System for making fat-containing skin graft therapeutic composition, fat-containing skin graft therapeutic composition and method of making same

Abstract

A system for preparing a wound treatment product is provided that includes an applicator (11) configured for applying a fat material onto a skin graft material (150). A wound treatment kit is provided that includes a skin graft material and an applicator configured to apply a fat material onto the skin graft material. A wound treatment composition is provided that includes a skin graft material and a fat material in order to promote regenerative ingrowth of cells into a wound. There is provided a method of making a wound treatment comprising providing a fat material, providing a skin graft material, and applying the fat material to the skin graft material. A method of treating a wound is provided, comprising providing a skin graft material, applying a fat material to the skin graft material, and applying a combined fat and skin graft material to the wound.

Description

Technical Field

[0001] The present disclosure generally relates to wound treatment, wound treatment products for stabilizing, protecting, and / or healing damaged tissue, and methods and systems for manufacturing wound treatment products. Background Art

[0002] Healthy skin has a variety of different functions, including protecting underlying tissues from abrasion, microbial invasion, water loss, and ultraviolet damage. The nervous system of healthy, normal skin also provides the sense of touch for touch, pressure, and vibration, the thermal senses of heat and cold, and the sense of pain. The body's thermoregulation depends on the ability of the skin to sweat and control the blood flow to the skin to increase or decrease heat loss. Healthy skin includes three distinct tissue layers: a thin outer layer of cells called the epidermis, a thicker middle layer of connective tissue called the dermis, and an inner subcutaneous tissue layer. The thin outer epidermis consists of flattened, keratinized, dead keratinocytes, forming a barrier to water loss and microbial entry. The dead keratinocytes are derived from living keratinocytes in the basal layer located above the dermis and are responsible for epithelial skin regeneration. The epidermis contains no nerves or blood vessels and obtains water and nutrients by diffusion from the dermis. The dermis lies beneath the epidermis and is mainly composed of collagen fibers produced by fibroblasts and some elastic fibers, together with water and large proteoglycan molecules, constituting the extracellular matrix (ECM). This skin layer provides mechanical strength and a matrix for the diffusion of water and nutrients. It contains blood vessels, nerves, sweat glands, hair follicles, and cells involved in immune function, growth, and repair. The subcutaneous layer consists of adipocytes, forming a thick layer of adipose tissue.

[0003] A wound can be considered a disruption of the structural and functional integrity of the skin. Thus, a "wound" can include those that result in, for example, skin cuts, tears, and / or destructive injuries such as lacerations, abrasions, incisions, punctures, avulsions, burns, or other such injuries.

[0004] Hemostasis typically follows a traumatic event, after which the main stages experienced during wound healing are: inflammation, proliferation, and remodeling. Chronic wounds can be considered those that fail to undergo the normal healing process in an orderly and timely manner. Chronic wounds generally remain in the inflammatory stage.

[0005] Typically, in the case of severe wounds, such as wounds that extend over a large area or are very deep, or wounds from large - area or severe burns, or in the case of chronic wounds, skin substitutes are usually used to assist the wound - healing process to more quickly restore at least some of the above - mentioned functions of healthy skin. Skin substitutes can be broadly regarded as a group of elements or materials capable of temporarily or permanently closing a wound. Skin substitutes can generally be classified into biological skin substitutes, synthetic skin substitutes, or hybrid skin substitutes that include both biological and synthetic components.

[0006] Biological skin substitutes generally have a more complete extracellular matrix structure, while synthetic skin substitutes can be synthesized on demand and can be tailored for specific purposes. Biological and synthetic skin substitutes each have their advantages and disadvantages. Biological skin substitutes allow for the construction of a more natural new dermis and have excellent epithelial regeneration properties due to the presence of a basement membrane. Synthetic skin substitutes can be chemically synthesized and offer the advantage of enhanced control over the scaffold components. Synthetic skin substitutes include synthetic biological layers, including, for example, synthetic collagen, or protein-based matrices, or combinations of collagen or protein-based components with silicone components. Hybrid skin substitutes can be partially synthesized or produced from living cells and partially chemically synthesized.

[0007] Biological skin substitutes can include, but are not limited to, skin grafts, including autologous skin grafts, isogeneic skin grafts, allogeneic skin grafts, xenogeneic skin grafts (such as porcine skin grafts), cadaveric allogeneic skin grafts, and amniotic tissue grafts.

[0008] Regardless of whether biological, synthetic, or hybrid skin substitutes are used, the purpose of using skin substitutes is to provide effective, timely, and scarless wound healing and to restore, as much as possible, the skin function prior to the occurrence of the wound.

[0009] Failure to protect the tissue conditions of traumatic wounds often leads to tissue drying and deterioration. In addition, many current treatment methods do not provide an adequate barrier against subsequent infections and / or do not keep the wound away from dirt and harmful pathogens. Moreover, current treatment methods are also not suitable for long-term field care. In summary, there is a need to improve methods for stabilizing and / or protecting wounds, especially in the field, to protect the patient and the wound and facilitate subsequent care.

[0010] In view of this, the inventors of the present application have found a need for a wound treatment method that is robust, lightweight, small in volume, easy to transport and handle, has a low dependence on external power sources or dedicated equipment, is modular, and can interoperate with existing care methods. In addition, there is a need for a sustainable, scalable, and safe wound treatment method for human use. Summary of the Invention

[0011] A system for preparing a wound dressing is provided, which includes an applicator configured to apply a fatty material to a skin graft material. The applicator can include one or more of a syringe, a plunger, a roller, a screw, a container, a preparation chamber, a loading chamber, an extruder, a vacuum source, a sieve, an input channel, an output channel, a blade, a frame, a fixture, and a handle.

[0012] There is provided a wound treatment kit, which includes a skin graft material and an applicator for applying a fat material onto the skin graft material. The kit may further include one or more of a syringe, a plunger, a roller, a screw, a container, a preparation chamber, a loading chamber, an extruder, a vacuum source, a sieve, an input channel, an output channel, a blade, a frame, a fixing member, a handle, and a sterile package.

[0013] There is provided a wound treatment composition, which includes a skin graft material and a fat material to promote in-growth of cell regeneration within a wound. The fat material may include a material taken from a human fat region. The skin graft material may include a biological and / or synthetic skin substitute material.

[0014] There is provided a method for preparing a wound treatment, including: providing a fat material; providing a skin graft material; and applying the fat material onto the skin graft material. Applying the fat material onto the skin graft material may include infiltrating, perfusing, impregnating, connecting, and / or binding the fat material and the skin graft material.

[0015] There is provided a wound treatment method, including: providing a skin graft material; applying a fat material onto the skin graft material; and applying the combined fat and skin graft material to a wound.

[0016] In addition, embodiments of the present disclosure are further extended to bandages for wound treatment. Thus, wound treatments, bandages, kits, and methods for stabilizing, protecting, and / or healing wounds are disclosed herein.

[0017] This Summary section provides for an introduction, in simplified form, of some concepts that are further described in the Detailed Description section below. The Summary section is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an indication of the scope of the claimed subject matter.

[0018] Additional features and advantages of the present disclosure will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the present disclosure. The features and advantages of the present disclosure may be realized and obtained by means of the instrumentalities and combinations particularly pointed out in the appended claims. These and other features of the present disclosure will become more apparent from the following description and the appended claims, or may be learned by the practice of the present disclosure as set forth hereinafter. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] These and other features, aspects, and advantages of the present disclosure will be better understood with reference to the following description, the appended claims, and the accompanying drawings.

[0020] Figure 1Schematic diagram of a system for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0021] Figure 2 Schematic diagram of an extrusion die in a system for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0022] Figure 3 Schematic diagram of a system for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0023] Figure 4 Schematic diagram of a preparation chamber according to an embodiment of the present disclosure.

[0024] Figure 5 Schematic diagram of a method for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0025] Figure 6A Schematic diagram of a system for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0026] Figure 6B Schematic diagram of a system for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0027] Figure 7 Schematic diagram of a method for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material impregnated with a fat material.

[0028] Figure 8 Schematic diagram of a system for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0029] Figure 9A Schematic diagram of an embodiment of a system for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0030] Figure 9B Schematic diagram of another embodiment of a system for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0031] Figure 9CSchematic diagram of another embodiment of a system for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0032] Figure 9D Schematic diagram of another embodiment of a system for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0033] Figure 9E Schematic diagram of another embodiment of a system for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0034] Figure 9F Schematic diagram of another embodiment of a system for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0035] Figure 10 Schematic diagram of a system for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0036] Figure 11 Schematic diagram of a method for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0037] Figure 12 Schematic diagram of a system for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0038] Figure 13 Schematic diagram of a system and corresponding method for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material with a fat material.

[0039] Figure 14A Hematoxylin and eosin staining of a skin graft material without annealing treatment.

[0040] Figure 14B Hematoxylin and eosin staining of a skin graft material without annealing treatment.

[0041] Figure 15 Schematic diagram of a method for preparing a wound dressing according to an embodiment of the present disclosure, the method including treating the skin graft material before applying the fat material.

[0042] Figure 16AIt is a hematoxylin and eosin staining image of a skin graft material that has been annealed according to an embodiment of the present disclosure.

[0043] Figure 16B It is a hematoxylin and eosin staining image of a skin graft material that has been annealed according to an embodiment of the present disclosure.

[0044] Figure 17 It is a schematic diagram of a method for preparing a wound dressing according to an embodiment of the present disclosure, the method including treating a skin graft material before applying a fat material.

[0045] Figure 18 It is a schematic diagram of another embodiment of a system for preparing a wound dressing according to an embodiment of the present disclosure, wherein the wound dressing is in the form of a skin graft material having a fat material. Detailed Description

[0046] Overview

[0047] The different embodiments of the present disclosure can be better understood by reading the following description in conjunction with the accompanying drawings, in which like reference numerals refer to like elements.

[0048] Although the present disclosure is susceptible to various modifications and alternative constructions, certain illustrative embodiments are shown in the accompanying drawings described below. However, it should be understood that it is not intended to limit the present disclosure to the specific embodiments disclosed, but rather, the intention is to cover all modifications, alternative constructions, combinations, and equivalents that fall within the spirit and scope of the present disclosure.

[0049] It should be understood that unless a term is explicitly defined in this application as having the described meaning, there is no intention to explicitly or implicitly limit the meaning of the term beyond its ordinary or common meaning.

[0050] Any element in a claim that does not explicitly recite a "means" for performing a particular function or a "step" for performing a particular function should not be construed as a "means" or "step" under 35 U.S.C. § 112.

[0051] As used in the present invention, the term "treatment" is intended to be understood by its general dictionary definition. That is, the term "treatment" broadly includes providing medical care and / or pharmaceuticals to a patient due to a disease or injury. "Treatment" can include using chemical, physical, or biological agents to protect or endow something with a particular property. Thus, "treatment" can be the medical care provided (i.e., in the form of a method or a series of prescribed acts), or it can refer to pharmaceuticals used to protect or endow something with a particular property.

[0052] The term "wound" as used in the present invention is intended to generally cover tissue damage. Thus, the term "wound" includes injuries that result in, for example, skin cuts, tears, and / or disruptions, such as lacerations, abrasions, incisions, punctures, avulsions, or other such injuries. A wound can be described by a wound of any size, shape, or magnitude. For example, a paper cut is a small paradigm, a straight incision is a relatively small level, and a blast shock that results in a large laceration covering one or more body parts is a paradigm of a relatively large wound at a larger level. However, each of the foregoing examples falls within the scope of the term "wound" as used in the present invention.

[0053] The term "wound" also includes injuries to underlying tissues, such as those caused by trauma. Thus, the term "wound" is intended to include combinations of a variety of different wounds. For example, a traumatic amputation caused by an explosion blast can generally be referred to as a wound, although it is a collection of a variety of different injuries, such as lacerations, abrasions, avulsions, injuries, and punctures. Additionally, any injury to underlying tissues caused by the foregoing explosion blast wave can further be included in the understanding of such a wound being referred to. The term "wound" is also intended to cover tissue damage caused by burns (e.g., thermal burns and / or chemical burns). In addition, the term "wound" is also intended to cover injuries caused by, for example, diabetic foot ulcers, venous leg ulcers, surgical procedures, pressure ulcers, and other causes.

