• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
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    • 专利摘要:
    METHOD FOR MAKING A PLURALITY OF PLATES FOR USE IN A DEVICE IN ORDER TO OBTAIN A SKIN GRAFT. These are methods of fabricating components for use in devices to produce a skin graft material. The invention provides fabrication methods for creating plates, preferably metal plates, for use in preparing skin grafts. Fabrication methods as described in this document are useful for fabricating boards for use in devices as described below. The methods of the invention result in plates for use in harvesting skin grafts produced by applying blisters to a donor site. The methods of the invention involve generating a plurality of boards having substantially flat mating surfaces from a material, preferably a metallic material. Preferably, at least one of the boards has a substantially uniform thickness across the board. In certain embodiments, each of the plurality of plates has a substantially uniform thickness across each plate and/or relative to one another. The plurality of plates can be generated from the same material or from different materials.
    公开号:BR112014013363B1
    申请号:R112014013363-8
    申请日:2012-12-07
    公开日:2021-05-04
    发明作者:Sameer Ahmed Sabir；Jeffrey Cerier；Andrew Ziegler
    申请人:3M Innovative Properties Company；
    IPC主号:
    专利说明:

    RELATED ORDER REFERENCE
    [001] The present application claims the benefit of and priority to Non-Provisional Application No. 13/346,329, filed January 9, 2012, which claims the benefit of and priority to Interim Application No. US 61/567,946, filed on 7 January December 2011, the contents of each of which are incorporated herein by reference in their entirety. FIELD OF THE INVENTION
    [002] The invention, in general, relates to devices for generating and transferring substantially flat skin grafts. BACKGROUND INFORMATION
    [003] The skin is the largest organ in the human body, representing approximately 16% of a person's total body weight. As it interfaces with the environment, the skin acts as an anatomical barrier against pathogens and other substances in the environment. The skin also provides a semi-permeable barrier that prevents excessive fluid loss while ensuring that essential nutrients are not removed from the body. Other skin functions include insulation, temperature regulation and feel. Skin tissue can be subjected to various forms of damage, including burns, trauma, disease, and depigmentation (eg, vitiligo).
    [004] Skin grafts are commonly used to repair skin damage. Traditional skin grafting is a surgical procedure in which a section of skin is removed from an area of a person's body (autograft), removed from another human source (allograft), or removed from another animal (xenograft), and transplanted into a recipient site of a patient, such as an injury site. As with any surgical procedure, skin grafting involves certain risks. Complications can include graft failure, skin graft rejection, infections at the donor or recipient site, or donor autograft sites releasing fluid and blood as they heal. Some of these complications (eg, graft failure and skin graft rejection) can be mitigated by using an autograft instead of an allograft or xenograft.
    [005] A problem encountered when using an autograft is that the skin is taken from another area of a person's body to produce the graft, resulting in trauma and injury generation at the donor site. In general, the size of the graft matches the size of the recipient site, and thus a large recipient site requires the removal of a large section of skin from a donor site, resulting in increased pain and discomfort and longer healing time. Additionally, as the size of the section of skin removed from the donor site increases, so does the possibility of infection.
    [006] In addition, skin grafts are typically difficult to obtain due to the tendency of the skin layer to be cut to curl or fold over itself or the surgical instrument (eg, dermatome), thereby compromising the integrity of the graft and making it unsuitable for use. This tendency to fold/curl is particularly problematic the thinner the layer being obtained, such as the epidermal layer.
    [007] Although techniques have been developed to obtain smaller micrografts that can be transferred over a substrate for expansion before transplantation, such micrografts tend to cluster together or may turn or bend during cutting, thus compromising the integrity of the micrograft so that it will not grow properly on the substrate. As such, multiple attempts to cut are usually required before a suitable flat graft or micrograft is obtained, thereby producing multiple wound sites, resulting in extreme discomfort, longer healing time and an increased risk of infection. SUMMARY
    [008] The invention provides methods for generating components for use in devices for producing skin graft material. The invention provides for the fabrication of methods for creating plates, preferably metal plates, for use in preparing skin grafts. Fabrication methods as described herein are useful for fabricating boards for use in devices as described below.
    [009] The methods of the invention result in plates for use in harvesting skin grafts produced by applying blister to a donor site. The methods of the invention involve generating a plurality of plates that have substantially flat mating surfaces of a material, preferably a metallic material. Preferably, at least one of the boards is of substantially uniform thickness across the board. In certain embodiments, each of the plurality of plates is of substantially uniform thickness across each plate and/or relative to one another. The plurality of plates can be generated from the same material, or from different materials.
    [010] A plurality of coupling members for coupling the plurality of plates together in a stacked configuration are preferably generated from the same material of at least one or more of the plate members so that the coupling members are substantially uniform in thickness relative to each other and the at least one plate member, and contain substantially the same flat surface relative to each other and the at least one of the plate member.
    [011] According to an aspect of the invention, a plurality of boards are manufactured from the same raw material sheet material. For example, a single sheet material raw material is divided into a plurality of sections that are uniform in size and shape relative to one another, with each section corresponding to an individual plate member. At least one opening (e.g., hole or slot) is formed in each of the plate members so that the openings are in concentric alignment when the plate members are mounted in a stacked configuration.
