WO2021090276A1

WO2021090276A1 - Means to reduce pressure reduction experienced with a collagen foam interface layer

Info

Publication number: WO2021090276A1
Application number: PCT/IB2020/060489
Authority: WO
Inventors: Christopher Brian Locke
Original assignee: Kci Licensing, Inc.
Priority date: 2019-11-07
Filing date: 2020-11-06
Publication date: 2021-05-14

Abstract

The present disclosure relates generally to wound dressing compositions and reduced-pressure wound dressing composition including fenestrated substrates and methods of using the same to reduce the pressure drop observed during negative pressure wound therapy (NPWT). Kits for use in practicing the methods are also provided.

Description

MEANS TO REDUCE PRESSURE REDUCTION EXPERIENCED WITH A COUUAGEN

FOAM INTERFACE UAYER

CROSS-REFERENCE TO REUATED APPUICATIONS [001] This application claims the benefit of priority to U.S. Provisional Application No. 62/932,189, filed on November 7, 2019, which is incorporated herein by reference in its entirety.

TECHNICAU FIEUD

[002] The present technology relates generally to wound dressing compositions including fenestrated substrates and methods of using the same to reduce the pressure drop observed during negative pressure wound therapy (NPWT). Kits for use in practicing the methods are also provided.

BACKGROUND

[003] The following description of the background of the present technology is provided simply as an aid in understanding the present technology and is not admitted to describe or constitute prior art to the present technology.

[004] Negative pressure wound therapy (NPWT) is a type of wound therapy that involves applying a negative pressure to a wound site to promote wound healing. Clinical studies have shown that providing a reduced pressure in proximity to a wound site can assist in wound healing by promoting blood flow to the wound, stimulating the formation of granulation tissue, and encouraging the migration of healthy tissue over the wound.

SUMMARY OF THE PRESENT TECHNOUOGY [005] In one aspect, the present disclosure provides a wound dressing composition comprising: a substrate comprising a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof; and wherein the substrate comprises a plurality of slits that are arranged in a plurality of rows, wherein each row is parallel to at least one other row.

[006] In one aspect, the present disclosure provides a wound dressing composition comprising: a substrate comprising a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof; and wherein the substrate comprises a plurality of slits, wherein the slits are arranged in a radiating arrangement or a plurality of radiating arrangements, wherein each radiating arrangement comprises a plurality of slits radiating outwardly from a center of the radiating arrangement. Additionally or alternatively, in some embodiments, the center of the radiating arrangement is circular in shape. Additionally or alternatively, in some embodiments, the radiating arrangement of the substrate comprises a single center. Additionally or alternatively, in some embodiments, the plurality of slits are arranged in a plurality rows.

[007] Additionally or alternatively, in any of the embodiments disclosed herein, the slits do not intersect each other. Additionally or alternatively, in any of the embodiments disclosed herein, at least one slit intersects one or more other slits. Additionally or alternatively, in some embodiments of the wound dressing composition, each slit comprises an external perimeter, and the external perimeter of at least one slit is in contact with the external perimeter of another slit.

[008] Additionally or alternatively, in any of the preceding embodiments of the wound dressing composition disclosed herein, each slit is about 0.3 to about 30 mm long, about 0.6 to about 15 mm long, about 1 to about 5 mm long or about 2 to about 4 mm long. Additionally or alternatively, in any of the preceding embodiments of the wound dressing composition disclosed herein, each slit has a width of less than 0.1 mm, less than 0.05 mm, or less than 0.01 mm. Additionally or alternatively, in any of the preceding embodiments of the wound dressing composition disclosed herein, no material from the substrate comprising the biopolymer is removed when making the wound dressing composition.

[009] Additionally or alternatively, in any of the preceding embodiments of the wound dressing composition disclosed herein, the slits are linear or curved.

[0010] Additionally or alternatively, in any of the preceding embodiments of the wound dressing composition disclosed herein, wherein the biopolymer further comprises a polysaccharide, chitosan, gelatin, hyaluronic acid, or any combination thereof. Additionally or alternatively, in some embodiments, the substrate comprises about 0.1 wt.% to about 100 wt.% biopolymer.

[0011] Additionally or alternatively, in any of the preceding embodiments of the wound dressing composition disclosed herein, the substrate comprises a wound-facing side and an environmental- facing side, wherein the environmental-facing side of the substrate is coupled with a second layer. Additionally or alternatively, in some embodiments, the second layer comprises a foam.

[0012] Additionally or alternatively, in any of the preceding embodiments of the wound dressing composition disclosed herein, further comprising an adhesive layer is located between the substrate and the second layer. Additionally or alternatively, in some embodiments, the adhesive layer comprises acetic acid, a sugar, an alginate, or any combination thereof. Additionally or alternatively, in any of the preceding embodiments of the method for treating a wound disclosed herein, the adhesive layer is a layer of a plurality of adhesive droplets or a screen-printed adhesive. Additionally or alternatively, in some embodiments, the adhesive layer is a freeze dried adhesive layer. Additionally or alternatively, in some embodiments, the adhesive layer further comprises at least one additive.

[0013] Additionally or alternatively, in any of the preceding embodiments of the wound dressing composition disclosed herein, one or more of the substrate, the second layer and the adhesive layer comprise an additive selected from the group consisting of a silver compound, an antimicrobial agent, an antioxidant, a signaling protein, and any combination thereof.

[0014] Additionally or alternatively, in any of the preceding embodiments of the wound dressing composition disclosed herein, the wound dressing composition is configured for use in negative pressure wound therapy.

[0015] Additionally or alternatively, in any of the preceding embodiments of the wound dressing composition disclosed herein, the wound dressing composition is configured to reduce a pressure drop in negative pressure wound therapy by about 50% to about 100% compared to that observed with a control wound dressing composition that does not comprise slits or perforations.

[0016] In one aspect, the present disclosure provides an apparatus for treating a wound, wherein the apparatus comprises: a substrate comprising a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof, wherein the substrate comprises a plurality of slits that are arranged in a plurality of rows, wherein each row is parallel to at least one other row; and a second layer. In one aspect, the present disclosure provides an apparatus for treating a wound, wherein the apparatus comprises: a substrate comprising a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof; wherein the substrate comprises a plurality of slits, wherein the slits are arranged in a radiating arrangement or a plurality of radiating arrangements, wherein each radiating arrangement comprises a plurality of slits radiating outwardly from a center of the radiating arrangement; and a second layer. Additionally or alternatively, in any of the preceding embodiments of the apparatus disclosed herein, the second layer comprises a foam.

[0017] In one aspect, the present disclosure provides a dressing system comprising: a negative pressure source; and the wound dressing composition of any of the embodiments disclosed herein, or the apparatus for treating a wound of any of the embodiments disclosed herein.

[0018] In one aspect, the present disclosure provides a method for treating a wound in a subject in need thereof, the method comprising administering to the wound the wound dressing composition of any of the embodiments disclosed herein, the apparatus of any of the embodiments disclosed herein, or the dressing system of any of the embodiments disclosed herein; optionally applying a retainer layer over the wound dressing composition, or the apparatus, or the dressing system, applying a drape over the wound dressing composition, or the apparatus, or the dressing system, wherein the drape is configured to seal the wound dressing composition, or the apparatus or the dressing system, and applying negative pressure to the wound using a vacuum, wherein the vacuum is configured to be fluidly connected to the drape through a tubing.

[0019] In one aspect, the present disclosure provides a method for treating a wound in a subject in need thereof, the method comprising administering the wound dressing composition of any of the embodiments disclosed herein, or the apparatus for treating a wound of any of the embodiments disclosed herein to the wound and applying negative pressure to the wound. [0020] Additionally or alternatively, in any of the preceding embodiments of the method for treating a wound disclosed herein, the wound is an acute wound or a chronic wound. Additionally or alternatively, in any of the preceding embodiments of the method for treating a wound disclosed herein, the wound dressing composition is applied directly to the wound. Additionally or alternatively, in any of the preceding embodiments of the method for treating a wound disclosed herein, the method is configured for use in negative pressure wound therapy.

[0021] Additionally or alternatively, in any of the preceding embodiments of the method for treating a wound disclosed herein, the method is configured to reduce a pressure drop in negative pressure wound therapy by about 50% to about 100% compared to that observed with a control wound dressing composition that does not comprise perforations or slits. Additionally or alternatively, in any of the preceding embodiments of the method for treating a wound disclosed herein, the method is configured to reduce a pressure drop in negative pressure wound therapy by about 50% to about 100% compared to that observed with a control wound dressing composition that comprises perforations.

[0022] In one aspect, the present disclosure provides a method for treating a wound in a subject in need thereof, comprising: (a) administering to the wound the wound dressing composition of any of the embodiments disclosed herein, the apparatus for treating a wound of any of the embodiments disclosed herein, or the dressing system of any of the embodiments disclosed herein; and (b) applying negative pressure on the wound.

[0023] Additionally or alternatively, in any of the preceding embodiments of the method for treating a wound disclosed herein, the method further comprises applying a retainer layer over the wound dressing composition, the apparatus or the dressing system. Additionally or alternatively, in any of the preceding embodiments, the method further comprises applying a drape over the wound dressing composition, the apparatus, or the dressing system disclosed herein, and/or the retainer layer, wherein the drape is configured to seal the wound dressing composition, the apparatus, or the dressing system, and/or the retainer layer, and the wound site. Additionally or alternatively, in any of the preceding embodiments of the method, the negative pressure is intermittently applied.

[0024] In one aspect, the present disclosure provides a wound dressing composition comprising: a substrate; wherein the substrate comprise a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof; the substrate comprising a plurality of slits. Additionally or alternatively, in any of the preceding embodiments of the wound dressing composition disclosed herein, the slits arranged in a plurality of rows of slits. In some embodiments, the slits in the rows of slits are collinear with each other. In some embodiments, the every of row of slits is parallel to at least one other row of slits.

[0025] Additionally or alternatively, in any of the preceding embodiments of the wound dressing composition disclosed herein, the substrate has a thickness of about 0.5 mm to about 5 mm. [0026] Additionally or alternatively, in any of the preceding embodiments of the method for treating a wound disclosed herein, one or more of the substrate and the second layer comprise a silver compound. Additionally or alternatively, in some embodiments, one or more of the substrate and the second layer comprise about 0.1 wt.% to about 3 wt.% of the silver compound. In some embodiments, the silver compound comprises one or more pharmaceutically acceptable silver salts.

In some embodiments, the one or more pharmaceutically acceptable silver salts is selected from the group consisting of silver oxide, silver chromate, silver allantoinate, silver borate, silver glycerolate, silver nitrate, silver acetate, silver chloride, silver sulfate, silver lactate, silver bromide, silver iodide, silver carbonate, silver citrate, silver laurate, silver deoxycholate, silver salicylate, silver p- aminobenzoate, silver p-aminosalicylate, nanocrystalline silver, any pharmaceutically acceptable salt thereof, and any combination thereof.

[0027] Additionally or alternatively, in some embodiments, one or more of the substrate, the second layer and the additive further comprise an antimicrobial agent. Additionally or alternatively, in some embodiments, one or more of the substrate, the second layer and the additive comprise about 0.001 wt.% to about 5 wt.% of the antimicrobial agent. In some embodiments, the antimicrobial agent comprises one or more of tetracycline, penicillins, terramycins, erythromycin, bacitracin, neomycin, polymycin B, mupirocin, clindamycin, colloidal silver, silver sulfadiazine, chlorhexidine, povidone iodine, triclosan, sucralfate, quaternary ammonium salts, pharmaceutically acceptable silver salts, or any combination thereof.

