIG. 3C, the application site 14 may include a reactive agent or reactant 107 disposed within the seal 104. In some implementations, the reactive agent 107 may be incorporated into the dressing 103. In other implementations, the reactive agent 107 may be a dissolvable film, powder, or a liquid applied via a spray, dribble, sponge, etc. In some implementations, the reactive agent 107 may be a liquid applied via a spray, dribble, sponge, etc., before the dressing 103 is applied. The reactive agent 107 may react with one or both of the first solution and the second solution to create a chemical reaction that produces a resultant liquid containing NO gas, or any other suitable product. In some implementations, the reactive agent 107 is configured to not contact the body of the patient until the reaction occurs. The adhesive of the seal 104 and the material of the drape 103 are configured to not react with the first solution, second solution, reactive agentl07 , or the resultant solution. The reactive agent 107 may be usedwith an adapter 400 connected to an NP monitor 310 with instill capabilities (FIG. 3 A) or without instill capabilities (FIG. 3B).

[0128] That is, another aspect of the disclosure provides a method where the at least one instill fluid is configured to contact and react with the reactant 107 on the skin of the patient or in one of the drape 103 or the dressing 104 to provide a therapeutic effect. In another implementation, the solution may be delivered to the drape 103 or dressing 104 or skin of the patient and mixed with the reactant 107 in the drape 103 or dressing 104 or present on the skin of the patient, resulting in a chemical reaction that produces NO gas in the solution. In a third implementation, the solution containing NO is produced by delivering a carrier fluid and injecting NO gas into the fluid stream in such a manner to cause turbulent mixing of the two fluids. In another implementation, the solution includes two or more solutions, and one of the two or more solutions includes a therapeutic fluid concentrate and another of the two or more solutions comprises a diluent.

[0129] FIG. 3D shows an example method 3000 of operating the adapter 400, which may be performed at least partially based on processing at data processing hardware instructions stored in the memory of a controller (e.g., controller 128) in communication with the adapter 400. At operation 3002, the method 3000 includes providing a negative pressure monitor 310 configured to instill a first solution to an application site 14. At operation 3004, the method 3000 includes providing a drape 104 configured to provide an airtight seal around the application site 14 and providing an open-celled foam dressing 103 under the drape 104. At operation 3006, the method 3000 includes providing at least one channel 426 in fluid communication between the drape 104 and the negative pressure monitor 310. At operation 3008, the method 3000 includes providing the adapter 400 configured to connect between the monitor 310 and the channel 426. The adapter includes a second solution and a sensor 444, and the adapter 400 is configured to motivate the second solution into the channel 426 to provide the second solution to the application site 14. At operation 310, the method 3000 includes receiving a signal from the sensor 444 indicating that the negative pressure monitor 310 is not providing suction or providing less suction and operating the adapter 400 to provide the second solution to the application site 14 through the channel 426.

[0130] As discussed above, the solution delivered to the application site 14 may contain or carry NO gas for interacting with the wound 12 of the patient. Optionally, the solution may react with the reactant 107 at or near the wound 12 of the patient for creating NO gas that interacts with the wound 12 of the patient. It should be understood that the solution may include a liquid, abiphasic solution (e.g., including a liquid and a gas, such as NO gas), a multiphasic solution (e.g., including a liquid, a gas such as NO gas, and a solid such as particulate suspended in the liquid), and the like. In examples where the solution includes a multiphasic solution, the solution may carry or include solid particles configured to provide a therapeutic effect to the wound 12 of the patient. For example, the solution may include collagen or other proteins.

[0131] Further, turbulent mixing of the at least one solution may occur at the application site 14 or as the at least one solution is carried or motivated to the application site 14 to ensure that NO gas is created and / or carried to the application site 14 for interacting with the wound 12. For example, the drape 103 at the wound 12 may be configured to promote turbulent mixing of the first solution and the second solution with one another at the application site 14. In some implementations, the first solution and the second solution may turbulently mix with one another as the solutions come together at a joining element, such as a T-junction, Y-junction, and the like.