    [012] In certain embodiments, the plurality of coupling members for coupling the plate members together in a stacked configuration are also formed from the same plate raw material from which the plate members are generated. The fabrication of the coupling members does not substantially change the flat surface of the plates, so that the plates are form-fittingly stackable and subsequently movable relative to one another. Coupling members are disposed between the plate members. Coupling members may be disposed along the outer surface of the plate members, or between one or more openings (e.g., holes or slots) formed within each plate. In certain respects, the coupling members form a frangible section between the plates that is broken by moving the plates relative to one another in operation, as described below. Optionally, a portion of the plate material in or around the coupling location is removed to accommodate at least a portion of the coupling member and form a depression in or around the frangible section.
    [013] The preferred methods for manufacturing the plates for use in skin graft generator devices involve obtaining one or more plates of substantially uniform thickness and forming holes in the plates that align by stacking. The plates preferably have integral coupling members that do not substantially change the thickness of the plates and allow coupling of the plates through frangible interlocking. In operation, the plates are moved in order to break the coupling and cut a graft from a skin blister formed by the device into which the plates are placed. Preferably, there are three plates, with a central plate having openings (e.g. holes or slits) that form a cutting surface. In operation, the boards are moved so that the cut surface interacts with bubbles that protrude through aligned openings in a board below. Ideally, the coupling members are substantially uniform in shape and size and the frangible linkage is laser welded, but it can also be a mechanical stamp, a mechanical perforation, a solder, epoxy or other adhesive, formed through mechanical compression, snap fit, tongue and groove, strut and shank, frangible pin or other known connectors.
    [014] Plates fabricated as described in this document are useful in a device to reliably generate skin micrografts in a single attempt. A device of the invention is configured to generate a plurality of substantially flat micrografts in a single cutting motion. The devices of the invention additionally have the ability to simultaneously transfer generated micrografts onto a substrate. The devices of the invention are particularly well suited to generating and transferring a plurality of substantially flat epidermal micrografts.
    [015] In certain aspects, the invention provides a device that includes a body having a bottom surface configured for placement on the skin, a mechanism for raising at least one blister in the skin, and a cutter configured to cut formed blisters in order to produce grafts for transplantation.
    [016] The cutter may include a plurality of boards, each board having an arrangement of openings (eg an arrangement of holes or slots). In certain embodiments, the openings are substantially cylindrical in shape. The openings in the arrays are of a size to facilitate the production of a plurality of grafts from formed blisters. Apertures can range in size from about 1 mm to about 12 mm in diameter. In a particular embodiment, the openings are no larger than about 2 mm in diameter.
    [017] At least one of the boards is mobile in relation to the other boards. The plurality of boards in the cutter are configured so that a substantially flat graft (i.e., one that is not rolled, folded, or bunched) is produced.
    [018] The mechanism for lifting the at least one skin blister can be a vacuum source, a heat source (eg, a light source or warm air) or a combination of both.
    [019] Once the bubble(s) is(are) generated, a removable substrate is applied to the bubble to simultaneously transfer/retain the bubble by cutting. The substrate may include an adhesive to facilitate attachment of the blister to the substrate.
    [020] The device of the invention may additionally include a strap to securely couple the device against a skin surface such as the inner thigh or buttocks. The strap can be adjustable in size or it can be a fixed size. In certain embodiments, the strap is a strap/loop clip. In other embodiments, the strap is a metal or plastic cuff configured for attachment around the upper thigh.
    [021] In another aspect, the invention provides a device for obtaining a skin graft that includes a hollow body having a bottom surface configured for placement on the skin, a mechanism for raising at least one blister and a plurality of plates, being that each plate includes an array of holes configured so as to maintain the integrity of a graft produced by cutting the erected blister.
    [022] In certain embodiments, the openings in the orifice arrangement of each plate are substantially cylindrical in shape and are of a size to facilitate production of a substantially flat graft. For example, holes can range in size from 1mm to 12mm in diameter, or any specific value within such range. In a particular embodiment, the openings in the orifice arrangements are not greater than about 2 mm in diameter.
    [023] The mechanism for lifting the at least one skin blister can be a vacuum source, a heat source (eg, a light source or warm air), or a combination of both.
    [024] A substrate detachably connected to the body of the device comes into direct contact with the blister(s) generated so that upon cutting the blister, the cut portion of the skin is secured to the substrate. The substrate may include an adhesive to facilitate attachment of the blister to the substrate.
    [025] The device may additionally include a strap to securely couple the device against a skin surface such as the inner thigh or buttocks. The strap can be adjustable in size, or it can be a fixed size. In certain embodiments, the strap is a strap/loop clip. In other embodiments, the strap is a metal or plastic cuff configured for attachment around the upper thigh.
    [026] In yet another aspect, the invention provides a cutting device that includes a first plate that has at least one opening, a second plate that has at least one opening, the second plate being secured to said first plate, and a third plate having at least one opening, the third plate being secured to said second plate. At least one of the boards is mobile relative to the other boards. For example, the second plate can be movable with respect to the first and/or third plates. In other embodiments, the third plate may be stationary in operation with respect to at least one of said first and second plates. In certain embodiments, the second plate is secured to said first plate through at least one frangible section. The frangible section is broken by moving said plates in relation to each other. The frangible coupling of the plate members to each other can be accomplished using a mechanical stamping technique, a mechanical punching technique, spot welding, an epoxy, an adhesive, mechanical compression, a press-fit assembly, a tongue and groove assembly, a stay and rod assembly, a frangible pin, or any combination thereof.
    [027] At least one of the openings in the first, second or third plate defines a cutting surface. In certain embodiments, the cutting surface on one of the boards engages a cutting surface on at least one other of said boards in operation (i.e., when at least one of the boards is moved relative to the other boards). In certain embodiments, the opening in at least one of the plates moves relative to the openings in at least another of said plates to thereby perform a cutting action.
