TECHNICAL FIELD

[0001] This application claims the benefit of and priority to U.S. Provisional Application No. 62/783,786, filed December 21, 2018, the entirety of which is incorporated herein by reference for any and all purposes.

TECHNICAL FIELD

[0002] The present technology relates generally to dressings useful for treating wounds that include a co-polymer of polyvinylpyrrolidone (PVP) and citric acid. Such dressings may be used to disrupt and/or prevent bio film formation in a wound upon application.

BACKGROUND

[0003] 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.

[0004] Infections can retard wound healing and, if untreated, can result in tissue loss, systemic infections, septic shock, and death. Moreover, in addition to vegetative or free- floating bacteria present in a wound, bacterial bio films may also form in a wound presenting further challenges in wound therapy, particularly chronic wounds. A biofilm comprises a polysaccharide extracellular matrix produced by an association of microorganisms ( e.g ., single or multiple species) that have adhered onto a surface, forming three-dimensional microbial communities. The ability of bacteria to form these complex bio films can impede a host’s defense mechanisms against pathogens. Currently, there is an unmet need for wound dressing products that can prevent, reduce, inhibit, or disrupt bio film formation in a wound upon application, and over time.

SUMMARY

[0005] In an aspect, a dressing composition is provided that includes a hydrogel, wherein the hydrogel includes a co-polymer of polyvinylpyrrolidone (PVP) and citric acid. The wound dressing may include a first layer that includes the hydrogel and a second layer that includes a mixture of a collagen and an oxidized regenerated cellulose (ORC).

[0006] In a related aspect, a kit is provided that includes a dressing composition of any embodiment described herein and instructions for use.

[0007] In another aspect, a wound dressing composition is provided that includes a mixture of a collagen, an oxidized regenerated cellulose (ORC), and a co-polymer of

polyvinylpyrrolidone (PVP) and citric acid.

[0008] In a related aspect, a kit is provided that includes a wound dressing composition of any embodiment described herein and instructions for use.

[0009] In another aspect, a method for treating a wound in a subject in need thereof is provided, where the method includes administering to the wound a dressing composition of any embodiment described herein and/or a wound dressing composition of any embodiment described herein.

DETAILED DESCRIPTION

[0010] 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.

Definitions

[0011] 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.

[0012] The following terms are used throughout as defined below.

[0013] 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.

[0014] 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 - for example,“about 10 wt.%” would be understood to mean“9 wt.% to 11 wt.%.” It is to be understood that when“about” precedes a term, the term is to be construed as disclosing “about” the term as well as the term without modification by“about” - for example,“about 10 wt.%” discloses“9 wt.% to 11 wt.%” as well as disclosing“10 wt.%.”

[0015] As used herein, the terms“moisture vapor transmission rate” and“MVTR” will be understood by persons of ordinary skill in the art as a measure of the passage of water vapor through a substance of a given unit area and unit time. The most common international unit for the MVTR is g/m ² /day, wherein 1 day = 24 hr.

[0016] As understood by one of ordinary skill in the art,“molecular weight” (also known as “relative molar mass”) is a dimensionless quantity but is 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.

[0017] As used herein, the term“dressing(s)”includes the dressing compositions, the wound dressing compositions, and the wound dressings of the present technology.

[0018] As used herein, the term“solid content” refers to the density of a material and/or film of the wound dressing of the present technology, which is its mass per unit volume.

[0019] The term“mammalian recombinant collagen" refers to collagen manufactured by culturing a non-human organism or mammalian or non-mammalian cells to express at least one exogenous gene encoding a collagen in the culturing system. The collagen may be recombinantly manufactured by a plant ( e.g ., CollPlant, CollPlant Holdings Ltd., Ness Ziona, Israel) such as tobacco, or in yeast. The term "human recombinant collagen" refers to collagen manufactured by culturing a non-human organism or mammalian or non

mammalian cells to express at least one human gene encoding a collagen. The human recombinant collagen may be selected from the group consisting of collagen type I, type II, type III, type IV, type V, type VI, type VII, type VIII, type IX, type X, type XI, type XII, type XIII, type XIV, type XV, type XVI, type XVII, type XVIII, type XIX, type XX, type XXI, type XXII, type XXIII, type XXIV, type XXV, type XXVI, and type XXVII. The human recombinant collagen can be collagen of one type free of any other type, or can be a mixture of collagen types. Suitably, the human recombinant collagen comprises collagens selected from the group consisting of collagen type I, collagen type III, and mixtures thereof. The term "bovine recombinant collagen" refers to collagen manufactured by culturing a non human organism or mammalian or non-mammalian cells to express at least one bovine gene encoding a collagen. The bovine recombinant collagen may be selected from the group consisting of collagen type I, type II, type III, and type IV. The bovine recombinant collagen can be collagen of one type free of any other type, or can be a mixture of collagen types. Suitably, the bovine recombinant collagen comprises collagens selected from the group consisting of collagen type I, collagen type III, and mixtures thereof.

[0020] As used herein, the term "biofilm" refers to an extracellular matrix created by an association of microorganisms, e.g., single or multiple species. The microorganisms can be encased or embedded in a matrix material, which may be self-produced by resident microorganisms. The biofilm may be present or adhere to living and/or non-living surfaces, e.g., tissue, a wound, medical implants, including but not limited to, orthopedic implants, dental implants, catheters, stents and so on. Exemplary microorganisms include, but are not limited to bacteria, e.g., Gram-negative bacteria, such as Pseudomonas aeruginosa, Gram positive bacteria, such as Staphylococcus aureus and Streptococcus mutans, and fungi, such as yeasts, e.g., Candida albicans. The term“matrix material” is intended to encompass extracellular polymeric substances. Exemplary matrix materials include, but are not limited to polysaccharides, glycoproteins and/or nucleic acids. The term "biofilm" is further intended to include biological films that develop and persist at interfaces in aqueous environments.

The language "bio film development" or "biofilm formation" is intended to include the formation, growth, and modification of the bacterial colonies contained with bio film structures, as well as the synthesis and maintenance of the exopolysaccharide of the biofilm structures. “Reducing” or“disrupting” a biofilm includes reducing the number of total viable microorganisms making up and/or embedded in at least part of the bio film, for example, as measured by total viable counts (TVC) of microorganisms (e.g., bacteria, yeast).

[0021] 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.

[0022] As used herein, pharmaceutically acceptable salts of compounds described herein are within the scope of the present technology and include acid or base addition salts which retain the desired pharmacological activity and is not biologically undesirable (e.g., the salt is not unduly toxic, allergenic, or irritating, and is bio available). When the compound of the present technology has a basic group, such as, for example, an amino group,

pharmaceutically acceptable salts can be formed with inorganic acids (such as hydrochloric acid, hydroboric acid, nitric acid, sulfuric acid, and phosphoric acid), organic acids (e.g., alginate, formic acid, acetic acid, benzoic acid, gluconic acid, fumaric acid, oxalic acid, tartaric acid, lactic acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, naphthalene sulfonic acid, and p-toluenesulfonic acid) or acidic amino acids (such as aspartic acid and glutamic acid). When the compound of the present technology has an acidic group, such as for example, a carboxylic acid group, it can form salts with metals, such as alkali and earth alkali metals (e.g., Na ⁺ , Li ⁺ , K ⁺ , Ca ²⁺ , Mg ²⁺ , Zn ²⁺ ), ammonia or organic amines (e.g. dicyclohexylamine, trimethylamine, triethylamine, pyridine, picoline, ethanolamine, diethanolamine, triethanolamine) or basic amino acids (e.g., arginine, lysine and ornithine). Such salts can be prepared in situ during isolation and purification of the compounds or by separately reacting the purified compound in its free base or free acid form with a suitable acid or base, respectively, and isolating the salt thus formed.

[0023] As used herein, the“administration” of a dressing to a subject includes any route of introducing or delivering to a subject a dressing 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.

[0024] As used herein, the term“effective amount” refers to a quantity sufficient to achieve a desired therapeutic and/or prophylactic effect, e.g., an amount which results in the decrease in a wound described herein or one or more signs or symptoms associated with a wound described herein. In the context of therapeutic or prophylactic applications, the amount of a dressing 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. The dressings can also be administered in combination with one or more additional therapeutic compounds. In the methods described herein, the therapeutic dressings may be administered to a subject having one or more wounds.

[0025] 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.

[0026] “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.

[0027] 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 few time administrations for the treatment of an acute wound.

The Dressings of the Present Technology

[0028] Wounds are typically contaminated by bacteria, however when the immune system cannot cope with normal bacterial growth, a wound can become infected. An infected wound is a wound in which bacteria or other microorganisms have colonized, causing a deterioration and delay in the healing of the wound. Thus, a reduction in bacterial colonization is vital in wound therapy.

[0029] A bio film consists of a polysaccharide extracellular matrix produced by an association of microorganisms (e.g., single or multiple species) that have adhered onto a surface. These three-dimensional microbial communities can have coordinated multi-cellular behavior, thereby forming an extracellular matrix in which the bacteria are embedded. The ability of bacteria to form these complex bio films can impede a host’s defense mechanisms against pathogens. As such, biofilms often display a heightened tolerance to antimicrobial treatment.

[0030] The present disclosure is directed to dressings that which may prevent, reduce, inhibit, or disrupt biofilm levels in a wound upon application, and over time.