[0132] As discussed above, the Re must be greater than about 2,000 for turbulent mixing to occur in flows in pipes. Re may be expressed as

[0133] where p is density, V is velocity, D is the internal diameter of the pipe or conduit, and is dynamic viscosity. Where v is the kinematic viscosity of (p I p), Re may be expressed asVD Re = — v

[0134] At room temperature (e.g., about 20 degrees Celsius), given that the dynamic viscosity of the first solution and the second solution may be about 0.4033 mPa*s, the kinematic viscosity of the first solution and the second solution may be about 0.4127 mm2 / s, the density of the first solution and the second solution may be about .9778 g / cm3, and the velocity of the first solution and the second solution at a flow rate of 1 mL / s may be about 141.47 mm / s, Re may be calculated for different operating conditions of the systems described herein. Example results are reflected in the table below.| 4 | 100100200 100 | 39.065.15266

[0135] As shown, each combination of flow rates and delivery volumes achieved a Re above 2,000, thus validating turbulent mixing of the first solution and the second solution to deliver NO gas to the wound 12 of the patient. In these examples, the first solution and the second solution may be motivated to the application site 14 by the pumps shown and described in FIGS. 1 A-1C, 2A-2D, 3 A, and 3B. It should be understood that, in some implementations, the first solution and the second solution may be motivated toward the application site 14 by gravity at sufficient flow rates to achieve turbulent mixing.

[0136] Moreover, control of the systems described herein may be based at least in part on the flow rate of the first solution and the second solution toward the application site 14 (and therefore the resultant Re as the first solution and second solution mix) and the volume of the application site 14 and / or the wound 12 or drape 103 at the application site 14. For example, the first solution and the second solution may be motivated to the application site 14 at a minimal speed to generate the desired Re (e.g., about 2,000 or about 2,100) for turbulently mixing the first solution and the second solution to maintain a level of control over the volume of solution delivered to the application site 14. The system may be programmed to deliver enough solution to fill or substantially fill (e g., up to 75 percent or more, up to 90 percent or more, up to 95 percent or more) the volume of the wound 12 or drape 103 or application site 14 without overfilling the wound 12 or drape 103 or application site 14. Overfilling the wound 12 or drape 103 or application site 14 may cause the seal of the application site 14 and / or the drape 103 to release from the skin of the patient. The volume of the wound 12 or drape 103 or application site 14 may be input to the system as an estimate, such as based on an estimate provided by a healthcare provider or based on a size of the drape 103 or dressing 14 used. Optionally, the systems may be manually controlled during a first instillation phase to set the instillation volume and subsequent instillation phases may be configured to deliver the same or similar volume to the application site 14.

[0137] The terminology used herein is for the purpose of describing particular exemplary configurations only and is not intended to be limiting. As used herein, the singular articles “a,” “an,” and “the” may be intended to include the plural forms as well, unless the context clearly indicates otherwise. The terms “comprises,” “comprising,” “including,” and “having,” are inclusive and therefore specify the presence of features, steps, operations, elements, and / orcomponents, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof. The method steps, processes, and operations described herein are not to be construed as necessarily requiring their performance in the particular order discussed or illustrated, unless specifically identified as an order of performance. Additional or alternative steps may be employed.

[0138] When an element or layer is referred to as being “on,” “engaged to,” “connected to,” “attached to,” or “coupled to” another element or layer, it may be directly on, engaged, connected, attached, or coupled to the other element or layer, or intervening elements or layers may be present. In contrast, when an element is referred to as being “directly on,” “directly engaged to,” “directly connected to,” “directly attached to,” or “directly coupled to” another element or layer, there may be no intervening elements or layers present. Other words used to describe the relationship between elements should be interpreted in a like fashion (e g., “between” versus “directly between,” “adjacent” versus “directly adjacent,” etc.). As used herein, the term “and / or” includes any and all combinations of one or more of the associated listed items.

[0139] The terms first, second, third, etc. may be used herein to describe various elements, components, regions, layers and / or sections. These elements, components, regions, layers and / or sections should not be limited by these terms. These terms may be only used to distinguish one element, component, region, layer or section from another region, layer or section. Terms such as “first,” “second,” and other numerical terms do not imply a sequence or order unless clearly indicated by the context. Thus, a first element, component, region, layer or section discussed above could be termed a second element, component, region, layer or section without departing from the teachings of the example configurations.

[0140] The foregoing description has been provided for purposes of illustration and description. It is not intended to be exhaustive or to limit the disclosure. Individual elements or features of a particular configuration are generally not limited to that particular configuration, but, where applicable, are interchangeable and can be used in a selected configuration, even if not specifically shown or described. The same may also be varied in many ways. Such variations are not to be regarded as a departure from the disclosure, and all such modifications are intended to be included within the scope of the disclosure.