    [028] In certain embodiments, the first, second and third plates each include a plurality of openings that are concentrically aligned with one another in an origin position, and offset relative to one another in an operating position (ie when at least one of the tiles moves relative to the other tiles).
    [029] These and other aspects of the devices of the invention are described in the Figures, description and claims below. BRIEF DESCRIPTION OF THE DRAWINGS
    [030] Figure 1 is a drawing that shows the anatomy of the skin.
    [031] Figure 2A is a schematic that depicts the components of an exemplary embodiment of a blister collection device, according to the invention; Figure 2B is a schematic depicting the components of an exemplary embodiment of a blister generation module for coupling with the blister collection device of Figure 2A.
    [032] Figures 3A to 3C are diagrams that depict the assembly procedure of the components pictured in Figures 2A and 2B. Figure 3A is a schematic depicting the step of assembling cutter module in top housing. Figure 3B is a schematic that depicts the step of mounting bottom housing and tightening screws. Figure 3C is a schematic that depicts the step of assembling bubble module.
    [033] Figure 4 is a diagram that depicts the components of an exemplary embodiment of a cutter assembly for use in devices according to the invention.
    [034] Figure 5A is a schematic that depicts an exemplary embodiment of a device, according to the invention, in a bubble generation mode; Figure 5B is a schematic depicting an exemplary embodiment of a device according to the invention in a blister collection mode.
    [035] Figures 6A to 6C are schematics that depict the bubble generation steps using device mode depicted in Figure 5A. Figure 6A is a schematic that depicts the step where the MBGED is placed at the donor site and the strip is secured. Figure 6B is a diagram depicting the step in which vacuum and heat are applied to generate bubbles. Figure 6C is a schematic depicting the step where the mounting bubble module is removed.
    [036] Figure 7A to 7C are schematics that depict the bubble harvesting steps using the device mode depicted in Figure 5B. Figure 7A is a schematic depicting the step of securing Tagaderm to the bubbles by applying light pressure. Figure 7B is a schematic that depicts the step where the bubbles are cut. Figure 7C is a schematic depicting the Tagaderm removal step. DETAILED DESCRIPTION
    [037] The skin consists of 2 layers. The outer layer or epidermis is derived from the ectoderm, and the thicker inner layer, or dermis, is derived from the mesoderm. The epidermis makes up about 5% of the skin, and the remaining 95% is the dermis. Figure 1 provides a diagram showing the anatomy of the skin. The skin varies in thickness depending on the anatomical location, sex and age of the individual. The epidermis, the outermost of the two layers, is a stratified squamous epithelium consisting essentially of melanocytes and keratinocytes in progressive stages of differentiation from deeper to more superficial layers. The epidermis has no blood vessels; therefore, it must receive nutrients by diffusion from the underlying dermis through the basement membrane, which separates the two layers.
    [038] Recently, research has shown that pluripotent stem cells are also located in the epidermal layer (Balaji et a., Biology and Medicine, 2(2): 57-67 (2010)). Epidermal grafting has been shown in the literature to have significant applications in a number of different indications, including wound care and vitiligo. However, an epidermal graft is difficult to perform in practice due to the extreme thickness (100 microns) and wet consistency of the tissue, as well as concerns related to morbidity at the donor site.
    [039] The dermis is a more complex structure. It is composed of 2 layers, the more superficial papillary dermis and the deeper reticular dermis. The papillary dermis is thinner, including loose connective tissue that contains capillaries, elastic fibers, reticular fibers, and some collagen. The reticular dermis includes a thicker layer of dense connective tissue containing larger blood vessels, tightly interwoven elastic fibers, and coarse branching collagen fibers arranged in layers parallel to the surface. The reticular layer also contains fibroblasts, mast cells, nerve endings, lymph vessels, and some epidermal appendages. Surrounding the dermis components is a gel-like background substance composed of mucopolysaccharides (essentially hyaluronic acid), chondroitin sulfates, and glycoproteins.
    [040] In a graft, the characteristics of the donor site that are more likely to be maintained after grafting into a recipient site is a function of the thickness of the dermal component of the graft. However, thicker grafts require more favorable conditions for survival due to the requirement for increased revascularization. It has been found, however, that a substantially epidermal graft in accordance with the invention is more likely to adapt to the characteristics of the recipient site, presumably due to the presence of pluripotent stem cells in the epidermal layer. INTEGRATED DEVICES TO GENERATE AND TRANSFER MICRO GRAFTS
    [041] In one aspect, the invention relates to an integrated device for generating micrografts and transferring micrografts. More specifically, the invention relates to a device for generating substantially flat micrografts and for preparing a surgical dressing to facilitate the presentation of the micrografts in a patient in need thereof. The device of the invention can be used to prepare any type of skin graft, such as an epidermal skin graft, a split thickness graft, or a full thickness graft. However, the device of the invention is particularly well suited to preparing skin grafts including only or substantially only the epidermal layer of skin. The device of the invention can be used for autografts, allografts or xenografts. In preferred embodiments, the grafts are autografts.
    [042] Referring now to Figures 2A and 2B, device 200 includes a top housing 201, a cutter assembly 202, and a base housing 203. cutter 202. The top housing further includes a strap 211 for coupling device 200 (once assembled) against a skin surface. The strap can be adjustable in size or it can be a fixed size. The top housing 201 is configured to removably receive a blister generating module 210 that includes a blister generating device 204 and an adapter plate 205 (Figure 2B).
