Patent Description:
An autograft can refer to tissue transplanted from one part of an individual's body (e.g., a "donor site") to another part (e.g., a "recipient site"). Autografts can be used, for example, to replace missing skin and other tissue and/or to accelerate healing resulting from trauma, wounds, burns, surgery and birth defects. Availability of tissue for autografting can be limited by characteristics of candidate donor sites, including a number and/or total area of tissue grafts, healing behavior of the donor site, similarity of the donor and recipient sites, aesthetic considerations, etc..

Skin grafting can be performed surgically. For example, a conventional autograft procedure may include excision or surgical removal of burn injured tissue, choosing a donor site, which may be an area from which healthy skin is removed to be used as cover for the cleaned burned area, and harvesting, where the graft may be removed from the donor site, e.g., using an instrument similar to an electric shaver. Such instrument (e.g., a dermatome) can be structured to gently shave a piece of tissue, which may be, e.g., about <NUM>/<NUM> of an inch thick for a split-thickness graft, from the skin at the unburned donor site to use as a skin graft. The skin graft can then be placed over the cleaned wound so that it can heal. Donor skin tissue can be removed to such a depth that the donor site can heal on its own, in a process similar to that of healing of a second degree burn.

Two conventional types of autografts which may be used for a permanent wound coverage include sheet grafts and meshed grafts. A sheet graft can refer to a piece of skin tissue removed from an undamaged donor site of the body, in a process that may be referred to as harvesting. The size of the donor skin piece that is used may be about the same size as the damaged area. The sheet graft can be laid over the excised wound, and stapled or otherwise fastened in place. The donor skin tissue used in sheet grafts may not stretch significantly, and a sheet graft can be obtained that is slightly larger than the damaged area to be covered because there may often be a slight shrinkage of the graft tissue after harvesting.

Sheet grafts can provide an improved appearance of the repaired tissue site. For example, sheet grafts may be preferred for use on large areas of the face, neck and hands if they are damaged, so that these more visible parts of the body can appear less scarred after healing. A sheet graft may be used to cover an entire burned or damaged region of skin, e.g., if the damaged site is small. Small areas of a sheet graft can be lost after placement because of a buildup of fluid (e.g., a hematoma) can occur under the sheet graft following placement the sheet graft.

Sheet grafts may be full-thickness or split-thickness. For example, split-thickness skin grafts can be used to cover wounds in burn and skin ulcer patients. A conventional split-thickness graft can be formed, e.g., by harvesting a sheet of epidermis and upper dermal tissue from a donor site, in a procedure similar to that of peeling an apple. The split-thickness graft can then be placed on the location of the burn or ulcer. The skin tissue may then grow back at the donor site following a generally extended healing time. Split-thickness grafts may be preferable to full-thickness grafts because removing large amounts of full-thickness skin tissue from the donor site can lead to scarring and extensive healing times at the donor site, as well as an increased risk of infection. However, skin tissue removed from the donor site for a split-thickness skin autograft can include only a thin epithelial layer, which can lack certain elements of the dermis that improve structural stability and normal appearance in the recipient site.

Full-thickness skin grafts can be formed using sheets of tissue that include the entire epidermis layer and a dermal component of variable thickness. Because the dermal component can be preserved in full-thickness grafts, more of the characteristics of normal skin can be maintained following the grafting procedure. Full-thickness grafts can contain a greater collagen content, dermal vascular plexus, and epithelial appendages as compared to split-thickness grafts. However, full-thickness grafts can require more precise conditions for survival because of the greater amount of tissue requiring revascularization.

Full-thickness skin grafts can be preferable for repairing, e.g., visible areas of the face that may be inaccessible by local flaps, or for graft procedures where local flaps are contraindicated. Such full-thickness skin grafts can retain more of the characteristics of normal skin including, e.g., color, texture, and thickness, as compared to split-thickness grafts. Full-thickness grafts may also undergo less contraction while healing. These properties can be important on more visible areas such as the face and hands. Additionally, full-thickness grafts in children can be more likely to grow with the individual. However, application of conventional full-thickness skin grafts can be limited to relatively small, uncontaminated, well-vascularized wounds, and thus may not be appropriate for as many types of graft procedures as split-thickness grafts. Additionally, donor sites for full-thickness grafts can require surgical closure or resurfacing with a split-thickness graft.

A meshed skin graft can be used to cover larger areas of open wounds that may be difficult to cover using sheet grafts because of, e.g., a lack of a sufficient area of healthy donor sites. Meshing of a skin graft can facilitate skin tissue from a donor site to be expanded to cover a larger area. It also can facilitate draining of blood and body fluids from under the skin grafts when they are placed on a wound, which may help prevent graft loss. The expansion ratio (e.g., a ratio of the unstretched graft area to the stretched graft area) of a meshed graft may typically be between about <NUM>:<NUM> to <NUM>:<NUM>. For example, donor skin can be meshed at a ratio of about <NUM>: <NUM> or <NUM>:<NUM> ratio, whereas larger expansion ratios may lead to a more fragile graft, scarring of the meshed graft as it heals, and/or extended healing times.