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A system comprising: a delivery solution that, when administered to a wound of a patient, comprises a nitric oxide gas component; and a negative pressure device configured to create subatmospheric pressure at an application site surrounding the wound and configured to provide instillation of the delivery solution to the wound of the patient.

2. The system of claim 1, wherein the delivery solution comprises a first solution and a second solution that mix with one another and react to produce the nitric oxide gas component.

3. The system of claim 2, wherein the first solution and the second solution turbulently mix with one another.

4. The system of claim 3, wherein the first solution and the second solution turbulently mix with one another at a Reynold’s Number of 2,000 or more.

5. The system of claim 2, wherein the first solution and the second solution are delivered to the application site as one selected from the group consisting of (i) laminar flow and (ii) transitional flow.

6. The system of claim 5, wherein the first solution and the second solution at least partially mix with one another at a drape at the wound of the patient.

7. The system of claim 1, wherein the delivery solution mixes with a reactant to generate the nitric oxide gas component to provide a therapeutic effect, and wherein the reactant is disposed at one selected from the group consisting of (i) the skin of the patient, (ii) a dressing at the application site and (iii) a drape at the wound of the patient.

8. The system of claim 1, wherein the wound comprises at least one selected from the group consisting of (i) a diabetic foot ulcer, (ii) a pressure ulcer, (iii) an arterial ulcer, (iv) a venous ulcer, (v) a surgical wound, (vi) an open fracture, (vii) a fasciotomy, (viii) a skin graft, (ix) a bum, (x) a deep tissue injury, (xi) an abrasion, (xii) a skin tear, (xiii) a tendon tear, and (xiv) a wound at risk of not healing.

9. The system of claim 1, wherein the delivery solution comprises a multiphasic liquid.

10. The system of claim 9, wherein the multiphasic liquid contains suspended particulates to provide additional therapy to the application site.

11. The system of claim 1, wherein the delivery solution comprises a biphasic liquid.

12. A method comprising: providing a negative pressure device configured to provide instillation of a delivery solution; creating, via the negative pressure device, subatmospheric pressure at an application site surrounding a wound of a patient; suspending, via the negative pressure device, creation of the subatmospheric pressure at the application site; delivering the delivery solution to the application site, the delivery solution comprising a nitric oxide gas component when delivered to the application site; and instilling the delivery solution into the wound.

13. The method of claiml2, wherein the delivery solution is produced by: simultaneously delivering a first solution and a second solution; and mixing the first solution and the second solution, resulting in a chemical reaction that produces the nitric oxide gas component of the delivery solution.

14. The method of claim 13, wherein the chemical reaction comprises an acidified nitrite reaction.

15. The method of claim 13, wherein the first solution and the second solution are stored separately from one another.

16. The method of claim 13, wherein the first solution and the second solution are delivered to the application site through separate channels.

17. The method of claim 16, wherein the channels for delivering the first solution and the second solution are each configured to prevent the first solution, the second solution, and the delivery solution from reentering the respective channels.

18. The method of claim 13, wherein the first solution and the second solution mix with one another at the application site.

19. The method of claim 13, wherein the first solution and the second solution mix with one another before entering the application site.

20. The method of claim 13, wherein the negative pressure device includes a dressing at the application site that is configured to promote mixing of the first solution and the second solution.

21. The method of claim 13, wherein the first solution and the second solution are each delivered to the application site in predetermined quantities.

22. The method of claim 13, wherein the delivery solution is removed from the application site via an off-take gas / liquid separator to sequester liquid from gas.

23. The method of claim 13, wherein the first solution and the second solution turbulently mix with one another.

24. The method of claim 13, further comprising delivering at least a third solution to the application site.

25. The method of claim 12, wherein the delivery solution comprises a multiphasic liquid.

26. The method of claim 25, wherein the multiphasic liquid contains suspended particulates to provide additional therapy to the application site.

27. The method of claim 12, wherein the delivery solution comprises a biphasic liquid.

28. A system comprising: a dressing configured to form an airtight seal on the skin of a patient at an application site surrounding a wound of the patient; and a device in fluid communication with the application site, the device alternating between exerting a subatmospheric force on the application site and instilling a delivery solution in the application site, the delivery solution comprising a nitric oxide gas component.

29. The system of claim 28, wherein the device includes a pump for exerting the subatmospheric force on the application site.

30. The system of claim 29, wherein the delivery solution comprises a first solution and a second solution that mix with one another and react to produce the nitric oxide gas component.

31. The system of claim 30, wherein the first solution and the second solution turbulently mix with one another to produce a biphasic flow of the delivery solution.