The Dressing Composition

[0031] In an aspect, the present disclosure provides a dressing composition that includes a hydrogel, where the hydrogel includes a co-polymer of polyvinylpyrrolidone (PVP) and citric acid (PVP-CA). The hydrogel also includes water. The co-polymer may be included in the hydrogel at about 5 % (w/v) to about 25 % (w/v) based on the total volume of the hydrogel. Thus, the co-polymer may be included in the hydrogel at about 5 % (w/v), about 5.2 % (w/v), about 5.4 % (w/v), about 5.6 % (w/v), about 5.8 % (w/v), about 6 % (w/v), about 6.2 % (w/v), about 6.4 % (w/v), about 6.6 % (w/v), about 6.8 % (w/v), about 7 % (w/v), about 7.2 % (w/v), about 7.4 % (w/v), about 7.6 % (w/v), about 7.8 % (w/v), about 8 % (w/v), about 8.2 % (w/v), about 8.4 % (w/v), about 8.6 % (w/v), about 8.8 % (w/v), about 9 % (w/v), about 9.2 % (w/v), about 9.4 % (w/v), about 9.6 % (w/v), about 9.8 % (w/v), about 10 % (w/v), about 10.5 % (w/v), about 11 % (w/v), about 11.5 % (w/v), about 12 % (w/v), about 12.5 % (w/v), about 13 % (w/v), about 13.5 % (w/v), about 14 % (w/v), about 14.5 % (w/v), about 15 % (w/v), about

15.5 % (w/v), about 16 % (w/v), about 16.5 % (w/v), about 17 % (w/v), about 17.5 % (w/v), about 18 % (w/v), about 18.5 % (w/v), about 19 % (w/v), about 19.5 % (w/v), about 20 % (w/v), about 20.5 % (w/v), about 21 % (w/v), about 21.5 % (w/v), about 22 % (w/v), about

22.5 % (w/v), about 23 % (w/v), about 23.5 % (w/v), about 24 % (w/v), about 24.5 % (w/v), about 25 % (w/v), or any range including and/or in between any two of these values.

[0032] The copolymer of any embodiment described herein may include a weight ratio of PVP to citric acid of about 25:1 to about 1:2. Thus, in any embodiment described herein, the weight ratio of PVP to citric acid in the co-polymer may be about 25:1, about 24:1, about 23:1, about 22:1, about 21:1, about 20:1, about 19:1, about 18:1, about 17:1, about 16:1, about 15:1, about 14:1, about 13:1, about 12:1, about 11:1, about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, about 1:1, about 1:2, or any range including and/or in between any two of these values.

[0033] In any embodiment disclosed herein, the hydrogel may include a wound-facing side and an environmental-facing side. The wound-facing side of the hydrogel may be configured to be in contact with a wound when in use.

[0034] In any embodiment disclosed herein, the thickness of the hydrogel may be about 50 mhi to about 2000 mhi. Thus, the thickness of the co-polymer may be about 50 mih, about 52 mhi, about 54 mih, about 56 mih, about 58 mih, about 60 mih, about 62 mih, about 64 mih, about 66 mih, about 68 mih, about 70 mih, about 72 mih, about 74 mih, about 76 mih, about 78 mih, about 80 mih, about 82 mih, about 84 mih, about 86 mhi, about 88 mih, about 90 mih, about 92 mhi, about 94 mih, about 96 mih, about 98 mih, about 100 mih, about 110 mih, about 120 mih, about 130 mih, about 140 mih, about 150 mih, about 160 mih, about 170 mih, about 180 mih, about 190 mih, about 200 mih, about 220 mih, about 240 mih, about 260 mih, about 280 mih, about 300 mih, about 320 mih, about 340 mih, about 360 mih, about 380 mih, about 400 mih, about 420 mih, about 440 mih, about 460 mih, about 480 mih, about 500 mih, about 520 mih, about 540 mih, about 560 mih, about 580 mih, about 600 mih, about 620 mih, about 640 mih, about 660 mih, about 680 mih, about 700 mih, about 720 mih, about 740 mih, about 760 mih, about 780 mih, about 800 mih, about 820 mih, about 840 mih, about 860 mih, about 880 mih, about 900 mih, about 920 mih, about 940 mih, about 960 mih, about 980 mih, about 1000 mih, about 1050 mih, about 1100 mih, about 1150 mih, about 1200 mih, about 1250 mih, about 1300 mhi, about 1350 mih, about 1400 mih, about 1450 mhi, about 1500 mih, about 1550 mih, about 1600 mih, about 1650 mih, about 1700 mih, about 1750 mih, about 1800 mih, about 1850 mih, about 1900 mih, about 1950 mih, about 2000 mih, or any range including and/or in between any two of these values.

[0035] The co-polymer of the dressing composition may be provided by any suitable method known in the art. In any embodiment disclosed herein, the co-polymer may be formed via high dose rate irradiation. For example, copolymerization of

polyvinylpyrrolidone (PVP) with citric acid using gamma irradiation may be achieved via the protocol described in Ajji, Z., Nucl. Instrum. Meth. B 265:179-182 (2007), the entire contents of which is incorporated herein by reference. Irradiation may include, but are not limited to, e-beam irradiation, gamma irradiation, x-ray irradiation, or a combination of any two or more thereof. In any embodiment herein, the co-polymer may be formed via an irradiation dose rate of about 50 kGy/h to about 100 kGy/h; thus, the irradiation dose rate may be about 50 kGy/h, about 52 kGy/h, about 54 kGy/h, about 56 kGy/h, about 58 kGy/h, about 60 kGy/h, about 62 kGy/h, about 64 kGy/h, about 66 kGy/h, about 68 kGy/h, about 70 kGy/h, about 72 kGy/h, about 74 kGy/h, about 76 kGy/h, about 78 kGy/h, about 80 kGy/h, about 82 kGy/h, about 84 kGy/h, about 86 kGy/h, about 88 kGy/h, about 90 kGy/h, about 92 kGy/h, about 94 kGy/h, about 96 kGy/h, about 98 kGy/h, about 100 kGy/h, or any range including and/or in between any two of these values.

[0036] In any embodiment disclosed herein, the dressing composition may further include an absorbent material disposed adjacent to the hydrogel.

[0037] In any embodiment disclosed herein, the absorbent material may include a wound facing side and an environmental-facing side. The wound-facing side of the absorbent material may be configured to be adjoined with the environmental-facing side of the co polymer.

[0038] In any embodiment disclosed herein, the thickness of the absorbent material may be about 15 pm to about 500 pm. Thus, the thickness of the absorbent material may be about 15 pm, about 16 pm, about 17 pm, about 18 pm, about 19 pm, about 20 pm, about 22 pm, about 24 pm, about 26 pm, about 28 pm, about 30 pm, about 32 pm, about 34 pm, about 36 pm, about 38 pm, about 40 pm, about 42 pm, about 44 pm, about 46 pm, about 48 pm, about 50 pm, about 52 pm, about 54 pm, about 56 pm, about 58 pm, about 60 pm, about 62 pm, about 64 pm, about 66 pm, about 68 pm, about 70 pm, about 72 pm, about 74 pm, about 76 pm, about 78 pm, about 80 pm, about 82 pm, about 84 pm, about 86 pm, about 88 pm, about 90 pm, about 92 pm, about 94 pm, about 96 pm, about 98 pm, about 100 pm, about 110 pm, about 120 pm, about 130 pm, about 140 pm, about 150 pm, about 160 pm, about 170 pm, about 180 pm, about 190 pm, about 200 pm, about 220 pm, about 240 pm, about 260 pm, about 280 pm, about 300 pm, about 320 pm, about 340 pm, about 360 pm, about 380 pm, about 400 pm, about 420 pm, about 440 pm, about 460 pm, about 480 pm, about 500 pm, or any range including and/or in between any two of these values.

[0039] Additionally or alternatively, in some embodiments, the absorbent material may include a superabsorbent polymer, a non- woven carboxymethyl cellulose (CMC) pad, polyester, rayon, nylon, or a combination of any two or more thereof. [0040] In any embodiment disclosed herein, the dressing composition may further include a backing layer. The backing layer may include a wound-facing side and an environmental- facing side. The wound facing side of the backing layer may be configured to be adjoined with the environmental-facing side of the absorbent material, and the wound-facing side of the absorbent material may be configured to be adjoined with the environmental-facing side of the co-polymer.

[0041] In any embodiment disclosed herein, the thickness of the backing layer may be about 10 pm to about 1000 pm. Thus, the thickness of the backing layer may be about 10 pm, about 11 pm, about 12 pm, about 13 pm, about 14 pm, about 15 pm, about 16 pm, about 17 pm, about 18 pm, about 19 pm, about 20 pm, about 22 pm, about 24 pm, about 26 pm, about 28 pm, about 30 pm, about 32 pm, about 34 pm, about 36 pm, about 38 pm, about 40 pm, about 42 pm, about 44 pm, about 46 pm, about 48 pm, about 50 pm, about 52 pm, about 54 pm, about 56 pm, about 58 pm, about 60 pm, about 62 pm, about 64 pm, about 66 pm, about 68 pm, about 70 pm, about 72 pm, about 74 pm, about 76 pm, about 78 pm, about 80 pm, about 82 pm, about 84 pm, about 86 pm, about 88 pm, about 90 pm, about 92 pm, about 94 pm, about 96 pm, about 98 pm, about 100 pm, about 110 pm, about 120 pm, about 130 pm, about 140 pm, about 150 pm, about 160 pm, about 170 pm, about 180 pm, about 190 pm, about 200 pm, about 220 pm, about 240 pm, about 260 pm, about 280 pm, about 300 pm, about 320 pm, about 340 pm, about 360 pm, about 380 pm, about 400 pm, about 420 pm, about 440 pm, about 460 pm, about 480 pm, about 500 pm, about 520 pm, about 540 pm, about 560 pm, about 580 pm, about 600 pm, about 620 pm, about 640 pm, about 660 pm, about 680 pm, about 700 pm, about 720 pm, about 740 pm, about 760 pm, about 780 pm, about 800 pm, about 820 pm, about 840 pm, about 860 pm, about 880 pm, about 900 pm, about 920 pm, about 940 pm, about 960 pm, about 980 pm, about 1000 pm, or any range including and/or in between any two of these values.

