US20120197267A1 - Devices for generating and transferring micrografts and methods of use thereof - Google Patents

Abstract

The invention generally relates to devices for generating and transferring micrografts and methods of use thereof. In certain embodiments, devices of the invention include a housing having an open configuration and a closed configuration, a micrograft generating station, and a micrograft transferring station.

Description

FIELD OF THE INVENTION
• The invention generally relates to devices for generating and transferring micrografts and methods of use thereof.
BACKGROUND
• Skin is the largest organ of the human body, representing approximately 16% of a person's total body weight. Because it interfaces with the environment, skin has an important function in body defense, acting as an anatomical barrier from pathogens and other environmental substances. Skin also provides a semi-permeable barrier that prevents excessive fluid loss while ensuring that essential nutrients are not washed out of the body. Other functions of skin include insulation, temperature regulation, and sensation. Skin tissue may be subject to many forms of damage, including burns, trauma, disease, and depigmentation (e.g., vitiligo).
• Skin grafts are often used to repair such skin damage. Skin grafting is a surgical procedure in which a section of skin is removed from one area of a person's body (autograft), removed from another human source (allograft), or removed from another animal (xenograft), and transplanted to a recipient site of a patient, such as a wound site. As with any surgical procedure, skin grafting includes certain risks. Complications may include: graft failure; rejection of the skin graft; infections at donor or recipient sites; or autograft donor sites oozing fluid and blood as they heal. Certain of these complications (e.g., graft failure and rejection of the skin graft) may be mitigated by using an autograft instead of an allograft or a xenograft.
• A problem encountered when using an autograft is that skin is taken from another area of a person's body to produce the graft, resulting in trauma and wound generation at the donor site. Generally, the size of the graft matches the size of the recipient site, and thus a large recipient site requires removal of a large section of skin from a donor site. As the size of the section of skin removed from the donor site increases, so does the probability that the donor site will not heal properly, requiring additional treatment and intervention. Additionally, as the size of the section of skin removed from the donor site increases, so does the possibility of infection. There is also increased healing time associated with removal of larger sections of skin because a larger wound is produced.
• To address those problems, techniques have been developed that allow for expansion of a skin graft so that a harvested graft can treat a recipient site that is larger than a donor site. Such methods involve cutting a skin graft into many smaller micrografts, transferring the micrografts onto a substrate, expanding the micrografts on the substrate, and applying the expanded substrate having the expanded micrografts to a recipient site. Producing micrografts and transferring micrografts is typically accomplished using two devices, one device to cut the skin graft into the many smaller micrografts, and a second device to transfer the micrografts from the cutting surface to a substrate for expansion. The need for two devices slows the grafting process and increases the risk of graft failure. Further, the need for separate devices has prevented development of an automated system for producing a skin graft.
SUMMARY
• The present invention provides a micrograft generating device integrated with a micrograft transferring device. The invention thus provides a single device that can generate a plurality of micrografts and transfer the micrografts to a substrate.
• In certain embodiments, devices of the invention include a housing having an open configuration and a closed configuration, a micrograft generating station, and a micrograft transferring station. The housing may include a bottom portion hingedly connected to a top portion. Generally, the top portion of the housing is movable in a vertical direction.
• In certain embodiments, the micrograft generating station includes a first member connected to the top portion of the housing, and a second member connected to the bottom portion of the housing, in which the first member is aligned with the second member. In certain embodiments, the micrograft transferring station includes a transfer pusher including a plurality of prongs, in which the pusher is connected to the top portion of the housing, and a transfer stage connected to the bottom portion of the housing, in which the pusher and the stage are aligned with each other. The transfer stage may be made of any material that is softer than that of the transfer pusher. In certain embodiments, the transfer stage is composed of a compressible material. In other embodiments, the transfer stage includes a spring loaded base. The spring loaded base may further include a ball to focus the force on the center of the stage.
• The housing may further include a cartridge receiving portion, in which the cartridge receiving portion is located between the top portion and the bottom portion of the housing. The cartridge receiving portion may include a first slot and a second slot, in which the first slot is aligned with the micrograft generating station and the second slot is aligned with the micrograft transferring station. Alternatively, the cartridge receiving portion may include a single slot and components of the micrograft generating station and the micrograft transferring station are removable from the top and bottom portions of the housing, thereby providing for the micrograft generating station and the micrograft transferring station to be located at a same place in the device.
• Devices of the invention may further include a cartridge that is compatible with the first slot and the second slot of the cartridge receiving portion. Further, the cartridge may be removable from the first and second slots of the cartridge receiving portion. The cartridge is configured to hold a skin graft. In certain embodiments, the cartridge includes a frame having a hollow inner portion, a removable first plate including a mesh grid, and a removable second plate including a mesh grid, in which, in an assembled configuration, the grid of the first plate and the grid of the second plate are aligned with the hollow portion of the frame, and the grid of the first plate is aligned with the grid of the second plate. In certain embodiments, holes in the grids of the first and second plates are generally larger than the prongs of the transfer pusher.
• Another aspect of the invention provides methods for generating and transferring micrografts, including providing a device having a housing having an open configuration and a closed configuration, a micrograft generating station, and a micrograft transferring station, inserting a skin graft into the device, engaging the micrograft generating station, thereby generating a plurality of micrografts, and engaging the micrograft transferring station, thereby transferring the plurality of micrografts to a substrate.
• In certain embodiments, inserting includes obtaining a cartridge having a frame including a hollow inner portion, a removable first plate having a mesh grid, and a removable second plate having a mesh grid, in which in an assembled configuration, the grid of the first plate and the grid of the second plate are aligned with the hollow portion of the frame, and the grid of the first plate is aligned with the grid of the second plate, and inserting the skin graft between the first and second plates such that the graft is aligned with the grids in the first and second plates.
• In certain embodiments, engaging the micrograft generating station includes inserting the cartridge into the micrograft generating station of the device while the housing is in the open configuration, and transforming the housing from the open configuration to the closed configuration, thereby generating a plurality of micrografts. In certain embodiments, engaging the micrograft transferring station includes inserting the cartridge into the micrograft transferring station of the device while the housing is in the open configuration, inserting a substrate below the cartridge, and transforming the housing from the open configuration to the closed configuration, thereby transferring the plurality of micrografts to the substrate. The substrate may be any biocompatible material. An exemplary substrate is a medical dressing.
• Methods of the invention are used with any type of skin graft, such as an epidermal skin graft, a split thickness graft, or a full thickness graft. In particular embodiments, methods of the invention are used with skin grafts including only or substantially only the epidermal layer of skin. Methods of the invention can be used with autografts, allografts, or xenografts. In preferred embodiments, the grafts are autografts.
• Methods of the invention may also include harvesting the skin graft. Harvesting of skin grafts can occur by any method known in the art. In certain embodiments, harvesting involves raising a blister, and cutting the blister to obtain the skin graft. In certain embodiments, raising involves contacting a device having a hole to skin, and applying heat and/or vacuum pressure, thereby raising the blister.
• Methods of the invention may further include expanding the micrografts, and applying the expanded grafts to a patient recipient site. Methods of the invention are used to prepare skin grafts for any recipient site of damaged skin. Exemplary types of skin damage include burns (e.g., thermal or chemical), infections, wounds, or depigmentation. In particular embodiments, the recipient site is an area of depigmented skin that has been prepared to receive a skin graft.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1 is a drawing showing the anatomy of skin.