[0028] Additionally or alternatively, in any of the preceding embodiments of the method for treating a wound disclosed herein, one or more of the substrate, the second layer and the additive further comprise an antioxidant. Additionally or alternatively, in some embodiments, one or more of the substrate, the second layer and the additive comprise about 0.001 wt.% to about 5 wt.% of the antioxidant. In some embodiments, the antioxidant comprises one or more of anthocyanins, astaxanthin, bilirubin, canthaxanthin, capsaicin, citric acid, curcumin, coenzyme Q10, eugenol, flavanols, flavonolignans, flavanones, flavones, flavonols, iodide, isoflavone phytoestrogens, lutein, lycopene, manganese, melatonin, N-acetylcysteine, oxalic acid, phenolic acids, phytic acid, R-a-lipoic acid, stilbenoids, tocopherol, tocotrienol, vitamin A, vitamin C, vitamin E, xanthones, zeaxanthin, a- carotene, b-carotene, or any combination thereof. In some embodiments, the anthocyanins are selected from the group consisting of cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin, and any combination thereof. In some embodiments, the flavanols are selected from the group consisting of catechin, epicatechin, theaflavin, thearubigins, gallocatechin, epigallocatechin, or any gallate ester thereof, and any combination thereof. In some embodiments, the flavanones are selected from the group consisting of eriodictyol, hesperetin, naringenin, and any combination thereof. In some embodiments, the flavones are selected from the group consisting of apigenin, luteolin, tangeritin, and any combination thereof. In some embodiments, the flavonols are selected from the group consisting of isorhamnetin, kaempferol, myricetin, proanthocyanidins, quercetin, rutin, and any combination thereof. In some embodiments, the isoflavone phytoestrogens are selected from the group consisting of daidzein, genistein, glycitein, and any combination thereof. In some embodiments, the phenolic acids are selected from the group consisting of chicoric acid, chlorogenic acid, cinnamic acid, ellagic acid, ellagitannins, gallic acid, gallotannins, rosmarinic acid, salicylic acid, or any ester thereof, and any combination thereof. In some embodiments, the stilbenoids are selected from the group consisting of resveratrol, pterostilbene, and any combination thereof.

[0029] Additionally or alternatively, in any of the preceding embodiments of the method for treating a wound disclosed herein, one or more of the substrate, the second layer and the additive further comprise a signaling protein. Additionally or alternatively, in some embodiments, one or more of the substrate, the second layer and the additive comprise about 0.001 wt.% to about 5 wt.% of the signaling protein. In some embodiments, the signaling protein comprises one or more of platelet- derived growth factor (PDGF), transforming growth factor beta (TGF ), fibroblast growth factors (FGFs), epidermal growth factor (EGF), or any combination thereof. In some embodiments, the fibroblast growth factors (FGFs) comprise one or more of fibroblast growth factor 1 (FGF1), fibroblast growth factor 2 (FGF2), fibroblast growth factor 3 (FGF3), fibroblast growth factor 4 (FGF4), fibroblast growth factor 5 (FGF5), fibroblast growth factor 6 (FGF6), fibroblast growth factor 7/keratinocyte growth factor (FGF7/KGF), fibroblast growth factor 8 (FGF8), fibroblast growth factor 9 (FGF9), fibroblast growth factor 10/keratinocyte growth factor 2 (FGF10/KGF2), fibroblast growth factor 11 (FGF11), fibroblast growth factor 12 (FGF12), fibroblast growth factor 13 (FGF13), fibroblast growth factor 14 (FGF14), fibroblast growth factor 15 (FGF15), fibroblast growth factor 16 (FGF16), fibroblast growth factor 17 (FGF17), fibroblast growth factor 18 (FGF18), fibroblast growth factor 19 (FGF19), fibroblast growth factor 20 (FGF20), fibroblast growth factor 21 (FGF21), fibroblast growth factor 22 (FGF22), fibroblast growth factor 23 (FGF23), or any combination thereof.

[0030] Additionally or alternatively, in any of the preceding embodiments of the method for treating a wound disclosed herein, the wound dressing composition is configured for use in negative pressure wound therapy. Additionally or alternatively, in any of the preceding embodiments of the method for treating a wound disclosed herein, the wound dressing composition is configured to reduce a pressure drop in negative pressure wound therapy by about 50% to about 100% compared to that observed with a control wound dressing composition that does not comprise slits or perforations. [0031] In one aspect, the present disclosure provides an apparatus for treating a wound comprising: a substrate; wherein the substrate comprise a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof; the substrate comprising a plurality of slits. Additionally or alternatively, in some embodiments, the plurality of slits are about 0.3 to about 30 mm long. In some embodiments, the plurality of slits are about 0.6 to about 15 mm long. In some embodiments, the plurality of slits are about 1 to about 5 mm long. In some embodiments, the plurality of slits are about 2 to about 4 mm long. [0032] In one aspect, the present disclosure provides a dressing system comprising: a substrate; wherein the substrate comprise a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof; the substrate comprising a plurality of slits. Additionally or alternatively, in some embodiments, the plurality of slits are about 0.3 to about 30 mm long. In some embodiments, the plurality of slits are about 0.6 to about 15 mm long. In some embodiments, the plurality of slits are about 1 to about 5 mm long. In some embodiments, the plurality of slits are about 2 to about 4 mm long.

[0033] In one aspect, the present disclosure provides a method for making a wound dressing composition: (a) providing a substrate comprising a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof; the substrate comprising a plurality of slits; wherein the substrate comprises a wound-facing side and an environmental-facing side; and a second layer comprising a foam; and (b) combining the substrate and the second layer such that the environmental-facing side of the substrate is coupled with the second layer. In some embodiments, the plurality of slits are about 0.3 to about 30 mm long. In some embodiments, the plurality of slits are about 0.6 to about 15 mm long. In some embodiments, the plurality of slits are about 1 to about 5 mm long.

[0034] Additionally or alternatively, in some embodiments, the substrate is made by fenestrating a layer comprising biopolymer using a clicker-press tool or a rotary cutting tool to generate slits. Additionally or alternatively, in some embodiments, the substrate is made by fenestrating a layer comprising biopolymer using LASER cutting or using heat to generate slits.

[0035] Additionally or alternatively, in some embodiments, the wound dressing composition is configured for use in negative pressure wound therapy.

[0036] In one aspect, the present disclosure provides a method for making a wound dressing composition comprising: (a) providing (i) a substrate comprising a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof; wherein the substrate comprises a plurality of slits that are arranged in a plurality of rows, wherein each row is parallel to at least one other row; and wherein the substrate comprises a wound-facing side and an environmental-facing side; and (ii) a second layer comprising a foam; and (b) combining the substrate and the second layer such that the environmental-facing side of the substrate is coupled with the second layer.

[0037] In one aspect, the present disclosure provides a method for making a wound dressing composition comprising: (c) providing (i) a substrate comprising a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof; wherein the substrate comprises a plurality of slits, wherein the slits are arranged in a radiating arrangement or a plurality of radiating arrangements, wherein each radiating arrangement comprises a plurality of slits radiating outwardly from a center of the radiating arrangement; and (ii) a second layer comprising a foam; and (d) combining the substrate and the second layer such that the environmental-facing side of the substrate is coupled with the second layer. Additionally or alternatively, in any of the embodiments of the method for making a wound dressing composition disclosed herein, the substrate is made by fenestrating a substrate comprising the biopolymer using a clicker-press tool or a rotary cutting tool to generate slits. Additionally or alternatively, in some embodiments, the substrate is made by fenestrating a substrate comprising the biopolymer using LASER cutting or using heat to generate slits. Additionally or alternatively, in any of the embodiments of the method for making a wound dressing composition disclosed herein, biopolymer material from the substrate comprising the biopolymer is not removed during fenestration.

[0038] In one aspect, the present disclosure provides a method for treating a wound in a subject in need thereof, the method comprising administering to the wound the wound dressing composition of any of the embodiments disclosed herein, the apparatus of any of the embodiments disclosed herein, or the dressing system of any of the embodiments disclosed herein; optionally applying a retainer layer over the wound dressing composition, or the apparatus, or the dressing system, applying a drape over the wound dressing composition, or the apparatus, or the dressing system, wherein the drape is configured to seal the wound dressing composition, or the apparatus, or the dressing system, and applying negative pressure to the wound using a vacuum, wherein the vacuum is configured to be fluidly connected to the drape through a tubing. In some embodiments, the wound is an acute wound or a chronic wound. Additionally or alternatively, in some embodiments, the wound dressing composition is applied directly to the wound.

[0039] In one aspect, the present disclosure provides a method for treating a wound in a subject in need thereof, the method comprising administering the wound dressing composition of any of the embodiments disclosed herein, the apparatus of any of the embodiments disclosed herein, or the dressing system of any of the embodiments disclosed herein to the wound and applying negative pressure to the wound. In some embodiments, the wound is an acute wound or a chronic wound. Additionally or alternatively, in some embodiments, the wound dressing composition of any of the embodiments disclosed herein, the apparatus of any of the embodiments disclosed herein, or the dressing system of any of the embodiments disclosed herein is applied directly to the wound.

[0040] In one aspect, the present disclosure provides a method for treating a wound in a subject in need thereof, comprising: providing a device to the wound, wherein the device comprises: the wound dressing composition of any of the embodiments disclosed herein, the apparatus of any of the embodiments disclosed herein, or the dressing system of any of the embodiments disclosed herein; optionally a retainer layer; a drape; and a vacuum for applying negative pressure to the wound, wherein the vacuum is configured to be fluidly connected to the drape through tubing, administering to the wound the wound dressing composition, the apparatus, or the dressing system; optionally applying the retainer layer over the wound dressing composition; applying the drape over the wound dressing composition and/or the retainer layer, wherein the drape is configured to seal the wound dressing composition and/or the retainer layer and the wound site; and applying negative pressure on the wound. Additionally or alternatively, in some embodiments, negative pressure is intermittently applied.

[0041] In one aspect, the present disclosure provides a method for making an apparatus for treating a wound, comprising: (a) providing a substrate comprising a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof; the substrate fenestrated with a plurality of nonintersecting rows of slits, each row of slits comprising a plurality of collinear slits, wherein biopolymer material is not removed when the substrate is fenestrated, wherein the substrate comprises a wound-facing side and an environmental -facing side; and a second layer comprising a foam; and (b) combining the substrate and the second layer such that the environmental- facing side of the substrate is coupled with a second layer. Additionally or alternatively, in any of the embodiments of the method for making an apparatus for treating a wound disclosed herein, the substrate is made by fenestrating a substrate comprising the biopolymer using a clicker-press tool or a rotary cutting tool to generate slits. Additionally or alternatively, in some embodiments, the substrate is made by fenestrating a substrate comprising the biopolymer using LASER cutting or using heat to generate slits. Additionally or alternatively, in any of the embodiments of the method for making an apparatus for treating a wound disclosed herein, biopolymer material from the substrate comprising the biopolymer is not removed during fenestration.

[0042] In one aspect, the present disclosure provides a kit comprising the wound dressing composition of any of the embodiments disclosed herein, the apparatus for treating a wound of any of the embodiments disclosed herein, or the dressing system of any of the embodiments disclosed herein, and instructions for use.

[0043] Also provided herein are kits comprising the wound dressing compositions of any embodiments disclosed herein and instructions for use.

BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 shows a diagrammatic representation of a fenestration pattern of an embodiment of a wound dressing composition of the present technology. This embodiment comprises parallel rows of collinear slits. Each slit 120 is 3 mm long and separated from its neighbor by 3 mm. The rows are 3 mm apart. Slits from adjacent rows are offset from each other.

[0045] Figure 2 shows a perspective view of an exemplary embodiment of a wound dressing composition of the present technology, having the fenestration pattern shown in Figure 1.

[0046] Figure 3 shows a diagrammatic representation of a positive control wound dressing used in the experiments described herein. The positive control wound dressing comprises laser cut perforations 4 mm diameter, spaced 10 mm apart.