[0042] Additionally or alternatively, in some embodiments, the backing layer may include a polyurethane, a polyalkoxy alkyl acrylate, a polyalkoxy alkyl methacrylate, or a combination of any two or more thereof.

[0043] In any embodiment disclosed herein, the backing layer may be substantially impermeable to liquid and wound exudate. The backing layer may be configured to be impermeable to microorganisms. The backing layer may be configured to be semi-permeable to water vapor. In any embodiment disclosed herein, the backing layer may be configured to exhibit a moisture vapor transmission rate (MVTR) of about 300 g/m ² /24hrs to about 20,000 g/m ² /24hrs at 37.5°C at 50% relative humidity difference as described in ASTM E96-00. Thus, the backing layer may be configured to exhibit a MVTR of about 300 g/m ² /24hrs, about 320 g/m ² /24hrs, about 340 g/m ² /24hrs, about 360 g/m ² /24hrs, about 380 g/m ² /24hrs, about 400 g/m ² /24hrs, about 420 g/m ² /24hrs, about 440 g/m ² /24hrs, about 460 g/m ² /24hrs, about 480 g/m ² /24hrs, about 500 g/m ² /24hrs, about 520 g/m ² /24hrs, about 540 g/m ² /24hrs, about 560 g/m ² /24hrs, about 580 g/m ² /24hrs, about 600 g/m ² /24hrs, about 620 g/m ² /24hrs, about 640 g/m ² /24hrs, about 660 g/m ² /24hrs, about 680 g/m ² /24hrs, about 700 g/m ² /24hrs, about 720 g/m ² /24hrs, about 740 g/m ² /24hrs, about 760 g/m ² /24hrs, about 780 g/m ² /24hrs, about 800 g/m ² /24hrs, about 820 g/m ² /24hrs, about 840 g/m ² /24hrs, about 860 g/m ² /24hrs, about 880 g/m ² /24hrs, about 900 g/m ² /24hrs, about 920 g/m ² /24hrs, about 940 g/m ² /24hrs, about 960 g/m ² /24hrs, about 980 g/m ² /24hrs, about 1000 g/m ² /24hrs, about 1100 g/m ² /24hrs, about 1200 g/m ² /24hrs, about 1300 g/m ² /24hrs, about 1400 g/m ² /24hrs, about 1500 g/m ² /24hrs, about 1600 g/m ² /24hrs, about 1700 g/m ² /24hrs, about 1800 g/m ² /24hrs, about 1900 g/m ² /24hrs, about 2000 g/m ² /24hrs, about 2200 g/m ² /24hrs, about 2400 g/m ² /24hrs, about 2600 g/m ² /24hrs, about 2800 g/m ² /24hrs, about 3000 g/m ² /24hrs, about 3200 g/m ² /24hrs, about 3400 g/m ² /24hrs, about 3600 g/m ² /24hrs, about 3800 g/m ² /24hrs, about 4000 g/m ² /24hrs, about 4200 g/m ² /24hrs, about 4400 g/m ² /24hrs, about 4600 g/m ² /24hrs, about 4800 g/m ² /24hrs, about 5000 g/m ² /24hrs, about 5200 g/m ² /24hrs, about 5400 g/m ² /24hrs, about 5600 g/m ² /24hrs, about 5800 g/m ² /24hrs, about 6000 g/m ² /24hrs, about 6200 g/m ² /24hrs, about 6400 g/m ² /24hrs, about 6600 g/m ² /24hrs, about 6800 g/m ² /24hrs, about 7000 g/m ² /24hrs, about 7200 g/m ² /24hrs, about 7400 g/m ² /24hrs, about 7600 g/m ² /24hrs, about 7800 g/m ² /24hrs, about 8000 g/m ² /24hrs, about 8200 g/m ² /24hrs, about 8400 g/m ² /24hrs, about 8600 g/m ² /24hrs, about 8800 g/m ² /24hrs, about 9000 g/m ² /24hrs, about 9200 g/m ² /24hrs, about 9400 g/m ² /24hrs, about 9600 g/m ² /24hrs, about 9800 g/m ² /24hrs, about 10000 g/m ² /24hrs, about 10500 g/m ² /24hrs, about 11000 g/m ² /24hrs, about 11500 g/m ² /24hrs, about 12000 g/m ² /24hrs, about 12500 g/m ² /24hrs, about 13000

g/m ² /24hrs, about 13500 g/m ² /24hrs, about 14000 g/m ² /24hrs, about 14500 g/m ² /24hrs, about 15000 g/m ² /24hrs, about 15500 g/m ² /24hrs, about 16000 g/m ² /24hrs, about 16500

g/m ² /24hrs, about 17000 g/m ² /24hrs, about 17500 g/m ² /24hrs, about 18000 g/m ² /24hrs, about 18500 g/m ² /24hrs, about 19000 g/m ² /24hrs, about 19500 g/m ² /24hrs, about 20000

g/m ² /24hrs, or any range including and/or in between any two of the preceding values. Such moisture vapor transmission rates allow the wound under the wound dressing to heal under moist conditions without causing the skin surrounding the wound to macerate. [0044] In any embodiment disclosed herein, the dressing composition may further include a bioresorbable layer comprising a mixture of a collagen and an oxidized regenerated cellulose (ORC).

[0045] In any embodiment disclosed herein, the collagen may include a type I collagen, a type II collagen, and/or a type III collagen. In any embodiment disclosed herein, the collagen may include mammalian collagen. In any embodiment disclosed herein, the collagen may include a human collagen. The human collagen may include human collagen type I and/or human collagen type III. In any embodiment disclosed herein, the collagen may include a bovine collagen, such as bovine collagen type I, bovine collagen type II, bovine collagen type III, and/or bovine collagen type IV. Collagen may be obtained from any natural source, may be chemically-modified collagen ( e.g ., an atelocollagen obtained by removing the

immunogenic telopeptides from natural collagen), or may be any combination thereof. For example, the collagen may include collagen obtained from bovine corium that has been rendered largely free of non-collagenous components, for example, including fat, non- collagenous proteins, polysaccharides, and other carbohydrates, such as by procedures described in U.S. Pat. Nos. 4,614,794 and 4,320,201, the entire contents of which are incorporated by reference. The collagen may be provided by any manner known in the art. For example, the collagen may be provided by a tissue sample and/or recombinantly manufactured. For example, human recombinant collagen may be provided via the protocol described in U.S. Pat. No. 5,962,648, the entire contents of which is incorporated herein by reference. Further recombinant processes are set forth in U.S. Pat. No. 5,593,859 and W02004/078120, which are also incorporated herein by reference. Collagen may be recombinantly manufactured by culturing a cell which has been transfected with at least one gene encoding a polypeptide that includes collagen. Collagen may be recombinantly manufactured by a plant (e.g., CollPlant, CollPlant Holdings Ltd., Ness Ziona, Israel) such as tobacco, or in yeast. Human recombinant collagen solution may be subsequently subjected to polymerization or cross-linking conditions to produce an insoluble fibrous collagen.

[0046] In any embodiment disclosed herein, the collagen may have a weight- average molecular weight of about 5,000 to about 100,000. Thus, the collagen may have a weight- average molecular weight of about 5,000, about 6,000, about 7,000, about 8,000, about 9,000, about 10,000, about 12,000, about 14,000, about 16,000, about 18,000, about 20,000, about 22,000, about 24,000, about 26,000, about 28,000, about 30,000, about 32,000, about 34,000, about 36,000, about 38,000, about 40,000, about 42,000, about 44,000, about 46,000, about 48,000, about 50,000, about 52,000, about 54,000, about 56,000, about 58,000, about 60,000, about 62,000, about 64,000, about 66,000, about 68,000, about 70,000, about 72,000, about 74,000, about 76,000, about 78,000, about 80,000, about 82,000, about 84,000, about 86,000, about 88,000, about 90,000, about 92,000, about 94,000, about 96,000, about 98,000, about 100,000, or any range including and/or in between any two of the preceding values.

[0047] In any embodiment disclosed herein, the bioresorbable layer may include about 0.1 wt.% to about 95 wt.% collagen. Thus, the amount of collagen in the bioresorbable layer may be about 0.1 wt.%, about 0.2 wt.%, about 0.3 wt.%, about 0.4 wt.%, about 0.5 wt.%, about 0.6 wt.%, about 0.7 wt.%, about 0.8 wt.%, about 0.9 wt.%, about 1 wt.%, about 1.1 wt.%, about 1.2 wt.%, about 1.3 wt.%, about 1.4 wt.%, about 1.5 wt.%, about 1.6 wt.%, about

1.7 wt.%, about 1.8 wt.%, about 1.9 wt.%, about 2 wt.%, about 2.2 wt.%, about 2.4 wt.%, about 2.6 wt.%, about 2.8 wt.%, about 3 wt.%, about 3.2 wt.%, about 3.4 wt.%, about 3.6 wt.%, about 3.8 wt.%, about 4 wt.%, about 4.2 wt.%, about 4.4 wt.%, about 4.6 wt.%, about

4.8 wt.%, about 5 wt.%, about 5.2 wt.%, about 5.4 wt.%, about 5.6 wt.%, about 5.8 wt.%, about 6 wt.%, about 6.2 wt.%, about 6.4 wt.%, about 6.6 wt.%, about 6.8 wt.%, about 7 wt.%, about 7.2 wt.%, about 7.4 wt.%, about 7.6 wt.%, about 7.8 wt.%, about 8 wt.%, about 8.2 wt.%, about 8.4 wt.%, about 8.6 wt.%, about 8.8 wt.%, about 9 wt.%, about 9.2 wt.%, about

9.4 wt.%, about 9.6 wt.%, about 9.8 wt.%, about 10 wt.%, about 11 wt.%, about 12 wt.%, about 13 wt.%, about 14 wt.%, about 15 wt.%, about 16 wt.%, about 17 wt.%, about 18 wt.%, about 19 wt.%, about 20 wt.%, about 22 wt.%, about 24 wt.%, about 26 wt.%, about 28 wt.%, about 30 wt.%, about 32 wt.%, about 34 wt.%, about 36 wt.%, about 38 wt.%, about 40 wt.%, about 42 wt.%, about 44 wt.%, about 46 wt.%, about 48 wt.%, about 50 wt.%, about 52 wt.%, about 54 wt.%, about 56 wt.%, about 58 wt.%, about 60 wt.%, about 62 wt.%, about 64 wt.%, about 66 wt.%, about 68 wt.%, about 70 wt.%, about 72 wt.%, about 74 wt.%, about 76 wt.%, about 78 wt.%, about 80 wt.%, about 82 wt.%, about 84 wt.%, about 86 wt.%, about 88 wt.%, about 90 wt.%, about 92 wt.%, about 94 wt.%, about 95 wt.%, or any range including and/or in between any two of these values.

