Compositions of decidual tissue and uses thereof

Abstract

Disclosed are compositions and methods for treating wounds and damaged tissue using decidual tissue.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 249,655, filed September 29, 2021, the contents of which are incorporated herein by reference.

[0002] The present invention relates generally to compositions comprising decidual tissue, preferably dehydrated decidual tissue, and to uses thereof in the fields of wound management and tissue repair. [Background technology]

[0003] A wound is a disruption of tissue structure and function. Dermal wounds involve the destruction of the skin and the soft tissue structures associated with the skin. Dermal wounds can be partial thickness or full thickness. Dermal wounds can also be acute, chronic, or burns (which can be acute or chronic). To ensure proper healing, the wound bed needs to be free of devitalized tissue, well vascularized, and moist. A wound dressing can help promote the wound healing process if it provides an environment that supports the wound healing process by allowing cell migration, vascularization, and / or granulation tissue formation. Many commercially available wound dressings do not have such capabilities to support the healing process, and some are not very effective in that regard. Additionally, some of these wound dressings are not cost-effective or difficult for medical personnel to handle. Summary of the Invention

[0004] The present disclosure provides a solution to at least one or more of the above limitations and deficiencies in the art related to wound management and tissue repair generally, the solution being premised on the use of a composition comprising decidual tissue as a wound dressing.

[0005] Decidua is a mucosal tissue of the uterus that is formed in preparation for pregnancy. Decidua includes decidua basalis, decidua capsularis, and decidua parietalis. Decidua basalis is the maternal portion of the placenta. Decidua is typically discarded, even when the remaining placental tissue is processed into placental products. The inventors of the present application have surprisingly found that a composition of decidual tissue provides an unexpectedly superior beneficial environment for cell attachment and proliferation of mesenchymal cells in culture, as compared to many commercially available wound dressing products. Thus, the decidual tissue composition of the present invention provides superior conditions to support the wound healing process over existing wound dressing products. Notably, decidua has long been considered a disposable material and is therefore available at little or no cost. Thus, the use of decidual tissue as a raw material for the composition of the present invention also provides a cost-effective product, which can help reduce medical costs associated with wound management and tissue repair.

[0006] In one aspect of the invention, what is disclosed is a composition comprising decidual tissue. In some embodiments, the decidual tissue is dehydrated decidual tissue. In some embodiments, the decidual tissue or the dehydrated decidual tissue comprises decidual basalis tissue, decidual capsular tissue, or decidual parietal tissue, or any combination thereof. In some embodiments, the decidual tissue or the dehydrated decidual tissue is non-viable. In some embodiments, the non-viable decidual tissue or the non-viable dehydrated decidual tissue is made non-viable by cell lysis. In some embodiments, the non-viable decidual tissue or the non-viable dehydrated decidual tissue is made non-viable by sterilization. Dehydrated decidual tissue can be obtained by lyophilization (freeze drying), evaporative air drying (e.g., thermal drying with heated air under gravity convection conditions or forced air convection conditions, or drying at ambient or room temperature conditions under gravity convection conditions or forced air convection conditions), indirect drying (e.g., vacuum drying), contact drying (e.g., drying by contact with a heated material or source), dielectric drying (e.g., using radio frequency or microwave), infrared drying, and / or supercritical drying. In some embodiments, the dehydrated decidual is dehydrated by lyophilization. In some embodiments, the dehydrated decidual tissue is a powder. In some embodiments, the dehydrated decidual tissue has a water content of less than 5% w / w, or less than 3% w / w. In some embodiments, the composition further comprises a carrier. In some embodiments, the carrier is a pharma- ceutically acceptable carrier. In some embodiments, the carrier or the pharma-ceutically acceptable carrier is aqueous-based. In some embodiments, the aqueous-based carrier comprises at least 50% w / w water. In some embodiments, the pharma- ceutically acceptable carrier comprises one or more cellulose ethers. In some embodiments, the cellulose ether is a non-ionic cellulose ether. In some embodiments, the non-ionic cellulose ether is selected from hydroxyethyl cellulose (HEC), or hydroxypropyl cellulose (HPC), or a mixture thereof.In some embodiments, the pharma- ceutically acceptable carrier further comprises one or more plasticizers. In some embodiments, the plasticizer is a hydrophilic polyol. In some embodiments, the hydrophilic polyol is a hydrophilic polymeric polyol. In some embodiments, the hydrophilic polymeric polyol is one or more polyethylene glycols. In some embodiments, the one or more polyethylene glycols comprise polyethylene glycol 600. In some embodiments, the composition is dehydrated. In some embodiments, the composition is dehydrated by evaporative air drying. In some embodiments, the evaporative air drying is thermal evaporative air drying using heated air under gravity convection conditions or forced air convection conditions. In other embodiments, the evaporative air drying is evaporative air drying at ambient or room temperature under gravity convection conditions or forced air convection conditions. In still other embodiments, the evaporative air drying is evaporative air drying at room temperature under gravity convection conditions. In other embodiments, the composition is dehydrated by lyophilization. In some embodiments, the dehydrated composition is a sheet or film. In some embodiments, the composition comprising decidual tissue is a powder. In some embodiments, the water content of the dehydrated composition is less than 5% w / w, or less than 3% w / w. In some embodiments, the sheet or film has a thickness of about 0.1 mm to about 25 mm, or about 0.5 mm to about 10 mm, or about 1 mm to about 5 mm. In some embodiments, the concentration of decidual tissue is about 1% w / w to about 75% w / w, or about 4% w / w to about 50% w / w of the dehydrated composition. In some embodiments, the dehydrated composition can form a hydrogel when the dehydrated composition contacts water or other aqueous media. In some embodiments, the dehydrated composition is opaque. In other embodiments, the dehydrated composition is transparent. In some embodiments, the dehydrated composition is translucent.In some embodiments, the dehydrating composition includes markings, symbols, letters, or numbers, which can be useful in identifying the source of the composition and / or can be useful in orienting the composition during use or application to a wound (e.g., with the top surface facing away from the wound and the bottom surface in contact with the wound).

[0007] In another aspect of the invention, disclosed is a method for treating a wound in a subject, the method comprising applying a composition of the invention (e.g., a composition or dehydration composition comprising decidual tissue, preferably dehydrated decidual tissue) to the wound. In some embodiments, the composition is applied in conjunction with applying another wound dressing. In some embodiments, the composition or dehydration composition is a powder. In some embodiments, the wound is a dermal wound. In some embodiments, the dermal wound is a partial thickness wound. In other embodiments, the dermal wound is a full thickness wound. In some embodiments, the dermal wound is a burn, a chronic wound, or an acute wound. In some embodiments, the dermal wound is a burn and is selected from a superficial (first degree) burn, a partial thickness (second degree) burn, a full thickness (third degree) burn, or a radiation burn. In other embodiments, the dermal wound is a chronic wound and is selected from a dermal ulcer, a diabetic ulcer, a diabetic foot ulcer, a venous ulcer, a venous leg ulcer, an arterial ulcer, an arterial leg ulcer, a decubitus ulcer, a stasis ulcer, an ischemic ulcer, a vascular ulcer, a decubitus (Stages I-IV), a podiatric wound, a draining wound, a tunnel wound, or an excavation wound. In yet other embodiments, the dermal wound is an acute wound and is selected from a trauma wound, a laceration, an abrasion, a skin laceration, a skin lesion, a blister, a surgical incision, a donor skin site, a skin graft, a laser surgery wound, a Mohs surgery wound, or an abrasion wound.

[0008] In another aspect of the invention, disclosed is a method for treating a wound in a subject, the method comprising applying a composition of the invention (e.g., a composition comprising decidual tissue, preferably dehydrated decidual tissue, or a dehydrated composition) to the wound.

[0009] In another aspect of the invention, disclosed is a method for producing a dehydrated composition comprising dehydrated decidual tissue, the method comprising: (a) preparing dehydrated decidual tissue; (b) preparing an aqueous-based pharma- ceutically acceptable carrier; (c) combining (a) and (b) and mixing until uniform; (d) dehydrating the resulting mixture to form a dehydrated composition; The aqueous-based carrier has a moisture content of at least 50% w / w and the dehydrated composition is rendered into a film or sheet, the film or sheet having a moisture content of less than 5% w / w or less than 3% w / w, hi some embodiments, the dehydration step (d) is performed by evaporative air drying or freeze drying.

[0010] In another aspect of the invention, disclosed is a dehydrated composition, the dehydrated composition comprising: (a) Dehydrated decidual tissue; (b) an aqueous-based pharma- ceutically acceptable carrier, the aqueous-based carrier comprising: (i) one or more cellulose ethers; (ii) one or more plasticizers; The aqueous-based carrier has a moisture content of at least 50% w / w prior to dehydration of the composition, the composition is dehydrated by evaporative air drying or by freeze-drying, and the dehydrated composition is formed into a film or sheet, the film or sheet having a moisture content of less than 5% w / w or less than 3% w / w. In some embodiments, the one or more cellulose ethers include hydroxyethyl cellulose (HEC), or hydroxypropyl cellulose (HPC), or mixtures thereof. In some embodiments, the one or more plasticizers include one or more polyethylene glycols. In some embodiments, the one or more polyethylene glycols include polyethylene glycol 600.