• FIG. 2A shows an embodiment of devices of the invention. This figure shows the device in an open configuration.FIG. 2B is an enlarged view of the transfer pusher. This figure shows the plurality of prongs of the pusher.
• FIG. 3 shows the device ofFIG. 2A in a closed configuration.
• FIGS. 4A and 4B show a cartridge that is compatible with devices of the invention.FIG. 4A shows an exploded view of the cartridge.FIG. 4B shows a view of a fully assembled cartridge.
• FIGS. 5A-5B show the process of generating the plurality of micrografts using devices of the invention.
• FIGS. 6A-6B show the process of transferring the plurality of micrografts to a substrate using devices of the invention.
• FIG. 7 shows another embodiment of devices of the invention.
• FIG. 8 shows the spring loaded base member of devices of the invention.
• FIG. 9 shows a latch that links a top portion of a frame to a cartridge receiving portion of devices of the invention.
DETAILED DESCRIPTION
• The skin consists of 2 layers. The outer layer, or epidermis, is derived from ectoderm, and the thicker inner layer, or dermis, is derived from mesoderm. The epidermis constitutes about 5% of the skin, and the remaining 95% is dermis.FIG. 1 provides a diagram showing the anatomy of skin. The skin varies in thickness depending on anatomic location, gender, and age of the individual. The epidermis, the more external of the two layers, is a stratified squamous epithelium consisting primarily of melanocytes and keratinocytes in progressive stages of differentiation from deeper to more superficial layers. The epidermis has no blood vessels; thus, it must receive nutrients by diffusion from the underlying dermis through the basement membrane, which separates the 2 layers.
• 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, closely interlaced elastic fibers, and coarse, branching collagen fibers arranged in layers parallel to the surface. The reticular layer also contains fibroblasts, mast cells, nerve endings, lymphatics, and some epidermal appendages. Surrounding the components of the dermis is the gel-like ground substance composed of mucopolysaccharides (primarily hyaluronic acid), chondroitin sulfates, and glycoproteins.
• In a graft, the characteristics of the donor site are more likely to be maintained after grafting to a recipient site as 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 discovered, however, that a substantially epidermal graft according to the invention is more likely to adapt to the characteristics of the recipient site.
• The invention generally relates to devices for generating and transferring micrografts and methods of use thereof. Reference is now made toFIG. 2A, which shows adevice100 of the invention.Device100 includes ahousing101. The housing has atop portion101aand abottom portion101b. Thetop portion101ais hingedly connected to thebottom portion101b. Thehousing101 has an open configuration and a closed configuration.FIG. 2A shows thehousing101 in the open configuration.FIG. 3 shows thehousing101 in a closed configuration. The hinges are connected todevice100 bybolts118.
• Device100 further includes amicrograft generating station104 and amicrograft transferring station105. Themicrograft generating station104 includes afirst member106 connected to thetop portion101aof thehousing101, and asecond member107 connected to thebottom portion101bof thehousing101. Thefirst member106 is aligned with thesecond member107. The second member may be a spring loaded base that includes astage401, coupled to a spring402 (FIG. 8). The spring loaded base may further include aball403 to focus the force on the center of thestage401.
• Themicrograft transferring station105 includes atransfer pusher108 including a plurality of prongs109 (FIG. 2B). Thetransfer pusher108 is connected to thetop portion101aof thehousing101 such that theprongs109 are oriented downward toward thebottom portion101bof thehousing101. Themicrograft transferring station105 further includes atransfer stage110, which is connected to thebottom portion101bof thehousing101. Thetransfer pusher108 and thetransfer stage110 are aligned with each other. Thetransfer stage110 may be made of any material that is softer than that of thetransfer pusher108. In certain embodiments, thetransfer stage110 is composed of a compressible material. In other embodiments, thesecond member107 includes a spring loaded base (FIG. 8). The spring loaded base includes astage401, coupled to aspring402. The spring loaded base may further include aball403 to focus the force on the center of thestage401. The base is generally has a flat top and is made of a relatively hard material, i.e., not easily deformable or compressible.
• Housing101 further includes acartridge receiving portion111. Thecartridge receiving portion111 is located between thetop portion101aand thebottom portion101bof thehousing101, and is also hingedly connected with thetop portion101aand thebottom portion101bof thehousing101. Thecartridge receiving portion111 includes a first slot112 and asecond slot113. The first slot112 is aligned with themicrograft generating station104 and thesecond slot113 is aligned with themicrograft transferring station105.
• Thehousing101 may further includemembers102 and103 that connect to thetop portion101a, thecartridge receiving portion111, and thebottom portion101b.Members102 and103 are movable and help control the position of thecartridge receiving portion111 asdevice100 is transformed from the open configuration to the closed configuration.
• Device100 also includes alever114 andlinkage arms115 and116. Thelever114 is connected to thetop portion101aof thehousing101. Thelever114 may include ahandle117 that may be used to transform thedevice100 from the open configuration to the closed configuration and back to the open configuration.Linkage arms115 and116 are connected to thelever114, thetop portion101aof thehousing101, andbottom portion101bof thehousing101. Thelinkage arms115 and116 act as force multipliers, such that upon engagement of thelever114, an exponential amount of force is transferred to themicrograft generating station104 and themicrograft transferring station105 as an operator transformsdevice100 from the open configuration to the closed configuration. The exponential amount of force transferred may be varied by varying the length of thelever114 or the length of thelinkage arms115 and116. In certain embodiments, thedevice100 is configured to provide for at least about a 50×, e.g. about 100×, increase in force transferred to themicrograft generating station104 as compared to the amount of force applied to thelever114 by an operator to transform the device from the open configuration to the closed configuration.
• Reference is now made toFIGS. 4A and 4B, which show acartridge119.FIG. 4A shows an exploded view of thecartridge119.FIG. 4B shows a fully assembledcartridge119. Thecartridge119 is compatible with the first slot112 andsecond slot113 of thecartridge receiving portion111 of thedevice100, and is removable from the first andsecond slots112 and113 of thecartridge receiving portion111 of thedevice100. Thecartridge119 is configured to hold askin graft120.
• Thecartridge119 includes aframe121. It is noted thatFIG. 4B shows theframe121 of thecartridge119 in the orientation in which it is inserted into thedevice100.FIG. 4A shows the frame upside down. Theframe121 includes abeveled edge122. Thebeveled edge122 aligns with beveled edges of the first slot112 andsecond slot113 of thecartridge receiving portion111 of thedevice100, ensuring that thecartridge119 is inserted into first slot112 andsecond slot113 with the proper orientation. Theframe121 also includes ahollow portion123. Upon insertion of thecartridge119 into the first andsecond slots112 and113, thehollow portion123 is aligned with the first andsecond members106 and107 of themicrograft generating station104 and is also aligned with thetransfer pusher108 and thetransfer stage110 of themicrograft transferring station105.
• Cartridge119 further includes afirst plate126 and asecond plate127. Thefirst plate126 includes amesh grid128, and thesecond plate127 includes amesh grid129. Once assembled, themesh grid128 of thefirst plate126 and themesh grid129 of thesecond plate127 are aligned with thehollow portion123 of theframe121, and holes of themesh grid128 of thefirst plate126 are aligned with holes of themesh grid129 of thesecond plate127. The holes in thegrids128 and129 of the first andsecond plates126 and127 are sized to provide an array of micrografts of a desired size, such as lateral sizes between about 100 microns and about 1000 microns or about 300 microns to about 500 microns.
• For example, for repigmenting skin tissue, the micrografts used may have a presence of melanocytes. Accordingly, a lateral dimension of such micrografts can be between less than about 1 mm, e.g., 200 to 1000 microns. Other exemplary sizes are between 400 and 800 microns. The area of the micrografts can be between about 0.04 mm²and about 1 mm². The exemplary sizes can provide micrografts large enough such that each micrograft is likely to contain some melanocytes, yet small enough to provide a large number of micrografts from a particular piece of graft tissue, which can facilitate a significant degree of expansion on the graft site.
• For treating burns or ulcers, where presence and proliferation of keratinocytes is important, the micrograft sizes may be smaller. For example, a lateral dimension of micrografts containing keratinocytes can be between about 50 microns and about 1000 microns, or between 100 microns and about 800 microns. The area of such micrografts can be between about 0.0025 mm²and about 1 mm². The exemplary size ranges provide micrografts large enough to contain viable and undamaged keratinocytes, and small enough to facilitate repair of a larger area of damaged skin.