[0054] Furthermore, wounds suitable for treatment by the wound treatment substances and methods disclosed by the present invention include injuries that can be located in any location, including internal, interfacial, external, interstitial, ex vivo, and / or in vivo. Examples of wounds suitable for covering with a scaffold material include cuts, chops, open wounds, tissue ruptures, pressure ulcers, dermatitis, injuries to body organ tissues, chronic wounds, battlefield wounds, necrotic wounds, acute wounds, chronic wounds, traumatic wounds, lacerations, abrasions, contusions, necrotizing fasciitis, toxic epidermal necrolysis, pressure ulcers, venous insufficiency ulcers, arterial ulcers, diabetic or neuropathic ulcers, pressure ulcers, mixed ulcers, burns, mucormycosis, vasculitic wounds, pyoderma, gangrene, and equivalents and / or combinations thereof known to those skilled in the art. Treatment of wounds in human and animal subjects can be contemplated.

[0055] The term "traumatic wound" as used herein refers to any wound caused by physical injury that damages the skin and cortical tissue. Gunshot wounds are a non-limiting example of a traumatic wound because they cause the skin to pierce (i.e., break) and rupture or otherwise damage the underlying tissue. As another non-limiting example, concussion or blast shock often results in traumatic wounds. Due to the nature of warfare and war-related damage, many (but not all) wartime wounds can be described as traumatic wounds. "Traumatic wounds" can include bleeding wounds, wounds that expose bones and / or tendons, severe burns, deep tissue wounds (e.g., asymmetric deep tissue wounds), and / or large surface area wounds.

[0056] As mentioned above, many different types of skin substitutes or skin graft materials can be used to aid the healing process of wounds and restore at least some of the above functions of healthy skin more quickly. Skin substitutes can be broadly considered as a group of elements or materials that are capable of temporarily or permanently closing wounds. Skin substitutes can generally be classified as biological skin substitutes, synthetic skin substitutes, or hybrid skin substitutes that include both biological and synthetic skin substitutes.

[0057] In this application, the terms "skin substitute", "skin graft material", "scaffold material", "graft product" or similar terms may include Kerecis TM Omega3Wound, from Atlantic cod Kerecis TM Omega3 acellular fish skin, or any other skin graft material known to be used for treating wounds, or materials similar to the above materials. The term "extracellular matrix" or "ECM" as used in the present invention refers to the non-cellular tissue material present in fish skin, which provides structural support for skin cells in addition to performing various other important functions. The ECM described in the present invention does not necessarily include a matrix material composed or re-formed entirely from extracted, purified or isolated ECM components (such as collagen). However, in some embodiments, the ECM used as a skin substitute may include a matrix material composed or re-formed entirely from extracted, purified or isolated ECM components (such as collagen).

[0058] The extracellular matrix (ECM) of vertebrates is a complex structural entity that surrounds and supports cells. The ECM consists of a complex mixture of structural proteins, the most abundant of which is collagen, as well as other specific proteins and proteoglycans. The scaffold material described in the present invention is a substantially complete acellular scaffold of natural biological ECM components from fish skin. The scaffold may also contain naturally occurring lipids from fish skin. The original three-dimensional structure, composition and function of the dermal ECM are substantially unchanged and provide a scaffold that supports cell migration, adhesion, proliferation and differentiation, thereby promoting the repair and / or replacement of tissues.

[0059] The terms "acellular", "decellularized", "decellularized fish skin", etc. used in the present invention refer to fish skin that has had a large amount of cells and nucleic acid content removed, leaving a complex three-dimensional interstitial structure of ECM. In some embodiments, "decellularized fish skin" may further require fish skin that includes omega3 polyunsaturated fatty acids (PUFAs) in addition to the complex three-dimensional interstitial structure of ECM lacking a large amount of cells and nucleic acid content.

[0060] Other scaffold materials or skin graft materials may include materials derived from mammalian skin / membranes, materials recombinantly produced from collagen materials, or artificially prepared materials. Generally, the thickness of the scaffold material is about 0.1 to 4.0 mm (i.e., cross-section), for example, a thickness of 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, or 3.5 mm. The thickness can depend on many factors, including the species of fish used as the starting material, processing, lyophilization, and / or rehydration. Of course, when the product contains more than one layer of scaffold material, the thickness can be proportionally greater.

[0061] In some embodiments, the scaffold material can be or include decellularized fish skin. Decellularized fish skin is configured as a scaffold material to support cell migration, adhesion, proliferation, and differentiation to promote tissue repair and / or replacement, as described in U.S. Patent No. 8,613,957, which was authorized on December 24, 2013, and has a filing date of October 6, 2010, the entire content of which is incorporated herein by reference. The decellularized fish skin product described in US8,613,957 can serve as a scaffold material to provide a complete scaffold for the ingrowth of endothelial cells and / or epithelial cells. The decellularized fish skin scaffold material is biocompatible and can thus be integrated by the host. Omega3Wound is a commercially available skin substitute made from the minimally processed skin of wild Atlantic cod from Iceland. The fish skin is structurally similar to human skin, having three basic layers: epidermis, dermis, and subcutaneous, and contains proteins, lipids, fatty acids, and other bioactive compounds homologous to human skin.

[0062] As described in U.S. Patent Application No. 17 / 704,539, filed on March 25, 2022, decellularized fish skin can be sliced, ground, or otherwise processed into various sizes and shapes, the content of which is incorporated herein by reference in its entirety. The size of individual ground particles can vary depending on the type and / or manner of grinding. For example, decellularized fish skin particles can be formed by a jet milling process, which is designed to produce particles below a specific size. In some embodiments, cutting, chopping, or grinding decellularized fish skin into particles can be done in a measured way to produce uniform particles or can be done roughly to produce various different-sized particles.

[0063] The scaffold material according to the present invention is obtained from intact fish skin. Any kind of fish, including bony fish or cartilaginous fish, can be used as a source of fish skin. For example, the source can be round fish (such as cod, haddock, and catfish), flatfish (such as halibut, flounder, and sole), salmon (such as chinook salmon and trout), mackerel (such as tuna), or small fish (such as herring, anchovy, king mackerel, and sardine). In certain embodiments, the fish skin is obtained from cold-water oily fish and / or fish known to contain a large amount of omega-3 oil. Examples of fish rich in omega-3 oil include salmon, European sardine, tuna, herring, cod, sardine, king mackerel, sablefish, smelt, whitefish, burbot, and certain varieties of trout.

[0064] The fish skin is removed from the fish before processing. If the fish skin is from a scaled fish species, the fish skin should be descaled to remove most of the scales or at least the hydroxyapatite on the scales. The term "removing most of the scales" or "substantially scale-free" means removing at least 95%, preferably at least 99%, more preferably 100% of the scales on the fish skin. "Substantially scale-free" fish skin can also refer to fish skin from fish species that do not have scales. Before all processing, the scales are removed using pure mechanical pressure (such as by a knife, abrasive vibration, water pressure, a dedicated descaling device using the same mechanical force as a knife or other pressure device, such as a ceramic or plastic polisher) or after some chemical treatment (such as decellularization), the scales are washed off with mechanical pressure. If the fish skin is first subjected to chemical and / or enzymatic treatment (such as treatment with X-100), the mechanical pressure usually needs to be gentle because the fish skin is more prone to tearing after decellularization. The scales can be removed in more than one step, for example, partially removed before decellularization and then further removed during and / or after decellularization. Alternatively, the scales can be removed solely by chemical treatment.

[0065] After descaling, the fish skin is optionally frozen before decellularization. It can be rapidly frozen by incubating the fish skin in liquid nitrogen or using other dedicated freezing equipment that can freeze the fish skin to -70°C or lower to preserve the collagen structure of the scaffold. The freezing process can lyse or partially lyse the cells that make up the intact fish skin and help promote the decellularization of the fish skin. If the fish skin has been frozen, it can be thawed later for further processing.

[0066] Whether the fish skin is frozen or not, it can be washed with a buffer solution before further processing. For example, it can be washed 1 to 3 times with a buffer solution optionally containing one or more antioxidants (such as ascorbic acid (such as 50 mM ascorbic acid), vitamin A, C, E, and β-carotene), antibiotics (such as streptomycin and penicillin), proteases (such as dispase II), and protease inhibitors (such as antipain, aprotinin, benzamidine, aminopeptidase inhibitor, DFP, EDTA, EGTA, leupeptin, pepstatin, phosphoramidon, and PMSF) to promote the disinfection and stabilization of the fish skin. The pH of the buffer solution can be at least 5.5, such as 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, or higher. In certain embodiments, the pH is between 7.0 and 9.0, such as between 7.5 and 8.5. The buffer solution can also be used as a medium in which the fish skin can be stored for several days to weeks or longer. In certain embodiments, the fish skin is stored in a buffer solution at a temperature of about 4°C.

[0067] After freezing and / or washing and / or storing in the buffer solution, the fish skin is treated with one or more decellularization solutions to remove cellular material, including antigenic material, from the fish skin in a manner that has minimal or no damage to the mechanical and structural integrity and the biological activity of the naturally occurring extracellular matrix.

[0068] A "decellularizing agent" is a reagent that can effectively remove a large amount of cellular and nucleic acid content from the ECM. The ECM is "decellularized" or "substantially free" of cellular and nucleic acid content (i.e., a "large amount" has been removed) when at least 50% of the active and inactivated nucleic acids and other cellular materials have been removed from the ECM. In certain embodiments, about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% of the active and inactivated nucleic acids and cellular materials are removed. For example, decellularization can be verified by testing the DNA content of the treated fish skin. The removal of nucleic acids from the ECM can be determined by, for example, histological examination of the ECM and / or by biochemical assays (such as assay, diphenylamine analysis) or by PCR.

[0069] Decellularization disrupts cell membranes and releases cellular contents. Decellularization can involve one or more physical treatments, one or more chemical treatments, one or more enzymatic treatments, or any combination thereof. Examples of physical treatments are ultrasound, mechanical agitation, mechanical massage, mechanical pressure, and freeze / thaw. Examples of chemical decellularizing agents are ionic salts (e.g., sodium azide), bases, acids, detergents (e.g., nonionic and ionic detergents), oxidizing agents (e.g., hydrogen peroxide and peroxyacids), hypotonic solutions, hypertonic solutions, chelating agents (e.g., EDTA and EGTA), organic solvents (e.g., tri(n-butyl)-phosphate), ascorbic acid, methionine, cysteine, maleic acid, and DNA-binding polymers (e.g., poly-L-lysine, polyethyleneimine (PEI), and polyamidoamine (PAMAM)). Nonionic detergents include 4-(1,1,3,3-tetramethylbutyl)phenyl polyethylene glycol, t-octylphenoxypolyethoxyethanol, poly(ethylene glycol) tert-octylphenyl ether ( X-100) (Dow Chemical). Ionic detergents include sodium dodecyl sulfate (SDS), sodium deoxycholate, X-200, and zwitterionic detergents (e.g., CHAPS). Other suitable decellularizing detergents include polyoxyethylene (20) sorbitan monooleate and polyoxyethylene (80) sorbitan monooleate (Tween 20 and 80), 3-[(3-chloroamidopropyl)-dimethylammonio]-1-propanesulfonate, octyl-β-D-glucopyranoside, and sodium dodecyl sulfate. Examples of enzymatic decellularizing agents are proteases, endonucleases, and exonucleases. Proteases include serine proteases (e.g., trypsin), threonine proteases, cysteine proteases, aspartic proteases, metalloproteases (e.g., thermolysin), and glutamic proteases. Decellularization is typically carried out at a pH of at least 5.5, such as 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, or higher. In certain embodiments, the pH is between 7.0 and 9.0, such as between 7.5 and 8.5.

[0070] One example of a decellularization step is to incubate fish skin in a solution containing 1 M NaCl, 2% deoxycholic acid, 0.02% sodium azide, and 500 ppm streptomycin. In another example, fish skin is incubated with a first decellularization solution containing a protease (e.g., 2.5 U / mL dispase II) and other components (e.g., 0.02% sodium azide). The first decellularization solution is poured off, and then the fish skin is treated with a second decellularization solution, such as a solution containing a detergent (e.g., X-100) and other components (e.g., 0.02% sodium azide). In another example, first a solution containing a detergent (e.g., The fish skin is treated with a decellularization solution of X-100) and other components (e.g., 0.02% EDTA, sodium azide, and / or deoxycholic acid), and then incubated in a second decellularization solution containing a detergent (e.g., SDS).

[0071] The decellularization step can be repeated as needed by pouring off any remaining decellularization solution, optionally washing the fish skin with a buffer solution (e.g., Hank's balanced salt solution), and then treating the fish skin again with an additional decellularization step. Once a sufficient amount of cellular material has been removed, the decellularization solution can be discarded (e.g., by aspiration or by gently pouring out the solution).

[0072] After decellularization, the fish skin can be optionally washed with water, a buffer solution, and / or a salt solution. Examples of suitable washing solutions include Dulbecco's phosphate buffered saline (DPBS), Hank's balanced salt solution (HBSS), Medium 199 (M199, SAFC Biosciences), and / or L-glutamine. The washing step is typically carried out at a pH of at least 5.5, such as 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, or higher. In certain embodiments, the pH is between 7.0 and 9.0, such as between 7.5 and 8.5.