[0048] In any embodiment disclosed herein, the collagen may include a weight ratio of human collagen type I to human collagen type III of about 100:0, about 90:10, about 80:20, about 70:30, about 60:40, about 50:50, about 40:60, about 30:70, about 20:80, about 10:90, about 0:100, or any range including and/or in between any two of the preceding values.

[0049] In any embodiment disclosed herein, the oxidized regenerated cellulose (ORC) may be produced by the oxidation of cellulose, for example with dinitrogen tetroxide and/or as described in U.S. Pat. No. 3,122,479 (incorporated herein by reference). Without wishing to be bound by theory, it is believed that this process may convert primary alcohol groups on the saccharide residues of the cellulose to carboxylic acid groups, for example, forming uronic acid residues within the cellulose chain. The oxidation need not proceed with complete selectivity, and as a result hydroxyl groups on carbons 2 and 3 of the saccharide residue may be converted to the keto form. These ketone units may introduce an alkali labile link, which at pH 7 or higher initiates the decomposition of the polymer via formation of a lactone and sugar ring cleavage. As a result, oxidized regenerated cellulose is biodegradable and bioresorbable under physiological conditions. ORC is available with a variety of degrees of oxidation and hence rates of degradation.

[0050] In any embodiment disclosed herein, the bioresorbable layer may include about 30 wt.% to about 70 wt.% ORC with a weight-average molecular weight of about 10,000 to about 1,000,000. The bioresorbable layer may include ORC in an amount (by weight of the bioresorbable layer) of about 30 wt.%, about 32 wt.%, about 34 wt.%, about 36 wt.%, about 38 wt.%, about 40 wt.%, about 42 wt.%, about 44 wt.%, about 46 wt.%, about 48 wt.%, about

50 wt.%, about 52 wt.%, about 54 wt.%, about 56 wt.%, about 58 wt.%, about 60 wt.%, about

62 wt.%, about 64 wt.%, about 66 wt.%, about 68 wt.%, about 70 wt.%, or any range including and/or in between any two of the preceding values. The ORC have a weight- average molecular weight of about 10,000, about 11,000, about 12,000, about 13,000, about 14,000, about 15,000, about 16,000, about 17,000, about 18,000, about 19,000, about 20,000, about 22,000, about 24,000, about 26,000, about 28,000, about 30,000, about 32,000, about 34,000, about 36,000, about 38,000, about 40,000, about 42,000, about 44,000, about 46,000, about 48,000, about 50,000, about 55,000, about 60,000, about 65,000, about 70,000, about 75,000, about 80,000, about 85,000, about 90,000, about 95,000, about 100,000, about 110,000, about 120,000, about 130,000, about 140,000, about 150,000, about 160,000, about 170,000, about 180,000, about 190,000, about 200,000, about 210,000, about 220,000, about 230,000, about 240,000, about 250,000, about 260,000, about 270,000, about 280,000, about 290,000, about 300,000, about 310,000, about 320,000, about 330,000, about 340,000, about 350,000, about 360,000, about 370,000, about 380,000, about 390,000, about 400,000, about 410,000, about 420,000, about 430,000, about 440,000, about 450,000, about 460,000, about 470,000, about 480,000, about 490,000, about 500,000, about 510,000, about 520,000, about 530,000, about 540,000, about 550,000, about 560,000, about 570,000, about 580,000, about 590,000, about 600,000, about 610,000, about 620,000, about 630,000, about 640,000, about 650,000, about 660,000, about 670,000, about 680,000, about 690,000, about 700,000, about 710,000, about 720,000, about 730,000, about 740,000, about 750,000, about 760,000, about 770,000, about 780,000, about 790,000, about 800,000, about 810,000, about 820,000, about 830,000, about 840,000, about 850,000, about 860,000, about 870,000, about 880,000, about 890,000, about 900,000, about 910,000, about 920,000, about 930,000, about 940,000, about 950,000, about 960,000, about 970,000, about 980,000, about 990,000, about 1,000,000, or any range including and/or in between any two of these values.

[0051] The ORC may include particles, fibers, or both; in any embodiment disclosed herein, the ORC may be in the form of particles, such as fiber particles or powder particles.

In embodiments that include ORC fibers, the ORC fibers may have a volume fraction such that at least 80% of the fibers have lengths in the range from about 5 pm to about 1,000 pm; thus, the ORC may include fiber lengths of about 5 pm, about 6 pm, about 7 pm, about 8 pm, about 9 pm, about 10 pm, about 11 pm, about 12 pm, about 13 pm, about 14 pm, about 15 pm, about 16 pm, about 17 pm, about 18 pm, about 19 pm, about 20 pm, about 22 pm, about 24 pm, about 26 pm, about 28 pm, about 30 pm, about 32 pm, about 34 pm, about 36 pm, about 38 pm, about 40 pm, about 42 pm, about 44 pm, about 46 pm, about 48 pm, about 50 pm, about 55 pm, about 60 pm, about 65 pm, about 70 pm, about 75 pm, about 80 pm, about 85 pm, about 90 pm, about 95 pm, about 100 pm, about 110 pm, about 120 pm, about 130 pm, about 140 pm, about 150 pm, about 160 pm, about 170 pm, about 180 pm, about 190 pm, about 200 pm, about 220 pm, about 230 pm, about 240 pm, about 250 pm, about 260 pm, about 280 pm, about 300 pm, about 320 pm, about 340 pm, about 360 pm, about 380 pm, about 400 pm, about 420 pm, about 440 pm, about 460 pm, about 480 pm, about 500 pm, about 550 pm, about 600 pm, about 650 pm, about 700 pm, about 750 pm, about 800 pm, about 850 pm, about 900 pm, about 950 pm, about 1,000 pm, or any range including and/or in between any two of these values.

[0052] The bioresorbable layer may include a weight ratio of collagen to ORC of about 90:10 to 10:90, such as from about 60:40 to about 40:60. The bioresorbable layer may include a weight ratio of collagen to ORC of about 90:10, about 85:15, about 80:20, about 75:25, about 70:30, about 65:35, about 60:40, about 55:45, about 50:50, about 45:55, about 40:60, about 35:65, about 30:70, about 25:75, about 20:80, about 15:85, about 10:90, or any range including and/or in between any two of these values. [0053] Each of the hydrogel, the optional absorbent material, the optional backing layer, and the optional bioresorbable layer may independently include a wound-facing side and an environmental-facing side. In any embodiment disclosed herein, the wound-facing side of the backing layer may be configured to be adjoined with the environmental-facing side of the absorbent material, wherein the wound-facing side of the absorbent material may be configured to be adjoined with the environmental-facing side of the hydrogel, and wherein the wound-facing side of the hydrogel may be configured to be in contact with a wound when in use. In any embodiment disclosed herein, the wound-facing side of the backing layer may be configured to be adjoined with the environmental-facing side of the absorbent material, wherein the wound-facing side of the absorbent material may be configured to be adjoined with the environmental-facing side of the bioresorbable layer, wherein the wound-facing side of the bioresorbable layer may be configured to be adjoined to with the environmental-facing side of the hydrogel, and wherein the wound-facing side of the hydrogel may be configured to be in contact with a wound when in use.

[0054] In any embodiment disclosed herein, the dressing composition of the present technology may be sterile and packaged in a microorganism-impermeable container.

Wound Dressing Compositions of the Present Technology

[0055] In a related aspect, the present technology provides a wound dressing composition that includes a mixture of a collagen of any embodiment disclosed herein, an oxidized regenerated cellulose (ORC) of any embodiment disclosed herein, and a co-polymer of any embodiment disclosed herein. In any embodiment disclosed herein, the wound dressing composition may include a wound-facing side and an environmental-facing side. The wound-facing side of the wound dressing composition may be configured to be in contact with a wound when in use.

[0056] The wound dressing composition may include about 0.1 wt.% to about 45 wt.% of the copolymer. Thus, the wound dressing composition may include about 0.1 wt.%, about 0.2 wt.%, about 0.3 wt.%, about 0.4 wt.%, about 0.5 wt.%, about 0.6 wt.%, about 0.7 wt.%, about 0.8 wt.%, about 0.9 wt.%, about 1 wt.%, about 1.1 wt.%, about 1.2 wt.%, about 1.3 wt.%, about 1.4 wt.%, about 1.5 wt.%, about 1.6 wt.%, about 1.7 wt.%, about 1.8 wt.%, about 1.9 wt.%, about 2 wt.%, about 2.2 wt.%, about 2.4 wt.%, about 2.6 wt.%, about 2.8 wt.%, about 3 wt.%, about 3.2 wt.%, about 3.4 wt.%, about 3.6 wt.%, about 3.8 wt.%, about 4 wt.%, about 4.2 wt.%, about 4.4 wt.%, about 4.6 wt.%, about 4.8 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 11 wt.%, about 12 wt.%, about 13 wt.%, about 14 wt.%, about 15 wt.%, about 16 wt.%, about 17 wt.%, about 18 wt.%, about 19 wt.%, about 20 wt.%, about 22 wt.%, about 24 wt.%, about 26 wt.%, about 28 wt.%, about 30 wt.%, about 32 wt.%, about 34 wt.%, about 36 wt.%, about 38 wt.%, about 40 wt.%, about 42 wt.%, about 44 wt.%, about 45 wt.%, or any range including and/or in between any two of these values.