[0011] Also disclosed in the context of the present invention are the following embodiments 1-43. Embodiment 1 is a composition comprising dehydrated decidual tissue. Embodiment 2 is a composition according to embodiment 1, wherein the dehydrated decidual tissue comprises decidual basalis tissue, decidual capsular tissue, or decidual parietal tissue, or any combination thereof. Embodiment 3 is a composition according to embodiment 1 or 2, wherein the dehydrated decidual tissue is non-viable. Embodiment 4 is a composition according to any one of embodiments 1-3, wherein the dehydrated decidual tissue is a powder. Embodiment 5 is a composition according to any one of embodiments 1-4, wherein the dehydrated decidual tissue is lyophilized. Embodiment 6 is a composition according to any one of embodiments 1-5, wherein the water content of the dehydrated decidual tissue is less than 5% w / w, or less than 3% w / w. Embodiment 7 is a composition according to any one of embodiments 1-6, further comprising a pharma-ceutically acceptable carrier. Embodiment 8 is the composition of embodiment 7, wherein the pharma- ceutically acceptable carrier is aqueous-based, preferably the composition comprises at least 50% w / w water. Embodiment 9 is the composition of any one of embodiments 1-8, wherein the pharma- ceutically acceptable carrier comprises one or more cellulose ethers. Embodiment 10 is the composition of embodiment 9, wherein the cellulose ether is a non-ionic cellulose ether. Embodiment 11 is the composition of embodiment 10, wherein the non-ionic cellulose ether is selected from hydroxyethyl cellulose (HEC), or hydroxypropyl cellulose (HPC), or a mixture thereof. Embodiment 12 is the composition of any one of embodiments 1-11, wherein the pharma- ceutical acceptable carrier further comprises one or more plasticizers. Embodiment 13 is the composition of embodiment 12, wherein the plasticizer is a hydrophilic polyol. Embodiment 14 is the composition of embodiment 13, wherein the hydrophilic polyol is a hydrophilic polymeric polyol. Embodiment 15 is the composition of embodiment 14, wherein the hydrophilic polymeric polyol is one or more polyethylene glycols. Embodiment 16 is the composition of embodiment 15, wherein the one or more polyethylene glycols comprises polyethylene glycol 600.Embodiment 17 is a composition according to any one of embodiments 1 to 16, wherein the composition is dehydrated. Embodiment 18 is a composition according to embodiment 17, wherein the composition is dehydrated by evaporative air drying. Embodiment 19 is a composition according to embodiment 18, wherein the evaporative air drying is evaporative air drying at room temperature under gravity convection conditions. Embodiment 20 is a composition according to embodiment 17, wherein the composition is dehydrated by freeze drying. Embodiment 21 is a composition according to any one of embodiments 17 to 20, wherein the water content of the dehydrated composition is less than 5% w / w, or less than 3% w / w. Embodiment 22 is a composition according to any one of embodiments 17 to 21, wherein the dehydrated composition is a sheet or film. Embodiment 23 is a composition according to embodiment 22, wherein the sheet or film has a thickness of about 0.1 mm to about 25 mm, or about 0.5 mm to about 10 mm, or about 1 mm to about 5 mm. Embodiment 24 is a composition according to any one of embodiments 17-23, wherein the concentration of decidual tissue is from about 1% w / w to about 75% w / w, or from about 4% w / w to about 50% w / w, of the dehydrated composition.Embodiment 25 is a composition according to any one of embodiments 17-24, wherein the dehydrated composition is capable of forming a hydrogel when the dehydrated composition contacts water or other aqueous media.Embodiment 26 is a composition according to any one of embodiments 17-25, wherein the dehydrated composition is opaque.Embodiment 27 is a composition according to any one of embodiments 17-25, wherein the dehydrated composition is transparent.

[0012] Embodiment 28 is a method for treating a wound in a subject, the method comprising applying to the wound the composition of any one of embodiments 1 to 27. Embodiment 29 is the method of embodiment 28, in which the composition is applied in conjunction with applying another wound dressing. Embodiment 30 is the method of embodiment 28 or 29, in which the composition is a powder. Embodiment 31 is the method of embodiment 28 to 30, in which the wound is a dermal wound. Embodiment 32 is the method of embodiment 31, in which the dermal wound is a partial thickness wound or a full thickness wound. Embodiment 33 is the method of embodiment 31 or 32, in which the dermal wound is a burn wound, a chronic wound, or an acute wound. Embodiment 34 is the method of embodiment 33, wherein the dermal wound is a burn and is selected from a superficial (first degree) burn, a partial thickness (second degree) burn, a full thickness (third degree) burn, or a radiation burn.Embodiment 35 is the method of embodiment 33, wherein the dermal wound is a chronic wound and is selected from a dermal ulcer, a diabetic ulcer, a diabetic foot ulcer, a venous ulcer, a venous leg ulcer, an arterial ulcer, an arterial leg ulcer, a pressure ulcer, a stasis ulcer, an ischemic ulcer, a vascular ulcer, a pressure ulcer (stages I-IV), a podiatric wound, a draining wound, a tunnel wound, or an undermining wound. Embodiment 36 is the method of embodiment 33, wherein the dermal wound is an acute wound and is selected from a trauma wound, a laceration, an abrasion, a skin laceration, a skin lesion, a blister, a surgical incision, a donor skin site, a skin graft, a laser surgery wound, a Mohs surgery wound, or an abrasion wound.

[0013] Embodiment 37 is a method for treating a wound in a subject, the method comprising applying a composition comprising decidual tissue to the wound.

[0014] Embodiment 38 is a method for producing a dehydrated composition comprising dehydrated decidual tissue, the method comprising: (a) preparing dehydrated decidual tissue; (b) preparing an aqueous-based pharma- ceutically acceptable carrier; (c) combining (a) and (b) and mixing until uniform; (d) dehydrating the resulting mixture to form a dehydrated composition; The aqueous-based carrier has a moisture content of at least 50% w / w, and the dehydrated composition is made into a film or sheet, the film or sheet having a moisture content of less than 5% w / w or less than 3% w / w.Embodiment 39 is the method of embodiment 38, wherein the dehydrating step (d) is performed by evaporative air drying or by freeze-drying. Embodiment 40 is a dehydrated composition comprising: (a) Dehydrated decidual tissue; (b) an aqueous-based pharma- ceutically acceptable carrier, the aqueous-based carrier comprising: (i) one or more cellulose ethers; (ii) one or more plasticizers; The aqueous-based carrier has a water content of at least 50% w / w before dehydration of the composition, the composition is dehydrated by evaporative air drying or by freeze-drying, and the dehydrated composition is made into a film or sheet, the film or sheet having a water content of less than 5% w / w or less than 3% w / w.Embodiment 41 is the composition of embodiment 40, wherein the one or more cellulose ethers comprise hydroxyethyl cellulose (HEC), or hydroxypropyl cellulose (HPC), or a mixture thereof.Embodiment 42 is the composition of embodiment 40 or 41, wherein the one or more plasticizers comprise one or more polyethylene glycols.Embodiment 43 is the composition of embodiment 42, wherein the one or more polyethylene glycols comprise polyethylene glycol 600.

[0015] As used herein, the term "subject" refers to a vertebrate, including a mammal, including a human. In some preferred embodiments, the subject is a human.

[0016] As used herein, the term "body" means the body of a subject.

[0017] The term "fragments" as used herein with respect to decidual tissue refers to tissue that has been subjected to a disruption process, such as shearing, mincing, dicing, chopping, cutting, homogenizing, macerating, grinding, etc., to form small individual pieces of tissue. The decidual fragments may be further subjected to dehydration, drying, and / or freeze-drying. The disruption process may occur before or after dehydration, evaporative air drying, or freeze-drying. The fragments may be uniform or irregular in size.

[0018] As used herein, the term "powder" means dry, fine, discrete particles, which may be uniform or irregular in particle size. The particle size may be as described later in this specification.

[0019] As used herein, the term "immune privilege" refers to a relatively high resistance to the stimulation of an immune response.

[0020] As used herein, the term "non-immunogenic" means not promoting an immune response.

[0021] As used herein, the term "room temperature" or "RT" means a temperature between 20°C and 25°C.

[0022] As used herein, the term "optional" or "optionally" means that the subsequently described event, circumstance, or material may or may not occur or be present, and is intended to mean that the specification includes instances in which the event, circumstance, or material occurs or is present as well as instances in which the event, circumstance, or material does not occur or be present.

[0023] As used herein, the terms "approximately" or "about" are defined as close to what would be understood by one of ordinary skill in the art, and in one non-limiting embodiment, these terms are defined as within 10%, preferably within 5%, more preferably within 1%, and most preferably within 0.5% of the relevant disclosed value. These terms may be removed from the relevant disclosed value and the exact value may be used instead.

[0024] If the lower limit of a given percentage range does not include a % symbol and / or a percentage type (e.g., w / w, v / v, etc.), the percentage type at the lower limit is the same as the percentage type at the upper limit of the given percentage range. For example, the percentage range "0.01-0.5% w / w" means "0.01% w / w to 0.5% w / w."

[0025] As used herein, "comprising" (and any form of comprising, such as "comprises" and "comprises"), "having" (and any form of having, such as "have" and "has"), "including" (and any form of including, such as "includes" and "include"), or "containing" (and any form of containing, such as "contains" and "contain") are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.

[0026] The use of the words "a" or "an" when used in conjunction with the terms "comprising," "having," "including," or "containing" (or any variation of these words) may mean "one," but is also consistent with the meanings of "one or more," "at least one," and "one or more."

[0027] For purposes of this specification, numbers with one or more decimal places may be rounded to the nearest integer using standard rounding guidelines, i.e., rounding up if the number being rounded is 5, 6, 7, 8, or 9, and rounding down if the number being rounded is 0, 1, 2, 3, or 4. For example, 0.42 may be rounded to 0.4.

[0028] The compositions and methods of use thereof can "comprise," "consist essentially of," or "consist of" any of the components or steps disclosed throughout this specification. With regard to the transitional phrases "comprise essentially" or "consist essentially of," in one non-limiting aspect, a basic and novel feature in the compositions and methods of the present invention is the ability to use a composition comprising decidual tissue or a dehydrated composition, preferably a composition comprising dehydrated decidual tissue, to treat a wound in a subject and / or repair tissue in a subject.

[0029] It is contemplated that any embodiment described herein can be implemented with respect to any method or any composition of the invention, and vice versa. Further, a composition of the invention can be used to achieve a method of the invention.

[0030] Other objects, features, and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and specific examples, while indicating particular embodiments of the present invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. [Brief description of the drawings]

[0031] [Figure 1] FIG. 1 is a micrograph of freeze-dried decidual tissue powder. 1 square = 250 microns.

[0032] [Figure 2A] FIG. 2A is a photograph of air-dried dehydrated film composition of lot 0055-0114L01 containing lyophilized decidual tissue powder.

[0033] [Figure 2B] FIG. 2B is a photograph of the air-dried dehydrated film composition of lot 0055-0127L01 containing lyophilized decidual tissue powder.

[0034] [Figure 2C] FIG. 2C is a photograph of evaporative air drying of a dehydrated film composition of lot 0055-0225L01 containing lyophilized decidual tissue powder.

[0035] [Figure 2D] FIG. 2D is a photograph of evaporative air drying of a dehydrated film composition of lot 0055-0331L01 containing lyophilized decidual tissue powder.

[0036] [Figure 3A] FIG. 3A is a photograph of a lyophilized dehydrated sheet composition from lot 0055-0114L01 that contained lyophilized decidual tissue powder.

[0037] [Figure 3B] FIG. 3B is a photograph of a lyophilized dehydrated sheet composition of lot 0055-0127L01 containing lyophilized decidual tissue powder.