[0047] Figure 4 shows a perspective view of a negative control wound dressing used in the experiments described herein. The negative control wound dressing comprises no perforations or fenestrations. [0048] Figures 5A-5B demonstrate the lack of pressure drop observed at various locations across a V.A.C.® GRANUFOAM™ layer of a dressing under negative pressure. The V.A.C.® GRANUFOAM™ layer was applied to an artificial wound model. Saline was continuously added to simulate wound exudate. About 125 mm Hg negative pressure was applied across the V.A.C.® GRANUFOAM™ layer and actual pressure was measured at the indicated points, which were distributed across the V.A.C.® GRANUFOAM™ layer. Measured actual pressure at the indicated points was plotted as a function of time (Figure 5A). The difference between the applied pressure at a SENSAT.R.A.C.™ Pad and the pressure measured at the different points across the foam was plotted as a function of time (Figure 5B).

[0049] Figures 6A-6B demonstrate the pressure drop observed at various locations across a negative control wound dressing under negative pressure. The experiment was performed as described in Figures 5A-5B. Measured actual pressure at the indicated points was plotted as a function of time (Figure 6A). The difference between the applied pressure at a SENSAT.R.A.C.™ Pad and the pressure measured at the different points across the foam was plotted as a function of time (Figure 6B).

[0050] Figures 7A-7B demonstrate the reduction in pressure drop observed at various locations across a positive control wound dressing, harboring large perforations (see Figure 3) under negative pressure. The experiment was performed as described in Figures 5A-5B. Measured actual pressure at the indicated points was plotted as a function of time (Figure 7A). The difference between the applied pressure at the SENSAT.R.A.C.™ Pad and the pressure measured at the different points across the foam was plotted as a function of time (Figure 7B).

[0051] Figure 8 demonstrates the lack of pressure drop observed at various locations across the wound dressing of the present technology under negative pressure. The experiment was performed as described in Figures 5A-5B. Measured actual pressure at the indicated points was plotted as a function of time. As shown, pressure at any tested points of the wound dressing of the present technology did not decrease compared to the SENSAT.R.A.C.™ Pad for 72 hours.

[0052] Figure 9 demonstrates transmission of the applied negative pressure at various locations across the wound dressing of the present technology. The experiment was performed as described in Figures 5A-5B except the negative pressure was withdrawn for one minute. Measured actual pressure at the indicated points was plotted as a function of time. As shown, the applied pressure was efficiently and dependably transmitted in real time across the wound dressing of the present technology.

DETAILED DESCRIPTION

[0053] It is to be appreciated that certain aspects, modes, embodiments, variations and features of the present methods are described below in various levels of detail in order to provide a substantial understanding of the present technology. [0054] Negative pressure wound therapy (NPWT) is a beneficial technique used for treating certain acute and chronic wounds. During NPWT, a dressing, typically an open celled foam, is placed at the wound site, a drape is sealed over a wound site and air is pumped out of the dressing to create negative pressure at the wound site. This leads to pumping of wound exudate and other fluids, improved blood flow, and micro-deformation of tissue at a wound site, etc., which are helpful for wound healing.

[0055] Dressings containing collagen and/or oxidized regenerated cellulose (ORC) are commonly used in wound treatment. ORC/collagen absorbs wound exudate and helps promote a moist microenvironment at the wound surface, which is conducive to granulation tissue formation, re- epithelialization, and optimal wound healing. Accordingly, ORC/collagen has been shown to cause measurable improvements in the histologic appearance of wound tissues. Further, ORC/collagen/silver-ORC has been shown to reduce bacterial bioburden/growth.

[0056] However, when used in conjunction with collagen or composite materials, a pressure drop of ~30 to 40 mm Hg is observed, potentially resulting in the wound site receiving less than the target negative pressure observed when the foam is used alone. This is because when the dressings containing collagen and/or oxidized regenerated cellulose (ORC) are used in conjunction with an NPWT foam manifold, ORC and collagen absorb wound exudate and swell. The swelling may result in a reduction of negative pressure at a wound surface compared to that observed when a foam manifold is used alone.

[0057] Current solutions to overcome this challenge require perforations in the collagen or composite material. Maintaining constant contact with the wound is crucial to ensure the uniform delivery of the negative pressure to the wound bed. Currently, there is an unmet need for wound dressing compositions to reduce the observed pressure drop over the area of the wound dressing composition whilst maintaining continuous surface contact with the wound.

[0058] The present disclosure is directed a wound dressing composition comprising a substrate, wherein the substrate includes a plurality of slits arranged in specific configurations. The wound dressing compositions of the present technology advantageously exhibit improved manifolding and decreased pressure drop during NPWT. The wound dressing compositions of the present technology are able to impart constant pressure distribution across a wound site upon application because of maintaining constant contact with the wound surface. The multi-layered construction of the wound dressing compositions may further include at least one additive in an adhesive solution to provide wound modulating components.

[0059] Figures 1 and 2 provide representative, non-limiting illustrations of embodiments of a wound dressing composition of the present technology.

[0060] Figures 3 and 4 provide the negative control wound dressing and the positive control wound dressing used for the experiments disclosed herein. [0061] Figures 5A-5B demonstrate the lack of the pressure drop observed at various locations across a V.A.C.® GRANUFOAM™ layer of a dressing under negative pressure.

[0062] Figures 6A-6B demonstrate the pressure drop observed at various locations across a negative control wound dressing, featuring no fenestration or perforations, under negative pressure. [0063] Figures 7A-7B demonstrate the reduction in pressure drop observed at various locations across a positive control wound dressing, harboring large perforations under negative pressure.

[0064] Figure 8 demonstrates the lack of pressure drop observed at various locations across the wound dressing of the present technology under negative pressure.

[0065] Figure 9 demonstrates steadfast transmission of the applied negative pressure at various locations across the wound dressing of the present technology when negative pressure is intermittently applied.

Definitions

[0066] The definitions of certain terms as used in this specification are provided below. Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this present technology belongs. [0067] The following terms are used throughout as defined below.

[0068] As used herein and in the appended claims, singular articles such as “a”, “an”, and “the” and similar referents in the context of describing the elements (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein, is intended merely to better illuminate the embodiments and does not pose a limitation on the scope of the claims unless otherwise stated. No language in the specification should be construed as indicating any non- claimed element as essential.

[0069] As used herein, “about” will be understood by persons of ordinary skill in the art and will vary to some extent depending upon the context in which it is used. If there are uses of the term which are not clear to persons of ordinary skill in the art, given the context in which it is used, “about” will mean up to plus or minus 10% of the particular term.

[0070] As used herein, the “apparatus” refers to any embodiment of a fenestrated substrate as described herein in combination with a second layer (e.g. a foam).

[0071] As used herein, the “administration” of a wound dressing composition to a subject includes any route of introducing or delivering to a subject a wound dressing composition to perform its intended function. Administration can be carried out by any suitable route, including but not limited to, topical administration. Administration includes self-administration and the administration by another.

[0072] As used herein, the terms “contain”, “contains”, or “containing” in the context of describing the elements (especially in the context of the following claims) are to be construed as comprising or including the elements being described herein.

[0073] As used herein, the term “effective amount” refers to a quantity sufficient to achieve a desired therapeutic effect, e.g., an amount that results in wound healing or a reduction of one or more signs or symptoms associated with a wound described herein. In the context of therapeutic applications, the wound dressing composition administered to the subject will vary depending on the composition, the degree, type, and severity of the wound and on the characteristics of the individual. [0074] As used herein, the term “fenestrated” refer to a property of the substrate of the dressings of the present technology, wherein the substrate of the dressings of the present technology has a plurality of slits as defined herein. The process of making the substrate of the wound dressing compositions of the present technology does not remove any significant amount of material from an unfenestrated substrate. Therefore, the weight of the substrate of the dressings of the present technology is about equal to the weight of an unfenestrated substrate of an otherwise identical wound dressing composition. The slits may have any geometric relationship with each other and to the geometry of the dressing. For example, the slits may radially extend outwardly from one or more points. Slits may or may not intersect each other, or may be joined at ends in any angle, e.g., a right angle. The slits may form a plurality of rows of collinear slits. The rows of slits may be parallel to the edge of the dressing or intersect the edge of the dressing at any angle. The rows of collinear slits may be parallel to each other.

[0075] As used herein, the terms “individual”, “patient”, or “subject” can be an individual organism, a vertebrate, a mammal, or a human. In some embodiments, the individual, patient or subject is a human.

[0076] As understood by one of ordinary skill in the art, “molecular weight” (also known as “relative molar mass”) is a dimensionless quantity that can be converted to molar mass by multiplying by 1 gram/mole - for example, collagen with a weight-average molecular weight of 5,000 has a weight-average molar mass of 5,000 g/mol.

[0077] As used herein, the term “Negative pressure,” or “vacuum” may refer to a pressure less than a local ambient pressure, such as the ambient pressure in a local environment that is external to a sealed therapeutic environment provided by a dressing. Additionally or alternatively, in some embodiments, the local ambient pressure may also be the atmospheric pressure proximate to a wound site. Additionally or alternatively, in some embodiments, the local ambient pressure may also be less than a hydrostatic pressure associated with a wound site. Additionally or alternatively, in some embodiments, NPWT may provide a number of benefits, including, but not limited to, migration of epithelial and subcutaneous tissues, improved blood flow, and micro-deformation of tissue at a wound site. These benefits may increase development of granulation tissue and reduce healing times. Additionally or alternatively, in some embodiments, a negative pressure applied across a wound, via the NPWT device may be effective to induce macrostrain and microstrain at wound site, as well as remove exudates and other fluids from the wound site. Examples of setups for use with NPWT are disclosed in U.S. Patent No. 7,534,240, U.S. Patent No. 8,188,331, U.S. Patent No. 8,529,526, and EP Patent 1758638, each incorporated by reference herein in their entirety.

[0078] As used herein, the term “NPWT” refers to negative pressure wound therapy, which is a type of wound therapy that involves applying negative pressure (relative to atmospheric pressure) to a wound bed to promote wound healing. Typically, a dressing is sealed over a wound site and air is pumped out of the dressing to create negative pressure at the wound site. In some NPWT systems, wound exudate and other fluid is pumped out of the dressing and collected by a canister.

[0079] As used herein, the term “pitch” refers to the distance between repeated elements in a structure. For example, a pitch between slits is the distance between one slit and another slit within the row of slits of the wound dressing composition; and a pitch between rows of slits is the distance between one row of slits and the adjacent rows of slits.

[0080] As used herein, the term “solid content” refers to the density of a material and/or film of a wound dressing composition or reduced-pressure wound dressing composition apparatus of the present technology, which is its mass per unit volume.

[0081] As used herein, the terms “perforation,” “porous,” and “perforated,” are used to described any suitable material having pores, or holes, and are intended to encompass apertures, holes, or pores across the substrate. Each perforation may have a depth equal to the thickness of the substrate, creating a channel for the transit of fluids across the substrate of the wound dressing composition of the present technology. The holes may have any shape, including circular, round, square, oblong, rectangular, star shaped, amorphous, etc. Perforation are created by puncturing an unfenestrated substrate by removing material of the shape of the perforation, such as circular, round, square, oblong, rectangular, star shaped, amorphous, etc. Perforated substrates are created by cutting an unfenestrated substrate by removing material of the size and shape of the perforations.

[0082] As used herein, the term “slit” refers to a cut or incision across the substrate of the wound dressing composition of the present technology. Each slit may have a depth equal to the thickness of the substrate, creating a channel for the transit of fluids across the substrate of the wound dressing composition of the present technology. The slits have no significant width because the slits are created by cutting an unfenestrated substrate without removing any material.