32. The system of claim 30, wherein the first solution and the second solution are instilled in the application site via one or more pumps.

33. The system of claim 30, wherein the first solution and the second solution are instilled in the application site in quantities sufficient to allow for full coverage of the application site without disrupting the airtight seal of the dressing.

34. The system of claim 30, wherein the system includes a wound dressing, tubing, entry ports, a canister, an offtake valve, and a pump system that are non-reactive with the first solution, the second solution, and the nitric oxide gas component.

35. The system of claim 28, wherein the device alternates between exerting the subatmospheric force on the application site and instilling the delivery solution in the application site for a predetermined period of time.

36. The system of claim 28, wherein the device alternates between exerting the subatmospheric force on the application site and instilling the delivery solution in the application site in a cyclical period.

37. The system of claim 28, wherein the device instills in the application site a steady amount of the delivery solution and outputs a steady amount of the delivery solution to provide a continuous flow of the delivery solution while maintaining a predetermined constant pressure in the application site.

38. The system of claim 28, wherein the device alternates between instilling in the application site a steady amount of the delivery solution maintained at a predetermined constant pressure and exerting the subatmospheric force on the application site without any of the delivery solution at the application site for a predetermined period of time.

39. The system of claim 28, wherein the device includes a release valve to release pressure in the dressing to maintain the airtight seal of the dressing while the nitric oxide gas component is produced in the application site.

40. A system comprising: a negative pressure wound therapy (NPWT) device capable of instillation of a delivery solution to an application site surrounding a wound of a patient; a lumen in fluid communication with the NPWT device and a drape at the wound of the patient;a multi-compartment reservoir that is in fluid communication with the NPWT device, the reservoir containing a first solution and a second solution to be used for instillation; and a joining element capable of introducing the first solution from a first compartment of the reservoir with a second solution from a second compartment of the reservoir in a manner to induce mixing of the delivery solution.

41. The system of claim 40, wherein the first solution and the second solution, when introduced, create a reaction that produces a therapeutic gas.

42. The system of claim 41, wherein the therapeutic gas comprises oxygen.

43. The system of claim 41, wherein the therapeutic gas comprises nitric oxide.

44. The system of claim 43, wherein the first solution comprises an acid and the second solution comprises a nitrite salt.

45. The system of claim 43, wherein the nitric oxide provides a therapeutic effect to the wound of at least one selected from the group consisting of (i) cleansing, (ii) debriding, (iii) aspirating, (iv) moistening, (v) vasodilating, (vi) removal of bioburden, (vii) reduce local edema and inflammatory exudate, (viii) promote tissue granulation, (ix) infection management, (x) antimicrobial effects, (xi) biofilm disruption, (xii) wound healing, and (xiii) cell signaling.

46. The system of claim 43, wherein the nitric oxide gas is generated from a donor that comprises at least one selected from the group consisting of (i) a nitrite salt, (ii) a nitrate, (iii) diazeniumdiolates, (iv) nitrosothiols, and (v) a nitric oxide-carrying polymer.

47. The system of claim 40, wherein back-flow preventers prevent the mixed delivery solution from entering the reservoirs.

48. The system of claim 40, wherein a pressure relief element is in fluid communication with the joining element to relieve pressure from mixing the delivery solution.

49. The system of claim 40, wherein the first solution comprises a concentrate and the second solution comprises a diluent.

50. The system of claim 40, wherein the drape is configured to be non-reactive with the delivery solution.

51. The system of claim 40, wherein the first solution and the second solution are dispensed in equal amounts.

52. The system of claim 40, wherein the first solution and the second solution are dispensed in unequal amounts.

53. The system of claim 40, wherein a cleansing solution is used to cleanse the lumen of residual mixed delivery solution between operations.

54. The system of claim 53, wherein the reservoir includes (i) a first compartment containing the first solution, (ii) a second compartment containing the second solution, and (iii) a third compartment containing the cleaning solution.

55. The system of claim 40, wherein the mixing comprises turbulent mixing.

56. A method of providing instillation to a site on a patient, the method comprising: providing a negative pressure wound therapy (NPWT) device capable of instillation; creating an airtight barrier around a wound at the site of application using a non-reactive dressing; providing a multi-compartment reservoir capable of dispensing a first solution and a second solution; mixing the first solution and the second solution; and sending the mixed solution to the site of application for therapeutic effect.