A conventional graft meshing procedure can include running the donor skin tissue through a machine that cuts slits through the tissue, which can facilitate the expansion in a pattern similar to that of fish netting or a chain-link fence. Healing can occur as the spaces between the mesh of the stretched graft, which may be referred to as gaps or interstices, fill in with new epithelial skin growth. However, meshed grafts may be less durable graft than sheet grafts, and a large mesh can lead to permanent scarring after the graft heals.

To help the graft heal and become secure, the area of the graft can preferably not be moved for at least about five days following each surgery. During this immobilization period, blood vessels can grow from underlying tissue into the skin graft, and can help to bond the two tissue layers together. About five days after the graft is placed, exercise therapy programs, tub baths, and other normal daily activities can often be resumed. Deep second-degree and full-thickness burns may require skin graft surgery for quick healing and minimal scarring. Large burn sizes can lead to more than one grafting procedure during a hospital stay, and may require long periods of immobilization for healing.

As an alternative to autografting, skin tissue obtained from recently-deceased people (which may be referred to, e.g. as a homograft, an allograft, or cadaver skin) can be used as a temporary cover for a wound area that has been cleaned. Unmeshed cadaver skin can be put over the excised wound and stapled in place. Post-operatively, the cadaver skin may be covered with a dressing. Wound coverage using cadaveric allograft can then be removed prior to permanent autografting.

A xenograft or heterograft can refer to skin taken from one of a variety of animals, for example, a pig. Heterograft skin tissue can also be used for temporary coverage of an excised wound prior to placement of a more permanent autograft, and may be used because of a limited availability and/or high expense of human skin tissue. In some cases religious, financial, or cultural objections to the use of human cadaver skin may also be factors leading to use of a heterograft. Wound coverage using a xenograft or an allograft is generally a temporary procedure which may be used until harvesting and placement of an autograft is feasible.

Epithelial appendages can preferably be regenerated following a grafting procedure. For example, hair can be more likely to grow from full-thickness grafts than from split-thickness grafts, but such hair growth may be undesirable based on the location of the wound. Accordingly, donor sites for full-thickness grafts can be carefully selected based in part, e.g., on patterns of hair growth at the time of surgery. Further, certain hair follicles may not be oriented perpendicular to the skin surface, and they can be transected if an incision provided to remove graft tissue is not oriented properly.

Sweat glands and sebaceous glands located in graft tissue may initially degenerate following grafting. These structures can be more likely to regenerate in full-thickness grafts than in split-thickness grafts because full-thickness grafts can be transferred as entire functional units. For example, sweat gland regeneration can depend in part on reinnervation of the skin graft with recipient bed sympathetic nerve fibers. Once such ingrowth has occurred, the skin graft can assume the sweating characteristics of the recipient site, rather than retaining the characteristics of the donor site. In contrast, sebaceous gland regeneration may be independent of graft reinnervation and can retain the characteristics of the donor site. Prior to the regeneration, the skin graft tissue may lack normal lubrication of sebum produced by these glands, which can make such grafts more susceptible to injury.

In general, grafting procedures may be limited by the amount of tissue which can be removed from the donor site without causing excessive adverse effects. Full-thickness grafts can provide improved tissue quality at the wound site, but the donor site may be more severely disfigured as described above. Split-thickness grafts can be a compromise between healing times and aesthetic and functional properties of the donor and recipient sites, whereas meshing can provide more extensive graft coverage at the expense of visible scarring.

Harvesting of graft tissue from the donor site generally can generate undesirable large-scale tissue damage to the donor site. On the other hand, small areas of skin wounding adjacent to healthy tissue can be well-tolerated and may heal quickly. Such healing of small wounds can occur in techniques such as "fractional photothermolysis" or "fractional resurfacing," in which patterns of damage having a small dimension can be created in skin tissue. These exemplary techniques are described, e.g., in <CIT> and <CIT>. Small-scale damage patterns can heal quickly by regrowth of healthy tissue, and can further provide desirable effects such as skin tightening without visible scarring.

<CIT> describes a method for excising skin.

<CIT> describes a combined multiple punch and single punch hair transplant cutting device.

<CIT> describes a collicular extraction method.

<CIT> describes a device for enhanced microneedle penetration of biological barriers.

In view of the shortcomings of the above described procedures for tissue grafting, it may be desirable to provide exemplary embodiments of an apparatus that can provide tissue suitable for grafting while minimizing unwanted damage to the donor sites.

Exemplary embodiments of the present disclosure provide an apparatus for obtaining small portions of graft tissue that can be accompanied by rapid healing of the donor site.