[0083] “Treating” or “treatment” as used herein covers the treatment of a wound described herein, in a subject, such as a human, and includes: (i) inhibiting a wound, i.e., arresting its development; (ii) relieving a wound, i.e., causing regression of the wound; (iii) slowing progression of the wound; and/or (iv) inhibiting, relieving, or slowing progression of one or more symptoms of the wound. In some embodiments, treatment means that the symptoms associated with the wound are, e.g., alleviated, reduced, cured, or placed in a state of remission.

[0084] As used herein, the term “% w/v” refers to the percent of weight of the solute in the total volume of the solution, i.e., the number of grams of solute in 100 mL of solution.

[0085] It is also to be appreciated that the various modes of treatment of wounds as described herein are intended to mean “substantial,” which includes total but also less than total treatment, and wherein some biologically or medically relevant result is achieved. The treatment may be a continuous prolonged treatment for a chronic wound or a single, or several administrations for the treatment of an acute wound.

The Wound Dressing Composition of the Present Technology

The Substrate

[0086] The present disclosure is directed to wound dressing compositions comprising a substrate comprising a biopolymer and a plurality of slits, which may advantageously exhibit decreased pressure drop observed during negative pressure wound therapy.

[0087] Figures 1 and 2 provide representative, non-limiting illustrations of embodiments of a wound dressing composition of the present technology.

[0088] Referring to Figures 1-2, the present disclosure provides a wound dressing composition comprising a substrate 110 comprising a biopolymer and a plurality of slits 120. Additionally or alternatively, in some embodiments, no biopolymer is removed while making the slits 120. Additionally or alternatively, in some embodiments, the slits 120 may be arranged in any orientation with respect to each other. In some embodiments, as shown in the exemplary embodiment in Figure 1, the slits 120 may be organized in rows of slits 130, each row of slits 130 comprising a plurality of slits 120, wherein the slits in a row are collinear to each other, with a pitch between slits 140. In some embodiments, the rows of slits may be arranged in a parallel orientation to each other with a pitch between rows of slits 150 (Figures 1-2). In some embodiments, the slits in a row may be offset from the slits in the adjacent row (Figures 1-2).

[0089] Additionally or alternatively, in any of the embodiments disclosed herein, the slits 120 do not intersect each other. Additionally or alternatively, in any of the embodiments disclosed herein, at least one slit intersects with at least one other slit. Additionally or alternatively, in some embodiments of the wound dressing composition, each slit 120 comprises an external perimeter, and the external perimeter of at least one slit is in contact with the external perimeter of another slit.

[0090] Additionally or alternatively, in some embodiments, of the wound dressing composition disclosed herein, each slit 120 may comprise a length. In some embodiments of the wound dressing composition disclosed herein, each slit 120 may be 0.3 to 30 mm. In some embodiments of the wound dressing composition disclosed herein, the length of each slit 120 may be about 0.3 mm, about 0.6 mm, about 1 mm, about 1 mm, about 1.5 mm, about 2 mm, about 2.5 mm, about 3 mm, about 3.5 mm, about 4 mm, about 4.5 mm, about 5 mm, about 7.5 mm, about 10 mm, about 12.5 mm, about 15 mm, about 20 mm, about 25 mm, about 30 mm, or any range including and/or in between any two of these values. Additionally or alternatively, in some embodiments, of the wound dressing composition disclosed herein, the length of each slit 120 may be from about 0.3 mm to about 2 mm, about 0.5 mm to about 3 mm, about 1 mm to about 6 mm, about 2.5 mm to about 10 mm, 5 mm to about 20 mm, about 10 mm to about 30 mm, or any range including and/or in between any two of these values.

[0091] Additionally or alternatively, of the wound dressing composition disclosed herein, the pitch between slits 140 may be from about 0.3 mm to about 2 mm, about 0.5 mm to about 3 mm, about 1 mm to about 6 mm, about 2.5 mm to about 10 mm, 5 mm to about 20 mm, about 10 mm to about 30 mm, or any range including and/or in between any two of these values. Additionally or alternatively, in some embodiments, of the wound dressing composition disclosed herein, the pitch between slits 140 may be from about 0.3 mm to about 2 mm, about 0.5 mm to about 3 mm, about 1 mm to about 6 mm, about 2.5 mm to about 10 mm, 5 mm to about 20 mm, about 10 mm to about 30 mm, or any range including and/or in between any two of these values.

[0092] Additionally or alternatively, in some embodiments, of the wound dressing composition disclosed herein, the pitch between the rows of slits 150 may be about 0.3 mm, about 0.6 mm, about 1 mm, about 1 mm, about 1.5 mm, about 2 mm, about 2.5 mm, about 3 mm, about 3.5 mm, about 4 mm, about 4.5 mm, about 5 mm, about 7.5 mm, about 10 mm, about 12.5 mm, about 15 mm, about 20 mm, about 25 mm, about 30 mm, or any range including and/or in between any two of these values. Additionally or alternatively, in some embodiments, of the wound dressing composition disclosed herein, the pitch between the rows of slits 150 may be from about 0.3 mm to about 2 mm, about 0.5 mm to about 3 mm, about 1 mm to about 6 mm, about 2.5 mm to about 10 mm, 5 mm to about 20 mm, about 10 mm to about 30 mm, or any range including and/or in between any two of these values. [0093] In any embodiment of the wound dressing composition disclosed herein, the substrate may include a wound-facing side and an environmental -facing side.

[0094] In any embodiment of the wound dressing composition disclosed herein, the substrate may have a thickness of about 0.5 mm to about 6 mm. Additionally or alternatively, in some embodiments, of the wound dressing composition disclosed herein, the substrate may have a thickness of about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 2.5 mm, about 3 mm, about 4 mm, about 6 mm, about 6 mm, or any range including and/or in between any two of the preceding values.

In any embodiment of the wound dressing composition disclosed herein, the substrate may have a thickness of about 0.5 mm to about 2 mm, about 1 mm to about 4 mm, about 2 mm to about 6 mm, about 2.5 mm to about 10 mm, 5 mm to about 20 mm, about 10 mm to about 30 mm, or any range including and/or in between any two of these values.

[0095] In any embodiment of the wound dressing composition disclosed herein, the shape of the slits 120 in the substrate may independently be a linear or curved. In some embodiments, the shape of the slits 120 is linear. [0096] In any embodiment of the wound dressing composition disclosed herein, the biopolymer of the substrate 110 may be one or more of a collagen, an oxidized cellulose, a polysaccharide, chitosan, gelatin, hyaluronic acid, or any combination thereof.

[0097] In any embodiment of the wound dressing composition disclosed herein, the substrate 110 may comprise about 0.1 wt.% to about 100 wt.% biopolymer. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the amount of biopolymer in the substrate 110 may be about 0.1 wt.%, about 0.5 wt.%, about 1 wt.%, about 2.5 wt.%, about 5 wt.%, about 10 wt.%, about 15 wt.%, about 20 wt.%, about 25 wt.%, about 30 wt.%, about 35 wt.%, about 40 wt.%, about 45 wt.%, about 50 wt.%, about 55 wt.%, about 60 wt.%, about 65 wt.%, about 70 wt.%, about 75 wt.%, about 80 wt.%, about 85 wt.%, about 90 wt.%, about 95 wt.%, about 98 wt. %, about 99 wt. %, about 100 wt.%, or any range including and/or in between any two of the preceding values.

[0098] In any embodiment of the wound dressing composition disclosed herein, the solid content of the substrate 110 may comprise about 0.1 wt.% to about 10 wt.%. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the solid content of the substrate 110 may comprise about 0.1 wt.%, about 0.5 wt.%, about 1 wt.%, about 1.5 wt.%, about 2 wt.%, about 2.5 wt.%, about 3 wt.%, about 3.5 wt.%, about 4 wt.%, about 4.5 wt.%, about 5 wt.%, about 5.5 wt.%, about 6 wt.%, about 6.5 wt.%, about 7 wt.%, about 7.5 wt.%, about 8 wt.%, about 8.5 wt.%, about 9 wt.%, about 9.5 wt.%, about 10 wt.%, or any range including and/or in between any two of the preceding values.

[0099] In any embodiment of the wound dressing composition disclosed herein, the substrate 110 may comprise a collagen. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the substrate 110 may comprise about 20 wt.% to about 80 wt.% of a collagen. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the substrate 110 may comprise about 20 wt.%, about 25 wt.%, about 30 wt.%, about 35 wt.%, about 40 wt.%, about 45 wt.%, about 50 wt.%, about 55 wt.%, about 60 wt.%, about 65 wt.%, about 70 wt.%, about 75 wt.%, about 80 wt.%, or any range including and/or in between any two of the preceding values, of the collagen. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the substrate 110 may comprise about 20 wt.% to about 40 wt.%, about 30 wt.% to about 50 wt.%, about 40 wt.% to about 60 wt.%, about 50 wt.% to about 70 wt.%, about 60 wt.% to about 80 wt.% of the collagen.

[00100] In any embodiment of the wound dressing composition disclosed herein, the substrate 110 may comprise an oxidized cellulose. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the substrate 110 may comprise about 20 wt.% to about 80 wt.% of an oxidized cellulose. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the substrate 110 may comprise about 20 wt.%, about 25 wt.%, about 30 wt.%, about 35 wt.%, about 40 wt.%, about 45 wt.%, about 50 wt.%, about 55 wt.%, about 60 wt.%, about 65 wt.%, about 70 wt.%, about 75 wt.%, about 80 wt.%, or any range including and/or in between any two of the preceding values, of the oxidized cellulose. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the substrate 110 may comprise about 20 wt.% to about 40 wt.%, about 30 wt.% to about 50 wt.%, about 40 wt.% to about 60 wt.%, about 50 wt.% to about 70 wt.%, about 60 wt.% to about 80 wt.% of the oxidized cellulose.

[00101] In any embodiment of the wound dressing composition disclosed herein, the substrate 110 may comprise a silver compound. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the substrate 110 may comprise about 0.1 wt.% to about 3 wt.% of a silver compound. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the substrate 110 may comprise about 0.1 wt.%, about 0.25 wt.%, about 0.50 wt.%, about 0.75 wt.%, about 0.8 wt.%, about 0.85 wt.%, about 0.9 wt.%, about 0.95 wt.%, about 1 wt.%, about 1.25 wt.%, about 1.5 wt.%, about 1.75 wt.%, about 2 wt.%, about 2.25 wt.%, about 2.5 wt.%, about 2.75 wt.%, about 3 wt.%, or any range including and/or in between any two of the preceding values, of the silver compound.

[00102] In any embodiment of the wound dressing composition disclosed herein, the silver compound of the substrate 110 comprises one or more pharmaceutically acceptable silver salts. Exemplary sources of the one or more pharmaceutically acceptable silver salts of the substrate 110 include, but are not limited to, silver oxide, silver chromate, silver allantoinate, silver borate, silver glycerolate, silver nitrate, silver acetate, silver chloride, silver sulfate, silver lactate, silver bromide, silver iodide, silver carbonate, silver citrate, silver laurate, silver deoxycholate, silver salicylate, silver / aminobenzoate. silver /^-aminosalicylate. nanocrystalline silver, any pharmaceutically acceptable salt thereof, or any combination thereof. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the silver compound of the substrate 110 comprises a silver (II) oxide, silver (III) oxide, a silver oxy-salt, or any combination thereof. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the silver oxy-salt may comprise a general formula of Ag(Ag₃0_a)X, wherein X can include, but is not limited to, one or more acid anions such as sulfates, chlorides, phosphates, carbonates, citrates, tartrates, or oxalates; and wherein a is at least two. [00103] In any embodiment of the wound dressing composition disclosed herein, the substrate 110 may comprise about 1 wt.% to about 15 wt.% of at least one plasticizer. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the substrate 110 may comprise about 1 wt.%, about 1.5 wt.%, about 2 wt.%, about 2.5 wt.%, about 3 wt.%, about 3.5 wt.%, about 4 wt.%, about 4.5 wt.%, about 5 wt.%, about 5.5 wt.%, about 6 wt.%, about 6.5 wt.%, about 7 wt.%, about 7.5 wt.%, about 8 wt.%, about 8.5 wt.%, about 9 wt.%, about 9.5 wt.%, about 10 wt.%, about 10.5 wt.%, about 11 wt.%, about 11.5 wt.%, about 12 wt.%, about 12.5 wt.%, about 13 wt.%, about 13.5 wt.%, about 14 wt.%, about 14.5 wt.%, about 15 wt.%, or any range including and/or in between any two of the preceding values, of the at least one plasticizer. Exemplary plasticizers include, but are not limited to, an acetylated monoglyceride, an alkyl citrate, methyl ricinoleate, glycerol, polyvinylpyrrolidone, and any combination thereof. Examples of alkyl citrates include, but are not limited to, triethyl citrate, acetyl triethyl citrate, tributyl citrate, acetyl tributyl citrate, trioctyl citrate, acetyl trioctyl citrate, trihexyl citrate, acetyl trihexyl citrate, butyryl trihexyl citrate, trimethyl citrate, and any combination thereof.