[0038] [Figure 3C] FIG. 3C is a photograph of a lyophilized dehydrated sheet composition of lot 0055-0225L01 containing lyophilized decidual tissue powder.

[0039] [Figure 3D] FIG. 3D is a photograph of a lyophilized dehydrated sheet composition of lot 0055-0331L01 containing lyophilized decidual tissue powder.

[0040] [Figure 4] FIG. 4 is a micrograph of a cell culture plate of freeze-dried decidual tissue powder after culturing with hMSCs.

[0041] [Diagram 5] FIG. 5 is a micrograph of a cell culture plate of freeze-dried decidual tissue powder after differentiation of hMSCs into adipocytes.

[0042] [Figure 6A] FIG. 6A is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0114L01 containing lyophilized decidual tissue powder and air dried for 2 days.

[0043] [Figure 6B] FIG. 6B is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0114L01 containing lyophilized decidual tissue powder and air dried for 4 days.

[0044] [Figure 6C]FIG. 6C is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0114L01 containing lyophilized decidual tissue powder and air dried for 8 days.

[0045] [Figure 6D] FIG. 6D is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0114L01 containing lyophilized decidual tissue powder and air dried at 16 days.

[0046] [Figure 7A] FIG. 7A is a photomicrograph of live / dead cell staining of cell cultures of dehydrated sheet composition lot 0055-0114L01 containing lyophilized decidual tissue powder and 2 days after lyophilization.

[0047] [Figure 7B] FIG. 7B is a photomicrograph of live / dead cell staining of cell cultures of dehydrated sheet composition lot 0055-0114L01 containing lyophilized decidual tissue powder and 4 days after lyophilization.

[0048] [Figure 7C] FIG. 7C is a photomicrograph of live / dead cell staining of cell cultures of dehydrated sheet composition lot 0055-0114L01 containing lyophilized decidual tissue powder and 8 days after lyophilization.

[0049] [Figure 7D] FIG. 7D is a photomicrograph of live / dead cell staining of cell cultures of dehydrated sheet composition lot 0055-0114L01 containing lyophilized decidual tissue powder and 16 days after lyophilization.

[0050] [Figure 8A]FIG. 8A is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0127L01 containing lyophilized decidual tissue powder and air dried for 2 days.

[0051] [Figure 8B] FIG. 8B is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0127L01 containing lyophilized decidual tissue powder and air dried for 4 days.

[0052] [Figure 8C] FIG. 8C is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0127L01 containing lyophilized decidual tissue powder and air dried for 8 days.

[0053] [Figure 8D] FIG. 8D is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0127L01 containing lyophilized decidual tissue powder and air dried at 16 days.

[0054] [Figure 9A] FIG. 9A is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0127L01 containing lyophilized decidual tissue powder and 2 days after lyophilization.

[0055] [Figure 9B] FIG. 9B is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0127L01 containing lyophilized decidual tissue powder and 4 days after lyophilization.

[0056] [Figure 9C]FIG. 9C is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0127L01 containing lyophilized decidual tissue powder and 8 days after lyophilization.

[0057] [Figure 9D] FIG. 9D is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0127L01 containing lyophilized decidual tissue powder and 16 days after lyophilization.

[0058] [Figure 10A] FIG. 10A is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0225L01 containing lyophilized decidual tissue powder and air dried for 6 days.

[0059] [Figure 10B] FIG. 10B is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0225L01 containing lyophilized decidual tissue powder and air dried at 13 days.

[0060] [Figure 10C] FIG. 10C is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0225L01 containing lyophilized decidual tissue powder and air dried at 19 days.

[0061] [Figure 10D] FIG. 10D is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0225L01 containing lyophilized decidual tissue powder and air dried at 27 days.

[0062] [Figure 11A]FIG. 11A is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0225L01 containing lyophilized decidual tissue powder and 6 days after lyophilization.

[0063] [Figure 11B] FIG. 11B is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0225L01 containing lyophilized decidual tissue powder and 13 days after lyophilization.

[0064] [Figure 11C] FIG. 11C is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0225L01 containing lyophilized decidual tissue powder and 13 days after lyophilization.

[0065] [Figure 11D] FIG. 11D is a photomicrograph of live / dead cell staining of cell cultures of dehydrated film composition lot 0055-0225L01 containing lyophilized decidual tissue powder and 27 days after lyophilization.

[0066] [Figure 12A] FIG. 12A is a photomicrograph of live / dead cell staining of Oasis® burn matrix cell cultures at 7 days.

[0067] [Figure 12B] FIG. 12B is a photomicrograph of live / dead cell staining of cell cultures on DermaGinate Ag™ calcium alginate dressing at 7 days.

[0068] [Figure 12C] FIG. 12C is a photomicrograph of live / dead cell staining of cell cultures on Healadex® dressings at 7 days.

[0069] [Figure 12D] FIG. 12D is a photomicrograph of live / dead cell staining of cell cultures on Mepitel® One dressings at 7 days.

[0070] [Figure 12E] FIG. 12E is a photomicrograph of live / dead cell staining of cell cultures on Integra® Dermal Regeneration Template at 7 days. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0071] The present invention relates to compositions comprising decidual tissue, and wound dressings comprising decidual tissue, and the use of such compositions in treating wounds, including dermal wounds. The compositions disclosed herein are also useful in repairing tissues, such as soft tissues, including, but not limited to, tendons, ligaments, cartilage, and other connective tissues. The decidual tissue compositions can further comprise a carrier, such as a pharma- ceutically acceptable carrier. Surprisingly, the decidual tissue compositions disclosed herein have been shown to provide an unexpectedly superior and beneficial environment for cell attachment and proliferation of mesenchymal cells in culture, compared to many commercially available wound dressings. Thus, the decidual tissue compositions described in this disclosure provide a superior context for supporting the wound healing process over existing wound dressing products. Decidua has long been considered a disposable waste product with little or no value, and is therefore available at little or no cost. Thus, the use of decidual tissue as a component of the compositions of the present invention provides a cost-effective product that can be economically manufactured.

[0072] I. Composition A. Decidual tissue Decidua is the mucosal tissue of the uterus that forms in preparation for pregnancy. It is composed of three parts: decidua basalis, decidua capsularis, and decidua parietalis. Decidua basalis is the maternal portion of the placenta. Decidua is normally discarded even when the remaining placental tissue is processed into a placenta product. The inventors of the present application have found that the normally discarded decidua can be used in a wound dressing product that has superior biological properties in terms of supporting the wound healing process by allowing cell proliferation and migration, vascularization, and / or granulation tissue formation.

[0073] The decidual tissue comprising the compositions disclosed herein can include decidual basalis tissue, decidual capsular tissue, or decidual parietal tissue, or any combination thereof. In some embodiments, the decidual tissue includes decidual basalis tissue. In some embodiments, the decidual tissue includes decidual basalis tissue. In some embodiments, the decidual tissue includes decidual capsular tissue. In some embodiments, the decidual tissue is decidual capsular tissue. In some embodiments, the decidual tissue includes decidual parietal tissue. In some embodiments, the decidual tissue is decidual parietal tissue. In some embodiments, the decidual tissue includes the entire decidua, i.e., includes all three parts of the decidua, i.e., decidual basalis tissue, decidual capsular tissue, and decidual parietal tissue. In some embodiments, the decidual tissue includes decidual basalis tissue and decidual capsular tissue, but does not include decidual parietal tissue. In some embodiments, the decidual tissue includes decidual basalis tissue and decidual parietal tissue, but does not include decidual basalis tissue. In some embodiments, the decidual tissue includes decidual basalis tissue and decidual parietal tissue, but does not include decidual basalis tissue. In some embodiments, the decidual tissue does not include amniotic tissue, chorionic tissue, and / or umbilical cord tissue. The decidual tissue can be dehydrated. Dehydration of the decidual tissue can be accomplished by any suitable means known to those of skill in the art, including, but not limited to, lyophilization (freeze-drying), evaporative air drying (e.g., thermal drying with heated air under gravity convection conditions or forced air convection conditions, or drying at ambient or room temperature conditions under gravity convection conditions or forced air convection conditions), indirect drying (e.g., vacuum drying), contact drying (e.g., drying by contact with a heated material or source), dielectric drying (e.g., using radio frequency or microwave), infrared drying, and / or supercritical drying.Dehydrated decidual tissue is considered "dehydrated" or "dried" when the water content (percentage of water) is less than 15% w / w, or less than 14% w / w, or less than 13% w / w, or less than 12% w / w, or less than 10% w / w, or less than 9% w / w, or less than 8% w / w, or less than 7% w / w, or less than 6% w / w, or less than 5% w / w, or less than 4% w / w, or less than 3% w / w, or less than 2% w / w, or less than 1% w / w, or less than 0.5% w / w. In some embodiments, the water content is less than 5% w / w, or less than 4% w / w, or less than 3% w / w. The dehydrated decidual tissue can have a water content of, for example, 0% w / w, 1% w / w, 2% w / w, 3% w / w, 4% w / w, 5% w / w, 6% w / w, 7% w / w, 8% w / w, 9% w / w, 10% w / w, 11% w / w, 12% w / w, 13% w / w, or 14% w / w, or any percentage derived therefrom. The water content (moisture content) of the dehydrated tissue can be determined by techniques known to those skilled in the art, such as Karl Fischer titration or oven drying. In a preferred embodiment, the dehydrated decidual tissue is freeze-dried decidual tissue. The decidual tissue can be non-viable, meaning that there are no viable cells in or on the tissue. Decidual tissue can be made non-viable by any suitable means known to those of skill in the art, including, but not limited to, cell lysis, sterilization, irradiation, or cell removal by enzymatic or physical means. In some embodiments, the decidual tissue is non-viable. In some embodiments, the compositions of the invention and / or the decidual tissue of the invention are sterilized. In some embodiments, the decidual tissue is viable, where viability means that the decidual tissue comprises viable cells. The viable cells can be native cells, foreign cells, or a mixture thereof. The decidual tissue or dehydrated decidual tissue, for example, evaporative air dried decidual tissue or freeze-dried decidual tissue, can be in the form of fragments or powder. In some embodiments, the decidual tissue is dehydrated by freeze-drying, resulting in freeze-dried decidual tissue.In some embodiments, the decidual tissue is rendered non-viable by cell lysis. In some embodiments, the decidual tissue is in the form of a powder. In some embodiments, the decidual tissue comprises decidual basalis tissue, is dehydrated to be non-viable, and is in the form of a powder. In some embodiments, the decidual tissue comprises decidual basalis tissue, is lyophilized to be non-viable, and is in the form of a powder. In some embodiments, the decidual tissue, or the dehydrated decidual tissue powder, is non-immunogenic and / or immunoprivileged.