The present invention is defined by the apparatus of independent claim <NUM>. In the following, parts of the description and drawing referring to embodiments, which are not covered by the claims are not presented as embodiments of the invention, but as examples useful for understanding the invention.

These and other objects, features and advantages of the present disclosure will become apparent upon reading the following detailed description of exemplary embodiments of the present disclosure, when taken in conjunction with the appended claims.

Further objects, features and advantages of the present disclosure will become apparent from the following detailed description taken in conjunction with the accompanying figures showing illustrative embodiments, results and/or features of the exemplary embodiments of the present disclosure, in which:.

Throughout the drawings, the same reference numerals and characters, unless otherwise stated, are used to denote like features, elements, components, or portions of the illustrated embodiments. Moreover, while the present disclosure will now be described in detail with reference to the figures, it is done so in connection with the illustrative embodiments and is not limited by the particular embodiments illustrated in the figures.

Exemplary embodiments of the present disclosure provide methods and apparati for producing autografts, and particularly such methods and apparati which can facilitate more rapid healing of the donor site while providing improved tissue characteristics at the recipient site. Exemplary embodiments of the present disclosure can include a plurality of small-scale tissue portions (e.g., micrografts) that can be used to provide autografts. Such micrografts can avoid significant permanent damage to the donor site while providing graft tissue that can heal rapidly and generate skin tissue having desirable properties at the recipient site. Methods and procedures for producing and harvesting autografts are not part of the claimed invention.

In exemplary embodiments of the present disclosure, a method can be provided for creating autografts in which tissue portions having at least one small dimension (e.g., micrografts) are harvested from an exemplary donor site <NUM>, as shown in <FIG>. The holes <NUM> shown in <FIG> represent regions of the exemplary donor site <NUM> from which tissue portions (e.g., micrografts) have been removed. These exemplary holes <NUM> may have an approximately round cross-sectional shape, although other shapes may be used.

The exemplary donor site <NUM> is shown in <FIG> after healing of the harvested tissue has occurred. The small regions of damage <NUM> created at the donor site by the removed tissue can heal rapidly and/or without visible scarring. For example, the residual pattern of the healed donor site <NUM> shown in <FIG> may not be easily perceptible by the naked eye under normal viewing conditions.

An exemplary micrograft <NUM> that can be formed, e.g., by harvesting or removing a portion of the tissue from the donor site <NUM> to form the hole <NUM> therein, is shown in <FIG>. The exemplary micrograft <NUM> can have an elongated shape that may be approximately cylindrical. The micrografts <NUM> can include both epidermal tissue <NUM> and dermal tissue <NUM> from the exemplary donor site <NUM>. For example, the exemplary micrograft <NUM> can be about <NUM> in length, which can correspond to a typical total depth of the skin layer (e.g., epidermal and dermal layers). A different length may be used based on the particular skin or tissue characteristics of the donor site <NUM>. In general, it can be preferable to avoid harvesting a significant amount of subcutaneous tissue, so the harvested micrografts <NUM> can include primarily the epidermal tissue <NUM> and the dermal tissue <NUM>. A lower portion <NUM> of the exemplary micrograft <NUM> can also include stem cells that can be present in a lower portion of the dermal layer of the donor site <NUM> (e.g., near a dermal/fatty layer boundary).

A width or diameter of the holes <NUM> produced during harvesting (which can correspond approximately to the diameters of the portions of the harvested micrografts <NUM>) can be less than about <NUM>, or less than about <NUM>. In certain exemplary embodiments, the diameter or width can be less than about <NUM>, or about <NUM>. The size of the exemplary holes <NUM> can be selected, e.g., based on the effects of creating small damage regions in the donor site <NUM> which can heal rapidly and/or without scarring, and on creating portions of tissue that may be large enough to form a sufficient amount of graft tissue.

For example, living tissue can be provided with nutrients via a diffusional transport over distances of about <NUM>. Accordingly, the exemplary micrografts <NUM> having at least one dimension that is less than about <NUM> or, e.g., about <NUM>, can exhibit improved viability and likelihood to survive, and grow when used in a graft. Such exemplary micrografts <NUM> can be better able to receive nutrients (including, e.g., oxygen) when placed in a recipient site, prior to revascularization of the tissue. Larger micrografts <NUM> can also benefit from such diffusional transport of nutrients, and can also be more likely to survive than significantly larger portions of graft tissue (e.g., conventional full-thickness, split-thickness or meshed grafts).

A fraction of surface tissue removed from the donor site <NUM> by harvesting (which can correspond to a fractional surface area of the exemplary donor site <NUM> occupied by the holes <NUM>) may be less than about <NUM>%, or more preferably less than about <NUM>%. The fraction of tissue removed can be sufficiently large to provide enough harvested micrografts <NUM> to form a graft therefrom of appropriate size, but small enough to facilitate rapid healing at the donor site <NUM> based on growth from the remaining undamaged tissue. Other fractions of tissue can be removed from a donor site <NUM> depending on factors such as, e.g., the particular characteristics of the donor site <NUM>, the size of the graft needed, and the overall amount of donor site tissue available.