[0057] In addition to the methods previously described for generating the co-polymer, the co-polymer of the wound dressing composition may be generated by drying a hydrogel of any embodiment described previously in this disclosure. The dried hydrogel may then be milled to provide a granular form of the co-polymer. In any embodiment disclosed herein, the dried hydrogel may be milled to provide a particle size less than 0.5 mm. Additionally or alternatively, in some embodiments, the dried hydrogel may be milled to provide a particle size of about 0.05 mm to about 0.5 mm. Thus, the dried hydrogel may be milled to provide a particle size of about 0.05 mm, about 0.06 mm, about 0.07 mm, about 0.08 mm, about 0.09 mm, about 0.1 mm, about 0.11 mm, about 0.12 mm, about 0.13 mm, about 0.14 mm, about 0.15 mm, about 0.16 mm, about 0.17 mm, about 0.18 mm, about 0.19 mm, about 0.2 mm, about 0.22 mm, about 0.24 mm, about 0.26 mm, about 0.28 mm, about 0.3 mm, about 0.32 mm, about 0.34 mm, about 0.36 mm, about 0.38 mm, about 0.4 mm, about 0.42 mm, about 0.44 mm, about 0.46 mm, about 0.48 mm, about 0.5 mm, or any range including and/or in between any two of these values.

[0058] In any embodiment disclosed herein, the wound dressing composition may include about 0.1 wt.% to about 95 wt.% collagen. Thus, the amount of collagen in the bioresorbable layer may be about 0.1 wt.%, about 0.2 wt.%, about 0.3 wt.%, about 0.4 wt.%, about 0.5 wt.%, about 0.6 wt.%, about 0.7 wt.%, about 0.8 wt.%, about 0.9 wt.%, about 1 wt.%, about 1.1 wt.%, about 1.2 wt.%, about 1.3 wt.%, about 1.4 wt.%, about 1.5 wt.%, about 1.6 wt.%, about 1.7 wt.%, about 1.8 wt.%, about 1.9 wt.%, about 2 wt.%, about 2.2 wt.%, about 2.4 wt.%, about 2.6 wt.%, about 2.8 wt.%, about 3 wt.%, about 3.2 wt.%, about 3.4 wt.%, about 3.6 wt.%, about 3.8 wt.%, about 4 wt.%, about 4.2 wt.%, about 4.4 wt.%, about 4.6 wt.%, about 4.8 wt.%, about 5 wt.%, about 5.2 wt.%, about 5.4 wt.%, about 5.6 wt.%, about 5.8 wt.%, about 6 wt.%, about 6.2 wt.%, about 6.4 wt.%, about 6.6 wt.%, about 6.8 wt.%, about 7 wt.%, about 7.2 wt.%, about 7.4 wt.%, about 7.6 wt.%, about 7.8 wt.%, about 8 wt.%, about 8.2 wt.%, about 8.4 wt.%, about 8.6 wt.%, about 8.8 wt.%, about 9 wt.%, about 9.2 wt.%, about 9.4 wt.%, about 9.6 wt.%, about 9.8 wt.%, about 10 wt.%, about 11 wt.%, about 12 wt.%, about 13 wt.%, about 14 wt.%, about 15 wt.%, about 16 wt.%, about 17 wt.%, about 18 wt.%, about 19 wt.%, about 20 wt.%, about 22 wt.%, about 24 wt.%, about 26 wt.%, about 28 wt.%, about 30 wt.%, about 32 wt.%, about 34 wt.%, about 36 wt.%, about 38 wt.%, about 40 wt.%, about 42 wt.%, about 44 wt.%, about 46 wt.%, about 48 wt.%, about 50 wt.%, about 52 wt.%, about 54 wt.%, about 56 wt.%, about 58 wt.%, about 60 wt.%, about 62 wt.%, about 64 wt.%, about 66 wt.%, about 68 wt.%, about 70 wt.%, about 72 wt.%, about 74 wt.%, about 76 wt.%, about 78 wt.%, about 80 wt.%, about 82 wt.%, about 84 wt.%, about 86 wt.%, about 88 wt.%, about 90 wt.%, about 92 wt.%, about 94 wt.%, about 95 wt.%, or any range including and/or in between any two of these values.

[0059] In any embodiment disclosed herein, the collagen may include a weight ratio of human collagen type I to human collagen type III of about 100:0, about 90:10, about 80:20, about 70:30, about 60:40, about 50:50, about 40:60, about 30:70, about 20:80, about 10:90, about 0:100, or any range including and/or in between any two of the preceding values.

[0060] In any embodiment disclosed herein, the collagen may have a weight- average molecular weight of about 5,000 to about 100,000. Thus, the collagen may have a weight- average molecular weight of about 5,000, about 6,000, about 7,000, about 8,000, about 9,000, about 10,000, about 12,000, about 14,000, about 16,000, about 18,000, about 20,000, about 22,000, about 24,000, about 26,000, about 28,000, about 30,000, about 32,000, about 34,000, about 36,000, about 38,000, about 40,000, about 42,000, about 44,000, about 46,000, about 48,000, about 50,000, about 52,000, about 54,000, about 56,000, about 58,000, about 60,000, about 62,000, about 64,000, about 66,000, about 68,000, about 70,000, about 72,000, about 74,000, about 76,000, about 78,000, about 80,000, about 82,000, about 84,000, about 86,000, about 88,000, about 90,000, about 92,000, about 94,000, about 96,000, about 98,000, about 100,000, or any range including and/or in between any two of the preceding values.

[0061] In any embodiment disclosed herein, the wound dressing composition may include about 5 wt.% to about 70 wt.% ORC. The bioresorbable layer may include ORC in an amount (by weight of the bioresorbable layer) of about 5 wt.%, about 6 wt.%, about 7 wt.%, about 8 wt.%, about 9 wt.%, about 10 wt.%, about 11 wt.%, about 12 wt.%, about 13 wt.%, about 14 wt.%, about 15 wt.%, about 16 wt.%, about 17 wt.%, about 18 wt.%, about 19 wt.%, about 20 wt.%, about 22 wt.%, about 24 wt.%, about 26 wt.%, about 28 wt.%, about 30 wt.%, about 32 wt.%, about 34 wt.%, about 36 wt.%, about 38 wt.%, about 40 wt.%, about 42 wt.%, about 44 wt.%, about 46 wt.%, about 48 wt.%, about 50 wt.%, about 52 wt.%, about 54 wt.%, about 56 wt.%, about 58 wt.%, about 60 wt.%, about 62 wt.%, about 64 wt.%, about 66 wt.%, about 68 wt.%, about 70 wt.%, or any range including and/or in between any two of the preceding values.

[0062] In any embodiment disclosed herein, the ORC may have a weight- average molecular weight of about 10,000 to about 1,000,000. Thus, the ORC may have a weight- average molecular weight of about 10,000, about 11,000, about 12,000, about 13,000, about 14,000, about 15,000, about 16,000, about 17,000, about 18,000, about 19,000, about 20,000, about 22,000, about 24,000, about 26,000, about 28,000, about 30,000, about 32,000, about 34,000, about 36,000, about 38,000, about 40,000, about 42,000, about 44,000, about 46,000, about 48,000, about 50,000, about 55,000, about 60,000, about 65,000, about 70,000, about 75,000, about 80,000, about 85,000, about 90,000, about 95,000, about 100,000, about 110,000, about 120,000, about 130,000, about 140,000, about 150,000, about 160,000, about

170,000, about 180,000, about 190,000, about 200,000, about 210,000, about 220,000, about

230,000, about 240,000, about 250,000, about 260,000, about 270,000, about 280,000, about

290,000, about 300,000, about 310,000, about 320,000, about 330,000, about 340,000, about

350,000, about 360,000, about 370,000, about 380,000, about 390,000, about 400,000, about

410,000, about 420,000, about 430,000, about 440,000, about 450,000, about 460,000, about

470,000, about 480,000, about 490,000, about 500,000, about 510,000, about 520,000, about

530,000, about 540,000, about 550,000, about 560,000, about 570,000, about 580,000, about

590,000, about 600,000, about 610,000, about 620,000, about 630,000, about 640,000, about

650,000, about 660,000, about 670,000, about 680,000, about 690,000, about 700,000, about

710,000, about 720,000, about 730,000, about 740,000, about 750,000, about 760,000, about

770,000, about 780,000, about 790,000, about 800,000, about 810,000, about 820,000, about

830,000, about 840,000, about 850,000, about 860,000, about 870,000, about 880,000, about

890,000, about 900,000, about 910,000, about 920,000, about 930,000, about 940,000, about

950,000, about 960,000, about 970,000, about 980,000, about 990,000, about 1,000,000, or any range including and/or in between any two of these values.

[0063] The ORC may include particles, fibers, or both; in any embodiment disclosed herein, the ORC may be in the form of particles, such as fiber particles or powder particles.