[0074] The dehydrated, e.g., evaporative air dried or freeze dried, decidual tissue powder can have a particle size 90% less than 250 microns. The dehydrated decidual tissue powder can have a particle size or particle size distribution (mean particle size) of about 425 microns to about 1000 microns, or about 216 microns to about 425 microns, or less than about 216 microns. The dehydrated decidual tissue powder can have a particle size of about 1 micron to about 1000 microns, or about 1 micron to about 500 microns, or about 1 micron to about 250 microns, or about 50 microns to about 1000 microns, or about 50 microns to about 500 microns, or about 50 microns to about 250 microns, or about 100 microns to about 1000 microns, or about 100 microns to about 500 microns, or about 100 microns to about 250 microns, or about 200 microns to about 1000 microns, or about 200 microns to about 500 microns, or about 200 microns to about 250 microns, or about 400 microns to about 1000 microns, or about 400 microns to about 500 microns. Particle size can be determined by particle size measurement methods known to those skilled in the art, including, but not limited to, microscopic analysis, layered sieving, and particle size analyzers. The particle size analyzer may employ light blocking or laser diffraction techniques. Suitable particle size analyzers include, but are not limited to, analyzers manufactured by Malvern, AccuSizer, Shimadzu, and Beckman Coulter, such as the Malvern Mastersizer™. Particle size distribution may be expressed as an average particle size based on a number distribution or a volume distribution.

[0075] The concentration of decidual tissue, dehydrated decidual tissue, freeze-dried decidual tissue, or evaporative air dried decidual tissue in the composition can be an amount effective to provide an environment that supports the wound healing process by allowing cell migration, vascularization, and formation of granulation tissue when the composition is applied to a wound or damaged tissue, as demonstrated in vitro by cell attachment and proliferation of mesenchymal cells cultured with the composition.

[0076] The concentration of decidual tissue, dehydrated decidual tissue, freeze-dried decidual tissue, or evaporated air dried decidual tissue in the hydrous compositions disclosed herein may range from about 0.05% w / w to about 50% w / w, or from about 0.05% w / w to about 40% w / w, or from about 0.05% w / w to about 30% w / w, or from about 0.05% w / w to about 25% w / w, or from about 0.05% w / w to about 20% w / w, or from about 0.05% w / w to about 15% w / w, or about 0.05% w / w to about 10% w / w, or about 0.05% w / w to about 5% w / w, or about 0.05% w / w to about 4% w / w, or about 0.05% w / w to about 3% w / w, or about 0.05% w / w to about 2% w / w, or about 0.05% w / w to about 1% w / w, or about 0.1% w / w to about 50% w / w, or about 0.1% w / w to about 40% w / w, or about 0.1% w / w to about 30% w / w, or from about 0.1% w / w to about 25% w / w, or from about 0.1% w / w to about 20% w / w, or from about 0.1% w / w to about 15% w / w, or from about 0.1% w / w to about 10% w / w, or from about 0.1% w / w to about 5% w / w, or from about 0.1% w / w to about 4% w / w, or from about 0.1% w / w to about 3% w / w, or from about 0.1% w / w to about 2% w / w, or from about 0.1% w / w to about 1% w / w, or from about 0.5% w / w to about 50% w / w, or From about 0.5% w / w to about 40% w / w, or from about 0.5% w / w to about 30% w / w, or from about 0.5% w / w to about 25% w / w, or from about 0.5% w / w to about 20% w / w, or from about 0.5% w / w to about 15% w / w, or from about 0.5% w / w to about 10% w / w, or from about 0.5% w / w to about 5% w / w, or from about 0.5% w / w to about 4% w / w, or from about 0.5% w / w to about 3% w / w, or from about 0.5% w / w to about 2% w / w, or about 0.It may be from 5% w / w to about 1% w / w, or from about 1% w / w to about 50% w / w, or from about 1% w / w to about 40% w / w, or from about 1% w / w to about 30% w / w, or from about 1% w / w to about 25% w / w, or from about 1% w / w to about 20% w / w, or from about 1% w / w to about 15% w / w, or from about 1% w / w to about 10% w / w, or from about 1% w / w to about 5% w / w, or from about 1% w / w to about 4% w / w, or from about 1% w / w to about 3% w / w, or from about 1% w / w to about 2% w / w.

[0077] The concentration of decidual tissue, dehydrated decidual tissue, freeze-dried decidual tissue, or evaporated air dried decidual tissue in the dehydrated compositions disclosed herein may range from about 1% w / w to about 75% w / w, or from about 1% w / w to about 60% w / w, or from about 1% w / w to about 50% w / w, or from about 2% w / w to about 50% w / w, or from about 3% w / w to about 50% w / w, or from about 4% w / w to about 50% w / w, or or about 5% w / w to about 50% w / w, or about 6% w / w to about 50% w / w, or about 7% w / w to about 50% w / w, or about 8% w / w to about 50% w / w, or about 9% w / w to about 50% w / w, or about 10% w / w to about 50% w / w, or about 15% w / w to about 50% w / w, or about 20% w / w to about 50% w / w, or about 1% w / w to about 40% w / w, or about 2% w / w to about 40% w / w, or about 3% w / w to about 40% w / w. w / w, or about 4% w / w to about 40% w / w, or about 5% w / w to about 40% w / w, or about 6% w / w to about 40% w / w, or about 7% w / w to about 40% w / w, or about 8% w / w to about 40% w / w, or about 9% w / w to about 40% w / w, or about 10% w / w to about 40% w / w, or about 15% w / w to about 40% w / w, or about 20% w / w to about 40% w / w, or about 1% w / w to about 30% w / w, or about 2% w / w to about 30 % w / w, or from about 3% w / w to about 30% w / w, or from about 4% w / w to about 30% w / w, or from about 5% w / w to about 30% w / w, or from about 6% w / w to about 30% w / w, or from about 7% w / w to about 30% w / w, or from about 8% w / w to about 30% w / w, or from about 9% w / w to about 30% w / w, or from about 10% w / w to about 30% w / w, or from about 15% w / w to about 30% w / w, or from about 20% w / w to about 30% w / w.

[0078] Decidual tissue can be processed as described in the following non-limiting exemplary embodiments: Unprocessed decidual tissue is added to water or to a buffer such as phosphate buffered saline (PBS), and then to an appropriate homogenizer, such as a blender or other type of homogenizer, and homogenized to form fragments. The homogenized tissue fragments are collected by centrifugation techniques. An appropriate lysis buffer, such as ACK RBC lysis buffer, is added to the tissue and contacted with the tissue for a sufficient time to lyse the cells. The lysis-processed tissue is then washed with water or a buffer and collected by centrifugation techniques. The tissue is then lyophilized (freeze-dried) using a lyophilizer or other appropriate lyophilization techniques. The lyophilized tissue is then processed into a powder form using an appropriate mill, grinder, or disaggregator. In some embodiments, the decidual tissue or the dehydrated decidual tissue powder is non-immunogenic and / or immunoprivileged. In some embodiments, the compositions disclosed herein comprising decidual tissue or dehydrated decidual tissue or dehydrated compositions are non-immunogenic and / or immunoprivileged.

[0079] B. Carrier The compositions comprising decidual tissue disclosed herein can further comprise a carrier, such as a pharma- ceutically acceptable carrier. Non-limiting examples of carriers include lotions, creams, emulsions, ointments, gels, hydrogels, pastes, solutions, aerosol sprays, aerosol foams, non-aerosol sprays, non-aerosol foams, powders, liquid solutions, liquid suspensions, films, and sheets. The carrier or pharma- ceutically acceptable carrier can be aqueous-based, anhydrous, hydrophilic, hydrophobic, or anhydrous hydrophilic. For example, the aqueous-based carrier or pharma- ceutically acceptable carrier can be an aqueous-based gel or hydrogel. The composition can be prepared by incorporating the decidual tissue into the carrier using methods known to those skilled in the art. Such methods can include the use of various types of mixers, blenders, and homogenizers. The composition consisting of the decidual tissue and the carrier can be impregnated into gauze, bandages, or other wound dressings. In some embodiments, the decidual tissue, dehydrated decidual tissue, freeze-dried decidual tissue, or evaporated air dried decidual tissue is in the form of a fragment or powder and uniformly dispersed in the carrier. In some embodiments, the carrier is a pharma- ceutically acceptable carrier. In some embodiments, the carrier or pharma-ceutically acceptable carrier is aqueous-based. The composition can be aqueous-based, anhydrous, or dehydrated. Non-limiting examples of dehydrated compositions comprising decidual tissue and a carrier include films, sheets, or powders. In some aspects of the invention, the aqueous-based composition, carrier, gel, or hydrogel can comprise at least 30% w / w, 40% w / w, 50% w / w, 60% w / w, 70% w / w, 80% w / w, or 90% w / w water or more, and preferably at least 50% w / w water.