• To ensure proper alignment,frame121 includesplate retaining pins124 and plate locating pins125.First plate126 includesplate retaining holes130 andplate locating holes131, andsecond plate127 includesplate retaining holes132 and plate locating holes133. Theplate retaining holes130 andplate locating holes131 of thefirst plate126 are aligned withplate retaining pins124 andplate locating pins125 offrame121. Similarly,plate retaining holes132 andplate locating holes133 of thesecond plate127 are aligned withplate retaining pins124 andplate locating pins125 offrame121. The alignment of theplate retaining holes130 andplate locating holes131 of thefirst plate126, theplate retaining holes132 andplate locating holes133 of thesecond plate127, and theplate retaining pins124 andplate locating pins125 offrame121 ensures that once assembled, themesh grid128 of thefirst plate126 and themesh grid129 of thesecond plate128 are aligned with thehollow portion123 of theframe121, and themesh grid128 of thefirst plate126 is aligned with themesh grid129 of thesecond plate127.
• Thefirst plate126 and thesecond plate127 are removable from theframe121. Removability allows for re-use of theframe121. Theskin graft120 is inserted such that at least a portion of thegraft120 is aligned with themesh grid128 of thefirst plate126 and themesh grid129 of thesecond plate127.
• In an alternative embodiment,cartridge retaining portion111 ofhousing101 includes only a single slot. In this embodiment, components of the micrograft generating station104 (first andsecond members105 and106) and components of the micrograft transferring station105 (transfer pusher108 and transfer stage110) are removable fromhousing101. Thus, instead of transferring thecartridge119 between first andsecond slots112 and113 that are aligned with a dedicatedmicrograft generating station104 and a dedicatedmicrograft transferring station105, thecartridge119 remains in a single slot for the generating and transferring process, and it is the components of themicrograft generating station104 and themicrograft transferring station105 that are interchanged within thehousing101 depending on the whether an operator is generating micrografts or transferring micrografts.
• Devices of the invention as described herein may be used to prepare skin grafts for any recipient site of damaged skin. Exemplary types of skin damage include burns (e.g., thermal or chemical), infections, wounds, or depigmentation. In particular embodiments, the recipient site is an area of depigmented skin that has been prepared to receive a skin graft.
• General methods for preparing skin grafts are described in co-owned and co-pending U.S. patent application Ser. No. 12/851,621, the content of which is incorporated by reference herein in its entirety. In certain embodiments, methods of the invention generally involve harvesting a skin graft from a donor site, such as an epidermal graft, generating an array of micrografts from the single graft, placing the graft on a first substrate, expanding a distance between the micrografts on a first substrate, optionally transferring the micrografts from the first substrate to a second substrate, and applying the micrografts to a recipient site.
• Harvesting of the skin grafts may be accomplished by any technique known in the art, and the technique employed will depend on the type of graft required (e.g., epidermal graft, split thickness graft, or full thickness graft). An epidermal graft refers to a graft that consists of substantially epidermal skin and does not include any substantial portion of the dermal layer. A split thickness graft refers to a graft that includes sheets of superficial (epithelial) and some deep layers (dermal) of skin. A full-thickness graft refers to a graft that includes all of the layers of the skin including blood vessels.
• In certain embodiments, harvesting a skin graft involves raising a blister and cutting the blister. In certain embodiments, the blister may be a fluid-filled blister (e.g. a suction blister). In other embodiments, the blister is not fluid-filled. Any type of raised blister may be used with methods of the invention.
• In certain embodiments, suction blister grafting is used. Suction blister grafting involves raising a blister, and then cutting off the raised blister. An exemplary suction blister grafting technique is shown in Awad, (Dermatol Surg, 34(9):1186-1193, 2008), the content of which is incorporated by reference herein in its entirety. This article also shows various devices used to form suction blisters. A suction blister device is also described in Kennedy et al. (U.S. Pat. No. 6,071,247), the content of which is incorporated by reference herein in its entirety. An exemplary device is commercially available from Electronic Diversities (Finksburg, Md.).
• A device for raising a suction blister typically operates by use of suction chambers that are attached to a patient's skin. An instrument typically contains a power source, a vacuum pump, temperature controls and all related controls to operate multiple suction chambers. The suction chambers are connected to the console by a flexible connection. Each of the chambers is controlled by a preset temperature control to provide an optimal skin warming temperature. Both chambers share an adjustable common vacuum source that affects all chambers equally.
• Blister formation is accomplished by attaching the suction blister device to a patient's skin. Typically hook & loop fastener straps are used to keep the device in place. The chamber heating system provides a slight warming of an orifice plate of the device, which is in direct contact with the patient's skin surface. The application of a moderate negative pressure from the instrument console, to the chamber interior, causes the patients skin to be gently drawn through the opening(s) in the orifice plate. The results are typical suction blisters, approximately the size of the opening(s) in the orifice plate. The skin and blister area is generally not damaged and patient discomfort is minimal.
• The negative pressure chamber is fabricated of mostly plastic components, with two removable threaded caps. The upper cap is fitted with a clear viewing lens so that the actual blister 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. Since this plate is simply threaded onto the chamber end, multiple plates with different opening patterns can be interchanged as desired.
• The interior of the device is warmed and illuminated by an array of low voltage incandescent lamps. This lamp array is controlled from the instrument console temperature controller, cycling as needed, to maintain the set point temperature. The heat from these lamps is radiated and conducted to the orifice plate, which then warms the patient's skin. The chamber is connected to the console via a composite vacuum and low voltage electrical system. Quick connections are used for the vacuum and electrical system to facilitate removal and storage.
• The Negative Pressure Instrument console is a self-contained fan cooled unit which is designed to operate on 120 VAC 60 Hz power. Vacuum is supplied by an industrial quality diaphragm type vacuum pump, capable of a typical vacuum of 20 in Hg (0-65 kpa) at 0 CFM. An analog controller that is preset to 40° C. provides the temperature control for each suction chamber. This provides accurate control of the orifice plate temperature. The instrument console has internal 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 gauge and vacuum bleeder adjustment to regulate the vacuum to both chambers. The console front panel also contains the connections for the chamber assemblies.
• Once the suction blister is raised, it is cut by methods known in the art (see e.g., Awad, Dermatol Surg, 34(9):1186-1193, 2008). Theskin graft120 is then inserted intocartridge119.Frame121 is turned upside down, as is shown inFIG. 4A.First plate126 is placed overframe121. Theplate retaining holes130 andplate locating holes131 of thefirst plate126 are aligned with theplate retaining pins124 and theplate locating holes125 of theframe121. Once aligned, thefirst plate126 is placed onto theframe121 such that theplate retaining pins124 and theplate locating holes125 of theframe121 go through theplate retaining holes130 andplate locating holes131 of thefirst plate126. Once placed on theframe121, themesh grid128 is aligned with thehollow portion123 of theframe121.
• Theskin graft120 is then placed on themesh grid128 of thefirst plate126. The graft should be roughly centered on the mesh grid128 (FIG. 4A). In certain embodiments, thegraft120 is placed on the grid such that a basal layer of thegraft120 is facing up. Epidermal skin includes a stratum corneum layer and a basal layer. The stratum corneum refers to the outermost layer of the epidermis, composed of large, flat, polyhedral, plate-like envelopes filled with keratin, which is made up of dead cells that have migrated up from the stratum granulosum. This layer is composed mainly of dead cells that lack nuclei. The thickness of the stratum corneum varies according to the amount of protection and/or grip required by a region of the body. In general, the stratum corneum contains 15 to 20 layers of dead cells, and has a thickness between 10 and 40 μm.
• The basal layer (or stratum germinativum or stratum basale) refers to the deepest layer of the 5 layers of the epidermis. The basal layer is a continuous layer of live cells and can be considered the stem cells of the epidermis. These cells are undifferentiated and proliferative, i.e., they create daughter cells that migrate superficially, differentiating during migration. Keratinocytes and melanocytes are found in the basal layer.
• For a graft to become integrated at a recipient site, the graft must be able to receive nutrients. Since the cells of the basal layer are live cells, orienting an epidermal graft such that the basal layer interacts with the recipient site allows the graft to receive nutrients, and thus remain viable. In contrast, since the cells of the stratum corneum are dead cells, orienting an epidermal graft such that the stratum corneum layer interacts with the recipient site prevents the graft from receiving nutrients, resulting in death of the graft tissue and graft failure. By placing thegraft120 on thecartridge119 with the basal layer facing up, proper orientation of thegraft120 is maintained, ensuring that once applied to the skin, it is the basal layer of thegraft120 that interacts with the tissue of the recipient site. Thus, methods of the invention ensure that during the grafting process, the basal layer of a graft interacts with the recipient site of a patient, allowing for the graft to receive nutrients and thus remain viable.