The Second Layer

[00104] The present disclosure provides a wound dressing that may include a second layer, wherein the second layer may include a wound-facing side and an environmental-facing side, and wherein the second layer may include a manifold for delivering negative pressure such as an open cell foam. In any embodiment disclosed herein, the environmental-facing side of the substrate is coupled with the wound-facing side of the second layer.

[00105] In any embodiment disclosed herein, the manifold component may include an open-celled foam. In some embodiments, the second layer may comprise a porous and permeable foam layer formed from a reticulated, open-cell polyurethane or polyether foam that facilitates good permeability of wound fluids while under a reduced pressure. In one non-limiting example, the the second layer may be an open-cell, reticulated polyurethane foam such as V.A.C.® GRANUFOAM™ dressing available from Kinetic Concepts, Inc. of San Antonio, Texas. In other embodiments the second layer may be an open-cell, reticulated polyurethane foam such as a V.A.C. VeraFlo® foam, also available from Kinetic Concepts, Inc., of San Antonio, Texas. In yet other embodiments, the second layer may be formed of un-reticulated open-cell foam. In some embodiments, the second layer may include one or more of a polyurethane foam, a polyether polyurethane foam, a polyester polyurethane foam, a polyalkylene foam, copolymers and blends thereof, or any combination thereof.

[00106] In any embodiment disclosed herein, the second layer may include fluid pathways interconnected so as to improve distribution or collection of fluids. For example, in any embodiment disclosed herein, the second layer may comprise a porous foam material having a plurality of interconnected cells, pores, edges, walls, or a combination of two or more thereof to form interconnected fluid pathways (e.g., channels). Suitable porous foam materials may include, but are not limited to, cellular foam, open-cell foam, reticulated foam, porous tissue collections, other porous materials (e.g. , gauze or felted mat), or a combination of two or more thereof. In any embodiment disclosed herein, the second layer may be a foam having pore sizes in of about 400 microns, about 420 microns, about 440 microns, about 460 microns, about 480 microns, about 500 microns, about 520 microns, about 540 microns, about 560 microns, about 580 microns, about 600 microns, or any range including and/or in between any two of the preceding values. Thus, in any embodiment herein, the second layer may be an open-cell, reticulated polyurethane foam.

[00107] The size, shape and thickness of the second layer may be varied as desired. In any embodiment disclosed herein, the second layer may have a thickness of about 0.3 mm to about 10 mm. Additionally or alternatively, in some embodiments, the second layer may have a thickness of about 0.3 mm, about 0.4 mm, about 0.5 mm, about 0.6 mm, about 0.8 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm, about 10 mm, or any range including and/or in between any two of the preceding values. The Wound Dressing Composition

[00108] When dressing compositions containing collagen and/or oxidized regenerated cellulose (ORC) are used in conjunction with NPWT foam manifold, ORC and collagen absorb wound exudate and swell. The swelling may result in a reduction of negative pressure at a wound surface compared to the applied pressure on the second layer (e.g., foam manifold). The wound dressing compositions of the present technology will advantageously allow improved manifolding and decreased pressure drop during NPWT. The wound dressing compositions of the present technology are able to impart constant pressure distribution across a wound site upon application by maintaining constant contact with the wound surface, which ensures the uniform delivery of the negative pressure to the wound bed. The multi-layered construction of the wound dressing compositions may further include at least one additive in an adhesive solution to provide wound modulating components.

[00109] In one aspect, the present disclosure provides a wound dressing composition comprising: a substrate comprising a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof, wherein the substrate comprises a plurality of slits. In some embodiments, the slits are arranged in a plurality of rows, wherein each row is parallel to at least one other row. Additionally or alternatively, in some embodiments, the slits are arranged in a radiating arrangement or a plurality of radiating arrangements, wherein each radiating arrangement comprises a plurality of slits radiating outwardly from a center of the radiating arrangement. Additionally or alternatively, in some embodiments, the center of the radiating arrangement is circular in shape. Additionally or alternatively, in some embodiments, the radiating arrangement of the substrate comprises a single center. Additionally or alternatively, in some embodiments, the plurality of slits are arranged in a plurality rows. Additionally or alternatively, in some embodiments, the slits do not intersect each other.

[00110] Additionally or alternatively, in any of the preceding embodiments of the wound dressing composition disclosed herein, the substrate comprises a wound-facing side and an environmental- facing side, wherein the environmental-facing side of the substrate is coupled with a second layer. Additionally or alternatively, in some embodiments, the second layer comprises a foam.

[00111] Additionally or alternatively, in any of the preceding embodiments of the wound dressing composition disclosed herein, further comprising an adhesive layer is located between the substrate and the second layer. Additionally or alternatively, in some embodiments, the adhesive layer comprises acetic acid, a sugar, an alginate, or any combination thereof. Additionally or alternatively, in any of the preceding embodiments of the method for treating a wound disclosed herein, the adhesive layer is a layer of a plurality of adhesive droplets or is a screen-printed adhesive. Additionally or alternatively, in some embodiments, the adhesive layer is a freeze dried adhesive layer. Additionally or alternatively, in some embodiments, the adhesive layer further comprises at least one additive.

[00112] Additionally or alternatively, in any of the preceding embodiments of the wound dressing composition disclosed herein, one or more of the substrate, the second layer and the adhesive layer comprise an additive selected from the group consisting of a silver compound, an antimicrobial agent, an antioxidant, a signaling protein, and any combination thereof.

[00113] In any embodiment disclosed herein, one or more of the substrate, the second layer and the adhesive layer may comprise an antimicrobial agent. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the substrate, the second layer and the adhesive layer may comprise about 0.01 % w/v to about 9 % w/v of the antimicrobial agent. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the antimicrobial agent may comprise about 0.01 % w/v, about 0.1 % w/v, about 1 % w/v, about 1.5 % w/v, about 2 % w/v, about 2.5 % w/v, about 3 % w/v, about 3.5 % w/v, about 4 % w/v, about 4.5 % w/v, about 5 % w/v, about 5.5 % w/v, about 6 % w/v, about 6.5 % w/v, about 7 % w/v, about 7.5 % w/v, about 8 % w/v, about 8.5 % w/v, about 9 % w/v, or any range including and/or in between any two of these values. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the antimicrobial agent may be one or more of tetracycline, penicillins, terramycins, erythromycin, bacitracin, neomycin, polymycin B, mupirocin, clindamycin, colloidal silver, silver sulfadiazine, chlorhexidine, povidone iodine, triclosan, sucralfate, quaternary ammonium salts, pharmaceutically acceptable silver salts, or any combination thereof.

[00114] In any embodiment disclosed herein, one or more of the substrate, the second layer and the adhesive layer may comprise an antioxidant. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the substrate, the second layer and the adhesive layer may comprise about 0.1 % w/v to about 9 % w/v of the antioxidant. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the antioxidant may comprise about 0.1 % w/v, about 1 % w/v, about 1.5 % w/v, about 2 % w/v, about 2.5 % w/v, about 3 % w/v, about 3.5 % w/v, about 4 % w/v, about 4.5 % w/v, about 5 % w/v, about 5.5 % w/v, about 6 % w/v, about 6.5 % w/v, about 7 % w/v, about 7.5 % w/v, about 8 % w/v, about 8.5 % w/v, about 9 % w/v, or any range including and/or in between any two of these values. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the antioxidant may be one or more of anthocyanins, astaxanthin, bilirubin, canthaxanthin, capsaicin, citric acid, curcumin, coenzyme Q10, eugenol, flavanols, flavonolignans, flavanones, flavones, flavonols, iodide, isoflavone phytoestrogens, lutein, lycopene, manganese, melatonin, N-acetylcysteine, oxalic acid, phenolic acids, phytic acid, R- a-lipoic acid, stilbenoids, tocopherol, tocotrienol, vitamin A, vitamin C, vitamin E, xanthones, zeaxanthin, a-carotene, b-carotene, or any combination thereof. [00115] In any embodiment of the wound dressing composition disclosed herein, the anthocyanins are selected from the group consisting of cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin, and mixtures thereof.

[00116] In any embodiment of the wound dressing composition disclosed herein, the flavanols are selected from the group consisting of catechin, epicatechin, theaflavin, thearubigins, gallocatechin, epigallocatechin, or any gallate ester thereof, and mixtures thereof.

[00117] In any embodiment of the wound dressing composition disclosed herein, the flavanones are selected from the group consisting of eriodictyol, hesperetin, naringenin, and mixtures thereof.

[00118] In any embodiment of the wound dressing composition disclosed herein, the flavones are selected from the group consisting of apigenin, luteolin, tangeritin, and mixtures thereof.

[00119] In any embodiment of the wound dressing composition disclosed herein, the flavonols are selected from the group consisting of isorhamnetin, kaempferol, myricetin, proanthocyanidins, quercetin, rutin, and mixtures thereof.

[00120] In any embodiment of the wound dressing composition disclosed herein, the isoflavone phytoestrogens are selected from the group consisting of daidzein, genistein, glycitein, and any combination thereof.

[00121] In any embodiment of the wound dressing composition disclosed herein, the phenolic acids are selected from the group consisting of chicoric acid, chlorogenic acid, cinnamic acid, ellagic acid, ellagitannins, gallic acid, gallotannins, rosmarinic acid, salicylic acid, or any ester thereof, and any combination thereof.

[00122] In any embodiment of the wound dressing composition disclosed herein, the stillbenoids are selected from the group consisting of resveratrol, pterostilbene, and any combination thereof.

[00123] In any embodiment disclosed herein, one or more of the substrate, the second layer and the adhesive layer may comprise a signaling protein. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the substrate, the second layer and the adhesive layer may comprise about 1 % w/v to about 9 % w/v of the signaling protein. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the signaling protein may comprise about 1 % w/v, about 1.5 % w/v, about 2 % w/v, about 2.5 % w/v, about 3 % w/v, about 3.5 % w/v, about 4 % w/v, about 4.5 % w/v, about 5 % w/v, about 5.5 % w/v, about 6 % w/v, about 6.5 % w/v, about 7 % w/v, about 7.5 % w/v, about 8 % w/v, about 8.5 % w/v, about 9 % w/v, or any range including and/or in between any two of these values. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the signaling protein may be one or more of platelet-derived growth factor (PDGF), transforming growth factor beta (TGF ), fibroblast growth factors (FGFs), epidermal growth factor (EGF), or any combination thereof. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the fibroblast growth factors (FGFs) may be one or more of fibroblast growth factor 1 (FGF1), fibroblast growth factor 2 (FGF2), fibroblast growth factor 3 (FGF3), fibroblast growth factor 4 (FGF4), fibroblast growth factor 5 (FGF5), fibroblast growth factor 6 (FGF6), fibroblast growth factor 7/keratinocyte growth factor (FGF7/KGF), fibroblast growth factor 8 (FGF8), fibroblast growth factor 9 (FGF9), fibroblast growth factor 10/keratinocyte growth factor 2 (FGF10/KGF2), fibroblast growth factor 11 (FGF11), fibroblast growth factor 12 (FGF12), fibroblast growth factor 13 (FGF13), fibroblast growth factor 14 (FGF14), fibroblast growth factor 15 (FGF15), fibroblast growth factor 16 (FGF16), fibroblast growth factor 17 (FGF17), fibroblast growth factor 18 (FGF18), fibroblast growth factor 19 (FGF19), fibroblast growth factor 20 (FGF20), fibroblast growth factor 21 (FGF21), fibroblast growth factor 22 (FGF22), fibroblast growth factor 23 (FGF23), or any combination thereof.