In further exemplary embodiments of the present disclosure, a graft <NUM> can be provided by embedding or inserting a plurality of micrografts <NUM> in a biocompatible matrix <NUM> as shown, e.g., in <FIG>. The exemplary matrix <NUM> containing the micrografts <NUM> can be exposed to nutrients to promote growth of the harvested micrografts <NUM>, e.g., to form a continuous or nearly continuous layer of tissue in the graft <NUM> after growth has occurred. The exemplary graft <NUM>, which can include the matrix <NUM> and the micrografts <NUM>, may be placed directly over a recipient site <NUM> (e.g., a cleaned wound area) as shown in <FIG>. The exemplary micrografts <NUM> can also include stem cells as described herein, which can also facilitate healing and integration of the exemplary micrografts <NUM> when they are transplanted to the recipient site <NUM>. The recipient site <NUM> can provide nutrients and/or promote revascularization of the harvested micrografts <NUM>, which can further enhance their growth through the matrix <NUM> to eventually fill in the spaces separating them. For example, <FIG> shows the micrografts <NUM> after they have begun to grow into the surrounding matrix <NUM>.

In one exemplary embodiment, the micrografts <NUM> can be placed in the matrix <NUM> at approximately the same spacing (e.g., a similar areal density) as they were removed from the donor site <NUM>. This exemplary configuration can generate an amount of graft tissue that may be approximately the same size as the overall harvested area of the donor site <NUM> after the micrografts <NUM> grow and fill in the spaces between them with new tissue. The average spacing of the micrografts <NUM> in the matrix <NUM> can also be increased to form a graft tissue that is larger than the overall area of the harvested donor site <NUM>. The particular spacing of the micrografts <NUM> in a particular graft <NUM> can be selected based on factors such as, e.g., the size and fractional damage of the donor site <NUM>, the size of the recipient site <NUM> to be covered by the skin graft <NUM>, the time needed for the micrografts <NUM> to regrow and form a continuous tissue layer, the desired appearance of the grafted recipient site, etc. For example, the exemplary micrografts <NUM> can be spaced far apart in a particular graft, which can provide a larger graft area but can also require longer healing time and the possibility of some visible scarring or texture in the healed graft <NUM>.

In a further exemplary embodiment, tissue portions <NUM> such as that shown in <FIG> can be harvested in an elongated, narrow strip-like shape. One or more of the exemplary tissue strips <NUM> can include both epidermal tissue <NUM> as well as dermal tissue <NUM>, which can be similar to the micrograft <NUM> shown in <FIG>. For example, the height of the exemplary tissue strip <NUM> may be about <NUM>, or another length that may correspond to a local depth of the dermal layer at the donor site <NUM>. Larger and/or smaller depths can also be selected when harvesting tissue strips <NUM> based on, e.g., characteristics of the donor and recipient sites, the wound to be repaired by grafting, etc..

Harvesting of such exemplary tissue strips <NUM> can leave long, narrow grooves <NUM> in a donor region <NUM> as shown, e.g., in <FIG>. A width of the grooves <NUM> (and thus a width of the harvested tissue strips <NUM>) can be less than about <NUM>, or less than about <NUM>. In certain exemplary embodiments, the width of such tissue strips can be less than about <NUM>, or about <NUM>. As described herein, such a small dimension can facilitate diffusional transport of nutrients to the graft tissue and can improve viability of the harvested tissue. A depth of the grooves <NUM> from the skin surface can correspond to the height of the harvested strips <NUM>.

A surface area fraction of the exemplary donor site <NUM> that is removed to form tissue strips <NUM> can be less than about <NUM>%, or about <NUM>% or less. Factors governing a selection of parameters associated with the harvested elongated tissue strips <NUM> (e.g., widths and area fractions removed from the donor site) may be similar to those described above with respect to the substantially cylindrical micrografts <NUM>. The length of the harvested strips <NUM> can be selected based on factors such as, for example, ease of cutting, removing, and handling the thin tissue strips <NUM>, the size of the donor site <NUM>, etc. The elongated grooves <NUM> formed in the donor site can may also be able to heal rapidly with little or no visible scarring as shown in <FIG>, because of the small lateral dimension and presence of adjacent healthy tissue that can support local tissue regrowth.

The harvested strips <NUM> can be placed, e.g., in a biocompatible matrix similar to the matrix <NUM> shown in <FIG>. The tissue strips <NUM> can be arranged in an approximately parallel configuration, e.g., corresponding to the configuration of the donor-site grooves <NUM> from which they were removed. The spacing between the strips <NUM> can alternatively be increased or decreased relative to the spacing of the grooves <NUM> in the donor site <NUM> as desired, e.g., to provide either larger overall areas of graft tissue or more densely packed graft tissue, respectively. Such harvested tissue strips <NUM> can be used for certain grafting procedures because the long dimension can preserve structures in the harvested skin tissue that may promote revascularization and improve healing of the graft formed therefrom.