• Once thegraft120 has been placed on thefirst plate126, thesecond plate127 is placed on top of thegraft120, sandwiching thegraft120 between the first andsecond plates126 and127 (FIG. 4A).Second plate127 is placed overframe121. Theplate retaining holes132 andplate locating holes133 of thesecond plate127 are aligned with theplate retaining pins124 and theplate locating holes125 of theframe121. Once aligned, thesecond plate127 is placed onto theframe121 such that theplate retaining pins124 and theplate locating holes125 of theframe121 go through theplate retaining holes132 andplate locating holes133 of thesecond plate127. Once placed on theframe121, themesh grid129 is aligned with thehollow portion123 of theframe121, and themesh grid129 of thesecond plate127 is aligned with themesh grid128 of thefirst plate126. Additionally, theskin graft120 is now sandwiched between the first andsecond plates126 and127. Themesh grid128 of thefirst plate126 and themesh grid129 of thesecond plate127 are only separated by the thickness of thegraft120.
• Now loaded into the cartridge, a plurality of micrografts may be generated from thesingle skin graft120. To generate the micrografts, thecartridge119 is flipped right side up and loaded into themicrograft generating station104 ofdevice100. Reference is now made toFIGS. 5A-5B which show the process of generating the plurality of micrografts.Cartridge119 is oriented such thatbevel122 onframe121 ofcartridge119 is aligned with a bevel in first slot112 ofcartridge receiving portion111 ofhousing101. Once aligned, thecartridge119 is slid into first slot112. Once in slot112, thehollow portion123 of theframe121 of thecartridge119 is aligned with thefirst member106 and thesecond member107 of themicrograft generating station104.
• Thedevice100 is then transformed from the open configuration to the closed configuration by engaginglever114, and moving thelever114 from an open configuration to a closed configuration. Such movement causes thetop portion101aand thecartridge receiving portion111 of thehousing101 to move vertically downward toward thebottom portion101bof thehousing101. With such movement, themesh grid129 of thesecond plate127 of thecartridge119 come in contact with thesecond member107 of themicrograft generating station104. Additionally, thefirst member106 of themicrograft generating station104 passes into thehollow portion123 of theframe121 ofcartridge119 and contacts themesh grid128 offirst plate126 of thecartridge119. The first andsecond members106 and107 compress themesh grids128 and129 of first andsecond plates126 and127 of thecartridge119. The compressive force results in themesh grids128 and129 cutting theskin graft120 that is sandwiched betweenplates126 and127, thereby generating the plurality of micrografts. The cuts may pass partially or completely through the graft tissue. The plurality of micrografts reside in the holes of themesh grids128 and129.
• Once the micrografts are generated, thelever114 is moved from the closed configuration to the open configuration, transformingdevice100 from the closed configuration to the open configuration.Cartridge119 is removed from first slot112 ofcartridge receiving portion111 ofhousing101. The cartridge is now ready to be transferred to themicrograft transferring station105.
• Reference is now made toFIGS. 6A-6D which show the process of transferring the plurality of micrografts to a substrate. Thecartridge119 is inserted into thesecond slot113 ofcartridge receiving portion111 ofhousing101.Cartridge119 is oriented such thatbevel122 onframe121 ofcartridge119 is aligned with a bevel insecond slot113 ofcartridge receiving portion111 ofhousing101. Once aligned, thecartridge119 is slid intosecond slot113. Once inslot113, thehollow portion123 of theframe121 of thecartridge119 is aligned with thetransfer pusher108 and thetransfer stage110 of themicrograft transferring station105.
• Asubstrate134 is placed on top oftransfer stage110. Generally, thesubstrate134 will have an adhesive side and thesubstrate134 should be placed onto thetransfer stage110 such that the adhesive side of thesubstrate134 is facing up. The substrate may be made from any material that is biocompatible. In certain embodiments, the substrate is biocompatible and made from a material that is capable of being stretched upon application of a moderate tensile force. Exemplary materials include medical dressings, such as TEGADERM (medical dressing, commercially available from 3M, St. Paul, Minn.) or DUODERM (medical dressing, commercially available from 3M, St. Paul, Minn.). The substrate may also be gas permeable.
• In certain embodiments,substrate134 includes an adhesive on one side that facilitates attachment of the micrografts to the substrates. The substrate material may have intrinsic adhesive properties, or alternatively, a side of the substrate may be treated with an adhesive material, e.g., an adhesive spray such as LEUKOSPRAY (Beiersdoerf GmbH, Germany).
• In certain embodiments, the material of thesubstrate134 is a deformable non-resilient material. A deformable non-resilient material refers to a material that may be manipulated, e.g., 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 may be stretched to an expanded configuration without returning to their original size. Such deformable non-resilient materials tend to be soft, stiff or both soft and stiff. 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 switched out for an aliphatic, which is more flexible as its 6 carbon ring has no double bonds. Therefore, all the segments are soft. On the Durometer Scale, a soft polyethylene is rated about Shore 80A. Other materials suitable for use with methods of the invention include low density polyethylene, linear low density polyethylene, polyester copolymers, polyamide copolymers, and certain silicones.
• Thedevice100 is then transformed from the open configuration to the closed configuration by engaginglever114, and moving thelever114 from an open configuration to a closed configuration. Such movement causes thetop portion101aand thecartridge receiving portion111 of thehousing101 to move vertically downward toward thebottom portion101bof thehousing101. With such movement, themesh grid129 of thesecond plate127 of thecartridge119 come in contact with thesubstrate134 that is on top of thetransfer stage110 of themicrograft generating station105. Additionally, the plurality ofprongs109 of thetransfer pusher108 of themicrograft generating station105 pass into thehollow portion123 of theframe121 ofcartridge119. Theprongs109 are small than the holes of themesh grids128 and129. The prongs pass through the holes of themesh grids128 and129 and push themicrografts135 residing in the holes of themesh grids128 and129 through themesh grids128 and129 and onto thesubstrate134.
• Once themicrografts135 are transferred tosubstrate134, thelever114 is moved from the closed configuration to the open configuration, transformingdevice100 from the closed configuration to the open configuration. Due to the adhesive layer of thesubstrate134, after contact with thesubstrate134, the plurality ofmicrografts135 remain adhered to thesubstrate134.
• Once themicrografts135 have been transferred to thesubstrate134, the substrate is stretched or expanded, resulting in increased distance between the individual micrografts, moving them apart and resulting in production of a skin graft that can repair a recipient site that is larger than the donor site from which the grafts were obtained. In methods of the invention, the individual grafts themselves are not expanded, i.e., the graft tissue is not stretched; rather, stretching of the substrate increases the space or distance between each individual micrograft. Methods of the invention thus minimize tissue manipulation. Methods for expanding micrografts on a substrate are described for example in U.S. patent application Ser. No. 12/851,621, the content of which is incorporated by reference herein in its entirety.
• The purpose of such processing is to use tissue from a donor site to cover a wound area that is larger than the donor site. The stretching of the substrate may be done manually, i.e., by hand, or may be done with the help of a machine. The stretching may be substantially uniform in all directions or may be biased in a certain direction. In a particular embodiment, the stretching is substantially uniform in all directions. Stretching of the substrate may be performed mechanically or may be accomplished by application of a pressurized fluid or gas. In certain embodiments, air pressure is used to expand the first substrate. Exemplary devices and methods are described in Korman (U.S. Pat. No. 5,914,264), the content of which is incorporated by reference herein in its entirety.
• Any minimum distance can be provided between micrografts after the first substrate is stretched. The amount of stretching can be large enough to provide a sufficiently large area of substrate containing micrografts to allow a larger area of damaged tissue to be repaired using a particular amount of graft tissue removed from the donor site, i.e., the area of the stretched first substrate containing the separated micrografts can be much larger than the total area of the donor site. For example, the distance between adjacent micrografts on the stretched first substrate can be greater than about 0.5 mm, although small separation distances may also be used. For repigmentation of skin tissue, an amount of stretching can be applied to the first substrate such that the distance between adjacent micrografts is less than about 4 mm, because it is known that melanocytes, when grafted to a depigmented region, can migrate up to about 2 mm from each micrograft to repigment regions between the micrografts. This average distance can be larger if keratinocyte migration is involved with the tissue being treated because keratinocytes typically migrate greater distances compared to melanocytes.