[00124] In any embodiment disclosed herein, the wound dressing of the present technology may be sterile and packaged in a microorganism-impermeable container.

[00125] In any embodiment of the wound dressing composition disclosed herein, the wound dressing of the present technology is configured for use in negative pressure wound therapy (NPWT). Additionally or alternatively, in some embodiments, NPWT may be performed such as by procedures described in U.S. Pat. Nos. 7,534,240 and 9,918,733, the entire contents of which are incorporated by reference.

[00126] In any embodiment of the wound dressing composition disclosed herein, the application of the wound dressing of the present technology causes about 50% to about 100% reduction in pressure drop observed in negative pressure wound therapy compared to that observed with a control wound dressing that does not comprise perforations or fenestrations. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the application of the wound dressing of the present technology causes about 50%, about 52%, about 54%, about 56%, about 58%, about 60%, about 62%, about 64%, about 66%, about 68%, about 70%, about 72%, about 74%, about 76%, about 78%, about 80%, about 82%, about 84%, about 86%, about 88%, about 90%, about 92%, about 94%, about 96%, about 98%, about 100%, or any range including and/or in between any two of these values, reduction in the pressure drop observed in negative pressure wound therapy compared to that observed with a control wound dressing that does not comprise perforations or fenestrations.

[00127] In any embodiment of the wound dressing composition disclosed herein, the application of the wound dressing of the present technology causes about 50% to about 100% reduction in pressure drop observed in negative pressure wound therapy compared to that observed with a control wound dressing that comprises a plurality of perforations. Additionally or alternatively, in some embodiments of the wound dressing disclosed herein, the application of the wound dressing of the present technology causes about 50%, about 52%, about 54%, about 56%, about 58%, about 60%, about 62%, about 64%, about 66%, about 68%, about 70%, about 72%, about 74%, about 76%, about 78%, about 80%, about 82%, about 84%, about 86%, about 88%, about 90%, about 92%, about 94%, about 96%, about 98%, about 100%, or any range including and/or in between any two of these values, reduction in the pressure drop observed in negative pressure wound therapy compared to that observed with a control wound dressing that comprises a plurality of perforations. [00128] In any embodiment disclosed herein, the wound dressings of the present technology advantageously exhibit improved manifolding and decreased pressure drop during NPWT. Without wishing to be bound by theory, it is believed that the wound dressings of the present technology are able to impart constant pressure distribution across a wound site upon application. Further, the wound dressings of the present technology exhibit increased contact across the surface of a wound.

[00129] In any embodiment disclosed herein, the wound dressing may be mated to a retainer layer while in use for NPWT. The retainer layer may be configured to be adjoined to the environmental- facing side of the wound dressing of the present technology. The retainer layer may include, but is not limited to, a cellular foam, an open-cell foam, a reticulated foam, porous tissue collections, and/or other porous material (e.g., gauze). The retainer layer may have pores that range in diameter from about 60 pm to about 2000 pm. Thus, the retainer layer may have pores that range in diameter from about 60 pm, about 100 pm, about 250 pm, about 500 pm, about 750 pm, about 1000 pm, about 1250 pm, about 1500 pm, about 1750 pm, about 2000 pm, or any range including and/or in between any two of these values. In some embodiments, the retainer layer may include an open-cell, reticulated polyurethane foam such as a V.A.C.® GRANUFOAM™ dressing available from Kinetic Concepts, Inc. of San Antonio, Texas. In some embodiments, the retainer layer may include an open-cell, reticulated polyurethane foam such as a V.A.C. VERAFLO™ dressing available from Kinetic Concepts, Inc. of San Antonio, Texas.

[00130] In any embodiment disclosed herein, the drape may be composed of a polyurethane fdm or an elastomeric fdm. The drape may be applied over the wound dressing of the present technology and/or the retainer layer during NPWT. The drape may be configured to seal the wound dressing and/or the retainer layer, and the wound site during NPWT. Examples of an elastomeric film include, but are not limited to, natural rubber, polyisoprene, styrene butadiene rubber, chloroprene rubber, polybutadiene, nitrile rubber, butyl rubber, ethylene propylene rubber, ethylene propylene diene monomer, chlorosulfonated polyethylene, polysulfide rubber, ethylene vinyl acetate (EVA) film, co-polyester, or silicone. Suitable drape materials and methods of use are described in U.S. Pat. Nos. 7,534,240,

7,611,500, 9,918,733, and U.S. Pat. App. No. 14/708,078, of which the entire contents are incorporated herein by reference.

[00131] In any embodiment disclosed herein, the wound dressing may be connected to tubing while in use for NPWT. The tubing may include, but is not limited to, a tube, pipe, hose, conduit, or any other structure with one or more lumina adapted to convey liquid between two ends. Additionally or alternatively, in some embodiments, the tubing may be composed of polyvinyl chloride, polyethylene, polypropylene, or any combination thereof. The tubing may be configured to connect the drape to a vacuum, such as a V.A.C.^® Therapy system, while in use for NPWT. Suitable tubing materials and methods of use are described in U.S. Pat. Nos. 7,534,240, 7,611,500, 9,918,733, and U.S. Pat. App. No. 14/708,078, of which the entire contents are incorporated herein by reference. [00132] In any embodiment disclosed herein, the wound dressing may be fluidly coupled to a vacuum via the tubing to apply negative pressure to a wound in need thereof. Additionally or alternatively, in some embodiments, negative pressure refers to a pressure less than local ambient pressure, such as the pressure in a local environment external to a sealed wound site. Additionally or alternatively, in some embodiments, the vacuum for applying negative pressure may be a vacuum pump, a suction pump, a micro-pump, or a wall vacuum port available in many healthcare facilities. Additionally or alternatively, in some embodiments, the vacuum is used to apply negative pressure to a wound. Additionally or alternatively, in some embodiments, the negative pressure applied to a wound may be about -5 mm Hg to about -500 mm Hg, or about -75 mm Hg to about -300 mm Hg. Thus, the negative pressure applied to a wound may be about -5 mm Hg, about -25 mm Hg, about -50 mm Hg, about -75 mm Hg, about -100 mm Hg, about -125 mm Hg, about -150 mm Hg, about -175 mm Hg, about -200 mm Hg, about -225 mm Hg, about -250 mm Hg, about -275 mm Hg, about -300 mm Hg, about -325 mm Hg, about -350 mm Hg, about -375 mm Hg, about -400 mm Hg, about -425 mm Hg, about -450 mm Hg, about -475 mm Hg, about -500 mm Hg, or any range including and/or in between any two of these values. Methods of use of negative pressure therapy devices are described in U.S. Pat. Nos. 7,534,240, 7,611,500, 9,918,733, and U.S. Pat. App. No. 14/708,078, of which the entire contents are incorporated herein by reference.

Therapeutic Methods of the Present Technology

[00133] In one aspect, the present disclosure provides a method for treating a wound in a subject in need thereof, wherein the method comprises administering to the wound a wound dressing of any embodiment disclosed herein. Additionally or alternatively, in some embodiments, of the methods disclosed herein, the wound may be an acute wound or a chronic wound. Additionally or alternatively, in some embodiments, of the methods disclosed herein, the wound is an acute wound selected from the group consisting of bums, skin grafts, and dehisced surgical wounds. Additionally or alternatively, in some embodiments, of the methods disclosed herein, the wound is a chronic wound selected from the group consisting of infectious wounds, venous ulcers, arterial ulcers, decubitus ulcers and diabetic ulcers.

[00134] In another aspect, the present disclosure provides a method for treating a wound in a subject in need thereof, wherein the method includes providing a device to the wound, wherein the device includes a wound dressing of any embodiment disclosed herein, optionally a retainer layer, a drape, and a vacuum for applying negative pressure to the wound, wherein the vacuum is configured to be fluidly connected to the drape through tubing; administering to the wound the wound dressing, applying the retainer layer over the wound dressing, and applying the drape over the wound dressing and/or the retainer layer, wherein the drape is configured to seal the wound dressing and/or the retainer layer and the wound site.

[00135] Any method known to those in the art for administering a wound dressing to an acute wound or a chronic wound disclosed herein may be employed. Suitable methods include in vitro or in vivo methods. In vivo methods typically include the administration of one or more wound dressings to a subject in need thereof, suitably a human. In some embodiments of the methods disclosed herein, the wound dressing is applied directly to the wound. When used in vivo for therapy, the one or more wound dressings described herein are administered to the subject in effective amounts (i.e.. amounts that have desired therapeutic effect). The dose and dosage regimen will depend upon the state of the wound of the subject, and the characteristics of the particular wound dressing used.

[00136] The effective amount may be determined during pre-clinical trials and clinical trials by methods familiar to physicians and clinicians. An effective amount of one or more wound dressings useful in the methods may be administered to a subject in need thereof by any number of well-known methods for administering wound dressings.

[00137] In some embodiments of the methods disclosed herein, the wound dressings or the apparatuses are administered daily for 1 hour or more, for 2 hours or more, for 3 hours or more, for 4 hours or more, for 5 hours or more, for 6 hours or more, for 12 hours or more. Additionally or alternatively, in some embodiments, of the methods disclosed herein, the wound dressings or the apparatuses are administered one, two, three, four, or five times per day. Additionally or alternatively, in some embodiments, of the methods disclosed herein, the wound dressings or the apparatuses are administered daily for one, two, three, four or five weeks. Additionally or alternatively, in some embodiments, of the methods disclosed herein, the wound dressings or the apparatuses are administered daily for less than 6 weeks. Additionally or alternatively, in some embodiments, of the methods disclosed herein, the wound dressings or the apparatuses are administered daily for 6 weeks or more. Additionally or alternatively, in some embodiments, of the methods disclosed herein, the wound dressings or the apparatuses are administered daily for 12 weeks or more. Additionally or alternatively, in some embodiments, of the methods disclosed herein, the wound dressings or the apparatuses are administered every day, every other day, every third day, every fourth day, every fifth day, or every sixth day. Additionally or alternatively, in some embodiments, of the methods disclosed herein, the wound dressings or the apparatuses are administered weekly, bi-weekly, tri-weekly, or monthly. Additionally or alternatively, in some embodiments, of the methods disclosed herein, the wound dressings or the apparatuses are administered for a period of one, two, three, four, or five weeks. Additionally or alternatively, in some embodiments, of the methods disclosed herein, the wound dressings or the apparatuses are administered for six weeks or more. Additionally or alternatively, in some embodiments, of the methods disclosed herein, the wound dressings or the apparatuses are administered for twelve weeks or more. Additionally or alternatively, in some embodiments, of the methods disclosed herein, the wound dressings or the apparatuses are administered for a period of less than one year. Additionally or alternatively, in some embodiments, of the methods disclosed herein, the wound dressings or the apparatuses are administered for a period of more than one year. [00138] In some embodiments of the methods disclosed herein, the wound dressings or the apparatuses can be changed for a chronic wound as appropriate. Additionally or alternatively, in some embodiments, of the methods disclosed herein, the wound is a chronic wound selected from the group consisting of infectious wounds, venous ulcers, arterial ulcers, decubitus ulcers and diabetic ulcers.