Harvested tissue portions can be removed from the donor site in other shapes, including tile patterns or fractal-like shapes. In general, each removed piece of tissue (and, e.g., each corresponding hole or void in the donor site) can have at least one small dimension that is less than about <NUM>, or less than <NUM>. In certain exemplary embodiments, this small dimension can be less than about <NUM>, or about <NUM>.

In further exemplary embodiments, the harvested tissue portions can be placed at the recipient site in a dense configuration. For example, <FIG> is a schematic top view of a plurality of substantially cylindrical micrografts <NUM> that can be gathered in an exemplary dense arrangement, e.g., where adjacent ones of the exemplary micrografts <NUM> are in at least partially direct contact each other. <FIG> is a schematic side view of the micrografts <NUM> shown in <FIG>. This exemplary dense configuration can provide a graft that is smaller than the overall area of the harvested donor site <NUM>, but which can tend to heal faster and be less likely to produce visible scarring than grafts formed using spaced-apart harvested tissue portions <NUM>, <NUM>. Similar exemplary dense configurations of harvested tissue can be formed using, e.g., elongated strips of tissue <NUM> shown in <FIG> or the like.

The exemplary biocompatible matrix <NUM> can be formed using one or more materials structured to provides mechanical stability and/or support to the harvested micrografts <NUM>, and/or which may promote tissue regrowth. Examples of materials which can be used to form the matrix <NUM> can include polylactic acid (PLA), collagen, or hyaluronic acid (e.g., hyaluranon). Nutrients or other additives can also be provided in the matrix <NUM> to further promote tissue regrowth. Red or near-infrared light can also be used to illuminate the donor site and/or the recipient site after tissue harvesting and placement of the graft tissue to further promote healing of the tissue.

In certain exemplary embodiments, techniques such as photochemical tissue bonding can be used to improve mechanical stability of the micrografts <NUM> and/or tissue strips <NUM> in the matrix <NUM>. For example, a technique for photochemical tissue bonding is described in <CIT>. This technique includes an application of a photosensitizer to a tissue, followed by irradiation with electromagnetic energy to produce a tissue seal. For example, a photosensitizer such as Rose Bengal can be applied to the matrix <NUM> containing the exemplary micrografts <NUM> and/or tissue strips <NUM>, followed by exposure of the matrix to green light for about two minutes. Photochemical tissue bonding can catalyze a polymerization reaction which may facilitate a stronger bonding of the micrografts <NUM> and/or tissue strips <NUM> to the matrix <NUM>, where the matrix <NUM> can include a protein such as, e.g., hyaluronic acid or collagen.

In further exemplary embodiments of the present disclosure, an apparatus <NUM> can be provided, such as that shown in <FIG>, which can facilitate harvesting of the exemplary micrografts <NUM> from the donor site <NUM> as described herein. The exemplary apparatus <NUM> can include a hollow tube <NUM> that can be formed of metal or another structurally rigid material. For example, the tube <NUM> can be formed using a stainless steel, a biopsy needle, or a similar structure. The tube <NUM> can be coated with a lubricant or low-friction material, such as Teflon®, to further facilitate the passage of the tubes <NUM> through the donor site tissue <NUM>.

The inner diameter of the tube <NUM> can be selected to approximately correspond to a particular diameter of a micrograft <NUM> to be removed from the donor site <NUM> as described herein. For example, <NUM> or <NUM> gauge biopsy needles (e.g., having an inner diameter of <NUM> and <NUM>, respectively) or the like can be used to form the tube. A biopsy tube having a larger gauge (and smaller inner diameter) can also be used. A width or diameter of the harvested micrograft <NUM> can be slightly smaller than the inside diameter of the apparatus <NUM> used to harvest it.

A distal end of the tube <NUM> can be shaped to form a plurality of points <NUM>. For example, the two exemplary points or extensions <NUM> shown in <FIG> can be formed by grinding opposite sides of the tube <NUM> at an angle relative to the long axis of the tube <NUM>. In a further exemplary embodiment as shown in <FIG>, an exemplary apparatus <NUM> can be provided that includes a tube <NUM> with three points or extensions <NUM> provided at a distal end thereof. This exemplary configuration can be formed, e.g., by grinding <NUM> portions of the tube <NUM> at an angle relative to the long axis thereof, where the three portions can be spaced apart by about <NUM> degrees around the perimeter of the tube <NUM>. In still further exemplary embodiments, an apparatus can be provided for harvesting micrografts that includes a tube having more than three points or extensions <NUM> provided at a distal end thereof, e.g., a tube <NUM> having four, five, six, seven or eight points <NUM>.