[0073] The fish skin can be selectively bleached to improve the appearance of the final product. Bleaching can be carried out before, after, and / or simultaneously with decellularization. For example, one or more bleaching agents can be incorporated into one or more decellularization solutions and / or into one or more buffer solutions. Examples of bleaching agents include sodium sulfite, hydrogen peroxide, ammonium persulfate, potassium persulfate, and sodium persulfate. In certain embodiments, if a strong bleaching agent such as persulfate is used, bleaching and decellularization can be combined in one step, including incubating the fish skin in a mixture of one or more bleaching agents, thickeners, and a peroxide source. For example, a dry bleaching mixture can be prepared (see, e.g., the "bleaching mixture" described in Example 5), and then water, hydrogen peroxide, or a combination thereof can be added to the dry mixture to form a bleaching solution that is also sufficient for decellularization. The bleaching agent (e.g., sodium sulfite, hydrogen peroxide, ammonium persulfate, potassium persulfate, and sodium persulfate) should account for about 40-60% w / w of the dry mixture. A combination of EDTA and persulfate can be added to the mixture to accelerate bleaching and decellularization.

[0074] In certain embodiments, the concentration of EDTA in the dry mixture is about 0.25 - 5% w / w. Hydrogen peroxide can account for about 15 - 25% of the mixture; the peroxide source can be sodium percarbonate and potassium percarbonate. Sodium phosphate perhydrate and sodium carbonate or magnesium metasilicate and silicon silicate can also be used as peroxide sources. The dry mixture can also contain, for example, 1 - 10% w / w of silica and hydrated silica, and optionally one or more stearates (such as ammonium stearate, sodium stearate, and / or magnesium stearate). Additionally, the dry mixture can optionally include thickeners such as hydroxypropyl methylcellulose, hydroxyethyl cellulose, alginic acid (i.e., alginate), organic gums (such as cellulose, xanthan gum), sodium metasilicate, and combinations thereof to increase the viscosity of the bleaching / demellularization solution and protect the protein fibers from damage. Bleaching and / or bleaching plus demellularization is typically carried out at a pH of at least 5.5, such as 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0 or higher. In certain embodiments, the pH is between 7.0 and 9.0, such as between 7.5 and 8.5. After bleaching and / or bleaching plus demellularization, the fish skin is optionally washed with a solution containing L - glutamine under the above pH conditions.

[0075] In certain embodiments, the fish skin is treated with digestive enzymes. Similar to bleaching, digestion can be carried out before, after, and / or simultaneously with demellularization. Suitable enzymes include proteases such as serine proteases, threonine proteases, cysteine proteases, aspartic proteases, metalloproteases, and glutamic proteases. In certain embodiments, the digestive enzyme is a serine protease, such as trypsin. The digestive enzyme can be an enzyme that acts in an alkaline environment, limits cross - linking within the ECM, and softens the fish skin. Digestion is typically carried out at a pH of at least 5.5, such as 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0 or higher. In certain embodiments, the pH is between 7.0 and 9.0, such as between 7.5 and 8.5.

[0076] The acellular fish skin can optionally be cryopreserved. Cryopreservation can involve immersing the fish skin in a cryoprotectant solution prior to freezing. The cryoprotectant solution generally comprises a suitable buffer, one or more cryoprotectants, and optionally a solvent, such as an organic solvent that expands and contracts minimally when combined with water. Examples of cryoprotectants include sucrose, raffinose, dextran, trehalose, dimethylacetamide, dimethyl sulfoxide, ethylene glycol, glycerol, propylene glycol, 2-methyl-2,4-pentanediol, certain antifreeze proteins and peptides, and combinations thereof. Alternatively, if the acellular fish skin is rapidly frozen (flash frozen) prior to sublimation to minimize ice crystal formation during the freezing step, the fish skin can optionally be frozen in a buffer solution that does not contain a cryoprotectant. Cryopreservation is generally carried out at a pH of at least 5.5, such as 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0 or higher. In certain embodiments, the pH is between 7.0 and 9.0, such as between 7.5 and 8.5.

[0077] The acellular fish skin can be packaged in a sterile container, such as a vial or a pouch. In one embodiment, a pouch is used. For example, the fish skin can be incubated in a cryoprotectant solution, packaged in a pouch, then placed in a freeze dryer and frozen at a rate compatible with the cryoprotectant.

[0078] The acellular fish skin can be lyophilized, i.e., frozen under low temperature and vacuum conditions, so that water is sequentially removed from each ice crystal phase without ice recrystallization. During the lyophilization process, water is generally removed first by sublimation and then, if necessary, by desorption. Another method for removing excess water after processing and prior to sterilization is vacuum pressing.

[0079] In certain embodiments, the acellular fish skin is sterilized before and / or after freezing. Sterilization methods are well known in the art. For example, the acellular fish skin can be placed in an ethylene oxide chamber and treated with an appropriate ethylene oxide cycle. Other sterilization methods include sterilization with ozone, carbon dioxide, gaseous formaldehyde, or radiation (such as gamma radiation, X-rays, electron beam treatment, and subatomic particles).

[0080] As an alternative or supplement to freezing, lyophilization, and / or vacuum pressing, the acellular fish skin can be stored in a non-aqueous solution (such as alcohol).

[0081] The resulting product (scaffold material) is a sterile, collagen-based matrix that has properties that promote tissue regeneration, repair, and / or replacement (e.g., repair, regeneration, and / or growth of endogenous tissue). In some embodiments, the term "scaffold material" refers to a material comprising fish skin that has been decellularized as described above and optionally bleached, digested, lyophilized, etc. In various aspects, the term "scaffold material" can refer to a graft product that has been granulated (i.e., chopped), such as decellularized fish skin.

[0082] The scaffold material can provide a complete scaffold for supporting endothelial cells and / or epithelial cells, can be integrated by the host, is biocompatible, has insignificant calcification, and can be stored and transported at ambient temperature. The phrase "integrated by the host" in the present invention means that the cells and tissues of a patient treated with the scaffold material can grow into the scaffold material, and the scaffold material is actually integrated / absorbed into the patient's body. The term "biocompatible" refers to a material that is substantially non-toxic in the in vivo environment in which it is intended to be used and is substantially not rejected by the patient's physiological system (i.e., is non-antigenic).

[0083] This can be judged by the ability of the material to pass biocompatibility tests as described in International Organization for Standardization (ISO) Standard No. 10993 and / or United States Pharmacopeia (USP) 23 and / or United States Food and Drug Administration (FDA) Blue Book Memorandum No. G95-1, titled "Use of International Standard ISO-10993, Biological Evaluation of Medical Devices - Part 1: Evaluation and Testing". Generally, these tests measure the toxicity, infectivity, pyrogenicity, potential irritancy, reactivity, hemolytic activity, carcinogenicity, and / or immunogenicity of the material. A biocompatible structure or material does not cause a significant adverse, persistent, or escalating biological reaction or response when introduced into most patients and is distinguishable from the mild, transient inflammation that typically accompanies surgery or the implantation of foreign bodies into a living organism.

[0084] The scaffold material contains proteins from the extracellular matrix (ECM) of fish skin cells. The ECM components in the scaffold material can include, for example, structural proteins, adhesive glycoproteins, proteoglycans, non-proteoglycan polysaccharides, and matricellular proteins. Examples of structural proteins include collagen (the most abundant protein in the ECM), such as fibrillar collagens (types I, II, III, V, and XI), facit collagens (types IX, XII, and XIV), short-chain collagens (types VIII and X), basement membrane collagen (type IV), and other collagens (types VI, VII, and XIII), elastin, and laminin. Examples of adhesive glycoproteins include fibronectin, tenascin, and thrombospondin. Examples of proteoglycans include heparan sulfate, chondroitin sulfate, and keratan sulfate. An example of a non-proteoglycan polysaccharide is hyaluronic acid. Matricellular proteins are a structurally diverse group of extracellular proteins that regulate cell function through interactions with cell surface receptors, cytokines, growth factors, proteases, and the ECM. Examples include thrombospondin (TSP) 1 and 2, tenascin, and SPARC (secreted protein, acidic and rich in cysteine).

[0085] In certain embodiments, the decellularization (and other optional processing steps) does not remove all of the naturally occurring lipids from the lipid layer of the fish skin. Thus, the scaffold material can contain one or more lipids from the fish skin, particularly from the lipid layer of the fish skin. For example, the scaffold material can include up to about 25% w / w of lipids (based on the dry weight of the total scaffold material after lyophilization), such as 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, or 24% w / w of lipids. The presence of lipids in the scaffold material can be verified, for example, by extraction with an organic solvent followed by chromatography. Examples of suitable organic solvents include acetone and chloroform.

[0086] The lipids in fish skin can include, for example, fatty acyls (i.e., fatty acids, their conjugates and derivatives), glycerides, glycerophospholipids (i.e., phospholipids), sphingolipids, glycolipids, polyketides, sterol lipids (i.e., sterols), certain fat-soluble vitamins, prenol lipids, and / or polyketides. Examples of fatty acyls include saturated fatty acids (e.g., polyunsaturated fatty acids), fatty esters, fatty amides, and eicosanoids. In certain embodiments, the fatty acids include omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (which are present in high concentrations in fish oil). Other fatty acids found in fish oil include arachidic acid, eicosenoic acid, arachidonic acid, butyric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, elaidic acid, linoleic acid, alpha-linolenic acid, gamma-linolenic acid, behenic acid, erucic acid, and lignoceric acid. Examples of glycerides include mono-, di-, and tri-substituted glycerols such as monoacylglycerols, diacylglycerols, and triacylglycerols (i.e., glycerol monoesters, glycerol diesters, and glycerol triesters). Examples of glycerophospholipids include phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Examples of sphingolipids include phosphosphingolipids and glycosphingolipids. Examples of sterol lipids include cholesterol, steroids, and secosteroids (various forms of vitamin D). Examples of prenol lipids include isoprenoids, carotenoids, and quinones and hydroquinones such as vitamins E and K.

[0087] The scaffold material can be used in a dry form. Alternatively, the scaffold material can be rehydrated prior to use. In certain embodiments, one or more scaffold materials are laminated together to form a thicker scaffold material.

[0088] In some embodiments, the scaffold material can be provided in the form of particles, each particle being configured as a physical scaffold for infiltrating cells involved in wound healing / repair (such as cell ingrowth and neovascularization), thereby actively promoting wound healing. The scaffold material particles in the embodiments of the present invention are configured to advantageously retain the three-dimensional ("3D") structure of the scaffold material, which has, for example, an ECM that can be identified by histological analysis. The size of the particles can also be additionally configured to facilitate molding, packaging, or otherwise applying the particles to the wound cavity with higher precision than existing wound treatment methods.

[0089] In some embodiments, the particles of the scaffold material have a maximum size within a predetermined maximum size threshold and a minimum size threshold, which can effectively protect the matrix structure of the acellular fish skin and promote cell regeneration to grow into the wound. That is, the maximum size of the particles, such as the largest one of the length, width, and / or thickness, can be less than the maximum size, such as 1 mm, and greater than the minimum size, such as the size at which the ECM is disrupted. In some embodiments, the shredded acellular fish skin particles are obtained by providing an acellular fish skin sheet as described above, then shredding the acellular fish skin sheet and optionally sieving the shredded particles until the shredded acellular fish skin particles are within the range of the predetermined minimum and maximum size thresholds.

[0090] Biological skin substitutes can include, but are not limited to, skin grafts, including autologous skin grafts, syngeneic skin grafts, allogeneic skin grafts, xenogeneic skin grafts (such as porcine skin grafts), cadaveric allogeneic skin grafts, and amniotic tissue grafts. Some biological skin substitutes can be made of biomaterials containing intact collagen or recombinant collagen. Examples thereof include the following brands: Oasis, Matristem, Integra, and Puracol. These products are commonly referred to as matrix products by clinicians. The matrix product is inserted into the wound to attract cells to grow inward. Then, a secondary wound dressing that changes from wet to dry is applied on top of the wound dressing. The acellular fish skin described in U.S. Patent 8,613,957 is an example of such a matrix product. The acellular fish skin product described in U.S. Patent 8,613,957 can be used as a scaffold material, which provides a complete scaffold for supporting the in-growth of endothelial and / or epithelial cells.