    [043] Figures 3A to 3C depict the assembly of the device 200. As shown in Figure 3A, the cutter assembly 202 is inserted into the top housing 201. The top housing 201 is then coupled to the base housing 203 through of one or more threaded screws 212 which are received by a corresponding threaded hole 218 in base housing 203, so that cutter assembly 202 is disposed between top housing 201 and bottom housing 203 (Figure 3B). As shown in Figure 3C, the blister generation module 210 is then inserted into the top housing 201. In certain embodiments, the bottom of the adapter plate 205 that interfaces with the top housing 201 includes a gasket around the perimeter plate 205 to create an airtight seal between adapter plate 205 and top housing 201 when mated together. The blister generating device 204 of the blister generating module 210 is coupled to an opening 205a within the adapter plate 205. In certain embodiments, a gasket is disposed within the opening 205a to form an airtight seal between the generating device. bubble 204 and adapter plate 205 when mated together.
    [044] Referring now to Figure 4, the cutter assembly 202 of the device 200 is shown. The cutter assembly 202 includes a bottom plate 202a, a middle plate 202b, and a top plate 202c, each of which includes an array of apertures 214 (e.g., holes or slots) (sometimes referred to herein as an array of slots). orifice 214). One or more openings of orifice array 214 in bottom 202a, middle 202b and/or top 202c plates define an edge or surface 215. Preferably, one or more openings in orifice array 214 at least of middle plate 202b define a edge or surface 215 (Figure 4). The three plates are mounted in a stacked configuration with the middle plate 202b being coupled to the bottom plate 202a, and the top plate 202c being coupled to the middle plate 202b. One or more of the plates 202a, 202b and 202c are configured to be movable in a lateral direction relative to each other. For example, the middle plate 202b may be movable laterally relative to the bottom plate 202a, the top plate 202c, or both. The top plate 202c may be movable relative to the middle plate 202b, the bottom plate 202a, or both. In certain embodiments, the one of more of the plates 202a, 202b and 202c are configured to move laterally within a fixed distance relative to one another.
    [045] The middle plate 202b and/or top plate 202c can be coupled to the respective plates thereof in the stacked configuration through at least one frangible section that serves to keep the plates in alignment until a lateral force is applied to the middle plate 202b and/or top 202c, which breaks the frangible section(s) and allows lateral movement of the plates relative to one another. In a particular embodiment, at least the middle plate 202b is coupled to the bottom plate 202a through at least one frangible section. The at least one frangible section is configured to rupture when a lateral force is applied to the middle plate 202b, allowing the middle plate 202b to move in a lateral direction relative to the bottom plate 202a, the top plate 202c, or both. Preferably, the middle plate 202b is configured to move laterally within a fixed distance relative to the bottom plate 202a and/or top plate 202c. In a particular embodiment, the middle plate 202b includes one or more slots or channels 216 that are configured to receive a pin 217 that extends vertically from the bottom plate 202a. Pin 217 is received at one end of channel 216 when frangible section is intact, and slides laterally within channel 216 to the opposite end when frangible section is ruptured, so that lateral movement of plate 202b relative to plate 202a and /or 202c is fixed by movement of pin 217 within channel 216.
    [046] One or more coupling members may be arranged between the plates to form frangible sections, as described in further detail below. The one or more coupling members are disposed between the openings within the orifice array 214. Alternatively, the one or more coupling members are disposed between the plates on the outside of the orifice array 214. another can be performed using a mechanical stamping technique, a mechanical punching technique, spot welding, photoengraving, an epoxy, an adhesive, mechanical compression, a snap-fit assembly, a tongue-and-groove assembly, a strut and rod assembly, a frangible pin or any combination thereof.
    [047] In certain embodiments, the medial plate 202b and/or top plate 202c can be coupled to the respective plates thereof in the stacked configuration through at least one elastic member or spring member that serves to keep the plates in alignment until a lateral force is applied to the middle plate 202b and/or top plate 202c which allows the elastic/spring section(s) to flex and allow lateral movement of the plates relative to one another. Upon removal of the lateral force, the elastic/spring sections relax, which allows the plates to return to their original positions so that the hole arrangements 214 between the plates are again in concentric alignment. The one or more elastic coupling members or spring members may be disposed between the openings within the orifice arrangement 214. Alternatively, the one or more elastic coupling members or spring members may be disposed between the plates on the outside of the hole arrangement. hole 214.
    [048] Preferably, the arrays of holes 214 of the bottom 202a, middle 202b and top 202c plates include holes that are substantially similar in size and substantially cylindrical in shape. The size of holes in each hole arrangement 214 will depend on the size of graft needed, with larger holes being used in each plate to produce larger grafts. In certain embodiments, the holes in hole arrangement 214 range between 1 mm and 12 mm in diameter, or any specific value within the range. For example, the diameter of holes in hole array 214 of one or more of plates 202a, 202b and 202c may be 1mm, 1.5mm, 2mm, 2.5mm, 3mm, 3.5mm, 4 mm, 4.5mm, 5mm, 5.5mm, 6mm, 6.5mm, 7mm, 7.5mm, 8mm, 8.5mm, 9mm, 9.5mm, 10mm, 10.5mm, 11mm, 11.5mm or 12mm. In certain embodiments, holes in hole array 214 vary in size and/or shape between bottom plate 202a, middle plate 202b, and/or top plate 202c. Once the plates 202a, 202b and 202c of the cutter assembly 202 are assembled (i.e., in the stacked configuration), the hole arrangement 214 of each of the plates 202a, 202b and 202c is aligned. In a particular embodiment, orifice arrangements 214 of plates 202a, 202b and 202c are concentrically aligned.