Methods of Making the Wound dressing compositions of the Present Technology [00139] Also disclosed herein are methods for making the wound dressing compositions of the present technology. In one aspect, the present disclosure provides a method for making a wound dressing composition, providing a substrate and a second layer, generating a plurality of slits in each of the substrate and the second layer, wherein each slit comprises a length and an external perimeter, and combining the substrate and the second layer such that the external perimeter of each slit in the substrate does not overlap or intersect with the external perimeter of each slit in the second layer. [00140] Additionally or alternatively, in some embodiments, the substrate is made by fenestrating a layer comprising biopolymer using a clicker-press tool or a rotary cutting tool to generate slits. Additionally or alternatively, in some embodiments, the substrate is made by fenestrating a layer comprising biopolymer using LASER cutting or using heat to generate slits. Additionally or alternatively, in any of the embodiments of the method for making the wound dressing compositions of the present technology disclosed herein, biopolymer material from the substrate comprising the biopolymer is not removed during fenestration. Additionally or alternatively, in any of the embodiments of the method for making the wound dressing compositions of the present technology disclosed herein, no material from the substrate is removed when the substrate is fenestrated. Additionally or alternatively, in any of the embodiments of the method for making the wound dressing compositions of the present technology disclosed herein, the substrate weight of the substrate does not substantially change when the substrate is fenestrated.

[00141] Additionally or alternatively, in any of the preceding embodiments of the wound dressing composition disclosed herein, one or more of the substrate, the second layer and the adhesive layer comprise an additive selected from the group consisting of a silver compound, an antimicrobial agent, an antioxidant, a signaling protein, and any combination thereof.

[00142] In any embodiment disclosed herein, one or more of the substrate, the second layer and the adhesive layer may comprise an antimicrobial agent. Additionally or alternatively, in some embodiments of the method, one or more of the substrate, the second layer and the adhesive layer may comprise an antimicrobial agent of any and all embodiments of the substrate, the second layer and the adhesive layer disclosed herein.

[00143] In any embodiment disclosed herein, one or more of the substrate, the second layer and the adhesive layer may comprise an antioxidant. Additionally or alternatively, in some embodiments of the method, one or more of the substrate, the second layer and the adhesive layer may comprise the antioxident of any and all embodiments of the substrate, the second layer and the adhesive layer disclosed herein.

[00144] In any embodiment disclosed herein, one or more of the substrate, the second layer and the adhesive layer may comprise a signaling protein. Additionally or alternatively, in some embodiments of the method, one or more of the substrate, the second layer and the adhesive layer may comprise the signaling protein of any and all embodiments of the substrate, the second layer and the adhesive layer disclosed herein.

Kits Comprising the Wound dressing compositions of the Present Technology [00145] In a further related aspect, the present disclosure provides kits that include a wound dressing compositions or apparatuses of any embodiment described herein and instructions for use. The kits of the present technology may also include instructions for treating a wound in a subject in need thereof. The kit may optionally comprise components such as antiseptic wipes, ointment, adhesive tape, tweezers, or scissors.

EXAMPLES

[00146] The present technology is further illustrated by the following Example, which should not be construed as limiting in any way. The examples herein are provided to illustrate advantages of the present technology and to further assist a person of ordinary skill in the art with preparing or using the compositions and systems of the present technology. The examples should in no way be construed as limiting the scope of the present technology, as defined by the appended claims. The examples can include or incorporate any of the variations, aspects, or embodiments of the present technology described above. The variations, aspects, or embodiments described above may also further each include or incorporate the variations of any or all other variations, aspects or embodiments of the present technology.

[00147] Typically, the dressings used in NPWT comprise a drape system, which is mated to a retainer layer which includes an open-cell, reticulated polyurethane foam, such as V.A.C.® GRANUFOAM™ available from Kinetic Concepts, Inc. of San Antonio, Texas. The open-cell, reticulated polyurethane foam is coupled to other layers of dressing, which optionally include layers comprising collagen and/or oxidized regenerated cellulose (ORC).

Example 1: The Lack of Pressure Drop Across Cellular Foam During Negative Pressure Wound Therapy

[00148] It has been observed that use of dressings containing certain hydrophilic materials, such as collagen and/or oxidized regenerated cellulose (ORC), exhibit a pressure drop at the wound surface when used in conjunction of negative pressure wound therapy (data not shown and see below). To determine the reduction in negative pressure drop transmitted through the retainer layer, an open-cell, reticulated polyurethane foam (V.A.C.® GRANUFOAM™) was placed on a wound model. Spigots, filtered spigots, and filtered traps placed at various points beneath the V.A.C.® GRANUFOAM™ layer were connected to tubing. A SENSAT.R.A.C.™ wound interface pad was used, and saline was delivered at a rate of 2.1 mL/hour into the NPWT system to simulate an exudating wound. An INFOV.A.C.™ NPWT System (Kinetic Concepts Inc., San Antonio, TX) was used, and a negative pressure of about 125 mm ofHg was applied. The applied negative pressure was measured at the SENSAT.R.A.C.™ Pad and negative pressure at wound surface was measured at the spigots, fdtered spigots, and fdtered traps. As shown in Figure 5A, the actual negative pressure at the wound surface, as measured at the spigots, fdtered spigots, and fdtered traps, was indistinguishable from the applied negative pressure, measured at the wound interface pad. The difference in applied negative pressure and actual negative pressure was plotted. As shown in Figure 5B, the actual negative pressure at all tested at the spigots, fdtered spigots, and fdtered traps did not significantly change compared to the applied negative pressure. Therefore, the V.A.C.® GRANUFOAM™ layer comprising open-cell, reticulated polyurethane foam, did not cause the reduction in negative pressure at wound surface. [00149] These results demonstrate that the lack of the negative pressure drop observed at various locations across a V.A.C.® GRANUFOAM™ layer of a dressing under negative pressure. Therefore, V.A.C.® GRANUFOAM™ is useful in NPWP methods of the present technology.

Example 2: Negative pressure Drop Across Wound Dressing_. Comprising Collagen and Oxidized Regenerated Cellulose (ORC) During_. Negative Pressure Wound Therapy [00150] To determine the reduction in negative pressure drop transmitted through a hydrophilic dressing that exhibits swelling upon contacting liquids using negative control wound dressing comprising no perforations or fenestration (e.g. Figure 4), a wound dressing comprising collagen and oxidized regenerated cellulose (ORC) (a PROMOGRAN PRISMA™) was placed on a wound model. Spigots, filtered spigots, and filtered traps placed at various points beneath the PROMOGRAN PRISMA™ layer were connected to tubing. A V.A.C.® GRANUFOAM™ layer and a SENSAT.R.A.C.™ Pad were added to the PROMOGRAN PRISMA™ layer. This dressing served as a negative control for lack of reliable transmission of negative pressure. Saline was delivered at a rate of 2.1 mL/hour into the NPWT system to simulate an exudating wound. An INFOV.A.C.™ NPWT System was used, and a negative pressure of was applied. The negative pressure in the NPWT system was monitored at various points across the control wound dressing composition as saline was delivered at a rate of 2.1 mL/hour. About 125 mm Hg negative pressure was applied across the dressing and measured at the SENSAT.R.A.C.™ Pad. Actual negative pressure was measured at the spigots, filtered spigots, and filtered traps placed under the dressing.

[00151] As shown in Figure 6A, the negative pressure at all points of the negative control dressing started to drop, as measured at the spigots, filtered spigots, and filtered traps, compared to the negative pressure at SENSAT.R.A.C.™ Pad soon as negative pressure was applied. The difference in applied negative pressure and actual negative pressure is plotted in Figure 6B. As shown in Figure 6B, the actual negative pressure at all tested at the spigots, filtered spigots, and filtered traps showed an immediate drop. The difference in applied and actual negative pressure kept on increasing (Figures 6A-6B). In about 24 hours, the difference in applied and actual negative pressure was 30-40 mm of Hg (Figure 6B). Therefore, the hydrophilic dressing layer that exhibits swelling, upon contacting liquids, caused a reduction in negative pressure at wound surface. Such drop was not observed when nonhydrophilic dressing that do not swell upon contacting liquids (data not shown). The observed pressure drop may potentially result in the wound site receiving less than the target negative pressure observed when the foam is used alone.

Example 3: Dressings having Perforations Decrease the Rate and Extent of Drop in Negative Pressure During Negative Pressure Wound Therapy

[00152] Without being bound by theory, it was hypothesized that hydrophilic dressings, which exhibit swelling upon contacting liquids, do not efficiently transmit the applied pressure during NPWT because of blockage of any spaces inside the dressings caused by swelling. Because of the observed swelling, the hydrophilic dressings resist the passage of fluids and air across the dressings, and thereby, do not efficiently transmit the applied pressure during NPWT. To test this hypothesis, a positive control dressing, harboring large perforations was created (See Figure 3).

[00153] To determine the reduction in pressure drop achieved by the positive control dressing compositions, a wound dressing comprising the positive control dressing (perforated PROMOGRAN PRISMA™) was placed on a wound model. Spigots, filtered spigots, and filtered traps placed at various points beneath the positive control dressing layer were connected to tubing. A V.A.C.® GRANUFOAM™ layer and a SENSAT.R.A.C.™ Pad were added. Saline was delivered at a rate of 2.1 mL/hour into the NPWT system to simulate an exudating wound. An INFOV.A.C.™ NPWT System was used, and a negative pressure of about 125 mm of Hg was applied. The negative pressure in the NPWT system was monitored at various points across the control wound dressing composition as saline was delivered at a rate of 2.1 mL/hour. About 125 mm Hg negative pressure was applied across the dressing and measured at the SENSAT.R.A.C.™ Pad. Actual negative pressure was measured at the spigots, filtered spigots, and filtered traps that were placed under the dressing.

[00154] As shown in Figure 7A, the negative pressure beneath the positive control dressing did not decrease significantly for the first 4-5 hours, as measured by the negative pressure at the spigots, filtered spigots, and filtered traps, compared to the negative pressure at SENSAT.R.A.C.™ Pad. Therefore, this dressing served as a positive control for efficient transmission of negative pressure. The negative pressure started to drop after that, albeit at a lower rate. The difference in applied negative pressure and actual negative pressure is plotted in Figure 7B. As shown in Figure 7B, the extent of drop in negative pressure observed after about five hours was about 5-15 mm of Hg compared to the 30-40 mm of Hg drop observed with the negative control dressing. Without being bound by theory, it was hypothesized that swelling of the dressing material in combination of flexible nature of the hydrophobic dressings used seal even the large perforations after about 5 hours. Moreover, the extent of drop in negative pressure generally correlated with distance from the wound surface and distance from the perforation. Furthermore, the rate of drop was lesser compared to the negative control dressing as shown by the slope of curves) (compare Figures 6B and 7B). Therefore, the positive control dressing, harboring large perforations, reduced the extent of drop of actual negative pressure at wound surface compared to the applied negative pressure. The skilled artisan recognizes that the positive control dressing, harboring large perforations, is helpful for NPWT for wounds depending on type of wound, type of use, the manner/ orientation in which the dressing is placed over the wound, frequency of change of dressings etc.

[00155] Therefore, hydrophilic dressing harboring large perforations reliably transmit the applied pressure during NPWT despite swelling upon contacting liquids.

Example 4: The Wound Dressing_. Compositions of the Present Technology do not Exhibit Drop in Negative Pressure during Negative Pressure Wound Therapy

[00156] The above data suggested that hydrophilic dressings, such as a PROMOGRAN PRISMA™, swell when they contact liquids, such as wound exudates. Large perforations allow liquids to pass through the dressings and relieve the extent of drop in negative pressure experienced at the wound surface during NPWT. It was expected that slits, instead of perforations, will not be sufficient to allow efficient transmission of negative pressure because when hydrophilic materials like collagen and/or ORC will close the slits even faster than the large perforations, and block any transfer of fluids across the slits.