[0091] Examples of other biological skin substitutes include those described in U.S. Patent 6,541,023, which describes the use of a porous collagen gel derived from fish skin as a tissue engineering scaffold. The preparation of the collagen gel includes grinding the fish skin. Additionally, Chinese Patent 1068703 describes a method for preparing fish skin for dressing burns, including separating the fish skin from the fish body and placing the fish skin in a preservation solution of iodine tincture, ethanol, borneol, zinc sulfadiazine, and hydrochloric acid, where the amount of hydrochloric acid is sufficient to make the preservation solution obtain a pH value of 2.5 - 3. However, these products may be difficult to handle because the product of U.S. Patent 6,541,023 is in gel form, while the product of Chinese Patent 1068703 is stored in a solution.

[0092] In addition, a variety of medical extracellular matrix products have also been derived from human skin ( RegenerativeTissueMatrix (LifeCell)); fetal bovine dermis (PRIMATRIX TMDermalRepair Scaffold(TEIBiosciences)); porcine bladder (MATRISTEM TM ExtracellularMatrixWound Sheet(MedlineIndustries, Inc.)); and porcine small intestinal submucosa( WoundMatrix(Healthpoint Ltd.)).

[0093] Examples of commercially available synthetic skin substitutes include and

[0094] U.S. Patent Publication 2003 / 0059460 discloses a hybrid polymer skin substitute material that includes synthetic and natural polymers useful for regenerating living tissue. The mixture includes a cross-linked naturally occurring polymer and a biodegradable and absorbable synthetic polymer. However, a series of complex process steps must be taken to produce the hybrid material. In addition, the resulting hybrid material includes synthetic materials and naturally occurring materials.

[0095] As described above, there is a wide variety of skin substitutes that can be used as examples of the skin substitutes according to the present disclosure. The AHRQ Technology Assessment Program (Project Number IDWNDT0818) titled "Skin Substitutes for Treating Chronic Wounds" published on February 2, 2020 identified 76 commercially available products in Table 2 on pages 9-13, but few studies have made internal comparisons of them. Each of these listed skin substitutes can be an embodiment of the skin substitute according to the present disclosure.

[0096] In various examples, a colorant may be considered for use with a skin graft material as described in U.S. Patent Application 17 / 703,650, filed on March 24, 2022, the content of which is incorporated herein by reference in its entirety. In its broadest sense, the colorant contemplated by the present invention is such a colorant, or a combination of pigments or colorants, that provides color to a skin substitute and changes or loses color based on changes in the conditions within the wound during the healing process or changes in the skin substitute. In a preferred embodiment, the colorant degrades when attacked by one or more proteases within the wound. For such a colorant, the colorant loses its color after being degraded by one or more proteases. For example, the colorant may provide a blue or purple color to the skin substitute. However, after administering a wound treatment comprising a skin substitute and a colorant, when attacked by one or more proteases within the wound, the color of the skin substitute of the wound treatment also degrades or disappears, whereby the color of the administered wound treatment changes to the original color or a different color of the skin substitute. However, the color change of the colorant is not limited to this and may include a color shift as the conditions within the wound change. For example, the color provided by the colorant may be triggered such that the original color of the skin substitute does not change upon application or addition of the colorant. However, the color change of the colorant may be triggered or caused by changes in the conditions within the wound, thereby changing the skin substitute of the wound treatment to a new or different color from the original color of the skin substitute.

[0097] In the present application, the terms "adipose material", "subcutaneous fat", "dermal adipose material", "adipose tissue", or "fat graft" may include biological components of fat, or biological components otherwise derived from fat. In various examples, the adipose material may include adipose tissue extract materials, such as materials resulting from liposuction or similar procedures. The adipose material may include one or more of adipocytes, endothelial cells, fibroblasts, B lymphocytes and T lymphocytes, macrophages, myeloid cells, pericytes, preadipocytes, smooth muscle cells, collagen, fibronectin, laminin, and stromal cells. The adipose material may also include blood, lipids, debris resulting from the rupture of adipocytes, and / or any surrounding biological components. It should be noted that visceral adipose material is not excluded from the disclosed embodiments, although the embodiments may be described with respect to subcutaneous adipose material for convenience and to reflect more common usage.

[0098] As described above, the adipose material may include an adipose tissue extract obtained by liposuction surgery. Generally, liposuction refers to a surgical procedure for removing adipose material from a part of the body using suction (such as through a cannula). Liposuction may include any known procedure for removing adipose material, such as tumescent liposuction, dry liposuction, wet liposuction, etc. In various aspects, the adipose material may include apical fat, pannicular fat, deep fat, hump fascia, sub-scar fascia, and / or another adipose layer material. The adipose material may be taken from any part of the human body having adipose material and associated tissues.

[0099] In some embodiments, the adipose material may be recently harvested or may have been stored for a longer period of time before use. Depending on the embodiment, the adipose material may be processed after extraction or may be provided directly to the skin graft material. In wound treatment according to the present disclosure, a skin graft material for use by a patient may be prepared by using adipose material extracted from the same patient, another patient, laboratory-cultured material, and / or an animal. Advantageously, using adipose material obtained from a patient having a wound to be treated can improve wound healing, provide a ready source of adipose material, and prevent allergic or similar complications.

[0100] Various embodiments and their components

[0101] Figure 1 Shown is a system 100 for preparing a wound dressing according to an embodiment of the present disclosure. The system 100 may include a syringe 110 or similar device for providing adipose material to a loading chamber 120. The loading chamber 120 may be connected to a preparation chamber 140 through an extrusion die 130, which is configured to hold a skin graft material 150 therein.

[0102] In one aspect, the system 100 may be provided as a kit or device for preparing a wound dressing for application to a patient's wound. In this regard, the skin graft material 150 may be loaded into the preparation chamber 140 through a closure 142 (in the form of a door, baffle, or similar access portion) of the preparation chamber 140. The skin graft material 150 may be held in a predetermined position in the preparation chamber 140 by using a table, clamp, closure 142, fixture, or the like.

[0103] The adipose material may be obtained from a patient or other source, such as by liposuction, through the syringe 110 or similar device. In Figure 1In an embodiment, the syringe 110 includes a syringe plunger 112 for generating positive or negative pressure in the syringe body 114 to load or unload adipose material therein through the cannula 116 or needle. The syringe 110 can be configured to cooperate with the input channel 122 of the loading chamber 120 for loading adipose material into the loading chamber 120. For example, the input channel 122 can have a length, diameter, or other dimensions that match the length, diameter, or other dimensions of the cannula 116. In some aspects, the inner diameter of the input channel 122 can be 6 millimeters or less, particularly 4 millimeters or less. In some embodiments, the input channel 122 can include an elastic material configured to elastically contract the cannula 116 such that the inner diameter of the input channel 122 is consistent with the outer diameter of the cannula 116. According to an embodiment of the present disclosure, adapting the input channel 122 and the cannula 116 can advantageously prevent any adipose material from escaping the loading chamber 120 through the input channel 122.

[0104] The loading chamber 120 can form an extrusion device by using the plunger 124, or form a similar pressure generating device configured to force the adipose material to flow out of the loading chamber 120 through the extrusion die 130. In some embodiments, the plunger 124 can be configured to apply and / or generate pressure in the loading chamber 120 by applying manual force, so that the adipose material can be manually extruded. The extrusion die 130 can be configured to shape the adipose material into smaller portions for application to the skin graft material 150 in the preparation chamber 140. In some aspects of the disclosed embodiments, applying the adipose material to the skin graft material 150 can include injecting, impregnating, mixing, or otherwise joining the adipose material and the skin graft material 150. In different embodiments, the preparation chamber 140 can be configured to directly hold the skin graft material 150 on the extrusion die 130, or configured to hold the skin graft material 150 at another predetermined position to receive the extruded adipose material.

[0105] See Figure 2 , according to some embodiments of the present disclosure, the extrusion die 230 can include a surface 232 having one or more openings 234 therethrough defined therein. The one or more openings 234 can be configured to be circular, square, rectangular, or any other shape. The minimum dimension perpendicular to the movement of the adipose material of the one or more openings can be 2 millimeters or less, 1 millimeter or less, or 0.5 millimeter or less, such that the individual portions of the adipose material will be separated and / or reduced in size for application to the scaffold material. To facilitate separating the individual portions of the adipose material, the one or more openings 234 can be provided with sharpened edges and / or blades facing the plunger 124.

[0106] On the other hand, according to Figure 3, a system 300 for preparing a wound dressing can be provided. In this system 300, a loading chamber 320 containing a fat material 326 can be connected to a preparation chamber 340 in which a skin graft material 350 is accommodated. The preparation chamber 340 may include an input channel 344 configured to cooperate with the loading chamber 320. In some examples, the loading chamber 320 may include a syringe or a syringe-like device. The input channel 344 may be configured to removably attach to the loading chamber 320 or have a shape corresponding to the end of the loading chamber 320, thereby facilitating the transfer of the fat material 326 from the loading chamber 320 to the preparation chamber 340. In some embodiments, the input channel 340 may be configured to open and close, for example, by applying a sealing element thereto or actuating a valve therein.

[0107] A screen 352 may be provided in the preparation chamber 340 between the input channel 344 and the output channel 346. The screen 352 may be configured to confine the skin graft material 350 in the preparation chamber 340 against positive or negative pressure therein while allowing the fat material 326 to pass therethrough. In some embodiments, a vacuum pump 360 may be connected to the output channel 346 for creating a negative pressure in the preparation chamber 340. The vacuum pump 360 may draw the fat material 326 from the loading chamber 320 into the preparation chamber 340 and through the skin graft material 350 and the screen 352. In this way, the fat material 326 can be applied to the skin graft material 350 to prepare a wound dressing according to the present disclosure.

[0108] In some embodiments, the vacuum pump 360 may include a peristaltic pump, a syringe, or a similar device. The loading chamber 320 may also be configured to press the fat material 326 into the preparation chamber 340 under a compressive force, for example, by actuating a plunger or a similar element, as described for the Figure 1 system 100 therein. In different aspects, the input channel 344 may be equipped with an extrusion die, a blade, or the like for separating the individual components or parts of the fat material 326 as the fat material 326 enters the preparation chamber 340.

[0109] In some embodiments, the mesh size of the sieve 352 can be 3 mm or less, 2 mm or less, or 1 mm or less. The sieve 352 can be disposed between the skin graft material 350 and the output channel 346 to prevent the skin graft material 350 from contacting or entering the output channel 346. In certain embodiments, the sieve 352 can be fixed to the preparation chamber 340, or have dimensions and a shape corresponding to those of the preparation chamber 340, such that the sieve 352 is substantially maintained in a predetermined position therein. In one aspect, another sieve 352 can be disposed between the skin graft material 350 and the input channel 344, such that when the adipose material 326 passes through the preparation chamber 340, the another sieve 352 can separate the various components or parts of the adipose material 326.

[0110] The preparation chamber 340 can include a flexible bag or a rigid chamber, and the accessible internal volume is defined by a closure (such as a door, a baffle, or a similar access part) of the preparation chamber 340. Similar to Figure 1 the system 100 in, platforms, clips, closures, jigs, etc. can be used to restrict the skin graft material 350 to a predetermined position in the preparation chamber 340.

[0111] Figure 4 An embodiment of the preparation chamber 440 is shown, which includes a flexible bag having a sealable sheet 448. The sealable sheet 448 can include an adhesive or a similar connector for closing and / or sealing the preparation chamber 440. As shown, the sieve 452 and the skin graft material 450 can be provided into the preparation chamber 440 and enclosed therein using the sealable sheet 448. In certain aspects, the sieve 452 can be configured as a tray for receiving the skin graft material 450, such as having a ridge member 454 defining its outer periphery. An input channel 444 can be provided in a first side 441 of the preparation chamber 440, opposite to an output channel 446 in a second side 443 of the preparation chamber 440.

[0112] Referring to Figure 5 the flowchart in, the operation of the system 300 for preparing a wound dressing can be better understood. As shown in the embodiment of Figure 5 , the loading chamber 520 is in the form of a syringe filled with adipose material. In a first step 502, the loading chamber 520 can be connected to the preparation chamber 540, which includes a skin graft material and a sieve, such as those described in the embodiment of Figure 4 . A vacuum pump 560 in the form of a peristaltic pump can be connected to the preparation chamber 540 through an outlet channel 546 in the form of a tube, such as connected to the preparation chamber 540 in the form of a surgical conduit.

[0113] In a second step 504, a vacuum pump 560 is activated to create a vacuum pressure in the preparation chamber 540 through an outlet channel 546. This vacuum pressure can draw the adipose material from the loading chamber 520 into the preparation chamber 540 and through the skin graft material and the screen, thereby applying the adipose material to the skin graft material. In various aspects, the outlet channel 546 can be configured to eject any adipose material drawn therethrough or can be configured to collect the adipose material, either for other uses or for single use. When the desired application level of the adipose material in the skin graft material 550 is reached, the preparation chamber 540 can be opened and the skin graft material 551 with the applied adipose material can be removed in step 506. The prepared skin graft material 551 can then be used as a wound dressing, such as by applying it to a wound, or can be stored for use on a wound at a predetermined time.