57. The method of claim 56, wherein the therapeutic effect comprises at least one selected from the group consisting of (i) cleansing, (ii) debriding, (iii) aspirating, (iv) moistening, (v) vasodilating, (vi) removal of bioburden, (vii) reduce local edema and inflammatory exudate, (viii) promote tissue granulation, (ix) infection management, (x) antimicrobial effects, (xi) biofilm disruption, (xii) wound healing, and (xiii) cell signaling.

58. The method of claim 56, wherein the first solution comprises a concentrate and the second solution comprises a diluent.

59. The method of claim 56, wherein the wound comprises at least one selected from the group consisting of (i) a diabetic foot ulcer, (ii) a pressure ulcer, (iii) an arterial ulcer, (iv) a venous ulcer, (v) a surgical wound, (vi) an open fracture, (vii) a fasciotomy, (viii) a skin graft, (ix) a bum, (x) a deep tissue injury, (xi) an abrasion, (xii) a skin tear, (xiii) a tendon tear, and (xiv) a wound at risk of not healing.

60. The method of claim 56, wherein sending the mixed solution to the site of application delivers nitric oxide to the wound.

61. The method of claim 60, wherein the nitric oxide is produced from a donor, and wherein the donor comprises one selected from the group consisting of (i) nitrite salt, (ii) a nitrate, (iii) diazeniumdiolates, (iv) nitrosothiols, and (v) nitric oxide-carrying polymers.

62. The method of claim 60, wherein the nitric oxide is produced from an acidified nitrite reaction.

63. A method of providing mixed delivery solution to an application site on a patient using negative pressure wound therapy (NPWT), the method comprising: providing a NPWT system configured to instill a first solution to the application site; providing a drape configured to provide an airtight seal around the application site and further configured to provide an open-celled foam dressing over the application site under the drape;providing at least one channel in fluid communication between the drape and the NPWT system; providing an adapter configured to connect between the NPWT system and the channel, the adapter comprising at least a second solution and at least one sensor, and the adapter being configured to motivate the second solution to enter the channel to provide the second solution to the application site; and receiving, by the adapter, a signal from the sensor indicating that the NPWT system is not providing suction or providing less suction and operating the adapter to provide the second solution to the application site through the channel.

64. The method of claim 63, wherein the first solution is provided by the NPWT system and mixes with the second solution provided by the adapter to produce the mixed instill solution.

65. The method of claim 63, wherein the first solution and the second solution are provided to the application site in sequence.

66. The method of claim 63, wherein the adapter further provides a third solution to the application site to mix with the second solution.

67. The method of claim 63, wherein the first solution and the second solution mix with one another to produce a therapeutic agent for at least one selected from the group consisting of (i) cleansing, (ii) debriding, (iii) aspirating, (iv) moistening, (v) vasodilating, (vi) removal of bioburden, (vii) reduce local edema and inflammatory exudate, (viii) promote tissue granulation, (ix) infection management, (x) antimicrobial effects, (xi) biofilm disruption, (xii) wound healing, and (xiii) cell signaling.

68. The method of claim 67, wherein the therapeutic agent comprises the mixed delivery solution including at least one selected from the group consisting of (i) nitric oxide, (ii) oxygen, (iii) an antimicrobial agent, (iv) an antiseptic agent, and (v) a debriding agent.

69. The method of claim 63, wherein the first solution and the second solution turbulently mix between the adapter and the application site.

70. The method of claim 63, wherein the first solution and the second solution are stored separately from one another.

71. The method of claim 63, wherein the first solution comprises a nitrite salt and the second solution comprises an acid.

72. The method of claim 63, wherein the first solution comprises a therapeutic solution concentrate and the second solution comprises a diluent.

73. The method of claim 63, wherein the second solution is a gas comprising nitric oxide.

74. The method of claim 63, wherein the adapter comprises at least one fluid pump for generating a pressure head in the second solution to motivate the second solution to enter the channel.

75. The method of claim 63, wherein the second solution is motivated by gravity to enter the channel, and the adapter is configured to adjust between blocking the second solution from entering the channel and allowing the second solution to enter the channel.

76. A method of providing delivery solution to a wound using negative pressure wound therapy (NPWT) comprising: providing a NPWT system; providing a drape configured to provide an airtight seal around an application site on a patient and further configured to provide an open-celled foam dressing over the site under the drape; providing a first channel in fluid communication between the drape and the NPWT system; providing an adapter configured to connect between the NPWT system and the first channel, the adapter comprising a solution and a method to motivate fluid flow;providing a connection to deliver the solution through a second channel to the first channel at a junction; closing off the first channel before the junction with the second channel; motivating flow of the solution in the first channel; and delivering the solution to the application site through the first channel.