    [049] The device 200 has two modes of operation: 1) a bubble generation mode (Figure 5A); and 2) a blister collection mode (Figure 5B). As shown in Figure 5A, the blister generation mode includes assembly with the blister generation module 210. The blister generation module 210 is removed from the device assembly for blister collection mode (Figure 5B). To produce and harvest a plurality of substantially flat micrografts, the device 200 in blister generation mode (i.e., with blister generation module 210 as shown in Figure 5A), is placed in a donor site 220 such as a thigh. of a patient (Figure 6A). A strap 211 is used to hold the device 200 in place against the skin surface of the donor site 220. The blister generating device 204 is activated by turning/moving the handle 204a of the blister generating device 204. The blister generating device 204. bubble 204 uses a vacuum component, a heating component, or a combination thereof, to lift skin blisters. An exemplary heating component is a light source. In a particular embodiment, the mechanism is a combination of a vacuum component and a heating component.
    [050] In certain embodiments, the blister generating device 204 is a suction blister device for suction blister graft. Suction blister graft involves erecting a skin blister and then cutting away the raised blister. An exemplary suction bubble grafting technique is shown in Awad, (Dermatol Surg, 34(9): 1186 to 1193, 2008), the contents of which are incorporated by reference herein in its entirety. This article also shows various devices used to form suction bubbles. A suction bubble device is also described in Kennedy et al. (U.S. 6,071,247), the contents of which are incorporated by reference into this document in its entirety. An exemplary device is the Negative Pressure Skin Suction System commercially available from Electronic Diversities (Finksburg, MD).
    [051] A device for lifting a suction bubble typically operates through the use of suction chambers that are attached to a patient's skin. An instrument typically contains a power supply, a vacuum pump, temperature controls and all related controls to operate multiple suction chambers. The suction chambers are connected to the console via a flexible connection. Each of the chambers is controlled by a preset temperature control to provide a favorable skin heating temperature. The two chambers share a common adjustable vacuum source that affects all chambers equally.
    [052] The chamber heating system provides light heating of an orifice plate of the device, which is in direct contact with the patient's skin surface. The negative pressure chamber is made of a majority of plastic components, with two removable screw caps. The top cover is fitted with a clear vision lens so that the actual bubble formation can be observed. The opposite end of the chamber is fitted with a removable orifice plate that is placed on the patient's skin. As this plate is simply threaded onto the end of the chamber, multiple plates with different opening patterns can be rotated as desired.
    [053] The interior of the device is heated and illuminated through an array of low voltage incandescent lamps. This lamp arrangement is controlled from the instrument console temperature controller, cycling as needed to maintain the set point temperature. Heat from these lamps is radiated and conducted to the orifice plate, which then heats the patient's skin. The chamber is connected to the console via a composite vacuum and low voltage electrical system. Quick-connects are used for the electrical and vacuum system to facilitate removal and storage.
    [054] The Negative Pressure Instrument console is a self contained ventilation cooled unit that is designed to operate at 120 VAC 60 Hz power. The vacuum is provided by an industrial quality diaphragm type vacuum pump, which has the capacity of a typical vacuum of 20 in Hg (0 to 65 kpa) at 0 CFM. An analog controller that is preset to 40 °C provides temperature control for each suction chamber. This provides precise control of orifice plate temperature. The instrument console has built-in adjustments that allow the user to recalibrate the temperature setting if desired. Other temperatures can be preset if desired. The front panel includes a vacuum bleeder adjustment and a vacuum gauge to regulate the vacuum in both chambers. The front panel of the console also contains the connections for the camera mounts.
    [055] The application of moderate negative pressure from the blister generating device 204 causes the patients' skin to be gently extracted through the concentrically aligned orifice arrangements 214 of the plates 202a, 202b and 202c in the cutter assembly 202 ( Figure 6B). Such action results in the generation of a plurality of upright microbubbles 221, particularly epidermal microbubbles. Bubbles 221 may or may not be filled with fluid. The plurality of suction bubbles 221 generated are of uniform size, approximately the size of the openings/holes in the orifice arrays 214 of the three plates of the cutter assembly 202, and are evenly spaced according to the configuration of the holes in the array. hole 214 such that a plurality of substantially flat microbubbles 221 are generated. The skin and blister area are generally undamaged and patient discomfort is minimal.
    [056] Once the substantially flat microbubbles 221 are erected/generated, the device is converted to bubble collection mode by removing the bubble generating module 210 from the top housing 201, thereby exposing the orifice arrangement 214 on the top plate 202c of the cutter assembly 202. At least a portion of the raised microbubbles 221 protrude through the top of the orifice array 214, as shown in Figures 6B and 6C. A substrate 219 is applied to the surface of the orifice array 214 as shown in Figures 5B and 7A so that the substrate 219 is in direct contact with the raised bubbles 221.
    [057] To cut the upright bubbles 221, the knob 213 is rotated in a clockwise or counterclockwise direction (Figure 7B). Handle 213 is coupled to middle plate 202b of cutter assembly 202 in a configuration that translates rotational movement of handle 213 into lateral movement of middle plate 202b. The lateral force applied to the middle plate 202b through the handle 213 causes the middle plate 202b to move in a lateral direction relative to the bottom plate 202a and/or top plate 202c, thereby un-aligning the orifice arrangements 214 between plates 202a, 202b and 202c. The lateral displacement of the orifice array 214 from the middle plate 202b causes the cut surface 215 defined by one or more holes in the orifice array 214 to cut the raised bubbles 221. As the raised bubbles 221 are cut, they are simultaneously transferred /retained in substrate 219 in the same configuration as generated within orifice array 214, resulting in a substrate containing a plurality of micrografts that are oriented and evenly spaced on substrate 219 (i.e., a substrate containing a plurality of micrografts substantially plans).