[0114] In embodiments according to Figure 6A and 6B systems 600A, 600B can be provided for preparing wound dressings using non-planar skin graft materials, aggregates of comminuted or granulated skin graft materials, or skin graft materials 650 provided in a curled or folded configuration. In some aspects similar to Figure 3 embodiments, in system 600A, a loading chamber 620A containing adipose material 626 can be connected to a preparation chamber 640 that houses a skin graft material 650. The preparation chamber 640 can include an input channel 644 that is configured to cooperate with the loading chamber 620A. In some examples, the loading chamber 620A can include a syringe or syringe-like device.

[0115] In some aspects similar to Figure 1 embodiments, system 600B can include a syringe 610 or similar device for providing adipose material to a loading chamber 620B. A loading chamber 620B containing adipose material 626 can be connected to a preparation chamber 640 that houses a skin graft material 650. The preparation chamber 640 can include an input channel 655 that is configured to cooperate with the loading chamber 620B. In some examples, the loading chamber 620B can include a sealable compartment that can receive adipose material from the syringe 610.

[0116] A vacuum pump 660 or a similar vacuum source can be connected to the output channel 646 of the preparation chamber 640 for generating a negative pressure in the preparation chamber 640. The vacuum pump 660 can draw the adipose material 626 from the loading chambers 620A, 620B into the preparation chamber 640 and through the non-planar, shredded or curled skin graft material 650. In certain embodiments, the dimensions of the input channel 655 and / or the output channel 646 can be configured to prevent the skin graft material 650 from being withdrawn or forced out of the preparation chamber 640, so that the adipose material 626 can be applied to the skin graft material 650. In certain embodiments, the vacuum pump 660 can include a syringe, such as the same syringe 610 used for loading the loading chamber or another syringe.

[0117] Reference Figure 7 to the flowchart of can better understand the operation of the systems 600A, 600B for preparing wound dressings. As Figure 7 shown in the embodiment of, in the first step 702, a syringe 710A containing adipose material 726 can be provided to the loading chamber 720. In the second step 704, the adipose material 726 from the syringe 710A can be loaded into the loading chamber 720, for example, by discharging the contents of the syringe 710 through the plunger of the syringe 710A. In the third step 706, a syringe 710B (whether the same or another syringe) can be connected to the preparation chamber 740, which includes a skin graft material 750, such as a curled skin graft material. The syringe 710B can be connected to the preparation chamber 740 through an outlet channel 746 opposite to the loading chamber 720 and can be used to generate a negative pressure in the preparation chamber 740 during the third step 706.

[0118] This negative pressure can draw the adipose material 726 from the loading chamber 720 into the preparation chamber 740 and through the skin graft material 750, thereby applying the adipose material 726 to the skin graft material 750. When the adipose material in the scaffold material 750 reaches the desired application level, the preparation chamber 740 can be opened and the skin graft material 751 with the applied adipose material can be removed in step 708. The prepared skin graft material 751 can then be used as a wound dressing, such as applying it to a wound, or can be stored for use on a wound at a predetermined time.

[0119] In different embodiments, the system 800 can be configured to move the adipose material over the skin graft material 850 contained in the preparation chamber 840 in a repetitive manner, such as according to Figure 8As shown, the fat material is drawn back and forth between two syringes 810A, 810B or a vacuum pump. By repeatedly cycling through the skin graft material 850, the fat material can be more thoroughly applied to the skin graft material 850 without increasing the amount of fat material required. This can advantageously reduce, for example, the amount of liposuction that may need to be removed from the patient.

[0120] As Figure 9A As shown, the system 900A can be configured to include two syringes 910A-1, 910A-2 or a vacuum pump, which are arranged on opposite sides of the preparation chamber 940A to move the fat material over the skin graft material 950 contained in the preparation chamber 940A in a repetitive manner, for example, by drawing the fat material back and forth. A screen 952A-1 can be provided between the syringe 910A-1 and the skin graft material 950 in the preparation chamber 940A, and a screen 952A-2 can be provided between the syringe 910A-2 and the skin graft material 950. The structure of the screens 952A-1, 952A-2 can be configured to retain the skin graft material 950 in the preparation chamber 940A while overcoming the positive or negative pressure therein, while allowing the fat material 926 to pass through. In this way, the fat material 926 can impregnate the skin graft material 950 to prepare a wound dressing according to the present disclosure. In some embodiments, the screens 952A-1 and 952A-2 can further separate the individual components or parts of the fat material 926 as the fat material 926 passes through the preparation chamber 940A, improving the application of the fat material 926 to or into the skin graft material 950.

[0121] In another related embodiment, as Figure 9BAs shown, system 900B can be configured to include two syringes 910B-1, 910B-2 or a vacuum pump, which are arranged on perpendicular (or almost perpendicular) sides of preparation chamber 940B perpendicular to each other, to move the adipose material over the skin graft material 950 contained in preparation chamber 940B in a repetitive manner, for example by drawing the adipose material back and forth. A screen 952B-1 can be disposed between syringe 910B-1 and skin graft material 950 in preparation chamber 940B, and a screen 952B-2 can be disposed between syringe 910B-2 and skin graft material 950. The structure of screens 952B-1, 952B-2 can be configured to retain skin graft material 950 in preparation chamber 940B against the positive or negative pressure therein, while allowing adipose material 926 to pass through. In this way, adipose material 926 can impregnate skin graft material 950 to prepare a wound dressing according to the present disclosure. In some embodiments, when adipose material 926 passes through preparation chamber 940B, screens 952B-1, 952B-2 can further separate the respective components or parts of adipose material 926, improving the application of adipose material 926 onto or into skin graft material 950.

[0122] In another related embodiment, as Figure 9C shown, system 900C can be configured to include two syringes 910C-1, 910C-2 or a vacuum pump, which are arranged on the same side of preparation chamber 940C, to move the adipose material over the skin graft material 950 contained in preparation chamber 940C in a repetitive manner, for example by drawing the adipose material back and forth. A screen 952C-1 can be disposed between syringes 910C-1, 910C-2 and skin graft material 950 in preparation chamber 940C, and a screen 952C-2 can be disposed on the side of skin graft material 950 opposite to screen 952C-1. The structure of screens 952C-1, 952C-2 can be configured to retain skin graft material 950 in preparation chamber 940C against the positive or negative pressure therein, while allowing adipose material 926 to pass through. In this way, adipose material 926 can impregnate skin graft material 950 by operating syringes 910C-1, 910C-2 in a repetitive manner, to prepare a wound dressing according to the present disclosure. In some embodiments, when adipose material 926 passes through preparation chamber 940C, screens 952C-1, 952C-2 can further separate the respective components or parts of adipose material 926, improving the application of adipose material 926 onto or into skin graft material 950.

[0123] In another related embodiment, as Figure 9DAs shown, the system 900D can be configured to include two syringes 910D-1, 910D-2 or a vacuum pump, which are arranged on the same side of the preparation chamber 940D to move the adipose material over the skin graft material 950 contained in the preparation chamber 940D in a repetitive manner, for example, by withdrawing and injecting the adipose material back and forth. A screen 952D-1 can be disposed between the syringe 910D-1 and the skin graft material 950 in the preparation chamber 940D, and a screen 952D-2 can be disposed on the side of the skin graft material 950 opposite to the screen 952D-1. The structure of the screens 952D-1, 952D-2 can be configured to retain the skin graft material 950 in the preparation chamber 940D while overcoming the positive or negative pressure therein, and at the same time allow the adipose material 926 to pass through. In this embodiment, a channel 970D can be selectively provided to facilitate the adipose material 926 injected by the second syringe 910D-2 to reach the bottom surface of the skin graft material 950 through the opening 975D as indicated by the arrow, which represents the movement of the adipose material 926 to the bottom surface of the skin graft material. In this way, the adipose material 926 can impregnate the skin graft material 950 from both sides to prepare a wound dressing according to the present disclosure. In some embodiments, when the adipose material 926 passes through the preparation chamber 940D, the screens 952D-1, 952D-2 can further separate the respective components or parts of the adipose material 926, improving the application of the adipose material 926 onto or into the skin graft material 950.

[0124] In another related embodiment, as Figure 9EAs shown, the system 900E can be configured to include two syringes 910E-1, 910E-2 or a vacuum pump, which are arranged on the same side of the preparation chamber 940E to move the adipose material over the skin graft material 950 contained in the preparation chamber 940E in a repetitive manner, for example, by withdrawing and injecting the adipose material back and forth. Although the first syringe 910E-1 is arranged vertically or substantially vertically with respect to the top surface of the preparation chamber 940E, the second syringe 910E-2 is angled by an angle α with respect to being perpendicular to the top surface of the preparation chamber 940E. A screen 952E-1 can be disposed in the preparation chamber 940E between the syringes 910E-1, 910E-2 and the skin graft material 950, and a screen 952E-2 can be disposed on the side of the skin graft material 950 opposite the first screen 952E-1. The structure of the screens 952E-1, 952E-2 can be configured to retain the skin graft material 950 in the preparation chamber 940E against positive or negative pressure therein while allowing the adipose material 926 to pass through. In this way, the adipose material 926 can impregnate the skin graft material 950 by operating the syringes 910E-1, 910E-2 in a repetitive manner to prepare a wound dressing according to the present disclosure. In some embodiments, when the adipose material 926 passes through the preparation chamber 940E, the screens 952E-1, 952E-2 can further separate the individual components or portions of the adipose material 926, improving the application of the adipose material 926 onto or into the skin graft material 950.

[0125] In another related embodiment, as Figure 9FAs shown, the system 900F can be configured to include two syringes 910F-1, 910F-2 or a vacuum pump, which are arranged on the same side of the preparation chamber 940F to move the adipose material over the skin graft material 950 contained in the preparation chamber 940F in a repetitive manner, for example, by withdrawing and injecting the adipose material back and forth. Although the first syringe 910F-1 is arranged vertically or substantially vertically with respect to the top surface of the preparation chamber 940F, the second syringe 910F-2 is angled α with respect to being perpendicular to the top surface of the preparation chamber 940F. A screen 952F-1 can be provided between the syringes 910F-1, 910F-2 and the skin graft material 950 in the preparation chamber 940F, and a screen 952F-2 can be provided on the side of the skin graft material 950 opposite the first screen 952F-1. In this embodiment, a channel 970F can be selectively provided to facilitate the adipose material 926 injected by the second syringe 910F-2 to reach the bottom surface of the skin graft material 950 through the opening 975F as indicated by the arrow, which represents the movement of the adipose material 926 to the bottom surface of the skin graft material. The structure of the screens 952F-1, 952F-2 can be configured to retain the skin graft material 950 in the preparation chamber 940F against the positive or negative pressure therein while allowing the adipose material 926 to pass through. In this way, the adipose material 926 can impregnate the skin graft material 950 by operating the syringes 910F-1, 910F-2 in a repetitive manner to prepare a wound dressing according to the present disclosure. In some embodiments, when the adipose material 926 passes through the preparation chamber 940F, the screens 952F-1, 952F-2 can further separate the individual components or parts of the adipose material 926, improving the application of the adipose material 926 onto or into the skin graft material 950.

[0126] In Figure 10 In another embodiment shown, the system 1000 for preparing a wound dressing can include a preparation chamber 1040, a support frame 1070, and a roller 1080. In this embodiment, a skin graft material 1050 and an adipose material 1026 can be provided to the preparation chamber 1040, and the preparation chamber 1040 can be placed against the frame 1070. The roller 1080 can be arranged on the side of the preparation chamber 1040 opposite the frame 1070 such that the roller 1080 can roll along the preparation chamber 1040 and apply pressure to the skin graft material 1050 and the adipose material 1026 therein to apply the adipose material onto the scaffold material 1050.

[0127] In some aspects, roller 1080 may have a smooth surface or a textured surface. For example, roller 1080 may include a plurality of protrusions on its surface to apply an irregular pressure on preparation chamber 1040, thereby breaking up adipose material 1026 into individual components and / or parts. Roller 1080 may include a handle or the like to, for example, allow a user to control roller 1080 and apply manual pressure thereto. In some embodiments, the interior of preparation chamber 1040 may include a textured surface facing skin graft material 1050. For example, there may be a plurality of protrusions on the inner surface of preparation chamber 1040 to apply an irregular pressure on skin graft material 1050, such that adipose material 1026 is broken up into individual components and / or parts as it is applied to skin graft material 1050.