77. The method of claim 76, wherein the adapter includes a negative pressure channel for delivering negative pressure to the application site.

78. The method of claim 76, wherein the solution from the adapter is configured to contact and react with a reactant to provide a therapeutic effect, and wherein the reactant is disposed at one or more of the group consisting of (i) skin of the patient, (ii) the drape, and (iii) the dressing.

79. The method of claim 78, wherein the reaction produces at least one selected from the group consisting of (i) nitric oxide and (ii) oxygen.

80. The method of claim 78, wherein the solution comprises one selected from the group consisting of (i) an acid and (ii) a nitrite salt, and wherein the reactant comprises the other from the group consisting of (i) the acid and (ii) the nitrite salt.

81. The method of claim 78, wherein the reactant is disposed at one selected from the group consisting of (i) the drape and (ii) the dressing, and wherein the reactant does not touch the patient and reacts in contact with the solution as it flows through the one selected from the group consisting of (i) the drape and (ii) the dressing to provide the therapeutic effect.

82. The method of claim 76, wherein the solution includes a first solution and a second solution that mix with one another to produce the solution comprising a therapeutic agent for at least one selected from the group consisting of (i) cleansing, (ii) debriding, (iii) aspirating, (iv) moistening, (v) vasodilating, (vi) removal of bioburden, (vii) reduce local edema and inflammatory exudate, (viii) promote tissue granulation, (ix) infection management, (x) antimicrobial effects, (xi) biofilm disruption, (xii) wound healing, and (xiii) cell signaling.

83. The method of claim 82, wherein the solution comprises one selected from the group consisting of (i) nitric oxide and (ii) oxygen.

84. The method of claim 83, wherein the solution is a mixture of two or more solutions.

85. The method of claim 84, wherein one of the two or more solutions comprises a nitrite salt and another of the two or more solutions comprises an acid.

86. The method of claim 84, wherein the two or more solutions are stored separately from one another.

87. The method of claim 84, wherein one of the two or more solutions comprises a therapeutic solution concentrate and another of the two or more solutions comprises a diluent.

88. The method of claim 84, wherein the adapter includes a mixing element to promote mixing of the two or more solutions.

89. The method of claim 88, wherein the mixing element comprises a shear inducing element, and wherein the shear inducing element includes at least one selected from the group consisting of (i) studs, (ii) channels, (iii) ribs, (iv) screens, (v) helix agitators, (vi) inline static mixers, (vii) T- junctions, (viii) Y-junctions, and (ix) impellers.

90. The method of claim 84, wherein the method further comprises providing a reactive agent surrounded by the seal that reacts with at least one selected from the group consisting of (i) the first solution, (ii) the second solution, and (iii) the mixed solution.

91. A computer-implemented method when executed on data processing hardware causes the data processing hardware to perform operations comprising: delivering a delivery solution to an application site covering a wound of a patient, the delivery solution including a nitric oxide gas component when delivered to the application site,and the application site in fluid communication with a negative pressure wound therapy (NPWT) system; and operating the NPWT system to create subatmospheric pressure at the application site.

92. The method of claim 91, wherein delivering the delivery solution includes causing a first solution to mix with a second solution, mixing of the first solution and the second solution causing a reaction that produces the nitric oxide gas component.

93. The method of claim 92, wherein the first solution and the second solution are stored separate from one another.

94. The method of claim 92, wherein mixing of the first solution and the second solution occurs within a conduit upstream of the application site.

95. The method of claim 92, wherein mixing of the first solution and the second solution occurs at the application site.

96. The method of claim 92, wherein the first solution and the second solution turbulently mix with one another.

97. The method of claim 96, wherein the first solution and the second solution turbulently mix with one another at a Reynold’s Number of 2,000 or more.

98. The method of claim 91, wherein operating the NPWT system to create subatmospheric pressure at the application site occurs prior to delivering the delivery solution.

99. The method of claim 98, wherein operating the NPWT system to create subatmospheric pressure at the application site occurs after delivering the delivery solution.

100. The method of claim 99, wherein operating the NPWT system to create subatmospheric pressure at the application site is paused while delivering the delivery solution.

101. The method of claim 99, wherein operating the NPWT system to create subatmospheric pressure at the application site occurs while delivering the delivery solution.