[0080] i. Dehydrated film and sheet compositions and methods of preparation In another aspect of the present invention, a dehydrated (dried) composition in the form of a dehydrated film or sheet is disclosed. The film or sheet can include a fragment or powder form of dehydrated decidual tissue, evaporative air dried decidual tissue, or freeze dried decidual tissue, and a carrier. As used herein, the terms "film" and "sheet" can be used interchangeably, although a film is generally thinner than a sheet. The carrier or pharma- ceutically acceptable carrier of the composition can be a dehydrated film or sheet. An exemplary method for preparing a dehydrated film or sheet composition includes dehydrating an aqueous gel or hydrogel composition comprising decidual tissue or dehydrated decidual tissue. The aqueous gel or hydrogel comprising decidual tissue or dehydrated decidual tissue can be cast into a suitable mold, such as a Petri dish, prior to dehydration. Decidual tissue or aqueous-based gels or hydrogels comprising dehydrated decidual tissue can be dehydrated by any suitable means, including, but not limited to, lyophilization (freeze-drying), evaporative air drying (e.g., thermal drying with heated air under gravity convection conditions or forced air convection conditions, or drying at ambient or room temperature conditions under gravity convection conditions or forced air convection conditions), indirect drying (e.g., vacuum drying), contact drying (e.g., drying by contact with a heated material or source), dielectric drying (e.g., using radio frequency or microwaves), infrared drying, and / or supercritical drying. Films or sheets resulting from evaporative air drying can be referred to as xerogels. Evaporative air drying can be performed under gravity convection conditions or forced air convection conditions at ambient or room temperature conditions or above. Drying using heated air can be performed under gravity convection conditions or forced air convection conditions in a heating chamber at a temperature above room temperature. Drying under gravity convection at ambient or room temperature can be done in a chamber or in an open air space such as on a table or bench, In some embodiments, the evaporative air drying is thermal evaporative air drying using heated air under gravity convection or forced air convection conditions.In other embodiments, the evaporative air drying is at ambient or room temperature under gravity or forced air convection conditions. In yet other embodiments, the evaporative air drying is at room temperature under gravity convection conditions. Lyophilization, also known as freeze-drying, can be accomplished by first freezing the aqueous gel or hydrogel in a freezer, e.g., at −80° C., and then drying in a freeze-dryer, or by freezing and drying in a freeze-dryer. In some embodiments, the gel or hydrogel comprising decidual tissue or dehydrated decidual tissue is dehydrated by evaporative air drying or by freeze-drying. A film or sheet is considered "dehydrated" or "dry" when the moisture content (moisture content) is less than 15% w / w, or less than 14% w / w, or less than 13% w / w, or less than 12% w / w, or less than 10% w / w, or less than 9% w / w, or less than 8% w / w, or less than 7% w / w, or less than 6% w / w, or less than 5% w / w, or less than 4% w / w, or less than 3% w / w, or less than 2% w / w, or less than 1% w / w, or less than 0.5% w / w. In some embodiments, the moisture content is less than 5% w / w, or less than 4% w / w, or less than 3% w / w. The dehydrated film or sheet can have a moisture content of, for example, 0% w / w, 1% w / w, 2% w / w, 3% w / w, 4% w / w, 5% w / w, 6% w / w, 7% w / w, 8% w / w, 9% w / w, 10% w / w, 11% w / w, 12% w / w, 13% w / w, or 14% w / w, or any percentage derived therefrom. The moisture content (moisture content) of the dehydrated film or sheet can be measured by techniques known to those skilled in the art, such as Karl Fischer titration or oven drying. For example, the dehydrated film or sheet can be placed in an oven at 65° C. for 3 minutes at atmospheric pressure, and the moisture content can be determined by measuring the weight loss after incubation.

[0081] Decidual tissue fragments or powder, dehydrated decidual tissue fragments or powder, evaporative air dried decidual tissue fragments or powder, or freeze dried decidual tissue fragments or powder are uniformly dispersed in an aqueous gel or hydrogel carrier and then subjected to a dehydration step to form a dehydrated film or sheet. A rheology modifier, such as a gelling agent, can be used to form an aqueous gel or hydrogel prior to dehydration by adding the rheology modifier to the water or aqueous medium. Decidual tissue fragments or powder can be added either before or after the addition of the rheology modifier. Decidual tissue fragments or powder can be first suspended in water or in a buffer such as PBS, and then the tissue can be wetted to form a slurry, which can then be homogenized with a homogenizer such as a Tissue Tearor™ to facilitate incorporation of the tissue into the aqueous gel or hydrogel carrier. The mixing of the rheology modifier with the decidual tissue fragments or powder in water or in an aqueous medium can be carried out using techniques known to those skilled in the art using suitable mixing equipment such as propeller mixers, dissolvers, homogenizers, and the like. Suitable rheology modifiers include, but are not limited to, cellulose ethers, microcrystalline cellulose, acrylic polymers, alginates, gums, and organoclays, examples of which can be found in "Rheology Modifiers Handbook, Practical Use and Application" William Andrew Publishing, 2000, which is incorporated herein by reference. In some embodiments, the carrier comprises one or more rheology modifiers. In some embodiments, the rheology modifier is a cellulose ether. In some embodiments, the carrier comprises one or more cellulose ethers.

[0082] Cellulose ethers include nonionic and anionic cellulose ethers, and are available in a variety of viscosity grades. Nonionic cellulose ethers are high molecular weight compounds that can be produced by replacing the hydrogen atoms of the hydroxyl groups in the glucose units of cellulose with alkyl groups or with hydroxyl alkyl groups. Non-limiting examples of nonionic alkyl cellulose ethers include methyl cellulose (MC), ethyl cellulose (EC), and ethyl methyl cellulose (EMC). Non-limiting examples of nonionic hydroxyalkyl cellulose ethers include hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxymethyl cellulose (HMC), hydroxypropyl methyl cellulose (HPMC), ethyl hydroxyethyl cellulose (EHEC), hydroxyethyl methyl cellulose (HEMC), methyl hydroxyethyl cellulose (MHEC), methyl hydroxypropyl cellulose (MHPC), and hydroxyethyl carboxymethyl cellulose (HECMC). Each of these cellulose ethers has a wide range of commercial products (e.g., Dow Chemical Company, Ashland, Spectrum Chemical). HEC is available from Ashland under the name NATROSOL™. HPC is available from Ashland under the name KLUCEL™. HPMC (also known as hypromellose) is available from Ashland under the name BENECEL™. An ​​example of an anionic cellulose ether is sodium carboxymethylcellulose (CMC), available from Ashland under the name AQUALON™. Cellulose ethers are available in cosmetic and pharmaceutical grades (USP / NF) and are suitable for use in the disclosed compositions. The concentration of cellulose ether in the composition can be varied as needed to achieve specific properties for the dehydrating film or sheet.The concentration of the cellulose ether in the composition (cumulative concentration when more than one cellulose ether is present) can be about 20% w / w to about 80% w / w, or about 30% w / w to about 80% w / w, or about 40% w / w to about 80% w / w, based on the dehydrated composition. The carrier can include one or more cellulose ethers. In some embodiments, the carrier includes one or more cellulose ethers. In some embodiments, the cellulose ether is a non-ionic cellulose ether. In some embodiments, the non-ionic cellulose ether is hydroxyethyl cellulose (HEC), or hydroxypropyl cellulose (HPC), or a mixture thereof.

[0083] The carrier may further include one or more plasticizers, which may function to enhance desired physical properties, such as brittleness and flexibility, of the dehydrated film or sheet. Non-limiting examples of plasticizers include hydrophilic polyols, hydrophilic polymeric polyols, propylene glycol, glycerol, polyethylene glycol (PEG), polypropylene glycol, poloxamer, and povidone. The concentration of the plasticizer in the composition may be about 0% w / w to about 30% w / w, or about 5% w / w to about 30% w / w, or about 10% w / w to about 25% w / w, based on the composition in the dehydrated state. In some embodiments, the plasticizer is a hydrophilic polyol. Suitable hydrophilic polyols are water-soluble polar aliphatic alcohols having at least two hydroxyl groups, and may include polymeric polyols, such as polyethylene glycol and poloxamer. In some embodiments, the hydrophilic polyol is a hydrophilic polymeric polyol. In some embodiments, the hydrophilic polymeric polyol is one or more polyethylene glycols. In some embodiments, the polyethylene glycol is polyethylene glycol 600.

[0084] Polyethylene glycol (PEG) has the formula H(OCH2CH2) n It is a homopolymer of ethylene glycol and water, represented by OH,where n represents the average number of oxyethylene groups. Polyethylene glycol can be either liquid or solid at 25° C., depending on its molecular weight. The following non-limiting examples are suitable for use with the disclosed compositions and are described using the United States Pharmacopeial Convention (USP) nomenclature: polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 500, and polyethylene glycol 600. The following non-limiting examples of solid polyethylene glycols are suitable for use with the disclosed compositions and are described using USP nomenclature: polyethylene glycol 700, polyethylene glycol 800, polyethylene glycol 900, polyethylene glycol 1000, polyethylene glycol 1100, polyethylene glycol 1200, polyethylene glycol 1300, polyethylene glycol 1400, polyethylene glycol 1450, polyethylene glycol 1500, polyethylene glycol 1600, polyethylene glycol 1700, polyethylene glycol 1800, polyethylene glycol 1900, polyethylene glycol 2000, polyethylene glycol 2100, polyethylene glycol 2200, polyethylene glycol 2300, polyethylene glycol 2400, polyethylene glycol 2500, polyethylene glycol 2600, polyethylene glycol 2700, polyethylene glycol 2800, polyethylene glycol 2900, polyethylene glycol 3000, polyethylene glycol 3100, polyethylene glycol 3200, polyethylene glycol 3300, polyethylene glycol 3400, polyethylene glycol 3500, polyethylene glycol 3600, polyethylene glycol 3700, polyethylene glycol 3800, polyethylene glycol 3900, polyethylene glycol 4000, polyethylene glycol 4100, polyethylene glycol 4200, polyethylene glycol 4300, polyethylene glycol 4400, polyethylene glycol 4500, polyethylene glycol 4600, polyethylene glycol 4700, polyethylene glycol 4800, polyethylene glycol 4900, polyethylene glycol 5000, polyethylene glycol 5100, polyethylene glycol 5200, polyethylene glycol 5300, polyethylene glycol 5400, polyethylene glycol 5500, polyethylene glycol 5600, polyethylene glycol 5700, polyethylene glycol 5800, polyethylene glycol 5900, polyethylene glycol 6000, polyethylene glycol 6100, polyethylene glycol 6200, polyethylene glycol 6300, polyethylene glycol 6400, polyethylene glycol 6500, polyethylene glycol polyethylene glycol 2300, polyethylene glycol 2400, polyethylene glycol 2500, polyethylene glycol 2600, polyethylene glycol 2700, polyethylene glycol 2800, polyethylene glycol 2900, polyethylene glycol 3000, polyethylene glycol 3250, polyethylene glycol 3350, polyethylene glycol 3750, polyethylene glycol 4000, polyethylene glycol 4250, polyethylene glycol 4500, polyethylene glycol 4750, polyethylene glycol 5000, polyethylene glycol 5500, polyethylene glycol 6000, polyethylene glycol 6500, polyethylene glycol 7000, polyethylene glycol 7500, and polyethylene glycol 8000.Such liquid and solid polyethylene glycols are commercially available under the names CARBOWAX™ and SENTRY™ from DOW Chemical Company and PLURACARE® and PLURIOL® from BASF Corporation. Polyethylene glycols are available in cosmetic and pharmaceutical grades (USP / NF) and are suitable for use in the disclosed compositions. The concentration of polyethylene glycol in the composition (cumulative concentration if more than one polyethylene glycol is present) can be from about 0% w / w to about 30% w / w, or from about 5% w / w to about 30% w / w, or from about 10% w / w to about 25% w / w of the dehydrated composition. In some embodiments, the carrier comprises polyethylene glycol (PEG) 600. PEG 600 is commercially available from BASF under the name PLURACARE® E600 and from Dow under the name CARBOWAX™ SENTRY™ Polyethylene Glycol 600NF.