    [058] Certain embodiments of device 200 integrate consumable/single-use components (eg substrate 219 and/or cutter assembly 202) and reusable, sterilizable or clean components (eg top housing 201, base housing 203 and bubble generation module 210, thereby providing a reliable system that is easy to maintain. All device 200 components that come into contact with the donor tissue and/or recipient (both single-use and reusable components) must be sterile/sterilized to reduce the risk of infection.
    [059] In certain embodiments, substrate 219 includes an adhesive on one side that facilitates the attachment of bubbles to the substrate. The substrate material may have intrinsic adhesive properties or alternatively one side of the substrate may be treated with an adhesive material, for example a spray adhesive such as LEUKOSPRAY (Beiersdoerf GmbH, Germany). The substrate may be a deformable, non-resilient material. A deformable non-resilient material refers to a material that can be manipulated, for example, stretched or expanded, from a first configuration to a second configuration and, once in the second configuration, there is no residual stress on the substrate. Such materials can be stretched to an expanded configuration without returning to their original size. Such deformable non-resilient materials tend to be soft, hard or both soft and hard. Softness is measured on the durometer scale. An example of such a material is a soft polyurethane. A soft polyurethane is produced as follows. Polyurethanes, in general, usually have soft and hard segments. The hard segments are due to the presence of phenyl bridges. In a soft polyurethane, the phenyl bridge is replaced by an aliphatic one, which is more flexible as the 6 carbon rings on the bridge do not have double bonds. Therefore, all threads are soft. On the Durometer Scale, a soft polyethylene is rated around Shore 80A. Other materials suitable for use with the device 200 of the invention include low density polyethylene, linear low density polyethylene, polyester copolymers, polyamide copolymers, and certain silicones. In a particular embodiment, substrate 219 is Tegaderm™.
    [060] Ultimately, the substrate containing the plurality of evenly spaced (i.e. substantially flat) oriented micrografts is applied to a recipient of a patient's site. Prior to application of the grafts to the recipient site, the site is prepared to receive the grafts using any technical procedure known in the art. Necrotic, fibrous or avascular tissue must be removed. The technique used to prepare the site will depend on the damage to the recipient site. For example, epidermal tissue, if present at the recipient site, can be removed to prepare the area for receiving micrografts. Burnt or ulcerated sites may not require removal of epidermal tissue, although some site cleaning or other site preparation can be done. Wounds should be shredded and then allowed to granulate for a few days before applying the grafts. Most of the granulation tissue must be removed as it has a tendency to harbor bacteria. Applying silver sulfadiazine to the wound for 10 days before grafting greatly reduces the bacterial count.
    [061] The size of the area at the recipient site can be about the same size as the area of the substrate containing micrografts adhered to it. This size will usually be larger than the area of original graft tissue that was removed from the donor site to form the micrografts. Damaged or depigmented skin can be dermabraded with sandpaper or other rough material. Alternatively, the epidermal tissue can be removed from the recipient site by forming one or more blisters over the area to be treated, for example, a suction blister or a freezing blister, and the raised epidermal blister tissue can then be removed by cutting or another procedure.
    [062] The substrate having the substantially flat micrografts can be placed over the area to be treated to form a dressing. A portion of the substrate that has the micrografts can be positioned over the area to be repaired, for example, the area from which epidermal tissue has been scraped or removed for re-pigmentation. The substrate can be fixed in place over the treatment area, for example, with the use of tape or the like. The substrate can be removed after sufficient time has elapsed to allow fixation and growth of the micrografts in the treatment area, for example, several days to a few weeks. MANUFACTURING UNIFORM COMPONENTS FOR USE IN INTEGRATED DEVICES OF THE INVENTION
    [063] The invention further relates to methods for manufacturing uniform components for use in the integrated devices of the invention.
    [064] In order to generate substantially flat micrografts, the components within the cutter assembly 202 must be substantially uniform with respect to one another. In particular, the flat surfaces of the components within the cutter assembly 202 must be substantially uniform.
    [065] In certain aspects, one or more coupling members are used to create a frangible coupling between at least two of the plate members 202a, 202b and 202c. Coupling members are disposed between two or more of the plate members to form a frangible section which is broken by moving said plates relative to one another as previously described. The tolerance for any inconsistency between the flat surfaces of the coupling members and one or more of the plate members and/or inconsistent dimensions (e.g., width) between the coupling members and one or more of the plate members is very low and may result in non-flat, non-uniform micrografts and device malfunction.
    [066] Inconsistencies between the flat surfaces of different sheet material raw materials, methods of manufacturing templates for the coupling members and/or plates, and methods of finishing the coupling members and/or plates may each , increasing tolerance stacks beyond an acceptable level, thereby decreasing the efficiency and functioning of the device and resulting in micrografts that are unusable, and increasing patient discomfort/suffering.