• The ratio of the wound area to the donor site area is referred to as the expansion ratio. A higher expansion ratio is desirable to minimize the trauma of the donor site, and to aid patients who have only a small amount of tissue available for grafting purposes. The amount of area expansion, e.g., the ratio of an area of damaged tissue that can be repaired compared to an area of graft tissue removed from a donor site, may be 500× or more. In particular embodiments, the area of expansion may be from about 10× to about 100×, which provides a more uniform coverage and/or repigmentation of the recipient site. For repairing burns or ulcerated tissue, the micrografts may be smaller than those used to repair other types of damaged tissue, and thus the distances between adjacent micrografts may be greater after stretching of the first substrate. In such an exemplary application, an area expansion of about 1000× or more may be used.
• In other embodiments and depending on the material of thesubstrate134, maintaining thesubstrate134 in a stretched configuration may result in stress on thesubstrate134 that is not optimal. Additionally, the stretchedsubstrate134 may not retain the same properties as the unstretched configuration of thesubstrate134, i.e., technological characteristics, such as physical, environmental and performance characteristics could be affected by the stretching of thesubstrate134. Additionally, methods used to maintain thesubstrate134 in its stretched condition may be physically cumbersome and prevent uniform application of the micrografts to uneven skin surfaces. Thus in certain embodiments, once thesubstrate134 has been stretched, the spaced apart micrografts are transferred to a second substrate. By transferring the micrografts to a second substrate, methods of the invention minimize manipulation and stress of the substrate that holds the graft to the recipient site.
• After stretching thesubstrate134, the second substrate is brought into contact with the grafts on the stretchedsubstrate134. Transfer is facilitated by the second substrate having greater affinity or more adhesive force toward the micrografts than thesubstrate134. In certain embodiments, the second substrate is coated with a hydrocolloid gel. In other embodiments, thesubstrate134 is wetted with a fluid such as water or a saline solution. Wetting the micrografts and thesubstrate134 provides lubrication between the grafts and thesubstrate134 and allows for easy transfer of the grafts from thesubstrate134 to the second substrate. After wetting thesubstrate134, the grafts have greater affinity for the second substrate than thesubstrate134. The wettedsubstrate134 is then removed from the second substrate and the grafts remain attached to the second substrate. The distance between the micrografts is maintained after transfer of the micrografts from the stretchedsubstrate134 to the second substrate.
• The second substrate may be made from any material known in the art that is compatible with biological tissue. The second substrate may also be capable of being stretched upon application of a moderate tensile force. Exemplary materials for the second substrates include medical dressings, such as TEGADERM (medical dressing, commercially available from 3M, St. Paul, Minn.) or DUODERM (medical dressing, commercially available from 3M, St. Paul, Minn.). The second substrate may also be gas permeable.
• In certain embodiments, the second substrate includes an adhesive on one side that facilitates attachment of the grafts to the second substrate. The second substrate material may have intrinsic adhesive properties, or alternatively, a side of the second substrate may be treated with an adhesive material, e.g., an adhesive spray such as LEUKOSPRAY (Beiersdoerf GmbH, Germany). In certain embodiments, thesubstrate134 and the second substrates are the same material. In other embodiments, thesubstrate134 and second substrate are different materials. In certain embodiments, the materials ofsubstrate134 and the second substrate are chosen to facilitate transfer of the micrografts from thesubstrate134 to the second substrate. For example, in certain embodiments, the material chosen forsubstrate134 has a weaker adhesive than the material chosen for the second substrate.
• In certain embodiments, the material ofsubstrate134 is a deformable non-resilient material as discussed above. Such materials may be stretched to an expanded configuration without returning to their original size, and thus in these embodiments it is not necessary to transfer the micrografts fromsubstrate134 to a second substrate. Instead, thesubstrate134 including the micrografts is applied to a recipient site.
• Ultimately, the grafts and substrate are applied to a recipient of site of a patient. Prior to applying the grafts to the recipient site, the site is prepared to receive the grafts using any technique known in the art. Necrotic, fibrotic or avascular tissue should be removed. The technique used to prepare the site will depend on damage to the recipient site. For example, epidermal tissue, if present at the recipient site, can be removed to prepare the area for receiving the micrografts. Burned or ulcerated sites may not need removal of epidermal tissue, although some cleaning of the site or other preparation of the site may be performed. Wounds should be debrided and then allowed to granulate for several days prior to applying the graft. Most of the granulation tissue should be removed since it has a tendency to harbor bacteria. Applying silver sulfadiazine to the wound for 10 days prior to grafting reduces the bacterial count greatly.
• The size of the area at the recipient site can be about the same size as the area of the stretchedsubstrate134 havingmicrografts135 adhered thereto. This size generally will be greater than the area of the original graft tissue that was removed from the donor site to form the micrografts. The depigmented or damaged skin can be dermabraded with sandpaper or another 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, e.g., a suction blister or a freezing blister, and the raised epidermal blister tissue can then be removed by cutting or another procedure.
• The substrate having the micrografts can be placed over the area to be treated to form a dressing. A portion of the substrate having the micrografts can be positioned over the area to be repaired, e.g., the area from which the epidermal tissue has been abraded or removed for repigmentation. The substrate can be fixed in place over the treatment area, e.g., using tape or the like. The substrate can be removed after sufficient time has elapsed to allow attachment and growth of the micrografts in the treatment area, e.g., several days to a few weeks.
• Reference is now made toFIG. 7, which shows adevice200 of the invention.Device200 includes abase member250, amicrograft generating station260 integrated with thebase member250, and amicrograft transferring station370 integrated with thebase member250. Integration of the micrograft generating station and the micrograft transferring station with the base member can be as a single unitary device or can be such that the micrograft transferring station and the micrograft generating station are removably coupled to the base member. In certain embodiments, the micrograft generating station and the micrograft transferring station are removed from the base member and are used as individual stand-alone devices.
• Themicrograft generating station260 comprises aframe201. The frame has atop portion201aand a bottom portion201b. Thetop portion201ais connected to the bottom portion201b. Theframe201 has an open configuration and a closed configuration.FIG. 7 shows theframe201 in the closed configuration. Themicrograft generating station260 further includes afirst member206 connected to thetop portion201aof theframe201, and asecond member207 connected to the bottom portion201bof theframe201. Thefirst member206 is aligned with thesecond member207.
• In certain embodiments, thesecond member207 includes a spring loaded base (FIG. 8). The spring loaded base includes astage401, coupled to aspring402. The spring loaded base may further include aball403 to focus the force on the center of thestage401.
• Frame201 further includes acartridge receiving portion211. Thecartridge receiving portion211 is located between thetop portion201aand the bottom portion201bof theframe201, and is also connected with thetop portion201aand the bottom portion201bof theframe201. Thecartridge receiving portion211 includes aslot212. Theslot212 is aligned with the first and second members of themicrograft generating station260. In this figure,slot212 is shown with a thecartridge119 loaded into theslot212.
• Themicrograft generating station260 also includes alever214. Thelever214 is connected to thetop portion201aof theframe201. Thelever214 is used to transform themicrograft generating station260 from the open configuration to the closed configuration and back to the open configuration.Linkage arms215 and216 are connected to thelever214, thetop portion201aof theframe201, and bottom portion201bof theframe201. Thelinkage arms215 and216 act as force multipliers, such that upon engagement of thelever214, an exponential amount of force is transferred to themicrograft generating station260 as an operator transformsmicrograft generating station260 from the open configuration to the closed configuration. The exponential amount of force transferred may be varied by varying the length of thelever214 or the length of thelinkage arms215 and216. In certain embodiments, themicrograft generating station260 is configured to provide for at least about a 50× increase in force transferred to themicrograft generating station260 as compared to the amount of force applied to thelever214 by an operator to transform themicrograft generating station260 from the open configuration to the closed configuration.
• Themicrograft transferring station370 comprises aframe301. The frame has a top portion301aand a bottom portion301b. The top portion301ais connected to the bottom portion301b. Theframe301 has an open configuration and a closed configuration.FIG. 7 shows theframe301 in the open configuration. Themicrograft transferring station370 further includes atransfer pusher308 including a plurality of prongs309. The prongs are similar to those shown inFIG. 2B. Thetransfer pusher308 is connected to the top portion301aof theframe301 such that the prongs309 are oriented downward toward the bottom portion301bof theframe301. Themicrograft transferring station370 further includes atransfer stage310, which is connected to the bottom portion301bof theframe301. Thetransfer pusher308 and thetransfer stage310 are aligned with each other. In certain embodiments, thetransfer stage310 may be made of any material that is softer than that of thetransfer pusher308. In certain embodiments, thetransfer stage310 is composed of a compressible material. In other embodiments, thetransfer stage310 includes a spring loaded base (FIG. 8). The spring loaded base includes astage401, coupled to aspring402. The spring loaded base may further include aball403 to focus the force on the center of thestage401.