In embodiments that include ORC fibers, the ORC fibers may have a volume fraction such that at least 80% of the fibers have lengths in the range from about 5 pm to about 1,000 pm; thus, the ORC may include fiber lengths of about 5 mih, about 6 mih, about 7 mih, about 8 mih, about 9 mih, about 10 mih, about 11 mih, about 12 mhi, about 13 mih, about 14 mih, about 15 mi¾ about 16 mih, about 17 mih, about 18 mih, about 19 mih, about 20 mih, about 22 mih, about 24 mih, about 26 mih, about 28 mih, about 30 mih, about 32 mih, about 34 mih, about 36 mih, about 38 mih, about 40 mih, about 42 mih, about 44 mi¾ about 46 mih, about 48 mih, about 50 mi¾ about 55 mih, about 60 mih, about 65 mih, about 70 mih, about 75 mih, about 80 mih, about 85 mih, about 90 mih, about 95 mih, about 100 mih, about 110 mih, about 120 mih, about 130 mhi, about 140 mih, about 150 mih, about 160 mih, about 170 mih, about 180 mih, about 190 mhi, about 200 mih, about 220 mih, about 230 mih, about 240 mih, about 250 mih, about 260 mi¾ about 280 mih, about 300 mih, about 320 mih, about 340 mih, about 360 mih, about 380 mhi, about 400 mih, about 420 mih, about 440 mih, about 460 mih, about 480 mih, about 500 mi¾ about 550 mih, about 600 mih, about 650 mih, about 700 mih, about 750 mih, about 800 mhi, about 850 mih, about 900 mih, about 950 mih, about 1,000 mih, or any range including and/or in between any two of these values.

[0064] The wound dressing composition may include a weight ratio of collagen to ORC of about 90:10 to 10:90, such as from about 60:40 to about 40:60. The bioresorbable layer may include a weight ratio of collagen to ORC of about 90:10, about 85:15, about 80:20, about 75:25, about 70:30, about 65:35, about 60:40, about 55:45, about 50:50, about 45:55, about 40:60, about 35:65, about 30:70, about 25:75, about 20:80, about 15:85, about 10:90, or any range including and/or in between any two of these values.

[0065] In any embodiment disclosed herein, the wound dressing composition may include a silver compound. The wound dressing composition may include about 0.1 wt.% to about 3 wt.% of a silver compound; thus, the silver compound of the wound dressing composition may be included in an amount of about 0.1 wt.%, about 0.11 wt.%, about 0.12 wt.%, about 0.13 wt.%, about 0.14 wt.%, about 0.15 wt.%, about 0.16 wt.%, about 0.17 wt.%, about 0.18 wt.%, about 0.19 wt.%, about 0.2 wt.%, about 0.22 wt.%, about 0.24 wt.%, about 0.26 wt.%, about 0.28 wt.%, about 0.3 wt.%, about 0.32 wt.%, about 0.34 wt.%, about 0.36 wt.%, about 0.38 wt.%, about 0.4 wt.%, about 0.42 wt.%, about 0.44 wt.%, about 0.46 wt.%, about 0.48 wt.%, about 0.50 wt.%, about 0.52 wt.%, about 0.54 wt.%, about 0.56 wt.%, about 0.58 wt.%, about 0.6 wt.%, about 0.62 wt.%, about 0.64 wt.%, about 0.66 wt.%, about 0.68 wt.%, about 0.7 wt.%, about 0.72 wt.%, about 0.74 wt.%, about 0.76 wt.%, about 0.78 wt.%, about 0.8 wt.%, about 0.82 wt.%, about 0.84 wt.%, about 0.86 wt.%, about 0.88 wt.%, about 0.9 wt.%, about 0.92 wt.%, about 0.94 wt.%, about 0.96 wt.%, about 0.98 wt.%, about 1 wt.%, about 1.1 wt.%, about 1.15 wt.%, about 1.2 wt.%, about 1.25 wt.%, about 1.3 wt.%, about 1.35 wt.%, about 1.4 wt.%, about 1.45 wt.%, about 1.5 wt.%, about 1.55 wt.%, about 1.6 wt.%, about 1.65 wt.%, about 1.7 wt.%, about 1.75 wt.%, about 1.8 wt.%, about 1.85 wt.%, about 1.9 wt.%, about 1.95 wt.%, about 2 wt.%, about 2.05 wt.%, about 2.1 wt.%, about 2.15 wt.%, about 2.2 wt.%, about 2.25 wt.%, about 2.3 wt.%, about 2.35 wt.%, about 2.4 wt.%, about 2.45 wt.%, about 2.5 wt.%, about 2.55 wt.%, about 2.6 wt.%, about 2.65 wt.%, about 2.7 wt.%, about 2.75 wt.%, about 2.8 wt.%, about 2.85 wt.%, about 2.9 wt.%, about 2.95 wt.%, about 3 wt.%, or any range including and/or in between any two of these values.

[0066] The silver compound of the wound dressing composition may include one or more pharmaceutically acceptable silver salts. Exemplary sources of the one or more

pharmaceutically acceptable silver salts may 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 p- aminobenzoate, silver p-aminosalicylate, nanocrystalline silver, or a combination of any two or more thereof. In any embodiment herin, at least a portion of any silver compound of the wound dressing composition of the present technology may be present as a complex of ORC with the silver compound (e.g., an ORC-silver complex).

[0067] In any embodiment disclosed herein, the wound dressing composition may optionally include one or more additional biomaterials. The one or more additional bio materials may be included in an amount of about 1 wt.% to about 25 wt.% of the wound dressing composition. Thus, the one or more additional biomaterials may be included in an amount of about 1 wt.%, about 2 wt.%, about 3 wt.%, about 4 wt.%, about 5 wt.%, about 6 wt.%, about 7 wt.%, about 8 wt.%, about 9 wt.%, about 10 wt.%, about 11 wt.%, about 12 wt.%, about 13 wt.%, about 14 wt.%, about 15 wt.%, about 16 wt.%, about 17 wt.%, about 18 wt.%, about 19 wt.%, about 20 wt.%, about 21 wt.%, about 22 wt.%, about 23 wt.%, about 24 wt.%, about 25 wt.%, or any range including and/or in between any two of these values. The one or more additional biomaterials may include gelatin, chitosan, fibronectin, hyaluronic acid, a polysaccharide, or a combination of any two or more thereof.

[0068] In any embodiment disclosed herein, the wound dressing composition may optionally include at least one plasticizer. The at least one plasticizer may be included in the wound dressing composition in an amount of about 1 wt.% to about 15 wt.%. Thus, the at least one plasticizer may be included in the wound dressing composition in an amount of about 1 wt.%, about 1.1 wt.%, about 1.2 wt.%, about 1.3 wt.%, about 1.4 wt.%, about 1.5 wt.%, about 1.6 wt.%, about 1.7 wt.%, about 1.8 wt.%, about 1.9 wt.%, about 2 wt.%, about

2.2 wt.%, about 2.4 wt.%, about 2.6 wt.%, about 2.8 wt.%, about 3 wt.%, about 3.2 wt.%, about 3.4 wt.%, about 3.6 wt.%, about 3.8 wt.%, about 4 wt.%, about 4.2 wt.%, about 4.4 wt.%, about 4.6 wt.%, about 4.8 wt.%, about 5 wt.%, about 5.2 wt.%, about 5.4 wt.%, about 5.6 wt.%, about 5.8 wt.%, about 6 wt.%, about 6.2 wt.%, about 6.4 wt.%, about 6.6 wt.%, about 6.8 wt.%, about 7 wt.%, about 7.2 wt.%, about 7.4 wt.%, about 7.6 wt.%, about 7.8 wt.%, about 8 wt.%, about 8.2 wt.%, about 8.4 wt.%, about 8.6 wt.%, about 8.8 wt.%, about 9 wt.%, about 9.2 wt.%, about 9.4 wt.%, about 9.6 wt.%, about 9.8 wt.%, about 10 wt.%, about

10.2 wt.%, about 10.4 wt.%, about 10.6 wt.%, about 10.8 wt.%, about 11 wt.%, about 11.2 wt.%, about 11.4 wt.%, about 11.6 wt.%, about 11.8 wt.%, about 12 wt.%, about 12.2 wt.%, about 12.4 wt.%, about 12.6 wt.%, about 12.8 wt.%, about 13 wt.%, about 13.2 wt.%, about 13.4 wt.%, about 13.6 wt.%, about 13.8 wt.%, about 14 wt.%, about 14.2 wt.%, about 14.4 wt.%, about 14.6 wt.%, about 14.8 wt.%, about 15 wt.%, or any range including and/or in between any two of the preceding values. Exemplary plasticizers include, but are not limited to, an acetylated monoglyceride, an alkyl citrate, methyl ricinoleate, glycerol,

polyvinylpyrrolidone, or a combination of any two or more 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, or a combination of any two or more thereof.