    [067] The accumulated variations in the production dimensions of the coupling members, variations in the production dimensions of the plate members and variation in the spacing between plate members, can each increase the stacking tolerance and decrease the operation of the device. In order to optimize tolerances within the cutter assembly 202, the plurality of coupling members are preferably formed from the same sheet material raw material as at least one plate member in the cutter assembly 202. In a particular embodiment , the plurality of coupling members and at least the middle plate member 202b in the cutter assembly 202 are preferably formed from the same sheet material raw material (e.g., a single sheet material raw material). The formation of the coupling members and the middle plate member 202b from the same sheet metal stock ensures a uniform thickness between the coupling members and between the coupling members and plate member 202b, and guarantees flat and mating surfaces. uniforms between the coupling members and plate member 202b, thereby decreasing tolerance stacks within the cutter assembly 202 and ensuring proper device operation.
    [068] The plate members 202a, 202b and 202c can be formed from the same material or from different materials relative to one another, as long as the materials used result in substantially flat mating surfaces between the three plates. Preferably, plate members 202a, 202b and 202c are formed of a metallic material (e.g., the same metallic material or different metallic materials).
    [069] In certain embodiments, each of the plate members 202a, 202b and 202c is formed from the same sheet material raw material, preferably a single sheet material raw material. One or more openings (e.g., holes or slots) are formed within each plate member to form orifice arrangements 214 that align when the plate members are assembled, as previously described. In certain embodiments, coupling members are formed from the same sheet stock from which the plurality of plate members are generated. The formation of the coupling members and plate members from the same sheet metal raw material ensures uniformity in thickness among and between the coupling members and plate members, and evenly flat mating surfaces between the coupling members and members. of board, thereby decreasing stacking tolerance within the cutter assembly 202 and ensuring device operation.
    [070] The coupling members can be of any shape or dimension sufficient to couple the plates together without obstructing the holes in the hole arrangements 214 through which the suction bubbles are lifted. For example, the coupling members can be substantially square or rectangular in shape. Alternatively, the coupling members are substantially circular in shape. In certain embodiments, the coupling members are of a shape and size sufficient to locate between the holes of the hole arrangements 214 of the plate members. In other embodiments, the coupling members are of a shape and size sufficient to locate along the edges of the plurality of plates.
    [071] Any method can be used to fabricate the plates and/or coupling members, such as drilling, milling, laser engraving, lithographic processing, photoengraving, laser ablation and the like. In a particular embodiment, a photoengraving process is used to manufacture the plates and/or coupling members.
    [072] The frangible coupling between coupling members and plate members can be accomplished using a variety of techniques. For example, the coupling members can be frangibly coupled between the board members through spot welding techniques (eg laser spot welding), through an adhesive such as epoxy, polyurethane, acrylic or a resin , through a frangible pin, a tongue and groove assembly or snap fit. Such frangible coupling techniques can be performed using one or more manufacturing processes such as cold heads, multiple die formation, multiple die progression, multiple die feeders, casting, stamping, drilling, atmospheric arc welding of hydrogen, bare metal arc welding, carbon arc welding, molten core arc welding, MIG arc welding, tungsten gas arc welding, plasma arc welding, shielded metal arc welding, steel welding submerged arc welding, oxyacetylene welding, oxyacetylene welding, oxygen/propane welding, oxyhydrogen welding, gas pressure welding, resistance spot welding, continuous resistance welding, rebound resistance welding, flash welding, resistance bond welding with upset, co-extrusion welding, cold pressure welding, diffusion welding, explosion welding, electromagnetic pulse welding, welding by forging, friction welding, friction stir welding, hot pressure welding, hot isostatic pressure welding, pressure welding between cylinders, ultrasonic welding, electron beam welding, electroslag welding, liquid metal spill welding in joint, induction welding, laser beam welding, autogenous impact welding, thermite aluminum welding, electrogas welding and stud arc welding.
    [073] Optionally, a portion of the plate material in or around the frangible coupling location is removed to accommodate at least a portion of the coupling member forming a depression in or around the frangible section. For example, in one embodiment, laser engraving or photo engraving on the plate member is used to circumscribe the coupling point at or proximal to the frangible coupling. In another embodiment, a depression in or proximal to the plate member can be removed with any method known in the art, for example, drilling, milling, laser engraving, photoengraving, laser ablation and the like. PREPARATION OF DRESSING/SKIN GRAFTS TO TREAT DAMAGED SKIN
    [074] The devices of the invention can be used to prepare a skin graft to repair numerous different types of skin damage. For example, the devices of the invention can be used to prepare grafts to treat burns (eg, both thermal burns and chemical burns), blister formation, dermatological conditions (eg, epidermolysis bullosa or pyoderma gangrenosum), radiation therapy ulcers , diabetic ulcers, ischemic ulcers, trophic ulcers, trauma, or depigmentation (eg, vitiligo).
    [075] In particular embodiments, the devices 200 of the invention are used to prepare a skin graft(s) for treating vitiligo. Vitiligo is a chronic disorder that causes depigmentation of skin fragments. It occurs when melanocytes, the cells responsible for skin pigmentation, die or are unable to function. Although fragments are initially small, they usually grow and change shape. When skin lesions occur, they are more prominent on the face, hands and wrists. Some lesions have hyperpigmentation around the edges. Depigmentation is particularly noticeable around body orifices such as the mouth, eyes, nostrils, genitalia and navel.
    [076] Vitiligo is generally classified into two categories, non-segmental vitiligo and segmental vitiligo. In non-segmental vitiligo (NSV), there is usually some form of symmetry in the location of depigmentation fragments. New fragments also appear over time and can be generalized over large portions of the body or located in a particular area. Vitiligo in which poorly pigmented skin remains is called vitiligo universalis. Non-segmental vitiligo can appear at any age, unlike segmental vitiligo which is by far more prevalent in adolescence.