102. The method of claim 91, wherein a reactant is disposed at the application site, and wherein delivering the delivery solution to the application site causes the delivery solution and reactant to react and produce the nitric oxide component.

103. The method of claim 102, wherein the reactant is disposed at one or more of the group consisting of (i) the skin of the patient, (ii) a dressing at the application site and (iii) a drape at the wound of the patient.

104. The method of claim 91, wherein delivering the delivery solution comprises operating a pump to motivate the delivery solution to the application site.

105. The method of claim 104, wherein the delivery solution comprises a first solution and a second solution, and wherein the first solution and the second solution mix to react and produce the nitric oxide gas component upstream of the pump and the application site.

106. The method of claim 91, wherein delivering the delivery solution comprises operating a first pump to motivate a first solution to the application site and operating a second pump to motivate a second solution to the application site, the first solution and the second solution mixing to react and produce the nitric oxide gas component at the application site.

107. The method of claim 91, wherein a flow rate of the delivery solution to the application site is based at least in part on a volume of the application site.

108. The method of claim 91, wherein the delivery solution is delivered to the application site via a conduit, and wherein the operations further comprise transmitting light along the conduit to at least partially illuminate the application site, the light comprising one selected from the group consisting of (i) near infrared light and (ii) far infrared light.

109. The method of claim 108, wherein transmitting light along the conduit occurs while delivering the delivery solution to the application site.

110. The method of claim 108, wherein transmitting light along the conduit occurs while operating the NPWT system to create subatmospheric pressure at the application site.

111. The method of claim 108, wherein a drape at least partially covers the wound of the patient, the conduit disposed at or near an opening in the drape to at least partially illuminate the wound of the patient through the opening in the drape.

112. The method of claim 108, wherein the light comprises near infrared light and far infrared light.

113. The method of claim 91, wherein the delivery solution comprises a biphasic solution.

114. The method of claim 91, wherein the delivery solution comprises a multiphasic solution.

115. The method of claim 114, wherein the multiphasic solution comprises solid particulates.

116. The method of claim 115, wherein the solid particulates include collagen.

117. A system comprising: memory hardware storing instructions that, when executed on data processing hardware in communication with the memory hardware, cause the data processing hardware to perform operations comprising: delivering a delivery solution to an application site covering a wound of a patient, the delivery solution including a nitric oxide gas component when delivered to the application site, and the application site in fluid communication with a negative pressure wound therapy (NPWT) system; andoperating the NPWT system to create subatmospheric pressure at the application site.

118. The system of claim 117, wherein delivering the delivery solution includes causing a first solution to mix with a second solution, mixing of the first solution and the second solution causing a reaction that produces the nitric oxide gas component.

119. The system of claim 118, wherein the first solution and the second solution are stored separate from one another.

120. The system of claim 118, wherein mixing of the first solution and the second solution occurs within a conduit upstream of the application site.

121. The system of claim 118, wherein mixing of the first solution and the second solution occurs at the application site.

122. The system of claim 118, wherein the first solution and the second solution turbulently mix with one another.

123. The system of claim 122, wherein the first solution and the second solution turbulently mix with one another at a Reynold’s Number of 2,000 or more.

124. The system of claim 117, wherein operating the NPWT system to create subatmospheric pressure at the application site occurs prior to delivering the delivery solution.

125. The system of claim 124, wherein operating the NPWT system to create subatmospheric pressure at the application site occurs after delivering the delivery solution.

126. The system of claim 125, wherein operating the NPWT system to create subatmospheric pressure at the application site is paused while delivering the delivery solution.

127. The system of claim 125, wherein operating the NPWT system to create subatmospheric pressure at the application site occurs while delivering the delivery solution.

128. The system of claim 117, wherein a reactant is disposed at the application site, and wherein delivering the delivery solution to the application site causes the delivery solution and reactant to react and produce the nitric oxide component.

129. The system of claim 128, wherein the reactant is disposed at one or more of the group consisting of (i) the skin of the patient, (ii) a dressing at the application site and (iii) a drape at the wound of the patient.

130. The system of claim 117, wherein delivering the delivery solution comprises operating a pump to motivate the delivery solution to the application site.

131. The system of claim 130, wherein the delivery solution comprises a first solution and a second solution, and wherein the first solution and the second solution mix to react and produce the nitric oxide gas component upstream of the pump and the application site.

132. The system of claim 117, wherein delivering the delivery solution comprises operating a first pump to motivate a first solution to the application site and operating a second pump to motivate a second solution to the application site, the first solution and the second solution mixing to react and produce the nitric oxide gas component at the application site.