[0128] The simplest frame 1070 may include a support surface 1072. In some embodiments, frame 1070 may include a fixture 1074 in the form of a clip or clamp. In Figure 10 the illustrated embodiment, the fixture may be movable between a first open configuration and a second closed configuration. In the closed configuration, fixture 1074 may be secured by a mating locking member such as protrusion 1076, or by another securing means configured to interact with a corresponding portion of fixture 1074.

[0129] Figure 11 An embodiment of method 1100 of using system 1000 is described. As shown, in a first step 1101, a skin graft material may be provided to the preparation chamber. In a second step 1102, adipose material may be added to the preparation chamber and then secured to the support frame in step 1103, for example, by tightening a clamping connection between the fixture and the support frame. Then, a roller may be rolled over the preparation chamber to apply the adipose material to the skin graft material in step 1104. Subsequently, the preparation chamber may be released from the frame in step 1105 and the prepared skin graft material may be removed from the preparation chamber in step 1106.

[0130] In different aspects, fixture 1074 may include a roller such that securing preparation chamber 1040 to frame 1070 as it is moved along the length of frame 1070 may allow fixture 1074 to perform both a securing and a rolling action simultaneously. In this way, system 1000 may form a grinder or a rolling press for applying pressure to skin graft material 1050 and adipose material 1026 in preparation chamber 1040.

[0131] As Figure 12As shown, the system 1200 for preparing a wound dressing may include rollers 1280 and a preparation chamber 1240, in which a skin graft material and a fat material are accommodated. The rollers 1280 may be configured to oppose each other at a predetermined distance, for example, by being mounted on a common or connectable frame 1270. Then, the rollers 1280 and the preparation chamber 1240 may be clamped or connected together such that the rollers 1280 can roll back and forth on the preparation chamber 1240, similar to a rolling mill in metalworking.

[0132] In some embodiments, the rollers 1280 and the preparation chamber 1240 may be equipped with corresponding protrusions 1282 and / or grooves to limit the movement of the preparation chamber 1240 to a predetermined path between the rollers 1280. The protrusions 1282 and / or grooves may be provided within or on the frame of the preparation chamber 1240, for example, in the form of thickened portions having a greater stiffness than the rest of the preparation chamber 1240. In this way, the preparation chamber can be more completely fixed between the rollers 1280, and the movement of the rollers 1280 on the preparation chamber 1240 can be more easily performed while maintaining precise control over the movement of the rollers 1280 and / or the preparation chamber 1240.

[0133] Referring Figure 13 , the system 1300 for preparing a wound dressing may have other configurations. In the system 1300, a loading chamber 1320 containing a fat material may be connected to a preparation chamber 1340 in which a skin graft material 1350 is accommodated. The preparation chamber 1340 may include an input channel 1344 configured to cooperate with the loading chamber 1320. In some examples, as shown, the loading chamber 1320 may include a syringe or a syringe-like device. In some embodiments, the preparation chamber 1340 may include mating parts connected to surround the skin graft material 1350 and a screen 1352.

[0134] In Figure 13 the illustrated embodiment, a plurality of output channels 1346 may be provided on a side of the preparation chamber 1340 opposite to the input channel 1344. The screen 1352 may be configured to overcome the positive pressure of the loading chamber 1320 to confine the skin graft material 1350 within the preparation chamber 1340 while allowing the fat material to pass through. In some embodiments, the fat material may impregnate the skin graft material 1350, and the excess fat material may be extruded out of the preparation chamber 1340 through the plurality of output channels 1346 and collected or disposed of. Then, the preparation chamber 1340 may be opened, and the prepared scaffold material 1351 may be taken out for use as a wound dressing.

[0135] In some embodiments, the preparation chamber 1340 may comprise a rigid material and / or be reused after cleaning and disinfection. A handle 1390 may be provided for receiving the loading chamber 1320 so that a user may obtain more geometric support or leverage when using the loading chamber 1320. In some embodiments, the handle 1390 may be configured to provide a predetermined resistance to reduce the pressure applied to the adipose material, or may be configured as an assist, such as a spring, etc., to increase the pressure applied to the adipose material.

[0136] In some embodiments, additional advantages can be achieved by a method of preparing a skin graft material to which adipose material can be applied. In particular, some components of the adipose material may be too large to infiltrate, impregnate, perfuse, or attach to the structure of existing scaffold materials, such as the collagen structure of acellular fish skin. As shown in the hematoxylin and eosin staining of the well-dried acellular fish skin scaffold material according to Figure 14A and Figure 14B , known methods of preparing the skin graft materials 1450A, 1450B may result in a tight packing of the collagen structure with openings too small to adequately infiltrate the adipose material according to the present disclosure. This may be because it is generally believed that more complete retention of the ECM structure (including pores) in the skin graft material improves wound healing, and expansion or disruption of the pores is generally considered unfavorable for wound healing.

[0137] For example, known scaffold materials can be frozen using liquid nitrogen or other specific freezing equipment, which can rapidly freeze the skin to minus 70 degrees Celsius or lower to preserve the collagen structure of the scaffold. In other common uses, the scaffold material can be lyophilized, i.e., frozen under low temperature and vacuum conditions to sequentially remove water from each ice crystal phase without ice recrystallization; or cryopreserved, i.e., immersing the fish skin in a cryoprotectant solution before freezing to preserve the collagen structure of the scaffold.

[0138] Different from the known methods of preparing scaffold materials, the method of preparing a scaffold material for a skin graft material according to the present application purposefully disrupts the collagen structure of the scaffold to promote the impregnation of the scaffold material with the adipose material, such as by annealing or rasterizing the scaffold material.

[0139] In accordance with Figure 15In the method 1500 of the embodiment, the scaffold material or skin graft material can be annealed so that the collagen structure of the scaffold material or skin graft material is damaged during the freeze-drying process. In one embodiment, the hydrated scaffold material can be provided either during the initial processing of the fish skin or during subsequent reprocessing (step 1502). The hydrated scaffold material can then be gradually frozen (step 1504). For example, the hydrated scaffold material can be cooled to 0 degrees Celsius and held at 0 degrees Celsius for 1 to 24 hours, or 2 to 12 hours, or 3 to 6 hours. In this way, the pores in the collagen structure will increase, and the pore size can be balanced with the degree of ECM damage, so that the scaffold material retains a sufficiently intact ECM, but the pore size is large enough to facilitate the impregnation of dermal adipose material. The freezing step can then reach a temperature of minus 30 degrees Celsius or lower, minus 40 degrees Celsius or lower, or minus 70 degrees Celsius or lower. During the freezing step, the pressure around the scaffold material can be maintained at atmospheric pressure or vacuum pressure, below the standard conditions for part or all of the freezing step. Then, the resulting dehydrated scaffold material with an annealed collagen structure can receive adipose material (step 1506), for example, through a system according to an embodiment of the present disclosure.

[0140] Surprisingly, as shown in the hematoxylin and eosin staining diagrams of the annealed acellular fish skin scaffold materials according to Figure 16A and Figure 16B , the pore sizes of the scaffold materials 1650A and 1650B are increased relative to the scaffold materials 1450A and 1450B, while the ECM structure is basically retained. According to the present disclosure, the increased pore size can provide unexpected and surprising new advantages, that is, it can improve the impregnation or binding with adipose material. Although it was previously thought that this would reduce the effectiveness of the skin graft material, the inventors of the present application unexpectedly found that the increased pore size of the skin graft material for use with adipose material according to the embodiment can improve wound healing, which is contrary to the current expectations in the art.

[0141] The pore size of the annealed scaffold material can be configured to accommodate adipose materials, such as including one or more of adipocytes, endothelial cells, fibroblasts, B lymphocytes and T lymphocytes, macrophages, myeloid cells, pericytes, preadipocytes, smooth muscle cells, collagen, fibronectin, laminin, stromal cells, blood, lipids, debris generated by adipocyte rupture, and / or any surrounding biological components. According to different embodiments of the present disclosure, the skin graft material can be annealed so that the skin graft material includes pores having a size, dimension, or diameter (e.g., average diameter) in the range of 10 μm to 1000 μm, 20 μm to 600 μm, 40 μm to 300 μm, 80 μm to 300 μm, 100 μm to 500 μm, 20 μm to 100 μm, or 30 μm to 80 μm. In some embodiments, annealing the scaffold material can increase the pore size of the scaffold material by at least 50%, at least 100%, at least 150%, at least 200%, or at least 1000%.

[0142] In another method 1700 according to an embodiment of Figure 17 , the scaffold material can be rasterized to disrupt the collagen structure of the scaffold material. In one embodiment, the scaffold material can be provided (step 1702), either during the initial processing of the fish skin or during subsequent reprocessing. Then, the scaffold material can be rasterized or cut (step 1704) to form a plurality of new openings in the scaffold material. The cutting can use a micro-rasterization program, such as a computer-controlled cutting machine with a blade size less than 2 mm or less than 1 mm. Then, the rasterized scaffold material can receive adipose material (step 1706), such as using a system according to an embodiment of the present disclosure. The pore size of the rasterized scaffold material is advantageously larger than the pore size of the starting scaffold material and increases the surface area for applying adipose material. Thus, according to an embodiment of the present disclosure, the application of adipose material in the scaffold material can be improved.

[0143] Rasterization according to the present disclosure can include grinding the surface of the scaffold material or the skin graft material to disrupt the surface of the scaffold material or the skin graft material for applying adipose material. In certain embodiments, rasterization can include cutting or forming openings in the scaffold material or the skin graft material using laser energy or similar means.

[0144] In another embodiment, as Figure 18As shown, a system 1800 for preparing a wound dressing in the form of a skin graft material with a fatty material is shown. The system includes a press 1801, which can be a handheld press, having opposing parts, including a first part 1810 and an opposing second part 1820. Handle portions 1815 and 1825 can be respectively provided on the first part 1810 and the second part 1820. The handle portions are configured to be grasped in a hand (or hands) or in the hands of a medical staff member and can include a gripping surface, but more importantly provide leverage during the respective pivoting movements of the first part 1810 and the second part 1820. Alternatively, the handle can be actuated by a robotic mechanism. The opposing parts 1810, 1820 can pivot at a hinge pivot point 1811, providing movement in the direction of arc β. The upper part 1810 has a convex pressing part with a convex pressing surface 1830, while the lower part 1820 has a concave pressing part 1840 with a concave pressing surface 1845. However, in a different embodiment, the upper part can have a concave part with a concave pressing surface, and the lower part can have a convex pressing part with a convex pressing surface. Alternatively, in another embodiment, the opposing pressing surfaces can be parallel planes, or substantially parallel planes.

[0145] In Figure 18 an embodiment, a syringe 1810 contains a fatty material 1826. The upper part 1810 also includes a narrow channel 1831 passing through the convex pressing part 1830. The skin graft material 1850 can be placed within the pressing area, in this case on the concave pressing surface 1845, although the opposing surface can also be configured to receive the skin graft material 1850. When closing the press 1801 or before closing, the syringe plunger 1812 is actuated so that the fatty material 1826 passes through the channel 1831 and contacts the skin graft material 1850. The opposing parts 1810, 1820 can be pressed together, applying force to the fatty material 1826 to prepare a wound dressing according to the present disclosure. The opposing parts 1810, 1820 can be relatively closed or opened to force the fatty material 1826 to penetrate the skin graft material 1850.

[0146] In certain embodiments, additional advantages can be achieved by using a kit that includes the system of the present disclosure and a corresponding skin graft material. These kits can be provided as sterile, single-use kits for wound dressing. When in use, the kit can be opened, the skin graft material can be cut or arranged into a desired shape, fatty material can be obtained from a patient, the fatty material can be applied to the skin graft material using the system of the present disclosure, and then the resulting skin graft material with the fatty material can be applied to the wound.

[0147] Subject to departures from the spirit and scope defined by the claims of the present invention, those skilled in the relevant art who have read this disclosure can make various changes and / or modifications to the inventive features shown in the present invention for the illustrated embodiments and to other applications of the principles of the present invention, and these are all considered to be within the scope of this disclosure. Therefore, although the present invention has disclosed multiple aspects and embodiments, other aspects and embodiments can also be envisioned. The present invention only describes certain components and methods, yet many methods and components similar or equivalent to those described in the present invention can be used to implement the embodiments of this disclosure.

[0148] It should also be understood that the systems, apparatuses, products, kits, methods, and / or processes according to certain embodiments of the present disclosure may include, incorporate, or otherwise contain the properties, features (e.g., components, members, elements, parts, and / or portions) described in other embodiments disclosed and / or described in the present invention. Therefore, the various features of certain embodiments can be compatible with, combined with, included in, and / or incorporated into other embodiments of the present disclosure. Therefore, the disclosure of certain features with respect to a particular embodiment of the present disclosure should not be construed as limiting such features to being applied to or contained in a particular embodiment. On the contrary, it should be understood that other embodiments may also include such features, members, elements, parts, and / or portions without departing from the scope of the present disclosure.