The exemplary points or extensions <NUM> can facilitate insertion of the apparatus <NUM>, <NUM> into tissue at the donor site <NUM>. The exemplary points or extensions <NUM> that are formed, e.g., by grinding portions of the distal end of the tube <NUM> can also have a beveled edge along their sides, which can further facilitate insertion of the apparatus <NUM>, <NUM> into donor-site tissue.

The exemplary apparatus <NUM> can also included a collar or stop <NUM> provided on an outer surface of the tube <NUM>. The exemplary stop <NUM> can be affixed to the tube <NUM> at a particular distance from the ends of the tips <NUM>, or this distance may be adjustable, e.g., over a range of lengths by moving the stop <NUM> along the axis of the tube <NUM>.

<FIG> illustrates the exemplary apparatus <NUM> after it is inserted into the tissue at the donor site <NUM>, e.g., until the stop <NUM> contacts the surface of the donor site <NUM>. A portion of tissue <NUM> can be present within a lower portion of the tube <NUM>. Lateral sides of this tissue portion <NUM> can be cut or severed from the surrounding tissue by the distal end of the tube <NUM> and/or points <NUM> as the tube <NUM> penetrates into the donor site tissue <NUM>. Such tissue <NUM> can remain within the tube <NUM>, and be separated from the donor site <NUM> to form the micrograft <NUM>, e.g., when the tube <NUM> is removed from the donor site <NUM> as shown in <FIG>. The exemplary micrograft <NUM> thus formed can include both epidermal tissue <NUM> and dermal tissue <NUM>.

The exemplary micrograft <NUM> can be removed from the apparatus, e.g., by providing pressure through an opening <NUM> at a proximal end of the tube <NUM> as shown, e.g., in <FIG>. Such pressure can be provided, e.g., by blowing into the opening, by squeezing a flexible bulb attached thereto, by opening a valve leading from a source of elevated pressure such as a small pump, etc. Alternatively, the exemplary micrografts <NUM> can be harvested by inserting the exemplary apparatus <NUM> into a plurality of locations of the donor site <NUM>. Each micrograft <NUM> within the tube <NUM> can then push any micrografts above it towards the opening <NUM>. Once the tube <NUM> has been filled with the harvested tissue, each additional insertion of the exemplary apparatus <NUM> into the donor site <NUM> can facilitate pushing of an uppermost micrograft <NUM> within the tube <NUM> out of the proximal opening <NUM>.

The exemplary apparatus <NUM> can be inserted into the donor site tissue <NUM> to a depth corresponding approximately to a desired length of the harvested micrografts <NUM>. Such distance can be determined and/or controlled, e.g., by appropriate placement or adjustment of the stop <NUM> on the exemplary apparatus <NUM>. For example, the exemplary apparatus <NUM> can be configured or structured such that the points or extensions <NUM> extend to a location at or proximal to the dermal/fatty layer junction <NUM> as shown in <FIG>. For example, the micrograft <NUM> can be removed from the donor site <NUM> by removing the apparatus <NUM> from the donor site without rotating the tube <NUM> around the axis thereof. In contrast, conventional biopsy needles and the like may require a rotation around the long axis to facilitate removal of tissue samples from the surrounding tissue. The points or extensions <NUM> provided on the exemplary apparatus <NUM> can facilitate such removal of the micrograft <NUM> from the surrounding tissue at the donor site <NUM>.

In certain exemplary embodiments, some or all of the tissue at the donor site can be cooled, frozen, or partially frozen prior to harvesting the micrografts <NUM>. Such freezing can facilitate cutting, removal, handling, and/or viability of the micrografts <NUM>. The donor site tissue <NUM> can be cooled or frozen using conventional cooling techniques such as, e.g., applying a crypspray or contacting a surface of the donor site <NUM> with a cooled object for an appropriate duration. The exemplary apparatus <NUM> can also be cooled prior to harvesting the micrografts <NUM>. Such cooling and/or freezing can, e.g., increase a mechanical stability of the micrografts <NUM> when they are harvested and/or placed in the matrix <NUM>.

The exemplary micrografts <NUM> can be provided into the matrix <NUM> using various techniques. For example, the individual micrografts <NUM> can be inserted into particular locations of the matrix <NUM> using, e.g., tweezers or the like. The exemplary apparatus <NUM> containing a harvested micrograft <NUM>, as shown in <FIG>, can also be inserted into a location of the matrix <NUM>, and pressure can be applied to the proximal opening <NUM> to push the micrograft <NUM> into the matrix <NUM>. The exemplary apparatus <NUM> can then be removed from the matrix <NUM>, and the procedure repeated to place a plurality of micrografts <NUM> in the matrix <NUM>. The proximal opening <NUM> can be covered while the apparatus <NUM> is being inserted into the matrix <NUM> to prevent the micrograft <NUM> from being pushed further up into the apparatus <NUM>. For example, the upper portion of the tube <NUM> can be filled with a fluid, e.g., water or a saline solution, to provide an incompressible volume that can further prevent the micrograft <NUM> from rising further up into the tube <NUM>. Such fluid can also facilitate a removal of the micrograft <NUM> from the exemplary apparatus <NUM> by providing pressure at the proximal opening <NUM>.