133. The system of claim 117, wherein a flow rate of the delivery solution to the application site is based at least in part on a volume of the application site.

134. The system of claim 117, wherein the delivery solution is delivered to the application site via a conduit, and wherein the operations further comprise transmitting light along the conduit to at least partially illuminate the application site, the light comprising one selected from the group consisting of (i) near infrared light and (ii) far infrared light.

135. The system of claim 134, wherein transmitting light along the conduit occurs while delivering the delivery solution to the application site.

136. The system of claim 134, wherein transmitting light along the conduit occurs while operating the NPWT system to create subatmospheric pressure at the application site.

137. The system of claim 134, wherein a drape at least partially covers the wound of the patient, the conduit disposed at or near an opening in the drape to at least partially illuminate the wound of the patient through the opening in the drape.

138. The system of claim 117, wherein the delivery solution comprises a biphasic solution.

139. The system of claim 117, wherein the delivery solution comprises a multiphasic solution.

140. The system of claim 139, wherein the multiphasic solution comprises solid particulates.

141. The system of claim 140, wherein the solid particulates include collagen.

142. A system comprising: a negative pressure wound therapy (NPWT) device configured to (i) deliver a delivery solution to an application site surrounding a wound of a patient and (ii) create subatmospheric pressure at the application site; a conduit in fluid communication with the NPWT device and a drape at the wound of the patient, the delivery solution delivered to the application site via the conduit during operation of the NPWT device; and a light emitter configured to transmit light along the conduit to at least partially illuminate the application site, the light comprising at least one selected from the group consisting of (i) near infrared light and (ii) far infrared light.

143. The system of claim 142, wherein the light emitter is configured to transmit light along the conduit while the conduit delivers the delivery solution to the application site.

144. The system of claim 142, wherein the light emitter is configured to transmit light along the conduit while the NPWT device creates subatmospheric pressure at the application site.

145. The system of claim 142, wherein the drape at least partially covers the wound of the patient, the conduit disposed at or near an opening in the drape to at least partially illuminate the wound of the patient through the opening in the drape.

146. The system of claim 142, wherein the delivery solution comprises a nitric oxide gas component when delivered to the application site.

147. A method of treating a wound in a patient in need of such treatment comprising administering nitric oxide to the patient using the system of any of claims 1-11, 28-55, and 117— 146.

148. The method of claim 147, wherein the wound includes at least one selected from the group consisting of (i) a diabetic foot ulcer, (ii) a pressure ulcer, (iii) an arterial ulcer, (iv) a venous ulcer, (v) a surgical wound, (vi) an open fracture, (vii) a fasciotomy, (viii) a skin graft, (ix) a bum, (x) a deep tissue injury, (xi) an abrasion, (xii) a skin tear, (xiii) a tendon tear, and (xiv) a wound at risk of not healing.

149. The method of claim 147, wherein the nitric oxide provides a therapeutic effect to the wound of at least one selected from the group consisting of (i) cleansing, (ii) debriding, (iii) aspirating, (iv) moistening, (v) vasodilating, (vi) removal of bioburden, (vii) reduce local edema and inflammatory exudate, (viii) promote tissue granulation, (ix) infection management, (x) antimicrobial effects, (xi) biofilm disruption, (xii) wound healing, and (xiii) cell signaling.

150. A method of treating a wound in a patient in need of such treatment comprising administering nitric oxide to the patient according to the method of any of claims 12-27 and 56- 116.

151. The method of claim 150, wherein the wound includes at least one selected from the group consisting of (i) a diabetic foot ulcer, (ii) a pressure ulcer, (iii) an arterial ulcer, (iv) a venous ulcer, (v) a surgical wound, (vi) an open fracture, (vii) a fasciotomy, (viii) a skin graft, (ix) a bum, (x) a deep tissue injury, (xi) an abrasion, (xii) a skin tear, (xiii) a tendon tear, and (xiv) a wound at risk of not healing.

152. The method of claim 150, wherein the nitric oxide provides a therapeutic effect to the wound of at least one selected from the group consisting of (i) cleansing, (ii) debriding, (iii) aspirating, (iv) moistening, (v) vasodilating, (vi) removal of bioburden, (vii) reduce local edema and inflammatory exudate, (viii) promote tissue granulation, (ix) infection management, (x) antimicrobial effects, (xi) biofilm disruption, (xii) wound healing, and (xiii) cell signaling.

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