[0149] In addition, unless a feature is described as requiring combination with another feature, any feature in the present invention can be combined with any other feature of the same or different embodiments disclosed in the present invention. In addition, various well-known aspects of exemplary systems, methods, devices, etc. are not described in particular detail in the present invention to avoid obscuring the aspects of the exemplary embodiments. However, these aspects can also be considered in the present invention.

[0150] This disclosure provides various examples, embodiments, and features that can improve the relevant performance. Unless explicitly stated, or unless these examples, embodiments, and features are mutually exclusive, the various examples, embodiments, and features disclosed herein should be understood to be combinable with other examples, embodiments, or functions described herein.

[0151] In addition to the above, further embodiments and examples also include the following listed embodiments, including the first group of embodiments of a system for preparing a wound dressing, the second group of embodiments of a wound dressing kit, the third group of embodiments of a wound dressing composition, the fourth group of embodiments of a method for preparing a wound dressing for a patient, the fifth group of embodiments of a method for treating a wound, the sixth group of embodiments of a wound dressing composition, and the seventh group of embodiments of a method for preparing a wound dressing for a patient. It should be noted that each of the groups of embodiments and examples listed below can be combined with any of the embodiments and examples of other groups.

[0152] 1. A system for preparing a wound dressing, the system comprising an applicator configured to apply a fatty material to a skin graft material.

[0153] 2. The system according to any one of item 1 above or any one of items 3 - 36 below or a combination thereof, further comprising a preparation chamber configured to retain the skin graft material therein.

[0154] 3. The system according to any one of items 1 - 2 above or any one of items 4 - 36 below or a combination thereof, wherein the applicator comprises one or more of a syringe, a plunger, a roller, a screw, and a container.

[0155] 4. The system according to any one of items 1 - 3 above or any one of items 5 - 36 below or a combination thereof, wherein the applicator comprises an extruder.

[0156] 5. The system according to any one of items 1 - 4 above or any one of items 6 - 36 below or a combination thereof, wherein the extruder comprises a loading chamber configured to receive the fatty material through an input channel, a plunger located at a first end of the loading chamber, and an extrusion die located at a second end of the loading chamber opposite the first end, wherein the extrusion die connects the loading chamber and the preparation chamber, and the plunger is configured to be able to force the fatty material from the loading chamber through the extrusion die and into the preparation chamber.

[0157] 6. The system according to any one of items 1 - 5 above or any one of items 7 - 36 below or a combination thereof, wherein the inner diameter of the input channel is 4 millimeters or less.

[0158] 7. The system according to any one of items 1 - 6 above or any one of items 8 - 36 below or a combination thereof, wherein the input channel comprises an elastic material configured to substantially seal the input channel onto a needle or cannula.

[0159] 8. The system according to any one of items 1 - 7 above or any one of items 9 - 36 below or a combination thereof, wherein the diameter of the plunger is substantially equal to the inner diameter of the loading chamber.

[0160] 9. The system according to any one of items 1 - 8 above or any one of items 10 - 36 below or a combination thereof, wherein the extrusion die comprises one or more openings connecting the loading chamber and the preparation chamber, and the diameter of each opening is 1 millimeter or less.

[0161] 10. The system according to any one of items 1 - 9 above or any one of items 11 - 36 below or a combination thereof, wherein the extrusion die comprises one or more blades facing the plunger.

[0162] 11. The system according to any one or combination of items 1-10 above or items 12-36 below, wherein one or more blades define the profile of one or more openings of the extrusion die.

[0163] 12. The system according to any one or combination of items 1-11 above or items 13-36 below, wherein one or more vanes are disposed in one or more openings of the extrusion die.

[0164] 13. The system according to any one or combination of items 1-12 above or items 14-36 below, wherein the preparation chamber includes a fixture for fixing the skin graft material.

[0165] 14. The system according to any one or combination of items 1-13 above or items 15-36 below, wherein the fixture is configured to fix the skin graft material to the extrusion die.

[0166] 15. The system according to any one or combination of items 1-14 above or items 16-36 below, further comprising: an output channel located at a second side of the preparation chamber opposite the first side, configured to cooperate with a vacuum source; and a screen disposed in the preparation chamber; wherein the vacuum source is configured to create a vacuum in the preparation chamber to draw the adipose material out of the loading chamber and through the skin graft material in the preparation chamber.

[0167] 16. The system according to any one or combination of items 1-15 above or items 17-36 below, wherein the vacuum source includes a peristaltic pump.

[0168] 17. The system according to any one or combination of items 1-16 above or items 18-36 below, wherein the aperture size of the screen is 1 millimeter or less.

[0169] 18. The system according to any one or combination of items 1-17 above or items 19-36 below, wherein the loading chamber includes a syringe.

[0170] 19. The system according to any one or combination of items 1-18 above or items 20-36 below, wherein the screen is disposed between the skin graft material and the output channel.

[0171] 20. The system according to any one or combination of items 1-19 above or items 21-36 below, including another screen disposed between the skin graft material and the input channel.

[0172] 21. The system according to any one or combination of items 1-20 above or items 22-36 below, wherein the preparation chamber includes a sealable bag.

[0173] 22. The system according to any one of items 1 - 21 above or any one of items 23 - 36 below or a combination thereof, wherein the output channel includes a tube configured to be used with a peristaltic pump.

[0174] 23. The system according to any one of items 1 - 22 above or any one of items 24 - 36 below or a combination thereof, wherein the mesh is larger than the skin graft material.

[0175] 24. The system according to any one of items 1 - 23 above or any one of items 25 - 36 below or a combination thereof, wherein the mesh has different sieve hole sizes.

[0176] 25. The system according to any one of items 1 - 24 above or any one of items 26 - 36 below or a combination thereof, further comprising: a support frame; and rollers configured to provide pressure to press the preparation chamber against the support frame.

[0177] 26. The system according to any one of items 1 - 25 above or any one of items 27 - 36 below or a combination thereof, wherein the roller includes a handle for operating the roller.

[0178] 27. The system according to any one of items 1 - 26 above or any one of items 28 - 36 below or a combination thereof, wherein the support frame includes a fixture for fixing the preparation chamber thereto.

[0179] 28. The system according to any one of items 1 - 27 above or any one of items 29 - 36 below or a combination thereof, wherein the fixture includes a clamping arm movable between a first open position and a second closed position, and the clamping arm projects from the surface of the support frame.

[0180] 29. The system according to any one of items 1 - 28 above or any one of items 30 - 36 below or a combination thereof, wherein the roller includes a plurality of protrusions on its surface.

[0181] 30. The system according to any one of items 1 - 29 above or any one of items 31 - 36 below or a combination thereof, wherein the support frame is configured to fix the preparation chamber between the roller and another opposing roller.

[0182] 31. The system according to any one of items 1 - 30 above or any one of items 32 - 36 below or a combination thereof, wherein the roller and the opposing roller are elastically fixed to the frame such that the distance between the roller and the opposing roller can vary according to the resistance provided by the preparation chamber.

[0183] 32. The system according to any one of items 1 - 31 above or any one of items 33 - 36 below or a combination thereof, wherein the mesh screen divides the preparation chamber into a first part and a second part.

[0184] 33. The system according to any one of items 1 - 32 above or any one of items 34 - 36 below or a combination thereof, including an opposing vacuum source opposite to a vacuum source, configured to create a counter - vacuum in the preparation chamber so that the fatty material is drawn back through the skin graft material in the preparation chamber.

[0185] 34. The system according to any one of items 1 - 33 above or any one of items 35 - 36 below or a combination thereof, wherein the frame includes a plurality of protrusions on its surface.

[0186] 35. The system according to any one of items 1 - 34 above or item 36 below or a combination thereof, wherein the preparation chamber includes a sealable container.

[0187] 36. The system according to any one of items 1 - 35 above or a combination thereof, wherein the applicator includes a heating element and / or a heat - conductive material.

[0188] 37. A wound - treatment kit, comprising: a skin graft material; and an applicator configured to apply a fatty material to the skin graft material.

[0189] 38. The kit according to any one of item 37 above or any one of items 39 - 40 below or a combination thereof, wherein the applicator includes one or more of a syringe, an extruder, a loading chamber, a preparation chamber, and / or a pressure source.

[0190] 39. The kit according to any one of items 37 - 38 above or item 40 below or a combination thereof, wherein one or more of the syringe, the extruder, the loading chamber, the preparation chamber, and / or the pressure source include fluid connectors for fluidly connecting them together.

[0191] 40. The kit according to any one of items 37 - 39 above or a combination thereof, further comprising a package that seals at least the skin graft material and the applicator in a sterile state.

[0192] 41. A wound - treatment composition, comprising a skin graft material and a fatty material.

[0193] 42. The composition according to any one of item 41 above or any one of items 43 - 60 below or a combination thereof, wherein the skin graft material includes a biological material.

[0194] 43. The composition according to any one of items 41 - 42 above or any one of items 44 - 60 below or a combination thereof, wherein the biological material includes fish skin.

[0195] 44. A composition according to any one or combination of items 41 - 43 above or items 45 - 60 below, wherein the biomaterial includes porcine skin.

[0196] 45. A composition according to any one or combination of items 41 - 44 above or items 46 - 60 below, wherein the skin graft material includes an extracellular matrix material.

[0197] 46. A composition according to any one or combination of items 41 - 45 above or items 47 - 60 below, wherein the skin graft material includes acellular skin.

[0198] 47. A composition according to any one or combination of items 41 - 46 above or items 48 - 60 below, wherein the skin graft material includes a synthetic scaffold material.

[0199] 48. A composition according to any one or combination of items 41 - 47 above or items 49 - 60 below, wherein the skin graft material includes a plurality of crushed particles.

[0200] 49. A composition according to any one or combination of items 41 - 48 above or items 50 - 60 below, wherein the pore size of the skin graft material is larger than that of adipocytes.

[0201] 50. A composition according to any one or combination of items 41 - 49 above or items 51 - 60 below, wherein the adipose material includes subcutaneous fat and / or visceral fat.

[0202] 51. A composition according to any one or combination of items 41 - 50 above or items 52 - 60 below, wherein the adipose material includes dermal fat.

[0203] 52. A composition according to any one or combination of items 41 - 51 above or items 53 - 60 below, wherein the adipose material includes liposuction aspirate.

[0204] 53. A composition according to any one or combination of items 41 - 52 above or items 54 - 60 below, wherein the adipose material includes a plurality of crushed particles.

[0205] 54. A composition according to any one or combination of items 41 - 53 above or items 55 - 60 below, wherein the skin graft material includes a plurality of pores.

[0206] 55. A composition according to any one or combination of items 41 - 54 above or items 56 - 60 below, wherein the pores of the skin graft material include adipose material located therein.

[0207] 56. A composition according to any one or combination of items 41 - 55 above or items 57 - 60 below, wherein the skin graft material is impregnated or infused with a fat material.

[0208] 57. A composition according to any one or combination of items 41 - 56 above or items 58 - 60 below, wherein the fat material accounts for at least 50% of the total weight of the composition.

[0209] 58. A composition according to any one or combination of items 41 - 57 above or items 59 - 60 below, wherein the fat material accounts for at least 50% of the total weight of the composition.

[0210] 59. A composition according to any one or combination of items 41 - 58 above or item 60 below, wherein the pore size of the skin graft material is larger than that of fat cells.

[0211] 60. A composition according to any one or combination of items 41 - 59 above, wherein the fat material includes subcutaneous fat and / or visceral fat.

[0212] 61. A method for preparing a wound dressing for a patient, comprising providing a skin graft material and applying a fat material to the skin graft material.

[0213] 62. A method according to any one or combination of item 61 above or items 63 - 80 below, wherein the step of providing the skin graft material includes providing the skin graft material to a preparation chamber.

[0214] 63. A method according to any one or combination of items 61 - 62 above or items 64 - 80 below, further comprising the step of preparing the skin graft material to receive the fat material.

[0215] 64. A method according to any one or combination of items 61 - 63 above or items 65 - 80 below, wherein the step of preparing the skin graft material includes increasing the pore size and / or surface area of the skin graft material by annealing, rasterizing, and / or pulverizing.

[0216] 65. A method according to any one or combination of items 61 - 64 above or items 66 - 80 below, wherein annealing the skin graft material includes freezing the skin graft material to form ice crystals therein.

[0217] 66. A method according to any one or combination of items 61 - 65 above or items 67 - 80 below, wherein the skin graft material is frozen at a temperature of 0°C for 1 to 24 hours.