[0085] The concentration of decidual tissue as fragments or powder, dehydrated decidual tissue as fragments or powder, evaporative air dried decidual tissue fragments or powder, or lyophilized decidual tissue fragments or powder in the dehydrated film composition or in the dehydrated sheet composition can be an amount effective to provide an environment that supports the wound healing process when the composition is applied to a wound or damaged tissue by allowing cell migration, vascularization, and formation of granulation tissue, as demonstrated in vitro by cell attachment and proliferation of mesenchymal cells cultured with the composition and cultured with an appropriate culture medium, such as MSC culture medium, e.g., DMEM + 10% FBS. The concentration of decidual tissue fragments or powder, dehydrated decidual tissue fragments or powder, evaporative air dried decidual tissue fragments or powder, or freeze-dried decidual tissue fragments or powder in the dehydrated film composition or in the dehydrated sheet composition may be from about 1% w / w to about 75% w / w, or from about 1% w / w to about 60% w / w, or from about 1% w / w to about 50% w / w, or from about 2% w / w to about 50% w / w, or from about 3% w / w to about 50% w / w, or from about 4% w / w to about 50% w / w, or from about 5% w / w to about 50% w / w, or from about 6% w / w to about 50% w / w, of the total composition with respect to the dehydrated composition. It can be 0% w / w, or about 7% w / w to about 50% w / w, or about 8% w / w to about 50% w / w, or about 9% w / w to about 50% w / w, or about 10% w / w to about 50% w / w, or about 1% w / w to about 40% w / w, or about 2% w / w to about 40% w / w, or about 3% w / w to about 40% w / w, or about 4% w / w to about 40% w / w, or about 5% w / w to about 40% w / w, or about 6% w / w to about 40% w / w, or about 7% w / w to about 40% w / w, or about 8% w / w to about 40% w / w, or about 9% w / w to about 40% w / w, or about 10% w / w to about 40% w / w.For example, the concentration of decidual tissue fragments or powder, dehydrated decidual tissue fragments or powder, evaporative air dried decidual tissue fragments or powder, or freeze-dried decidual tissue fragments or powder in the dehydrated film composition or in the dehydrated sheet composition is about 1% w / w, or about 2% w / w, or about 3% w / w, or about 4% w / w, or about 5% w / w, or about 10% w / w. , or about 11% w / w, or about 15% w / w, or about 20% w / w, or about 25% w / w, or about 30% w / w, or about 39% w / w, or about 40% w / w, or about 42% w / w, or about 45% w / w, or about 50% w / w, or about 55% w / w, or about 60% w / w, or about 65% w / w, or about 70% w / w, or about 75% w / w. In some embodiments, the dehydrated decidual tissue, the evaporative air dried decidual tissue, or the lyophilized decidual tissue is in the form of a powder.

[0086] Disclosed are non-limiting exemplary methods for producing a dehydrated composition comprising dehydrated decidual tissue, the method comprising: (a) preparing dehydrated decidual tissue; (b) preparing an aqueous-based pharma- ceutically acceptable carrier; (c) combining (a) and (b) and mixing until uniform; (d) dehydrating the resulting mixture to form a dehydrated composition; The aqueous-based carrier has a moisture content of at least 50% w / w and the dehydrated composition is rendered into a film or sheet, the film or sheet having a moisture content of less than 5% w / w or less than 3% w / w, hi some embodiments, the dehydration step (d) is performed by evaporative air drying or freeze drying.

[0087] Disclosed are non-limiting exemplary dehydrating compositions, comprising: (a) Dehydrated decidual tissue; (b) an aqueous-based pharma- ceutically acceptable carrier, the aqueous-based carrier comprising: (i) one or more cellulose ethers; (ii) one or more plasticizers; The aqueous-based carrier has a moisture content of at least 50% w / w prior to dehydration of the composition, the composition is dehydrated by evaporative air drying or by freeze-drying, and the dehydrated composition is formed into a film or sheet, the film or sheet having a moisture content of less than 5% w / w or less than 3% w / w. In some embodiments, the one or more cellulose ethers include hydroxyethyl cellulose (HEC), or hydroxypropyl cellulose (HPC), or mixtures thereof. In some embodiments, the one or more plasticizers include one or more polyethylene glycols. In some embodiments, the one or more polyethylene glycols include polyethylene glycol 600.

[0088] The dehydrated film and sheet compositions disclosed herein are characterized by their ability to form hydrogels when exposed to water, or other aqueous media such as buffer or saline, or when exposed to liquid from the wound itself. Thus, when the dehydrated film or sheet composition is applied to a wound, liquid from the wound or from the outside reconstitutes the composition into a hydrogel. The hydrogel formed may be sufficiently viscous to remain on the wound and not run off. The dehydrated film or sheet cannot disintegrate like other film wound dressings, but rather forms a hydrogel that remains on the wound, forming an environment and physical matrix or scaffold that provides conditions that support the wound healing process by allowing cell migration, vascularization, and granulation tissue formation. The amount of cellulose ether and / or plasticizer in the dehydrated film or sheet composition can be varied as necessary to achieve the desired viscosity for the resulting hydrogel formed when the dehydrated film or sheet is contacted with water or other aqueous medium. In some embodiments, the resulting hydrogel has sufficient viscosity to remain in the wound bed and not flow out of the wound. The viscosity of the resulting hydrogel can be measured using a viscometer such as a Brookfield Viscometer. A preferred method for measuring the viscosity of the resulting hydrogel is to use a Brookfield Viscometer Model RV-DV2T Cone and Plate Viscometer using a cone spindle CP-52, run at 0.5 RPM for 1 minute at RT. Samples for viscosity measurements are prepared by contacting about 1 part by weight of the dehydrated film or sheet with about 20 parts by weight of water or an aqueous medium such as saline. Viscosity values ​​are reported in centipoise (cps). Viscosity values ​​using the preferred method are from about 100 cps to about 100,000 cps, or from about 100 cps to about 75,000 cps, or from about 100 cps to about 50,000 cps, or from about 100 cps to about 40,000cps, or about 100cps to about 30,000cps, or about 100cps to about 25,000cps, or about 100cps to about 20,000cps, or about 100cps to about 19,000cps, or about 100cps to about 18,000cps, or about 100cps to about 17,000cps, or about 100cps to about 16,000cps, or about 100cps to about 15,000cps, or about 100cps to about 14,000cps, or about 100cps to about 13,000cps, or about 100cps to about 12,000cps s, or about 500cps to about 100,000cps, or about 500cps to about 75,000cps, or about 500cps to about 50,000cps, or about 500cps to about 40,000cps, or about 500cps to about 30,000cps, or about 500cps to about 25,000cps, or about 500cps to about 20,000cps, or about 500cps to about 19,000cps, or about 500cps to about 18,000cps, or about 500cps to about 17,000cps, or about 500cps to about 16,000cps, or is about 500cps to about 15,000cps, or about 500cps to about 14,000cps, or about 500cps to about 13,000cps, or about 500cps to about 12,000cps, or about 1000cps to about 100,000cps, or about 1000cps to about 75,000cps, or about 1000cps to about 50,000cps, or about 1000cps to about 40,000cps, or about 1000cps to about 30,000cps, or about 1000cps to about 25,000cps, or about 1000cps to about 20,000cps , or about 1000cps to about 19,000cps, or about 1000cps to about 18,000cps, or about 1000cps to about 17,000cps, or about 1000cps to about 16,000cps, or about 1000cps to about 15,000cps, or about 1000cps to about 14,000cps, or about 1000cps to about 13,000cps, or about 1000cps to about 12,000cps, or about 5000cps to about 100,000cps, or about 5000cps to about 75,000cps, or about 5000cps to about 50,000cps, or about 5000cps to about 40,000cps, or about 5000cps to about 30,000cps, or about 5000cps to about 25,000cps, or about 5000cps to about 20,000cps, or about 5000cps to about 19,000cps, or about 5000cps to about 18,000cps, or about 5000cps to about 17,000cps, or about 5000cps to about 16,000cps, or about 5000cps to about 15,000cps, or about 5000cps to about 14,000cps, or about 5000cps ~ about 13,000cps, or about 5000cps to about 12,000cps, or about 10,000cps to about 100,000cps, or about 10,000cps to about 75,000cps, or about 10,000cps to about 50,000cps, or about 10,000cps to about 40,000cps, or about 10,000cps to about 30,000cps, or about 10,000cps to about 25,000cps, or about 10,000cps to about 20,000cps, or about 10,000cps to about 19,000cps, or about 10,000cps s to about 18,000 cps, or about 10,000 cps to about 17,000 cps, or about 10,000 cps to about 16,000 cps, or about 10,000 cps to about 15,000 cps, or about 10,000 cps to about 14,000 cps, or about 10,000 cps to about 13,000 cps, or about 10,000 cps to about 12,000 cps, or about 12,000 cps to about 100,000 cps, or about 12,000 cps to about 75,000 cps, or about 12,000 cps to about 50,000 cps, or about 12,00 0 cps to about 40,000 cps, or about 12,000 cps to about 30,000 cps, or about 12,000 cps to about 25,000 cps, or about 12,000 cps to about 20,000 cps, or about 12,000 cps to about 19,000 cps, or about 12,000 cps to about 18,000 cps, or about 12,000 cps to about 17,000 cps, or about 12,000 cps to about 16,000 cps, or about 12,000 cps to about 15,000 cps, or about 12,000 cps to about 14,000 cps, or about 12,000cps to about 13,000cps, or about 15,000cps to about 100,000cps, or about 15,000cps to about 75,000cps, or about 15,000cps to about 50,000cps, or about 15,000cps to about 40,000cps, or about 15,000cps to about 30,000cps, or about 15,000cps to about 25,000cps, or about 15,0 00 cps to about 20,000 cps, or about 20,000 cps to about 100,000 cps, or about 20,000 cps to about 75,000 cps, or about 20,000 cps to about 50,000 cps, or about 20,000 cps to about 40,000 cps, or about 20,000 cps to about 30,000 cps, or about 20,000 cps to about 25,000 cps.