    [077] Segmental vitiligo (VS) differs in appearance, etiology, and prevalence of associated diseases. Its treatment is different from that of non-segmental vitiligo. It tends to affect areas of the skin that are associated with the dorsal roots of the spine. It expands much faster than non-segmental vitiligo and, without treatment, is much more stable/static in progress and not associated with autoimmune diseases. MERGER AS REFERENCE
    [078] References and citations to other documents, such as patents, patent applications, patent publications, periodicals, books, journals, web content, have been made throughout this disclosure. All such documents are incorporated herein by reference in their entirety for all purposes. EQUIVALENTS
    [079] The invention can be incorporated in other specific forms without departing from the spirit or essential characteristics of the same. The foregoing embodiments are, therefore, to be considered in all respects illustrative rather than limiting to the invention described herein. The scope of the invention is thus indicated by the appended claims and not by the foregoing description, and all changes which are within the meaning and equivalence range of the claims are therefore intended to be included therein.
    权利要求:
    Claims (10)
    [0001]
    1. METHOD FOR MAKING A PLURALITY OF PLATES (202a, 202b, 202c) FOR USE IN A DEVICE (200) IN ORDER TO OBTAIN A SKIN GRAFT, comprising the steps of: obtaining a plurality of plates (202a, 202b, 202c) , wherein at least one of said plates (202a, 202b, 202c) comprises a uniform thickness; and forming a plurality of openings (214) in said plates (202a, 202b, 202c) so that the openings (214) align by stacking said plates (202a, 202b, 202c); forming a plurality of coupling members on at least one of said plates (202a, 202b, 202c), wherein said coupling members do not change said uniform thickness; characterized in that said coupling members create a frangible link between at least two of said plates (202a, 202b, 202c).
    [0002]
    A METHOD according to claim 1, characterized in that at least one of said plates (202a, 202b, 202c) comprises one or more openings (214) that form an edge (215).
    [0003]
    3. METHOD according to claim 2, characterized in that it additionally comprises the step of securing two or more plates (202a, 202b, 202c) to each other through said coupling members.
    [0004]
    4. METHOD, according to claim 1, characterized in that said training steps comprise laser engraving, photoengraving or lithographic processing.
    [0005]
    5. METHOD according to claim 4, characterized in that said frangible thread is selected from a mechanical stamp, a mechanical perforation, a welding, an epoxy, an adhesive, a mechanical compression, a snap fit, a tongue and slot, a strut and shank, or a frangible pin.
    [0006]
    6. METHOD, according to claim 1, characterized in that said coupling members are of uniform size and shape.
    [0007]
    Method according to claim 3, characterized in that one or more of said coupling members are arranged between at least two of said plates (202a, 202b, 202c).
    [0008]
    8. METHOD according to claim 1, characterized in that it additionally comprises the step of coupling two or more plates (202a, 202b, 202c) to each other by means of said coupling members.
    [0009]
    9. METHOD, according to claim 2, characterized in that it additionally comprises the step of coupling two or more plates (202a, 202b, 202c) to each other by means of said coupling members.
    [0010]
    10. METHOD, according to claim 9, characterized in that said plates (202a, 202b, 202c) are slidable in relation to one another by breaking said frangible chain.
    类似技术:
    公开号 | 公开日 | 专利标题
    BR112014013363B1|2021-05-04|method of fabricating a plurality of plates for use in one device to obtain a skin graft
    US10603072B2|2020-03-31|Methods for preparing a skin graft without culturing or use of biologics
    US10537355B2|2020-01-21|Microblister skin grafting
    AU2016204210B2|2018-08-02|Methods for preparing a skin graft
    US11083487B2|2021-08-10|Methods for preparing a skin graft
    JP6665257B2|2020-03-13|Vesicle skin transplant
    同族专利:
    公开号 | 公开日
    BR112014013363A2|2017-06-13|
    US20150238212A1|2015-08-27|
    US20130145596A1|2013-06-13|
    CA2857995C|2019-09-17|
    EP2787905A1|2014-10-15|
    US8978234B2|2015-03-17|
    EP2787905A4|2015-05-20|
    AU2012347592A1|2014-06-05|
    WO2013086400A1|2013-06-13|
    AU2017279616B2|2019-07-18|
    EP3420981A1|2019-01-02|
    CA2857995A1|2013-06-13|
    EP2787905B1|2018-05-30|
    EP3420981B1|2020-06-03|
    AU2017279616A1|2018-01-18|
    US9848908B2|2017-12-26|
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    法律状态:
    2018-12-04| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2019-06-11| B25A| Requested transfer of rights approved|Owner name: KCI HOLDING COMPANY, INC. (US) |
    2019-06-25| B25A| Requested transfer of rights approved|Owner name: KCI LICENSING, INC. (US) |
    2019-11-26| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2020-10-27| B06A| Notification to applicant to reply to the report for non-patentability or inadequacy of the application [chapter 6.1 patent gazette]|
    2021-01-26| B25A| Requested transfer of rights approved|Owner name: 3M INNOVATIVE PROPERTIES COMPANY (US) |
    2021-02-23| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2021-05-04| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 07/12/2012, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    US201161567946P| true| 2011-12-07|2011-12-07|
    US61/567,946|2011-12-07|
    US13/346,329|2012-01-09|
    US13/346,329|US8978234B2|2011-12-07|2012-01-09|Methods of manufacturing devices for generating skin grafts|
    PCT/US2012/068551|WO2013086400A1|2011-12-07|2012-12-07|Methods of manufacturing devices for generating skin grafts|
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