Exemplary procedures for harvesting and implanting the micrografts <NUM> described herein can be used to provide the micrografts <NUM> directly into, e.g., substantially whole tissue at the recipient site. For example, the micrografts <NUM> can be harvested from the donor site <NUM> that can contain melanocytes, and inserted directly into tissue at a recipient site that lacks sufficient melanocytes. Such exemplary procedure can be used to repigment skin tissue, e.g., to treat vitiligo or similar conditions. Tissue at the recipient site can also be frozen or partially frozen, as described herein, prior to the insertion of the micrografts <NUM> therein.

The exemplary micrografts <NUM> can also be harvested from a healthy donor site and placed directly into scar tissue to facilitate growth of healthy tissue in the scar. Optionally, portions of tissue can be removed from the recipient site prior to placing micrografts in holes at the recipient site that are formed by the removal of these tissue portions. The holes can be about the same size or slightly larger than the size of the micrografts <NUM> to be inserted therein, to facilitate such insertion. The holes can be formed at the recipient site, e.g., using one or more of the tubes <NUM> as described herein, by removing or ablating the tissue using, e.g., an ablative laser, etc..

In an embodiment in accordance with the claimed invention, an apparatus <NUM> is provided as shown in <FIG>. The apparatus <NUM> includes, a plurality of tubes <NUM> affixed or mechanically coupled to a base <NUM>. The tubes <NUM> can be provided in various configurations, e.g., in a linear array, or in any one of various two-dimensional patterns along the base <NUM>. The number of tubes <NUM> provided in the exemplary apparatus <NUM> can be, for example, greater than five tubes <NUM>, more than about <NUM> tubes, or more than about <NUM> tubes <NUM>.

An enclosure <NUM> may be provided in communication with proximal openings <NUM> of the tubes <NUM>. The enclosure <NUM> can also be provided in communication, e.g., with a pressure source <NUM>. For example, the pressure source <NUM> can include a pump or a deformable bulb or the like. The pressure source <NUM> can include, e.g., a flexible membrane provided in communication with the enclosure <NUM>, such that an elevated pressure can be provided within the enclosure <NUM> when the membrane is deformed. Such configurations can facilitate applying pressure to the proximal openings <NUM> for removal and/or insertion of the micrografts <NUM> that can be harvested in the tubes <NUM>, as described herein.

A vibrating arrangement <NUM> may optionally be provided in the apparatus <NUM>. The vibrating arrangement <NUM> can be mechanically coupled to the base <NUM> and/or the tubes <NUM> to facilitate the insertion of the tubes <NUM> into the tissue or matrix material for harvesting or placement of micrografts <NUM>. The vibrating arrangement <NUM> can have an amplitude of vibration in the range of about <NUM>-<NUM>, or between about <NUM>-<NUM>. The frequency of the induced vibrations can be between about <NUM> and about <NUM>, or between about <NUM> and about <NUM>, or even about <NUM>. Particular vibration parameters can be selected based on, e.g., the size, average spacing, and material of the tubes <NUM>, the number of tubes <NUM> in the exemplary apparatus <NUM>, and/or the tissue being treated. The vibrating arrangement <NUM> can include circuitry configured to adjust the amplitude and/or frequency of the vibrations.

The exemplary apparatus <NUM> can be used to simultaneously obtain a plurality of the micrografts <NUM> in the plurality of the tubes <NUM>. Exemplary procedures for obtaining and removing such micrografts <NUM> using the exemplary apparatus <NUM> can be similar to the procedures described herein for obtaining single micrografts <NUM> using the exemplary apparatus <NUM> shown in <FIG>.

The vibration can also assist in severing tissue proximal to the distal end of the tubes <NUM> after they are fully inserted into the donor site <NUM>. This can facilitate separation and/or extraction of the tissue portions within the tubes <NUM> from the donor site <NUM>. These tissue portions are held by friction within the tubes <NUM> as the tubes <NUM> are withdrawn from the donor site <NUM>.

In further embodiments, the donor site tissue can be pre-cooled prior to insertion of the tubes <NUM>, e.g., using convective or conductive techniques such as applying a cryospray or contacting the tissue surface with a cooled object. Cooling of the donor site <NUM> can reduce a sensation of pain when the tubes <NUM> are inserted into the donor site tissue <NUM>, and can also make the tissue <NUM> more rigid and facilitate a more accurate severing of tissue portions (e.g., micrografts <NUM>) by the tubes <NUM>.