[0089] As used herein, the terms "film" and "sheet" may be used interchangeably, although generally, a film is thinner than a sheet. The thickness of a film or sheet is a function of the amount of hydrogel placed into a mold prior to dehydration; i.e., the more hydrogel placed into a given mold, the thicker the film or sheet will be after dehydration. The thickness of a dehydrated film or sheet is about 0.1 mm to about 25 mm, or about 0.1 mm to about 20 mm, or about 0.1 mm to about 15 mm, or about 0.1 mm to about 10 mm, or about 0.1 mm to about 9 mm, or about 0.1 mm to about 8 mm, or about 0.1 mm to about 7 mm, or about 0.1 mm to about 6 mm, or about 0.1 mm to about 5 mm, or about 0.1 mm to about 4 mm, or about 0.1 mm to about 3 mm, or about 0.1 mm to about 2 mm, or about 0.1 mm. to about 1.5 mm, or about 0.1 mm to about 1 mm, or about 0.2 mm to about 25 mm, or about 0.2 mm to about 20 mm, or about 0.2 mm to about 15 mm, or about 0.2 mm to about 10 mm, or about 0.2 mm to about 9 mm, or about 0.2 mm to about 8 mm, or about 0.2 mm to about 7 mm, or about 0.2 mm to about 6 mm, or about 0.2 mm to about 5 mm, or about 0.2 mm to about 4 mm, or about 0.2 mm to about 3 mm, or about 0.2 mm to about 2 mm, or about 0.2 mm to about 1.5 mm, or about 0.2 mm to about 1 mm, or about 0.3 mm to about 25 mm, or about 0.3 mm to about 20 mm, or about 0.3 mm to about 15 mm, or about 0.3 mm to about 10 mm, or about 0.3 mm to about 9 mm, or about 0.3 mm to about 8 mm, or about 0.3 mm to about 7 mm, or about 0.3 mm to about 6 mm, or about 0.3 mm to about 5 mm, or about 0.3 mm to about 4 mm, or about 0.3 mm to about 3 mm, or about 0.3 mm to about 2 mm, or about 0.3 mm to about 1.5 mm, or about 0.3 mm to about 1 mm, or about 0.4 mm to about 25 mm, or about 0.4 mm to about 20 mm, or about 0.4 mm to about 15 mm, or about 0.4 mm to about 10 mm, or about 0.4 mm to about 9 mm, or about 0.4 mm to about 8 mm, or about 0.4 mm to about 7 mm, or about 0.4 mm to about 6 mm, or about 0.4 mm to about 5 mm, or about 0.4 mm to about 4 mm, or about 0.4 mm to about 3 mm, or about 0.4mm to about 2mm, or about 0.4mm to about 1.5mm, or about 0.4mm to about 1mm, or about 0.5mm to about 25mm, or about 0.5mm to about 20mm, or about 0.5mm to about 15mm, or about 0.5mm to about 10mm, or about 0.5mm to about 9mm, or about 0.5mm to about 8mm, or about 0.5mm to about 7mm, or about 0.5mm to about 6mm, or about 0.5mm to about 5mm, or about 0.5mm to about 4mm, or about 0.5mm to about 3mm, or about 0.5mm to about 2 mm, or about 0.5 mm to about 1.5 mm, or about 0.5 mm to about 1 mm, or about 1 mm to about 25 mm, or about 1 mm to about 20 mm, or about 1 mm to about 15 mm, or about 1 mm to about 10 mm, or about 1 mm to about 9 mm, or about 1 mm to about 8 mm, or about 1 mm to about 7 mm, or about 1 mm to about 6 mm, or about 1 mm to about 5 mm, or about 1 mm to about 4 mm, or about 1 mm to about 3 mm, or about 1 mm to about 2 mm, or about 1 mm to about 1.5 mm. The film or sheet can be cut or pre-cut to any size suitable for application to the wound or tissue. The film or sheet can be transparent or opaque. In general, dehydrated compositions dehydrated by lyophilization (freeze drying) are thicker and more opaque than dehydrated compositions dehydrated by evaporative air drying. Although not limiting, an evaporative air dried composition can be considered a film, whereas a freeze dried composition can be considered a sheet.

[0090] C. Excipients and Additional Ingredients The compositions disclosed herein can further include excipients, functional ingredients, and additional ingredients. Non-limiting examples of such ingredients include active pharmaceutical ingredients (APIs), absorbents, antimicrobials, antioxidants, anti-biofilm agents, binders, buffers (e.g., Tris buffer and PBS), bulking agents, chelating agents, colorants, release agents, dyes, biocides, deodorants, emulsion stabilizers, film formers, fragrance ingredients, humectants, gelling agents (e.g., cellulose ethers, microcrystalline cellulose, acrylic polymers, alginates, gums, organoclays), solubilizers, enzymes, proteases, opacifying agents, oxidizing agents, pH adjusters, plasticizers, preservatives (e.g., methylparaben, propylparaben, benzyl alcohol), reducing agents, emollients, moisturizers, hydrophilic polyols, hydrophilic polymeric polyols, polyethylene glycols, humectants, surfactants, emulsifiers, cleaning agents, foaming agents, hydrotopes, solvents, suspended agents, rheology modifiers, viscosity modifiers, viscosity increasing agents (e.g., thickeners), wound care agents, and propellants. In some embodiments, the composition does not include or does not contain enzymes, proteolytic enzymes, anti-biofilm agents, and / or delaminating agents, hi some embodiments, the composition does not include or does not contain active pharmaceutical ingredients.

[0091] II.How to use The compositions disclosed herein are useful in treating wounds in a subject by applying the compositions to or on the wound. Wounds can include tissue structure destruction and tissue function destruction. Non-limiting examples of wounds include visceral wounds, mucosal wounds, vascular tissue wounds, soft tissue wounds including ligaments, tendons, and cartilage, bone wounds, and dermal wounds. In some embodiments, the wound is a dermal wound. In some embodiments, the composition is topically applied to the dermal wound. In some embodiments, the composition after application directly contacts at least a portion of the wound surface.

[0092] Dermal wounds can involve destruction of the skin and associated soft tissue. Dermal wounds can be partial thickness or full thickness. Dermal wounds can also be acute, chronic, or burn wounds, and burns can be acute or chronic. Non-limiting examples of burns include superficial (first degree), partial thickness (second degree), full thickness (third degree), or radiation burns. Non-limiting examples of chronic wounds include dermal ulcers, diabetic ulcers, diabetic foot ulcers, venous ulcers, venous leg ulcers, arterial ulcers, arterial leg ulcers, pressure ulcers, stasis ulcers, ischemic ulcers, vascular ulcers, pressure ulcers (Stages I-IV), podiatric wounds, draining wounds, tunnel wounds, or undermining wounds. Non-limiting examples of acute wounds include traumatic wounds, lacerations, abrasions, skin lacerations, skin lesions, blisters, surgical incisions, donor skin sites, skin grafts, laser surgery wounds, Mohs surgery wounds, or abrasion wounds. In some embodiments, the dermal wound comprises necrotic tissue. In other embodiments, the dermal wound does not comprise necrotic tissue.

[0093] The composition of the present invention can be applied to the wound periodically, for example daily. A treatment regimen can be followed that includes regular dressing changes with wound cleaning and application of fresh composition between changes until the wound heals. The composition can be applied in combination with application of other wound dressings, including but not limited to gauze dressings, sponge wound dressings, foam wound dressings (e.g., Allevyn™ foam dressings), antimicrobial wound dressings, ECM-based wound dressings, placental tissue wound dressings, wound abrasion dressings, calcium alginate dressings, hydrogels, and medicated wound dressings. For example, after application of the composition, the wound can be covered by another wound dressing. The composition can be applied before or after application of another wound dressing. In some embodiments, the composition includes lyophilized decidual tissue powder and is applied to the wound before application of another wound dressing, and in other embodiments, the composition is applied after application of another wound dressing. The dehydrated film and sheet compositions can be applied to the wound in a dry state, or they can be applied to the wound in a moistened state with an aqueous medium, such as saline, either before or after application.

[0094] The compositions of the present invention can allow cell migration, vascularization, and formation of granulation tissue when applied to a wound or damaged tissue, as can be demonstrated in a non-limiting manner in vitro by cell attachment and proliferation of mesenchymal cells cultured with the compositions, thus supporting and promoting the wound healing process with the use of the compositions.

[0095] III. Packaging The composition of the present invention can be packaged in any suitable package configuration, for example, for storage, shipping, and / or use of the composition of the present invention. External preparation. Non-limiting examples of package configurations can include containers such as plastic packages, foil packages, pouches, packets, boxes, etc. In certain embodiments where the composition is fluid (e.g., in the form of liquid or hydrogel), bottles, jars, bottles with pumps, toddlers, tubes (aluminum, plastic, or laminate), jars, non-aerosol pump sprays, and / or aerosol containers of the composition can be used. The package can be configured for single dose or multiple doses.

[0096] Containers such as kits with multiple compartments can also be used. For example, the composition of the present invention can be in the form of a film or sheet and can be placed in one compartment. The second compartment can contain a composition that can include, for example, water or other aqueous solution. This allows the film or sheet to be mixed with the second composition, thereby forming a hydrogel. The kit can also include a mixer (e.g., spoon or rod or paddle, etc.) for mixing the two compositions and / or an applicator (e.g., spoon or rod or paddle, etc.) for applying the hydrogel to a wound or tissue, such as damaged tissue. The kit can also include three, four, five, or more additional compartments or containers.

[0097] The packaging may also include instructions regarding the compositions of the present invention. The instructions may include instructions regarding how to apply, use, and maintain the product or composition. EXAMPLES

[0098] Example 1 - Freeze-dried decidual tissue powder For preparation of lyophilized decidual tissue powder, the raw decidual tissue was weighed and transferred to a Retsch GM200 blender along with an equal weight of PBS to the tissue. The blender was then run at 7000 rpm for 1.5 minutes to form homogenized tissue. The tissue was collected by centrifugation. ACK RBC lysis buffer was added to the tissue in a volume ratio of 3:1 and kept in contact with the tissue for 30 minutes. After the lysis procedure, the tissue was washed twice with PBS by centrifugation. The tissue was then dehydrated by freeze-drying in a lyophilizer. The lyophilized tissue was then powdered using a MACS Octo dissociator, which formed a coarse white to off-white powder. The particle size of the powder was approximately 90% less than 250 microns as determined by microscopy (see FIG. 1).