[00157] To test this hypothesis, the wound dressing compositions of the present technology, shown in Figures 1-2 was created. To determine the reduction in pressure drop achieved by the wound dressing compositions of the present technology, (e.g., a PROMOGRAN PRISMA™ comprising slits) was placed on a wound model. Spigots, filtered spigots, and filtered traps placed at various points beneath the positive control dressing layer were connected to tubing. A V.A.C.® GRANUFOAM™ layer and a SENSAT.R.A.C.™ Pad were added. Saline was delivered at a rate of 2.1 mL/hour into the NPWT system to simulate an exudating wound. An INFOV.A.C.™ NPWT System was used, and a negative pressure of about 125 mm of Hg was applied. The negative pressure in the NPWT system was monitored at various points across the control wound dressing composition as saline was delivered at a rate of 2.1 mL/hour. About 125 mm Hg negative pressure was applied across the dressing. Applied negative pressure and actual negative pressure was measured at the SENSAT.R.A.C.™ Pad, spigots, filtered spigots, and filtered traps as discussed above.

[00158] As shown in Figure 8, surprisingly, the negative pressure beneath the wound dressing compositions of the present technology did not decrease significantly for the duration of the experiment (72 hr), as measured by the negative pressure at the spigots, filtered spigots, and filtered traps, compared to the negative pressure at SENSAT.R.A.C.™ Pad. Therefore, the wound dressing compositions of the present technology showed no drop of actual negative pressure at wound surface compared to the applied negative pressure.

[00159] Moreover, comparison of Figures 7 and 8 shows that whereas the positive control dressing, harboring large perforations, reduced the extent of drop of actual negative pressure at wound surface compared to the applied negative pressure, the wound dressing compositions of the present technology, (e.g., a PROMOGRAN PRISMA™ comprising slits) showed no drop of actual negative pressure at wound surface compared to the applied negative pressure. Moreover, whereas the positive control dressing, harboring large perforations, resisted for the first 4-5 hours the decrease in the drop of actual negative pressure at wound surface compared to the applied negative pressure, the wound dressing compositions of the present technology, (e.g., a PROMOGRAN PRISMA™ comprising slits) resisted the decrease in the drop of actual negative pressure at wound surface compared to the applied negative pressure for at least 72 hr.

[00160] Without being bound by theory, these data led to the hypothesis that the wound dressing compositions of the present technology efficiently allow the transit of fluids through the slits because the slits deform maintaining the passages for fluid transmission. The wound dressing compositions of the present technology, therefore, allow combination of the beneficial effects dressings comprising collagen and/or oxidized regenerated cellulose (ORC) with those of NPWT. Therefore, the wound dressing compositions of the present technology are useful in treatment of wounds using NPWT. Example 5: Use of the Wound Dressing_. Compositions of the Present Technology During Use of Discontinuous Pressure in Negative pressure Wound Therapy

[00161] During NPWT, the vacuum may be applied continuously or intermittently, depending on the type of wound being treated and the clinical objectives. To understand whether the wound dressing compositions of the present technology during intermittent use of negative pressure, an experiment was carried out as described in Example 4, except the application of negative pressure was stopped and restarted during the experiment. Applied negative pressure and actual negative pressure was measured at the SENSAT.R.A.C.™ Pad, spigots, filtered spigots, and filtered traps as discussed above both during the entirety of the experiment.

[00162] As shown in Figure 9, the actual negative pressure beneath the wound dressing compositions of the present technology measured at spigots, filtered spigots, and filtered traps completely paralleled the applied negative pressure measured at the SENSAT.R.A.C.™ Pad. Therefore, the wound dressing compositions of the present technology efficiently transmit the applied negative pressure to the wound surface.

[00163] Therefore, the wound dressing compositions of the present technology are useful in treatment of wounds using NPWT using either continuous negative pressure or intermittent negative pressure.

EQUIVALENTS

[00164] The present technology is not to be limited in terms of the particular embodiments described in this application, which are intended as single illustrations of individual aspects of the present technology. Many modifications and variations of this present technology can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. Functionally equivalent methods and apparatuses within the scope of the present technology, in addition to those enumerated herein, will be apparent to those skilled in the art from the foregoing descriptions. Such modifications and variations are intended to fall within the scope of the present technology. It is to be understood that this present technology is not limited to particular methods, reagents, compounds, compositions, or biological systems, which can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

[00165] In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group. [00166] As will be understood by one skilled in the art, for any and all purposes, particularly in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third, and upper third, etc. As will also be understood by one skilled in the art all language such as “up to,” “at least,” “greater than,” “less than,” and the like, include the number recited and refer to ranges which can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1-3 cells refers to groups having 1, 2, or 3 cells. Similarly, a group having 1-5 cells refers to groups having 1, 2, 3, 4, or 5 cells, and so forth.

[00167] All patents, patent applications, provisional applications, and publications referred to or cited herein are incorporated by reference in their entirety, including all figures and tables, to the extent they are not inconsistent with the explicit teachings of this specification.

Claims

1. A wound dressing composition comprising: a substrate comprising a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof; and wherein the substrate comprises a plurality of slits that are arranged in a plurality of rows, wherein each row is parallel to at least one other row.

2. A wound dressing composition comprising: a substrate comprising a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof; and wherein the substrate comprises a plurality of slits, wherein the slits are arranged in a radiating arrangement or a plurality of radiating arrangements, wherein each radiating arrangement comprises a plurality of slits radiating outwardly from a center of the radiating arrangement.

3. The wound dressing composition of claim 2, wherein the center of the radiating arrangement is circular in shape.

4. The wound dressing composition of claim 2 or claim 3, wherein the radiating arrangement of the substrate comprises a single center.

5. The wound dressing composition of any one of claims 2-4, wherein the plurality of slits are arranged in a plurality rows.

6. The wound dressing composition of any one of claims 2-5, wherein the slits do not intersect each other.

7. The wound dressing composition of any one of claims 1-6, wherein each slit comprises an external perimeter, and wherein the external perimeter of at least one slit is in contact with the external perimeter of another slit.

8. The wound dressing composition of any one of claims 1-7, wherein each slit is about 0.3 to about 30 mm long, about 0.6 to about 15 mm long, about 1 to about 5 mm long or about 2 to about 4 mm long.

9. The wound dressing composition of any one of claims 1-8, wherein each slit has a width of less than 0.1 mm, less than 0.05 mm, or less than 0.01 mm.

10. The wound dressing composition of any one of claims 1-9, wherein the slits are linear or curved.

11. The wound dressing composition of any one of claims 1-10, wherein the substrate comprises a wound-facing side and an environmental-facing side, wherein the environmental-facing side of the substrate is coupled with a second layer.

12. The wound dressing composition of claim 11, wherein the second layer comprises a foam.

13. The wound dressing composition of any one of claims 1-12, wherein the biopolymer further comprises a polysaccharide, chitosan, gelatin, hyaluronic acid, or any combination thereof.

14. The wound dressing composition of any one of claims 1-13, wherein an adhesive layer is located between the substrate and the second layer.

15. The wound dressing composition of claim 14, wherein the adhesive layer comprises acetic acid, a sugar, an alginate, or any combination thereof.

16. The wound dressing composition of any one of claims 1-15, wherein one or more of the substrate, the second layer and the adhesive layer comprise an additive selected from the group consisting of a silver compound, an antimicrobial agent, an antioxidant, a signaling protein, and any combination thereof.

17. The wound dressing composition of any one of claims 1-16, wherein the wound dressing composition is configured for use in negative pressure wound therapy.

18. The wound dressing composition of any one of claims 1-17, wherein the wound dressing composition is configured to reduce a pressure drop in negative pressure wound therapy by about 50% to about 100% compared to that observed with a control wound dressing composition that does not comprise slits or perforations.

19. An apparatus for treating a wound, wherein the apparatus comprises: a substrate comprising a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof, wherein the substrate comprises a plurality of slits that are arranged in a plurality of rows, wherein each row is parallel to at least one other row; and a second layer.

20. The apparatus of claim 19, wherein the second layer comprises a foam.

21. A dressing system comprising: a negative pressure source; and the wound dressing composition of any one of claims 1-18, or the apparatus for treating a wound of claim 19 or claim 20.

22. A method for treating a wound in a subject in need thereof, the method comprising administering the wound dressing composition of any one of claims 1-18, or the apparatus of claim 19 or 20 to the wound and applying negative pressure to the wound.

23. A method for treating a wound in a subject in need thereof, the method comprising administering the wound composition of any one of claims 1-18, or the apparatus of claim 19 or claim 20 to the wound, optionally applying a retainer layer over the wound dressing composition, or the apparatus, applying a drape over the wound dressing composition, or the apparatus, wherein the drape is configured to seal the wound dressing composition, or the apparatus, and applying negative pressure to the wound using a vacuum, wherein the vacuum is configured to be fluidly connected to the drape through a tubing.

24. The method of claim 22 or 23, wherein the wound is an acute wound or a chronic wound.

25. The method of any one of claims 22-24, wherein the wound dressing composition is applied directly to the wound.

26. The method of any one of claims 22-25, wherein the method is configured for use in negative pressure wound therapy.

27. The method of any one of claims 22-26, wherein the method is configured to reduce a pressure drop in negative pressure wound therapy by about 50% to about 100% compared to that observed with a control wound dressing composition that does not comprise perforations or slits.

28. The method of any one of claims 22-27, wherein the method is configured to reduce a pressure drop in negative pressure wound therapy by about 50% to about 100% compared to that observed with a control wound dressing composition that comprises perforations.

29. A method for treating a wound in a subject in need thereof, comprising:

(a) administering to the wound the wound dressing composition of any one of claims 1-18, or the apparatus of claim 19 or claim 20, or the dressing system of claim 21; and

(b) applying negative pressure on the wound.

30. The method of claim 29, further comprising applying a retainer layer over the wound dressing composition.

31. The method of claim 29 or claim 30 further comprising applying a drape over wound composition, the apparatus, or the dressing system, and/or the retainer layer, wherein the drape is configured to seal the composition, the apparatus, or the dressing system, and/or the retainer layer, and the wound site.

32. The method of any one of claims 29-31, wherein negative pressure is intermittently applied.

33. A method for making a wound dressing composition comprising:

(a) providing

(i) a substrate comprising a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof; wherein the substrate comprises a plurality of slits that are arranged in a plurality of rows, wherein each row is parallel to at least one other row; and wherein the substrate comprises a wound-facing side and an environmental-facing side; and

(ii) a second layer comprising a foam; and

(b) combining the substrate and the second layer such that the environmental-facing side of the substrate is coupled with the second layer.

34. A method for making a wound dressing composition comprising:

(a) providing

(i) a substrate comprising a biopolymer, wherein the biopolymer comprises collagen, oxidized regenerated cellulose (ORC) or a combination thereof; wherein the substrate comprises a plurality of slits, wherein the slits are arranged in a radiating arrangement or a plurality of radiating arrangements, wherein each radiating arrangement comprises a plurality of slits radiating outwardly from a center of the radiating arrangement; and (ii) a second layer comprising a foam; and

35. The method of claim 33 or 34, wherein the substrate is made by fenestrating a substrate comprising the biopolymer using a clicker-press tool or a rotary cutting tool to generate slits.

36. The method of any one of claims 33-34, wherein the substrate is made by fenestrating a substrate comprising the biopolymer using LASER cutting or using heat to generate slits.

37. The method of any one of claims 33-36, wherein biopolymer material from the substrate comprising the biopolymer is not removed during fenestration.

38. A kit comprising the composition of any one of claims 1-18, or the apparatus of claim 19 or claim 20, or the dressing system of claim 21, and instructions for use.