[0069] In any embodiment disclosed herein, a solid content of the wound dressing composition may be about 0.1 wt.% to about 10 wt.%; thus, the solid content of the wound dressing composition may be about 0.1 wt.%, about 0.11 wt.%, about 0.12 wt.%, about 0.13 wt.%, about 0.14 wt.%, about 0.15 wt.%, about 0.16 wt.%, about 0.17 wt.%, about 0.18 wt.%, about 0.19 wt.%, about 0.2 wt.%, about 0.22 wt.%, about 0.24 wt.%, about 0.26 wt.%, about 0.28 wt.%, about 0.3 wt.%, about 0.32 wt.%, about 0.34 wt.%, about 0.36 wt.%, about 0.38 wt.%, about 0.4 wt.%, about 0.42 wt.%, about 0.44 wt.%, about 0.46 wt.%, about 0.48 wt.%, about 0.5 wt.%, about 0.55 wt.%, about 0.6 wt.%, about 0.65 wt.%, about 0.7 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 1.1 wt.%, about 1.2 wt.%, about 1.3 wt.%, about 1.4 wt.%, about 1.5 wt.%, about 1.6 wt.%, about 1.7 wt.%, about 1.8 wt.%, about 1.9 wt.%, about 2 wt.%, about 2.1 wt.%, about

2.2 wt.%, about 2.3 wt.%, about 2.4 wt.%, about 2.5 wt.%, about 2.6 wt.%, about 2.7 wt.%, about 2.8 wt.%, about 2.9 wt.%, about 3 wt.%, about 3.1 wt.%, about 3.2 wt.%, about 3.3 wt.%, about 3.4 wt.%, about 3.5 wt.%, about 3.6 wt.%, about 3.7 wt.%, about 3.8 wt.%, about 3.9 wt.%, about 4 wt.%, about 4.1 wt.%, about 4.2 wt.%, about 4.3 wt.%, about 4.4 wt.%, about 4.5 wt.%, about 4.6 wt.%, about 4.7 wt.%, about 4.8 wt.%, about 4.9 wt.%, about 5 wt.%, about 5.1 wt.%, about 5.2 wt.%, about 5.3 wt.%, about 5.4 wt.%, about 5.5 wt.%, about 5.6 wt.%, about 5.7 wt.%, about 5.8 wt.%, about 5.9 wt.%, about 6 wt.%, about 6.1 wt.%, about 6.2 wt.%, about 6.3 wt.%, about 6.4 wt.%, about 6.4 wt.%, about 6.6 wt.%, about 6.7 wt.%, about 6.8 wt.%, about 6.9 wt.%, about 7 wt.%, about 7.1 wt.%, about 7.2 wt.%, about 7.3 wt.%, about 7.4 wt.%, about 7.5 wt.%, about 7.6 wt.%, about 7.7 wt.%, about 7.8 wt.%, about 7.9 wt.%, about 8 wt.%, about 8.1 wt.%, about 8.2 wt.%, about 8.3 wt.%, about 8.4 wt.%, about 8.5 wt.%, about 8.6 wt.%, about 8.7 wt.%, about 8.8 wt.%, about 8.9 wt.%, about

9 wt.%, about 9.1 wt.%, about 9.2 wt.%, about 9.3 wt.%, about 9.4 wt.%, about 9.5 wt.%, about 9.6 wt.%, about 9.7 wt.%, about 9.8 wt.%, about 9.9 wt.%, about 10 wt.%, or any range including and/or in between any two of the preceding values.

[0070] In any embodiment disclosed herein, the wound dressing composition of the present technology may be sterile and packaged in a microorganism-impermeable container.

[0071] The wound dressing composition may be in the form of a freeze-dried sponge or a film material. In any embodiment disclosed herein, a suitable sponge may be generated by freeze-drying or solvent drying an aqueous dispersion of collagen, ORC, and co-polymer, similar to the protocols described in EP-A-1153622, the entire content of which is

incorporated herein by reference. In any embodiment disclosed herein, the wound dressing composition may be in the form of a freeze-dried sponge with an average pore size of about

10 to about 500 pm, such as about 100 to about 300 pm. Thus, the average pore size may be about 10 pm, about 12 pm, about 14 pm, about 16 pm, about 18 pm, about 20 pm, about 22 pm, about 24 pm, about 26 pm, about 28 pm, about 30 pm, about 32 pm, about 34 pm, about 36 pm, about 38 pm, about 40 pm, about 42 pm, about 44 pm, about 46 pm, about 48 pm, about 50 pm, about 52 pm, about 54 pm, about 56 pm, about 58 pm, about 60 pm, about 62 pm, about 64 pm, about 66 pm, about 68 pm, about 70 pm, about 72 pm, about 74 pm, about 76 pm, about 78 pm, about 80 pm, about 82 pm, about 84 pm, about 86 pm, about 88 pm, about 90 pm, about 92 pm, about 94 pm, about 96 pm, about 98 pm, about 100 pm, about 105 pm, about 110 pm, about 115 pm, about 120 pm, about 125 pm, about 130 pm, about 135 pm, about 140 pm, about 145 pm, about 150 pm, about 155 pm, about 160 pm, about 165 mih, about 170 mih, about 175 mih, about 180 mih, about 185 mih, about 190 mih, about

195 mih, about 200 mih, about 210 mih, about 220 mih, about 230 mih, about 240 mih, about

250 mih, about 260 mih, about 270 mih, about 280 mih, about 290 mih, about 300 mih, about

320 mih, about 340 mih, about 360 mih, about 380 mih, about 400 mih, about 420 mih, about

440 mih, about 460 mih, about 480 mih, about 500 mih, or any range including and/or in between any two of the preceding values.

[0072] In any embodiment disclosed herein, the dressing compositions and/or the wound dressing compositions (collectively referred to herein as“the dressings”) of the present technology may be capable of preventing, reducing, inhibiting, or disrupting biofilm formation in a wound. Reducing a bio film includes reducing the number of total viable microorganisms making up at least part of the bio film, for example, as measured by total viable counts (TVC) of microorganisms (e.g., bacteria, yeast). The bio film may comprise bacteria including, but not limited to Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus mutans. The bio film may also include fungi including but not limited to yeasts, such as Candida albicans. Additionally or alternatively, the dressings of the present technology may be capable of preventing, reducing, inhibiting, or disrupting a bio film in a wound by > about 10% to > about 100% after about 12 hours to about 24 hours in vitro exposure, or by > about 1 logio units to by > about 6 logio units after about 12 hours to about 24 hours in vitro exposure, compared to that observed in a wound of a control patient that does not receive the dressings of the present technology. Additionally or alternatively, the dressings of the present technology may be capable of preventing, reducing, inhibiting, or disrupting a biofilm in a wound by > about 10%, > about 15%, > about 20%, > about 25%, > about 30%, > about 35%, > about 40%, > about 45%, > about 50%, > about 55%, > about 60%, > about 65%, > about 70%, > about 75%, > about 80%, > about 85%, > about 90%, > about 95%, > about 99%, > about 100%, or any range including and/or in between any two of the preceding values, compared to that observed in a wound of a control patient that does not receive the dressings of the present technology. Additionally or alternatively, the dressings of the present technology may be capable of preventing, reducing, inhibiting, or disrupting a biofilm in a wound by > about 1 logio units, by > about 1.5 logio units, by > about 2 logio units, by > about 2.5 logio units, by > about 3 logio units, by > about 3.5 logio units, by > about 4 logio units, by > about 4.5 logio units, by > about 5 logio units, by > about 5.5 logio units, by > about 6 logio units, or any range including and/or in between any two of the preceding values, compared to that observed in a wound of a control patient that does not receive the dressings of the present technology.

[0073] The therapeutic efficacy of the dressings of the present technology may be assayed using any method known to those in the art. An exemplary method to test the therapeutic efficacy of the dressings of the present technology is the colony drip flow reactor (C-DFR) assay ( see Lipp, C., et al., J. Wound Care 19:220-226(2010)).

Therapeutic and Prophylactic Methods of the Present Technology

[0074] In an 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 one or more dressings of any embodiment disclosed herein. The wound may be an acute wound or a chronic wound. The wound may be an acute wound, such as a burn, a skin graft, and/or a dehisced surgical wound. The wound may be a chronic wound, such as an infectious wound, a venous ulcer, an arterial ulcer, a decubitis ulcer, and/or a diabetic ulcer. The dressing may protect the wound from infection, such as a bacterial infection ( e.g caused by gram-negative and/or gram-positive bacteria) or a fungal infection.

[0075] Examples of gram-positive bacteria include, but are not limited to Actinomyces sp., Arcanobacterium sp., Bacillus sp., Bavariicoccus sp., Brachybacterium sp., Clostridium sp., Cnuibacter sp., Corynebacterium sp., Enterococcus sp., Desulfitobacterium sp.,

Fervidobacterium sp., Georgenia sp., Janibacter sp., Lactobacillales sp., Microbispora sp., Nocardia sp., Pasteuria sp., Pilibacter sp., Propionibacterium sp., Rathayibacter sp., Rhodococcus sp., Roseburia sp., Rothia sp., Sarcina sp., Solibacillus sp., Sporosarcina sp., Staphylococcus sp., Streptococcus sp., Syntrophomonas sp., or Tepidibacter sp.

[0076] Examples of gram-negative bacteria include, but are not limited to Acetobacter sp., Acidaminococcus sp., Acinetobacter sp., Agrobacterium sp., Akkermansia sp.,

Anaerobio spirillum sp., Anaerolinea sp., Arcobacter sp., Armatimonas sp., Azotobacter sp., Bacteroides sp., Bacteroidetes sp., Bartonella sp., Bdellovibriosp., Brachyspira sp.,

Bradyrhizobium sp., Caldilinea sp., Cardiobacterium sp., Christensenella sp., Chthonomonas sp., Coxiella sp., Cyanobacteria sp., Cytophaga sp., Dehalogenimonas sp.,

Desulfurobacterium sp., Devosia sp., Dialister sp., Dictyo glomus sp., Dinoroseobacter sp., Enterobacter sp., Escherichia sp., Fimbriimonas sp., Flavobacterium sp., Francisella sp., Fusobacterium sp., Gluconacetobacter sp., Haemophilus sp., Helicobacter sp., Kingella sp., Klebsiella sp., Kluyvera sp., Kozakia sp., Legionella sp. Leptonema sp. Leptotrichia sp., Levilinea sp. Luteimonas sp. Megamonas sp., Megasphaera sp., Meiothermus sp.,

Methylobacterium sp., Moraxella sp., Morganella sp., Mycoplasma sp., Neisseria sp., Nitrosomonas sp., Pectinatus sp., Pedobacter sp., Pelosinus sp., Propionispora sp., Proteus sp., Pseudomonas sp., Pseudoxanthomonas sp., Rickettsia sp., Salinibacter sp., Salmonella sp., Samsonia sp., Serratia sp., Shigella sp., Shimwellia sp., Sphingomonas sp.,

Stenotrophomonas sp., Thorselliaceae sp., Vampirococcus sp., Verminephrobacter sp., Vibrio sp., Victivallis sp., Vitreoscilla sp., and Wolbachia sp.