• Frame301 further includes acartridge receiving portion311. Thecartridge receiving portion311 is located between the top portion301aand the bottom portion301bof theframe301, and is also hingedly connected with the top portion301aand the bottom portion301bof theframe301. Thecartridge receiving portion311 includes aslot312. Theslot312 is aligned with transfer pusher and the transfer stage of themicrograft transferring station370. In this figure,slot312 is shown with a thecartridge119 loaded into theslot312.
• Frame301 further includes astripper plate320. Thestripper plate320 is located above the bottom portion301bof theframe301 and below thecartridge receiving portion311 and the top portion301aof theframe301. Thestripper plate320 includes an innerhollow portion321 such that thecartridge receiving portion311, the transferpusher transfer pusher308 and thetransfer stage310 fit within the innerhollow portion321 of thestripper plate320. Such configuration is important for transfer of micrografts from the cartridge to the substrate, which is described in greater detail below.
• Themicrograft transferring station370 also includes alever314. Thelever314 runs through the center offrame301 and is connected to the top portion301a, thecartridge receiving portion311, thestripper plate320, and the bottom portion301b. Thelever314 is used to transform themicrograft transferring station370 from the open configuration to the closed configuration and back to the open configuration. Thelever314 acts as a force multiplier, such that upon engagement of thelever314, an exponential amount of force is transferred to themicrograft transferring station370 as an operator transformsmicrograft transferring station370 from the open configuration to the closed configuration. The exponential amount of force transferred may be varied by varying the length of thelever314. In certain embodiments, thelever314 is configured to provide for at least about a 50× increase in force transferred to themicrograft transferring station370 as compared to the amount of force applied to thelever314 by an operator to transform themicrograft transferring station370 from the open configuration to the closed configuration.
• Cartridges that may be used withdevice200 are the same as those described above in connection withdevice100.
• Device200 as described herein may be used to prepare skin grafts for any recipient site of damaged skin. General methods for preparing skin grafts are described in co-owned and co-pending U.S. patent application Ser. No. 12/851,621, the content of which is incorporated by reference herein in its entirety. In certain embodiments, methods of the invention generally involve harvesting a skin graft from a donor site, such as an epidermal graft, generating an array of micrografts from the single graft, placing the graft on a first substrate, expanding a distance between the micrografts on a first substrate, optionally transferring the micrografts from the first substrate to a second substrate, and applying the micrografts to a recipient site. Harvesting of the skin grafts and placing of the harvested skin graft into a cartridge for use withdevice200 is described above.
• Now loaded into the cartridge, a plurality of micrografts may be generated usingdevice200. To generate the micrografts, thecartridge119 is flipped right side up and loaded into themicrograft generating station260 ofdevice200.Cartridge119 is oriented such thatbevel122 onframe121 ofcartridge119 is aligned with a bevel inslot212 ofcartridge receiving portion211 offrame201. Once aligned, thecartridge119 is slid intoslot212. Once inslot212, thehollow portion123 of theframe121 of thecartridge119 is aligned with thefirst member206 and thesecond member207 of themicrograft generating station260.
• Themicrograft generating station260 is then transformed from the open configuration to the closed configuration by engaginglever214. Such movement causes thetop portion201aand thecartridge receiving portion211 of theframe201 to move vertically downward toward the bottom portion201bof theframe201. With such movement, themesh grid129 of thesecond plate127 of thecartridge119 come in contact with thesecond member207 of themicrograft generating station260. Additionally, thefirst member206 of themicrograft generating station260 passes into thehollow portion123 of theframe121 ofcartridge119 and contacts themesh grid128 offirst plate126 of thecartridge119. The first andsecond members206 and207 compress themesh grids128 and129 of first andsecond plates126 and127 of thecartridge119. The compressive force results in themesh grids128 and129 cutting theskin graft120 that is sandwiched betweenplates126 and127, thereby generating the plurality of micrografts. The cuts may pass partially or completely through the graft tissue. The plurality of micrografts reside in the holes of themesh grids128 and129.
• Once the micrografts are generated, thelever214 is used to transform themicrograft generating station260 back to the open configuration.Cartridge119 is removed fromslot212 ofcartridge receiving portion211 offrame201. The cartridge is now ready to be transferred to themicrograft transferring station370.
• Usingmicrograft transferring station370, the micrografts are transferred to a substrate, as described here. Thecartridge119 is inserted into the312 ofcartridge receiving portion311 offrame301.Cartridge119 is oriented such thatbevel122 onframe121 ofcartridge119 is aligned with a bevel in slot313 ofcartridge receiving portion311 offrame301. Once aligned, thecartridge119 is slid into slot313. Once in slot313, thehollow portion123 of theframe121 of thecartridge119 is aligned with thetransfer pusher308 and thetransfer stage310 of themicrograft transferring station370.
• Asubstrate134 is placed on top oftransfer stage310. Generally, thesubstrate134 will have an adhesive side and thesubstrate134 should be placed onto thetransfer stage310 such that the adhesive side of thesubstrate134 is facing up. Further description of types of substrates to me used with devices of the invention is provided above.
• Themicrograft transferring station370 is then transformed from the open configuration to the closed configuration by engaginglever314. Engagement of the lever results in movement that causes the top portion301a, thecartridge receiving portion311, and thestripper plate320 to move vertically downward toward the bottom portion301bof theframe301. With such movement, thestripper plate320 moves downward and contacts the outer perimeter of thesubstrate134. The hollowinner portion321 surrounds thattransfer stage310 and leaves thetransfer stage310 accessible to interact with thecartridge119. Then, thecartridge receiving portion311 and thetransfer pusher308 move downward and into the hollowinner portion321 of thestripper plate320, resulting in themesh grid129 of thesecond plate127 of thecartridge119 coming in contact with thesubstrate134 that is on top of thetransfer stage310 of themicrograft transferring station370.
• As this is occurring, the plurality of prongs309 of thetransfer pusher308 of themicrograft transferring station370 pass into thehollow portion123 of theframe121 ofcartridge119. The prongs309 are small than the holes of themesh grids128 and129. The prongs pass through the holes of themesh grids128 and129 and push themicrografts135 residing in the holes of themesh grids128 and129 through themesh grids128 and129 and onto thesubstrate134. Once themicrografts135 are transferred tosubstrate134, thelever314 is used to transformmicrograft transferring station370 back to the open configuration.
• In greater detail, themesh grid129 holding the tissue is the first component to contact thesubstrate134 on thetransfer stage310. Thegrid129, thepusher308, and the transfer stage move downward together a small amount before thecartridge receiving portion311 that is holding thecartridge119 holding themesh grid129 hits a stop. The prongs309 of thepusher308 continue pushing the tissue held in thegrid129 and thetransfer stage310 downward until the top portion301aof theframe301 hits a second stop. At this point, themicrografts135 have been pushed through thegrid129 and onto thesubstrate134 and themicrografts135 are no longer in contact with thegrid129. Just prior to thepusher310 hitting the second stop, alatch340 on the top portion301ainteracts with ahasp341 on thecartridge receiving portion311, locking the top portion301ato thecartridge receiving portion311 so that their upward movement is linked (FIGS. 7 and 9). Thelever314 is then reengaged to transform themicrograft transferring station370 back to the open configuration. This results in the pusher top portion301aand linkedcartridge receiving portion311 to move upward until there is no longer contact with thesubstrate134, leaving the micrografts fully transferred to thesubstrate134. During this process, thestripper plate320 also moves upward, releasing itself from the edges of thesubstrate134.
• Once themicrografts135 have been transferred to thesubstrate134, the substrate is stretched or expanded, the micrografts are optionally transferred to a second substrate, and the expanded micrografts are applied to a recipient site, all of which is described above.
INCORPORATION BY REFERENCE
• References and citations to other documents, such as patents, patent applications, patent publications, journals, books, papers, web contents, have been made throughout this disclosure. All such documents are hereby incorporated herein by reference in their entirety for all purposes.
EQUIVALENTS
• The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting on the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.