The positions and spacing of the tubes <NUM> in the exemplary apparatus <NUM> can be determined, e.g., based on characteristics of the micrografts <NUM> to be obtained, a damage pattern to the donor site <NUM>, and/or other factors as described herein above. The number of the tubes <NUM> provided in the exemplary apparatus <NUM> can be selected based on various factors. For example, a larger number of tubes <NUM> may be desirable to allow more micrografts <NUM> to be harvested simultaneously from a donor site <NUM>. Such exemplary configuration can facilitate a more efficient harvesting process. A smaller number of the tubes <NUM> can be easer to insert simultaneously into the donor site tissue <NUM>. Further, the exemplary apparatus <NUM> having a very large number of the tubes <NUM> can be difficult to manufacture and/or maintain.

The harvested tissue portions can be deposited directly from the tubes <NUM> into the biocompatible matrix material <NUM>. The tubes <NUM> and tissue portions contained therein can be cooled before removal of the tissue portions. This can stiffen the tissue portions within the tubes <NUM> and make them easier to manipulate and position.

In a further exemplary embodiment, an apparatus can be provided that includes a plurality of substantially parallel blades. The ends of certain ones of the adjacent blades can be connected or closed off to provide, e.g., narrow rectangular openings between adjacent blades. Such an exemplary apparatus can be used, e.g., to form the tissue strips <NUM> such as that shown in <FIG>. Spacings, lengths, and other features of this exemplary apparatus can be selected based on factors similar to those described herein, e.g., for the exemplary apparati <NUM>, <NUM>.

In further exemplary embodiments of the present disclosure, the exemplary methods and apparati described herein can be applied to other tissues besides skin tissue, e.g., internal organs such a s a liver or heart, and the like. Thus, grafts can be formed for a variety of tissues while producing little damage to a donor site and facilitating rapid healing thereof, while creating graft tissue suitable for placement at recipient sites.

An image of a distal end of an exemplary apparatus that includes two points is shown in <FIG>. This apparatus is similar to the exemplary apparatus <NUM> illustrated, e.g., in <FIG>. A further rotated image of this exemplary apparatus is shown in <FIG>. The exemplary apparatus was formed using a tube having an outside diameter of about <NUM>, and an inside diameter of about <NUM>. The points or extensions were formed by grinding two opposite sides of the distal end of the tube at an appropriate angle relative to the axis of the tube. The angle used was about <NUM> degrees, although other angles may also be used. A beveled edge of the tube wall can be seen along the sides of the points or extensions. The shape of these points can facilitate insertion of the apparatus into tissue of a donor site and/or separation of a portion of micrograft tissue from the donor site, as described in more detail herein. For example, such micrografts can be separated and removed from the donor site by inserting and withdrawing the apparatus from the donor site tissue without rotating the tube along its axis.

<FIG> is an image of a plurality of micrografts obtained from a donor site of ex vivo skin tissue using the apparatus shown in <FIG>. The micrografts are elongated and substantially similar in shape, although details of the shapes may be somewhat irregular. An upper portion of these micrografts includes epidermal tissue, and the lower portion of these micrografts include dermal tissue removed from the donor site. The width of these micrografts is slightly smaller than the internal diameter of the tube shown in <FIG> that was used to harvest them.

The micrografts shown in <FIG> were removed from the apparatus by inserting the exemplary apparatus into donor site a plurality of times, until the tube was filled with harvested tissue. Each subsequent insertion of the apparatus into the donor site tissue then forced the uppermost micrograft out of the proximal end of the tube, where it was retrieved individually for analysis. Such micrografts can also be removed by applying pressure to the proximal end of the tube containing the micrograft, to force it out of the distal end of the tube as described herein.

Claim 1:
An apparatus (<NUM>) configured for obtaining skin micrografts (<NUM>) from a donor site (<NUM>), the apparatus comprising:
a plurality of hollow tubes (<NUM>), each of the plurality of hollow tubes (<NUM>) comprising:
at least two points (<NUM>) disposed at a distal end thereof;
a bevel disposed between the at least two points (<NUM>), the at least two points (<NUM>) and the bevel configured to sever and capture a corresponding skin micrograft (<NUM>) upon insertion of the respective hollow tube (<NUM>) into the donor site (<NUM>); and
an inner diameter of <NUM> millimeter or less configured to retain the skin micrograft (<NUM>) upon withdrawal of the respective hollow tube (<NUM>) from the donor site (<NUM>); and
a base (<NUM>) configured to secure the plurality of hollow tubes (<NUM>), such that the distal ends of the plurality of hollow tubes (<NUM>) are aligned during insertion into the donor site (<NUM>);
wherein a friction between the skin micrograft (<NUM>) and the hollow tube (<NUM>) retains the skin micrograft (<NUM>) within the hollow tube (<NUM>) upon withdrawal from the donor site (<NUM>).