[0077] Fungal infections may be caused by Aspergillus sp., Aureobasidium sp., Candida sp., Cladosporium sp., Curvularia sp., Engodontium sp., Epicoccum sp., Gibberella sp., Hypocreales sp., Eeptosphaerulina sp., Malessezia sp., Penicillium sp., Rhodosporidium sp., Trichosporon sp., Trichtophyton sp., and/or Ulocladium sp.

[0078] In any embodiment herein, the wound may include a biofilm and the dressings of the present technology prevent, reduce, inhibit, and/or disrupt the bio film.

[0079] In another aspect, the present disclosure provides a method for maintaining reduced biofilm levels in a wound in a subject in need thereof, wherein the method includes administering to the wound one or more dressings of any embodiment disclosed herein. The wound may be an acute wound or a chronic wound. The wound may be an acute wound, such as a burn, a skin graft, and/or a dehisced surgical wound. The wound may be a chronic wound, such as an infectious wound, a venous ulcer, an arterial ulcer, a decubitis ulcer, and/or a diabetic ulcer. The dressing may protect the wound from infection, such as a bacterial infection ( e.g caused by gram-negative and/or gram-positive bacteria) or a fungal infection.

[0080] Any method known to those in the art for administering dressings to an acute 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 dressings to a subject in need thereof, suitably a human. When used in vivo for therapy, the one or more 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 dressing used.

[0081] 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 dressings useful in the methods may be administered to a subject in need thereof by any number of well-known methods for administering dressings.

Methods of Making the Wound Dressings of the Present Technology

[0082] The wound dressings of the present technology may be produced by adding a collagen (either in paste or powder form) to an acidic solution ( e.g ., about 0.05 M acetic acid or other soluble organic acids), which may result in a final solution with 1.1 g solid collagen weight per 100 mL acid solution. The collagen will then be blended with the acid solution and allowed to swell to produce a homogenous slurry, at which point the ORC is blended into the collagen slurry (0.7 g ORC per 100 mL slurry) along with powdered PVP-CA material (0.2 g PVP-CA per 100 mL slurry) to generate a slurry material with about 2% solid content. Additionally or alternatively, in some embodiments, a slurry material may be generated with a solid content of about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 5.6%, about 5.7%, about 5.8%, about 5.9%, about 6%, about 6.1%, about 6.2%, about 6.3%, about 6.4%, about 6.5%, about 6.6%, about 6.7%, about 6.8%, about 6.9%, about 7%, about 7.1%, about 7.2%, about 7.3%, about 7.4%, about 7.5%, about 7.6%, about 7.7%, about 7.8%, about 7.9%, about 8%, about 8.1%, about 8.2%, about 8.3%, about 8.4%, about 8.5%, about 8.6%, about 8.7%, about 8.8%, about 8.9%, about 9%, about 9.1%, about 9.2%, about 9.3%, about 9.4%, about 9.5%, about 9.6%, about 9.7%, about 9.8%, about 9.9%, about 10%, or any range including and/or in between any two of these values. The resulting slurry is then degassed using a vacuum to remove trapped air and dispensed into a container before being flash frozen in a -70°C freezer to form a block. Additionally or alternatively, in some embodiments, the resulting slurry may be flash frozen in a freezer at a temperature of about -70°C, about -65°C, about -60°C, about - 55°C, about -50°C, about -45°C, about -40°C, about -35°C, about -30°C, about -25°C, about - 20°C, or any range including and/or in between any two of these values. The resulting block of collagen/ORC/PVP-CA may then freeze dried to produce a bioresorbable sponge material, which may be further trimmed to produce wound dressing compositions of different thicknesses.

Kits Comprising the Dressings of the Present Technology

[0083] In a further related aspect, the present disclosure provides kits that include a dressing of any embodiment described herein and instructions for use. The instructions may describe performing any method described herein and any embodiment described herein of such methods. The kit may optionally comprise components such as antiseptic wipes, ointment, adhesive tape, tweezers, and/or scissors.

EQUIVALENTS

[0084] 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.

[0085] 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.

[0086] 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.

[0087] All publications, patent applications, issued patents, and other documents referred to in this specification are herein incorporated by reference as if each individual publication, patent application, issued patent, or other document was specifically and individually indicated to be incorporated by reference in its entirety. Definitions that are contained in text incorporated by reference are excluded to the extent that they contradict definitions in this disclosure.

[0088] The present technology may include, but is not limited to, the features and combinations of features recited in the following lettered paragraphs, it being understood that the following paragraphs should not be interpreted as limiting the scope of the claims as appended hereto or mandating that all such features must necessarily be included in such claims:

A. A dressing composition comprising a hydrogel, wherein the hydrogel comprises a co

polymer of polyvinylpyrrolidone (PVP) and citric acid.

B. The dressing composition of Paragraph A, wherein the hydrogel comprises about 5 %

(w/v) to about 25 % (w/v) co-polymer.

C. The dressing composition of Paragraph A or Paragraph B, wherein the hydrogel has a thickness of about 50 pm to about 2000 pm.

D. The dressing composition of any one of Paragraphs A-C, wherein the hydrogel comprises a wound-facing side and an environmental facing side.

E. The dressing composition of any one of Paragraphs A-D, further comprising an absorbent material disposed adjacent to the hydrogel.

F. The dressing composition of Paragraph E, wherein the absorbent material comprises a superab sorbent polymer, a non-woven carboxymethyl cellulose (CMC) pad, polyester, rayon, nylon, or a combination of any two or more thereof. G. The dressing composition of any one of Paragraphs A-F, further comprising a backing layer.

H. The dressing composition of Paragraph G, wherein the backing layer comprises a

polyurethane, a polyalkoxy alkyl acrylate, a polyalkoxy alkyl methacrylate, or a combination of any two or more thereof.

I. The dressing composition of Paragraph G or Paragraph H, wherein the thickness of the backing layer has a thickness of about 10 pm to about 1000 pm.

J. The dressing composition of any one of Paragraphs G-I, wherein the backing layer is configured to exhibit a moisture vapor transmission rate (MVTR) of about 300 g/m ² /24hrs to about 20,000 g/m ² /24hrs.

K. The dressing composition of any one of Paragraphs A-J, wherein dressing comprises a first layer comprising the hydrogel; and

a second layer comprising a mixture of a collagen and an oxidized regenerated

cellulose (ORC).

L. The dressing composition of Paragraph K, wherein the second layer comprises about 30 wt.% to about 70 wt.% ORC and about 0.1 wt.% to about 60 wt.% collagen.

M. The dressing composition of Paragraph K or Paragraph L, wherein the ORC of the

second layer has a weight- average molecular weight of about 10,000 to about 1,000,000.

N. The wound dressing of any one of Paragraphs K-M, wherein the ORC of the second layer comprises fiber lengths of about 5 pm to about 1,000 pm.

O. The wound dressing of any one of Paragraphs K-N, wherein the collagen of the second layer is a mammalian collagen.

P. The wound dressing of any one of Paragraphs K-O, wherein the collagen comprises a bovine collagen, a human collagen, a recombinantly derived collagen, and a combination of any two or more thereof.

Q. The wound dressing of any one of Paragraphs K-P, wherein the collagen of the second layer has a weight- average molecular weight of about 5,000 to about 100,000. R. A wound dressing composition comprising:

a mixture of a collagen, an oxidized regenerated cellulose (ORC), and a co-polymer of polyvinylpyrrolidone (PVP) and citric acid.

S. The wound dressing composition of Paragraph R, wherein the co-polymer comprises a weight ratio of PVP to citric acid of about 25:1 to about 1:2.

T. The wound dressing composition of Paragraph R or Paragraph S, wherein the wound dressing composition comprises about 0.1 wt.% to about 45 wt.% of the copolymer.

U. The wound dressing composition of any one of Paragraphs R-T, wherein the wound

dressing composition comprises about 30 wt.% to about 70 wt.% ORC.

V. The wound dressing composition of any one of Paragraphs R-U, wherein the collagen comprises a mammalian collagen.

W. The wound dressing composition of any one of Paragraphs R-V, wherein the collagen comprises a bovine collagen, a human collagen, a recombinantly derived collagen, or a combination of any two or more thereof.

X. The wound dressing composition of any one of Paragraphs R-W, wherein the wound dressing composition comprises about 0.1 wt.% to about 60 wt.% collagen.

Y. The wound dressing composition of any one of Paragraphs R-X, wherein the collagen has a weight- average molecular weight of about 5,000 to about 100,000.

Z. A method for treating a wound in a subject in need thereof, comprising administering to the wound:

(a) a dressing composition of any one of Paragraphs A-Q; and/or

(b) a wound dressing composition of any one of Paragraphs R-Y.

AA. The method of Paragraph Z, wherein the wound comprises a bio film and the dressing composition and/or the wound dressing composition prevents, reduces, inhibits, or disrupts the biofilm.

AB. The method of Paragraph Z or Paragraph AA, wherein the dressing composition and/or the wound dressing composition is administered directly to the wound. AC. A kit comprising the dressing composition of any one of Paragraphs A-Q, and instructions for use.

AD. The kit of Paragraph AC, wherein the instructions for use comprise instructions for performing a method according to any one of Paragraphs Z-AB.

AE. A kit comprising the wound dressing composition of any one of Paragraphs R-Y, and instructions for use.

AF. The kit of Paragraph AE, wherein the instructions for use comprise instructions for performing a method according to any one of Paragraphs Z-AB.

[0089] Other embodiments are set forth in the following claims.