Claims (56)

1. A device for generating and transferring micrografts, the device comprising:

a housing comprising an open configuration and a closed configuration;

a micrograft generating station; and

a micrograft transferring station.

2. The device according toclaim 1, wherein the housing comprises a bottom portion hingedly connected to a top portion.

3. The device according toclaim 2, wherein the top portion of the housing is movable in a vertical direction.

4. The device according toclaim 3, wherein the micrograft generating station comprises:

an first member connected to the top portion of the housing; and

a second member connected to the bottom portion of the housing, wherein the first member is aligned with the second member.

5. The device according toclaim 4, wherein the second member comprises a spring loaded base.

6. The device according toclaim 3, wherein the micrograft transferring station comprises:

a transfer pusher comprising a plurality of prongs, wherein the pusher is connected to the top portion of the housing; and

a transfer stage connected to the bottom portion of the housing, wherein the pusher and the stage are aligned with each other.

7. The device according toclaim 6, wherein the transfer stage comprises a compressible material.

8. The device according toclaim 6, wherein the transfer stage comprises a spring loaded base.

9. The device according toclaim 3, wherein the housing further comprises a cartridge receiving portion that is located between the top portion and the bottom portion of the housing.

10. The device according toclaim 9, wherein the cartridge receiving portion comprises a first slot and a second slot, wherein the first slot is aligned with the micrograft generating station and the second slot is aligned with the micrograft transferring station.

11. The device according toclaim 9, wherein the cartridge receiving portion comprises a single slot and components of the micrograft generating station and the micrograft transferring station are removable from the top and bottom portions of the housing, thereby providing for the micrograft generating station and the micrograft transferring station to be located at a same place in the device.

12. The device according toclaim 10, further comprising a cartridge that is compatible with the first slot and second slots of the cartridge receiving portion and is removable from the first and second slots of the cartridge receiving portion.

13. The device according toclaim 12, wherein the cartridge is configured to hold a skin graft.

14. The device according toclaim 12, wherein the cartridge comprises:

a frame comprising a hollow inner portion;

a removable first plate comprising a mesh grid;

a removable second plate comprising a mesh grid;

wherein in an assembled configuration, the mesh grid of the first plate and the mesh grid of the second plate are aligned with the hollow portion of the frame, and the grid of the first plate is aligned with the grid of the second plate.