[0218] 67. A method according to any one of items 61 - 66 above or items 68 - 80 below, or a combination thereof, wherein a cryopreserved skin graft material is used to increase the pore size of the skin graft material.

[0219] 68. A method according to any one of items 61 - 67 above or items 69 - 80 below, or a combination thereof, wherein rasterization includes cutting the skin graft material with a blade of 1 mm or less.

[0220] 69. A method according to any one of items 61 - 68 above or items 70 - 80 below, or a combination thereof, wherein rasterization includes applying laser energy to the skin graft material to form openings therein.

[0221] 70. A method according to any one of items 61 - 69 above or items 71 - 80 below, or a combination thereof, wherein rasterization includes applying an abrasive to the skin graft material to form openings therein.

[0222] 71. A method according to any one of items 61 - 70 above or items 72 - 80 below, or a combination thereof, further comprising the step of obtaining adipose material.

[0223] 72. A method according to any one of items 61 - 71 above or items 71 - 80 below, or a combination thereof, wherein the step of obtaining adipose material includes performing liposuction.

[0224] 73. A method according to any one of items 61 - 72 above or items 74 - 80 below, or a combination thereof, wherein the step of obtaining adipose material includes separating the adipose material from the liposuction fluid obtained from liposuction.

[0225] 74. A method according to any one of items 61 - 73 above or items 75 - 80 below, or a combination thereof, wherein the step of obtaining adipose material includes cutting the adipose material into a predetermined size.

[0226] 75. A method according to any one of items 61 - 74 above or items 76 - 80 below, or a combination thereof, wherein the step of obtaining adipose material includes crushing the adipose material into particles of a predetermined size.

[0227] 76. A method according to any one of items 61 - 74 above or items 76 - 80 below, or a combination thereof, wherein the step of applying the adipose material to the skin graft material includes applying pressure to the adipose material and / or the skin graft material such that the adipose material and the skin graft material are pressed together or pulled together under the pressure.

[0228] 77. A method according to any one or combination of items 61 - 76 above or items 78 - 80 below, wherein the step of applying pressure to the adipose material and / or the skin graft material includes applying pressure for a predetermined period of time.

[0229] 78. A method according to any one or combination of items 61 - 77 above or items 79 - 80 below, wherein the step of applying the adipose material to the skin graft material includes impregnating and / or perfusing the skin graft material with the adipose material.

[0230] 79. A method according to any one or combination of items 61 - 78 above or item 80 below, wherein the step of applying the adipose material to the skin graft material includes impregnating the pores of the skin graft material with the adipose material.

[0231] 80. A method according to any one or combination of items 61 - 79 above, wherein the step of applying the adipose material to the skin graft material includes applying thermal energy to the adipose material and / or the skin graft material.

[0232] 81. A method of treating a wound, the method comprising: providing a skin graft material; applying an adipose material to the skin graft material to form a combined adipose and skin graft material; and applying the combined adipose and skin graft material to the wound.

[0233] 82. A method according to any one or combination of item 81 above or items 83 - 90 below, wherein the step of applying the combined adipose and skin graft material to the wound occurs within 12 hours after the step of applying the adipose material to the skin graft material.

[0234] 83. A method according to any one or combination of items 81 - 82 above or items 84 - 90 below, wherein the step of applying the combined adipose and skin graft material to the wound occurs within 12 hours after the step of removing the adipose from the patient.

[0235] 84. A method according to any one or combination of items 81 - 83 above or items 85 - 90 below, wherein the adipose material is taken from the patient having the wound.

[0236] 85. A method according to any one or combination of items 81 - 84 above or items 86 - 90 below, further comprising the step of cutting the skin graft material into the shape of the wound.

[0237] 86. A method according to any one of items 81 - 85 above or items 87 - 90 below, or a combination thereof, wherein the skin graft material and / or the fat material comprises a plurality of comminuted particles, and the step of applying the combined fat and skin graft material to the wound further comprises shaping the combined fat and skin graft material to fit the wound.

[0238] 87. A method according to any one of items 81 - 86 above or items 88 - 90 below, or a combination thereof, wherein the step of applying the combined fat and skin graft material to the wound comprises sealing the wound.

[0239] 88. A method according to any one of items 81 - 87 above or items 89 - 90 below, or a combination thereof, wherein the wound is sealed by a bandage and / or suture that at least partially covers the combined fat and skin graft material.

[0240] 89. A method according to any one of items 81 - 88 above or item 90 below, or a combination thereof, wherein the step of applying the combined fat and skin graft material to the wound is carried out within 2 hours after the step of applying the fat material to the skin graft material.

[0241] 90. A method according to any one of items 81 - 89 above, or a combination thereof, wherein the step of applying the combined fat and skin graft material to the wound occurs within 2 hours after the fat material is removed from the patient.

[0242] 91. A wound treatment composition comprising a skin graft material having a plurality of pores, wherein the average diameter of the pores is 20 to 1000 microns. Optionally, the skin graft material is annealed, rasterized, and / or comminuted to increase the pore size and / or surface area of the skin graft material, or the skin graft material is annealed by freezing the skin graft material to form ice crystals to increase the pore size and / or surface area of the skin graft material.

[0243] 92. A composition according to any one of item 91 above or items 93 - 100 below, or a combination thereof, wherein the skin graft material comprises a biomaterial.

[0244] 93. A composition according to any one of items 91 - 92 above or items 94 - 100 below, or a combination thereof, wherein the biomaterial comprises fish skin.

[0245] 94. A composition according to any one of items 91 - 93 above or any one of items 95 - 100 below, or a combination thereof, wherein the biomaterial comprises pig skin.

[0246] 95. A composition according to any one or combination of any of the above items 91 - 94 or items 96 - 100 below, wherein the skin graft material comprises an extracellular matrix material.

[0247] 96. A composition according to any one or combination of any of the above items 91 - 95 or items 97 - 100 below, wherein the skin graft material comprises acellular skin.

[0248] 97. A composition according to any one or combination of any of the above items 91 - 96 or items 98 - 100 below, wherein the skin graft material comprises a synthetic scaffold material.

[0249] 98. A composition according to any one or combination of any of the above items 91 - 97 or items 99 - 100 below, wherein the average diameter of the pores is from 20 to 600 microns.

[0250] 99. A composition according to any one or combination of any of the above items 91 - 98 or item 100 below, wherein the average diameter of the pores is from 20 to 300 microns.

[0251] 100. A composition according to any one or combination of any of the above items 91 - 99, wherein the average diameter of the pores is from 20 to 100 microns.

[0252] 101. A method of preparing a wound dressing for a patient, comprising: providing a skin graft material; and treating the skin graft material to increase the pore size and / or surface area of the skin graft material.

[0253] 102. A method according to any one or combination of any of the above item 101 or items 103 - 110 below, wherein the step of treating the skin graft material comprises increasing the pore size and / or surface area of the skin graft material by annealing, rasterizing, and / or comminuting.

[0254] 103. A method according to any one or combination of any of the above items 101 - 102 or items 104 - 110 below, wherein annealing the skin graft material comprises freezing the skin graft material to form ice crystals therein.

[0255] 104. A method according to any one or combination of any of the above items 101 - 103 or items 105 - 110 below, wherein the skin graft material is frozen at a temperature of 0 °C for 1 to 24 hours.

[0256] 105. A method according to any one or combination of any of the above items 101 - 104 or items 106 - 110 below, wherein the frozen skin graft material is used to increase the pore size of the skin graft material.

[0257] 106. A method according to any one or combination of items 101 - 105 above or items 107 - 110 below, wherein rasterization includes cutting the skin graft material with a blade of 1 millimeter or less.

[0258] 107. A method according to any one or combination of items 101 - 106 above or items 108 - 110 below, wherein rasterization includes applying laser energy to the skin graft material to form openings therein.

[0259] 108. A method according to any one or combination of items 101 - 107 above or items 109 - 110 below, wherein rasterization includes applying an abrasive to the skin graft material to form openings therein.

[0260] 109. A method according to any one or combination of items 101 - 108 above or item 110 below, wherein the skin graft material includes a biomaterial.

[0261] 110. A method according to any one or combination of items 101 - 109 above, wherein treating the skin graft material is for increasing the average diameter of the pores to a range of 20 to 1000 micrometers.

[0262] Those skilled in the art can recognize the interchangeability of the various features disclosed. In addition to the variations described herein, those of ordinary skill in the art can also mix and match other known equivalents of each feature to prepare wound dressings and use the same manufacturing methods in accordance with the principles of the present disclosure. Those skilled in the art can understand that the features described herein can be applied to other types of wound treatment and general healthcare applications.

[0263] Although a system or method for preparing a wound dressing of a skin graft material containing a fat material is disclosed in some preferred embodiments and examples, those skilled in the art will understand that the present disclosure can extend beyond the disclosed embodiments to other alternative embodiments and / or uses of a system or method for preparing a wound dressing of a skin graft material containing a fat material, as well as obvious modifications and equivalents. The scope of the present system or method for preparing a wound dressing of a skin graft material containing a fat material should not be limited to the disclosed embodiments above, but should be determined only by a fair reading of the claims that follow.

Claims

1. A system for preparing a wound treatment product, the system comprising an applicator configured to apply a fatty material onto a skin graft material.

2. The system according to claim 1, further comprising a preparation chamber configured to retain the skin graft material therein.

3. The system according to claim 1 or 2, wherein The applicator includes one or more of a syringe, a plunger, a roller, a screw, and a container.

4. The system according to any one of claims 1 to 3, wherein, The applicator includes an extruder.

5. The system according to any one of claims 1 to 4, wherein, The extruder includes: a loading chamber configured to receive the fatty material through an input channel; a plunger located at a first end of the loading chamber; and an extrusion die located at a second end of the loading chamber opposite the first end; wherein the extrusion die connects the loading chamber and the preparation chamber, and the plunger is configured to be able to force the fatty material from the loading chamber through the extrusion die and into the preparation chamber.

6. The system according to any one of claims 1 to 5, wherein, The extrusion die includes one or more openings connecting the loading chamber and the preparation chamber, and the diameter of each of the openings is 1 millimeter or less.

7. The system according to any one of claims 1 to 6, wherein, The extrusion die includes one or more blades facing the plunger, wherein the one or more blades define the contour of one or more openings of the extrusion die, or the one or more blades are disposed in one or more openings of the extrusion die.

8. The system according to any one of claims 1 to 7, wherein The preparation chamber includes a fixture for fixing the skin graft material, wherein the fixture is configured to fix the skin graft material on the extrusion die.

9. The system according to any one of claims 1 to 7, further comprising: an output channel located at a second side of the preparation chamber opposite the first side, the output channel being configured to cooperate with a vacuum source; and a screen disposed in the preparation chamber; wherein the vacuum source is configured to create a vacuum in the preparation chamber, causing the fatty material to be drawn out of the loading chamber and pass through the skin graft material in the preparation chamber.

10. The system according to any one of claims 1 to 9, wherein, The loading chamber includes a syringe.

11. The system according to any one of claims 1 to 9, wherein, The preparation chamber includes a sealable bag.

12. The system according to any one of claims 1 to 11, further comprising: a support frame; and a roller configured to provide pressure to press the preparation chamber against the support frame.

13. The system according to claim 12, wherein, The roller includes a handle for operating the roller.

14. The system according to any one of claims 1 to 13, further comprising an opposing vacuum source opposite the vacuum source, the opposing vacuum source being configured to create an opposing vacuum in the preparation chamber, thereby causing the fatty material to be drawn back through the skin graft material in the preparation chamber.

15. The system according to claim 2, wherein The applicator includes a plurality of syringes, each syringe being configured to inject the fatty material into the preparation chamber, and optionally, each syringe being configured to draw the fatty material out of the preparation chamber.

16. The system according to claim 2, wherein, The applicator includes two opposing pressure members including a first pressure member and a second pressure member configured to pivot relative to each other at a hinge point, each pressure member having a respective pressure surface, the pressure surfaces facing each other and defining the preparation chamber, and the opposing pressure surfaces providing pressure to press the fatty material into the skin graft material.

17. The system according to claim 16, wherein The opposing pressure surfaces include a convex pressure surface and a concave pressure surface.

18. The system according to claim 17, wherein, The system includes a syringe disposed on the back of a first pressure member, wherein the first pressure member includes a protruding pressure surface and has a passage therethrough to allow the fat material ejected from the syringe to enter the preparation chamber.

19. A method for preparing a skin graft material, comprising: providing a skin graft material; providing the system according to any one of claims 1 to 18; using the system to apply a fat material to the skin graft material.

20. A wound treatment kit, comprising: a skin graft material; an applicator according to any one of claims 1 to 18, configured to apply a fat material to the skin graft material.

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