[0099] Example 2 - Dehydrating film composition and dehydrating sheet composition For all lots, the film and sheet compositions shown in Tables 1, 2, 3, 4, and 5 below were prepared by first preparing a hydrogel (hydrated state) containing lyophilized decidual tissue powder, and then dehydrating the hydrogel by evaporative air drying at room temperature and / or by lyophilization to form a film or sheet (dehydrated state). The formulas show the amount of components of the hydrogel in the hydrated state before dehydration for each lot in grams, and the components of the resulting film or sheet in the dehydrated state after dehydration in calculated % w / w. For all lots, the HPC (hydroxypropyl cellulose) used was product number HY121, 4,000-6,500 cP, NF from Spectrum, and the HEC (hydroxyethyl cellulose) used was NATROSOL™ 250HX Pharm from Ashland. For all lots, films and sheets were prepared by first making a hydrogel by the following process: adding HEC, HPC, and PEG-600 to deionized water at RT and mixing until a clear hydrogel was formed. Dehydrated decidual tissue powder was wetted with a small amount of standard phosphate buffered saline (PBS), approximately 20 parts PBS to 1 part decidual tissue powder by weight, to form a slurry, which was then homogenized using a Tissue Tearor™ mini homogenizer. The homogenized slurry was then added to the hydrogel and mixed until uniform. Each lot of hydrogel was divided into samples for dehydration by evaporative air drying and / or for dehydration by freeze drying to form the resulting film and sheet compositions in a dehydrated state.

[0100]

Table 1

[0101]

Table 2

[0102]

Table 3

[0103]

Table 4

[0104]

Table 5

[0105] For the lots in Table 5, the particle size of the lyophilized decidual tissue powder was between 425 microns and 1000 microns for the powder used in lot 0055-1102L01, between 216 microns and 425 microns for the powder used in lot 0055-1102L02, and less than 216 microns for the powder used in lot 0055-1102L03. The powders used in the lots were prepared using stacked sieves of sizes 1000 microns, 425 microns, and 216 microns, where the lyophilized decidual tissue powder was added to the 1000 micron sieve and after shaking, the powder retained on the 425 micron sieve (425 microns to 1000 microns), the powder retained on the 216 micron sieve (216 microns to 425 microns), and the powder that passed through the 216 micron sieve (<216 microns) were collected.

[0106] Evaporative air dried samples were dehydrated by the following process: Approximately 2-3 grams of hydrogel was poured into a 16-well plate used as a mold. The mold was covered for 1 hour to ensure that the gel was spread evenly within the mold. The mold was left uncovered at RT under gravity convection conditions to dry for up to 120 hours.

[0107] The freeze-dried samples were dehydrated by the following process: Approximately 2-3 grams of hydrogel was poured into a 16-well plate used as a mold. The mold was covered for 1 hour to ensure that the gel was spread evenly within the mold. The mold was placed in a -80°C freezer for at least 1 hour to ensure freezing. After freezing, the mold was placed in a freeze dryer and dried for at least 1 week.

[0108] result:

[0109] The evaporative air-dried films, also referred to as xerogels, from the lots in Tables 1, 2, 3, and 4 were thin and transparent with an average thickness of 0.8 mm (see Figures 2A, 2B, 2C, and 2D). The lyophilized sheets from the lots in Tables 1, 2, 3, and 4 were spongy and opaque with an average thickness of 5.1 mm (see Figures 3A, 3B, 3C, and 3D). The thickness of the lyophilized sheets from the lots in Table 5 was 2 mm for all lots. The moisture content (moisture content) of the lyophilized sheets from the lots in Table 5 was measured by placing the sheets in a 65°C oven at atmospheric pressure for 3 minutes and determining the weight loss by taking weight readings before and after incubation. The moisture content of lot 005-1102L01 was 0.745% w / w, the moisture content of lot 005-1102L02 was 1.07% w / w, and the moisture content of lot 005-1102L03 was 2.59% w / w.

[0110] Example 3 - Cell culture of MSCs using freeze-dried decidual tissue powder, dehydrated film composition and dehydrated sheet composition Lyophilized decidual tissue powder: Human mesenchymal cells (hMSCs) were cultured in hMSC medium, i.e., DMEM+10% FBS, in petri dishes at 37° C. using the lyophilized decidual tissue powder from Example 1. The micrograph of the cell culture plate after culture in FIG. 4 shows that the lyophilized decidual tissue powder induces cell growth, migration, and proliferation of hMSCs. Additional studies show differentiation of the expanded hMSCs into adipocytes, as seen in the micrograph of FIG. 5.

[0111] Dehydrated film and sheet compositions: Human mesenchymal cells (hMSCs) were cultured in hMSC medium, i.e., DMEM+10% FBS, in 12-well cell culture plates at 37° C. using the evaporative air-dried dehydrated film and freeze-dried dehydrated sheet from Example 2. 0.5M cells per well were added to 3 ml of medium and cultured for several days up to 27 days. ThermoFisher LIVE / DEAD® mammalian cell viability / cytotoxicity kit protocol was used and was based on the ThermoFisher webpage https: / / www.thermofisher.com / us / en / home / references / protocols / cell-and-tissue-analysis / protocols / live-dead-viability-cytoxycity-kit, which is incorporated herein by reference. Following the protocol outlined at t-for-mammalian-cells.html, live / dead staining was obtained at various time points after initiation of culture, and photomicrographs were taken of the staining at those time points (see Figures 6A, 6B, 6C, 6D, 7A, 7B, 7C, 7D, 8A, 8B, 8C, 8D, 9A, 9B, 9C, 9D, 10A, 10B, 10C, 10D, 11A, 11B, 11C, and 11D). As can be seen in the photomicrographs, both the evaporative air-drying dehydrated film and the freeze-drying dehydrated sheet induce cell growth, migration, and proliferation of hMSCs in culture. For comparison purposes, various commercially available wound dressings were also cultured with hMSCs. Live / dead staining was performed and micrographs were taken 7 days after initiation of culture (see Figures 12A, 12B, 12C, and 12D). As can be seen in the micrographs, these commercially available wound dressing products showed much less cell growth and proliferation compared to the dehydrated film or sheet compositions.Thus, the results show that the dehydrated film and sheet compositions exhibit cell growth, migration, and proliferation of hMSCs in culture, and exhibit superior properties with respect to cell growth, migration, and proliferation of hMSCs in culture, as compared to various commercially available wound dressings.

[0112] Example 4 - Rehydration of Dehydrated Film and Sheet Compositions to Form Hydrogels and Viscosity Measurement of Hydrogels The dehydrated lyophilized compositions of the lots from Table 5 above were rehydrated to form hydrogels by adding about 1 part by weight of the lyophilized dehydrated sheets to about 20 parts by volume of normal saline. Viscosity measurements were performed on samples of the resulting hydrogels using a Brookfield Viscometer Model RV-DV2T Cone and Plate Viscometer using a cone spindle CP-52 at 0.5 RPM. Measurements were taken for 1 minute at RT. Viscosity results are reported in centipoise (cps). The viscosity value for lot 0055-1102L01 was 12,900 cps, the viscosity value for lot 0055-1102L01 was 13,250 cps, and the viscosity value for lot 0055-1102L03 was 12,870 cps.

[0113] Example 5 - In vivo animal studies Objective: To evaluate local tissue response and wound closure following treatment with a dehydrated decidual composition using a porcine animal model.

[0114] Pig animal model: A full-thickness excision wound of 3 cm x 3 cm and 3 mm to 6 mm deep (varies by pig) is created in the pig. A dehydrated decidual composition is placed on the wound as a treatment. A control such as a medical device product is also set.

[0115] In-life time points: Weekly images of the wounds and measurements of the wounds are taken along with recording of all other gross observations.

[0116] Histological time points: H&E and Masson's trichrome staining of a single section through the center of the wound will be performed along with pathological scoring at a single time point on day 28. Additional immunohistochemistry may be added later.

[0117] Endpoints: At the end of the study, histological evaluation is performed on the dehydrated decidual tissue compositions and on the controls to determine the extent of wound closure in the animals.

Claims

1. A composition comprising dehydrated decidual tissue.

2. 10. The composition of claim 1, wherein the dehydrated decidual tissue comprises decidual basalis tissue, decidual capsular tissue, or decidual parietal tissue, or any combination thereof.

3. 3. The composition of claim 1 or 2, wherein the dehydrated decidual tissue is non-viable.

4. The composition of claim 1 or 2, further comprising a pharmaceutically acceptable carrier.

5. The composition of claim 4 , wherein the pharmaceutically acceptable carrier comprises one or more cellulose ethers.

6. The composition of claim 5 , wherein the cellulose ether is a nonionic cellulose ether.

7. 7. The composition of claim 6, wherein the nonionic cellulose ether is selected from hydroxyethyl cellulose (HEC), or hydroxypropyl cellulose (HPC), or a mixture thereof.

8. The composition of claim 4 , wherein the pharmaceutically acceptable carrier further comprises one or more plasticizers.

9. The composition of claim 8 wherein the plasticizer is a hydrophilic polyol.

10. The composition of claim 9 , wherein the hydrophilic polyol is a hydrophilic polymeric polyol.

11. The composition of claim 10 , wherein the hydrophilic polymeric polyol is one or more polyethylene glycols.

12. 12. The composition of claim 11, wherein the one or more polyethylene glycols comprises polyethylene glycol 600.

13. 10. The composition of claim 1, wherein the composition is dehydrated. Optionally, the composition is dehydrated by evaporative air drying or by freeze-drying.

14. 14. The composition of claim 13, wherein the water content of the dehydrated composition is less than 5% w / w, or less than 3% w / w.

15. 15. The composition of claim 13 or 14, wherein the dehydrated composition is a sheet or film.

16. 1. A dehydrated composition comprising: (a) dehydrated decidual tissue; (b) an aqueous-based pharmaceutically acceptable carrier, wherein the aqueous-based carrier comprises: (i) one or more cellulose ethers; (ii) one or more plasticizers; The aqueous-based carrier has a moisture content of at least 50% w / w prior to dehydration of the composition, the composition is dehydrated by evaporative air drying or by freeze-drying, and the dehydrated composition is formed into a film or sheet, the film or sheet having a moisture content of less than 5% w / w or less than 3% w / w.

17. 17. The composition of claim 16, wherein the one or more cellulose ethers comprise hydroxyethyl cellulose (HEC), or hydroxypropyl cellulose (HPC), or a mixture thereof.

18. 18. The composition of claim 16 or 17, wherein the one or more plasticizers comprise one or more polyethylene glycols.

19. 20. The composition of claim 18, wherein the one or more polyethylene glycols comprises polyethylene glycol 600.

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