15. The device according toclaim 14, wherein holes of the grids of the first and second plates are larger than prongs of the transfer pusher.

16. A method for generating and transferring micrografts, the method comprising:

providing a device comprising a housing having an open configuration and a closed configuration; a micrograft generating station; and a micrograft transferring station;

inserting a skin graft into the device,

engaging the micrograft generating station, thereby generating a plurality of micrografts; and

engaging the micrograft transferring station, thereby transferring the plurality of micrografts to a substrate.

17. The method according toclaim 16, wherein inserting comprises:

obtaining a cartridge comprising: a frame comprising a hollow inner portion; a removable first plate comprising a mesh grid; a removable second plate comprising a mesh grid;

wherein in an assembled configuration, the grid of the first plate and the grid of the second plate are aligned with the hollow portion of the frame, and the grid of the first plate is aligned with the grid of the second plate; and

inserting the skin graft between the first and second plates such that the graft is aligned with the grids in the first and second plates.

18. The method according toclaim 17, wherein engaging the micrograft generating station comprises:

inserting the cartridge into the micrograft generating station of the device while the housing is in the open configuration; and

transforming the housing from the open configuration to the closed configuration, thereby generating a plurality of micrograft.

19. The method according toclaim 17, wherein engaging the micrograft transferring station comprises:

inserting the cartridge into the micrograft transferring station of the device while the housing is in the open configuration;

inserting a substrate below the cartridge; and

transforming the housing from the open configuration to the closed configuration, thereby transferring the plurality of micrografts to the substrate.

20. The method according toclaim 19, wherein the substrate is a medical dressing.

21. The method according toclaim 16, wherein the graft is an autograft.

22. The method according toclaim 16, further comprising prior to the providing step: harvesting the skin graft.

23. The method according toclaim 22, wherein harvesting comprises:

raising a blister; and

cutting the blister to obtain the skin graft.

24. The method according toclaim 22, wherein raising comprises:

contacting a device having a hole to skin; and

applying heat and/or vacuum pressure, thereby raising the blister.

25. The method according toclaim 16, wherein the skin graft is selected from the group consisting of: an epidermal skin graft, a split thickness graft, and a full thickness graft.

26. The method according toclaim 16, further comprising:

expanding the micro grafts; and

applying the expanded grafts to a patient recipient site.

27. The method according toclaim 26, wherein the recipient site is an area of depigmented skin that has been prepared to receive a skin graft.

28. A device for generating and transferring micrografts, the device comprising:

a base member;

a micrograft generating station integrated with the base member; and

a micrograft transferring station integrated with the base member.

29. The device according toclaim 28, wherein the micrograft generating station comprises:

a frame comprising an open configuration and a closed configuration;

a first member connected to a top portion of the frame; and

a second member connected to a bottom portion of the frame, wherein the first member is aligned with the second member.

30. The device according toclaim 29, wherein the second member comprises a spring loaded base.

31. The device according toclaim 29, wherein the frame further comprises a cartridge receiving portion that is located between the top portion and the bottom portion of the frame.

32. The device according toclaim 31, wherein the cartridge receiving portion comprises a slot that is aligned with the first and second members of the micrograft generating station.

33. The device according toclaim 28, wherein the micrograft transferring station comprises:

a frame comprising an open configuration and a closed configuration;

a transfer pusher comprising a plurality of prongs, wherein the pusher is connected to a top portion of the frame; and

a transfer stage connected to a bottom portion of the frame, wherein the pusher and the stage are aligned with each other.

34. The device according toclaim 33, wherein the transfer stage comprises a compressible material.

35. The device according toclaim 33, wherein the transfer stage comprises a spring loaded base.

36. The device according toclaim 33, wherein the frame further comprises a cartridge receiving portion that is located between the top portion and the bottom portion of the frame.

37. The device according toclaim 36, wherein the cartridge receiving portion comprises a slot that is aligned with the pusher and the stage of the micrograft generating station.

38. The device according toclaim 37, wherein the top portion of the frame further comprises a latch that allows for the top portion of the frame to lock with the cartridge receiving portion.

39. The device according toclaim 36, wherein the frame further comprises a stripper plate that comprises a hollow inner portion such that the cartridge receiving portion, the pusher, and the stage can fit within the hollow inner portion of the stripper plate.

40. The device according toclaim 28, further comprising a cartridge that is compatible with the cartridge receiving portions of the micrograft generating station and the micrograft transferring station.

41. The device according toclaim 40, wherein the cartridge is configured to hold a skin graft.

42. The device according toclaim 40, wherein the cartridge comprises:

a frame comprising a hollow inner portion;

a removable first plate comprising a mesh grid;

a removable second plate comprising a mesh grid;

wherein in an assembled configuration, the mesh grid of the first plate and the mesh grid of the second plate are aligned with the hollow portion of the frame, and the grid of the first plate is aligned with the grid of the second plate.

42. The device according toclaim 42, wherein holes of the grids of the first and second plates are larger than prongs of the transfer pusher.

43. A method for generating and transferring micrografts, the method comprising:

providing a device comprising a base member; a micrograft generating station integrated with the base member; and a micrograft transferring station integrated with the base member;

inserting a skin graft into the device,

engaging the micrograft generating station, thereby generating a plurality of micrografts; and

engaging the micrograft transferring station, thereby transferring the plurality of micrografts to a substrate.

44. The method according toclaim 43, wherein inserting comprises:

obtaining a cartridge comprising: a frame comprising a hollow inner portion; a removable first plate comprising a mesh grid; a removable second plate comprising a mesh grid; wherein in an assembled configuration, the grid of the first plate and the grid of the second plate are aligned with the hollow portion of the frame, and the grid of the first plate is aligned with the grid of the second plate; and

inserting the skin graft between the first and second plates such that the graft is aligned with the grids in the first and second plates.

45. The method according toclaim 44, wherein engaging the micrograft generating station comprises:

inserting the cartridge into the micrograft generating station while a frame of the station is in an open configuration; and

transforming the frame from the open configuration to a closed configuration, thereby generating a plurality of micrograft.

46. The method according toclaim 44, wherein engaging the micrograft transferring station comprises:

inserting the cartridge into the micrograft transferring station while a frame is in an open configuration;

inserting a substrate below the cartridge; and

transforming the frame from the open configuration to a closed configuration, thereby transferring the plurality of micrografts to the substrate.

47. The method according toclaim 46, wherein the substrate is a medical dressing.

48. The method according toclaim 43, wherein the graft is an autograft.

49. The method according toclaim 43, further comprising prior to the providing step: harvesting the skin graft.

50. The method according toclaim 49, wherein harvesting comprises:

raising a blister; and

cutting the blister to obtain the skin graft.

51. The method according toclaim 50, wherein raising comprises:

contacting a device having a hole to skin; and

applying heat and/or vacuum pressure, thereby raising the blister.

52. The method according toclaim 43, wherein the skin graft is selected from the group consisting of: an epidermal skin graft, a split thickness graft, and a full thickness graft.

53. The method according toclaim 43, further comprising:

expanding the micro grafts; and

applying the expanded grafts to a patient recipient site.

54. The method according toclaim 53, wherein the recipient site is an area of depigmented skin that has been prepared to receive a skin graft.

55. A device for generating and transferring micrografts, the device comprising:

a base member;

a micrograft generating station integrated with the base member;

a micrograft transferring station integrated with the base member; and

a micrograft expansion station integrated with the base member.

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