Patent Description:
Various approaches to tissue copying and grafting are being developed, in which small columns of tissue (microscopic tissue columns, or MTCs) are removed from a donor site and can be used in various procedures such as, e.g., being introduced into a recipient site, implanted in a matrix, etc. Such approaches are described, e.g., in International Patent Publication No. <CIT>. <CIT> relates to a hair follicle harvesting device. <CIT> relates to an apparatus for obtaining one or more portions of biological tissue to form grafts.

The MTCs are typically less than about <NUM> in diameter and their removal is well-tolerated by the donor site. For example, the holes formed in a donor site by removal of MTCs can heal rapidly with little or no visible scar or marking formed because of the small size of the holes and their being surrounded by healthy tissue. These columns of living tissue can nucleate and/or stimulate growth of new tissue. The small size of the MTCs favors their survival in various environments.

The MTCs can be harvested using a hollow needle. However, they tend to be fragile tissue samples that can be adversely affected by their surroundings and handling, e.g., they may be contaminated or mechanically stressed after being cut or otherwise separated and then removed from the donor site. Accordingly, it is desirable to provide an apparatus for harvesting MTCs that facilitates their rapid extraction from a donor site and subsequent retrieval and storage without damaging them.

Accordingly, there may be a need to address and/or overcome at least some of the issues indicated herein above.

The present invention is defined by the subject-matter of claim <NUM>.

According to exemplary embodiments of the present disclosure, method and apparatus can be provided for harvesting small samples of biological tissue (e.g. microscopic tissue columns, or MTCs) that are typically less than about <NUM> in width, and may be longer in length. The removal of such small MTCs can be well-tolerated by the donor site. For example, the small regions of damage in the donor site caused by removal of the tissue samples (e.g., MTCs) heal rapidly with little or no formation of visible scars.

In certain exemplary embodiments of the present disclosure, the method and apparatus can facilitate harvesting MTCs that uses one or more hollow needles to extract the MTCs from a tissue donor site. For example, an apparatus can be provided that includes one or more hollow harvesting or 'coring' needles, preferably extending from a housing. The distal end of the needle is configured to penetrate the tissue, so that a portion of tissue (an MTC) will be cut away from the surrounding tissue by the needle tip and walls, and located in a distal portion of the hollow lumen of the needle. The MTC can be removed from the surrounding tissue and remain in the lumen of the needle when the needle is withdrawn. An inner diameter of the hollow needle can be less than about <NUM> in diameter, e.g., between about <NUM> and <NUM>, for cosmetic treatments involving skin. In further exemplary embodiments, larger diameters may be used to harvest samples from other tissues or organs that may be more tolerant of damage and/or for which visible scarring is not problematic.

A conduit can be provided in the apparatus that is configured to circulate a fluid past a proximal end of each coring needle. The lumen of the hollow needle can be in fluid communication with the conduit. The flowing fluid helps to draw the MTC up through the lumen of the needle and into the fluid path after the MTC is separated from surrounding tissue, where the MTC can then be surrounded by a protective fluid environment.

A filter arrangement that can include, e.g., a filter element, a mesh basket, or the like, can be provided in the flow path of the circulating fluid such that the harvested MTCs within the flowing fluid can then be trapped in the filter arrangement while the fluid passes through. In certain exemplary embodiments of the present disclosure, the filter arrangement can be provided in a chamber, and a cap or cover can be provided to facilitate access to the harvested MTCs. A vent can optionally be provided to release air that may be entrained in the fluid during harvesting of the MTCs.

According to further exemplary embodiments of the present disclosure, the fluid containing entrained MTCs can be directed by a delivery arrangement onto a porous dressing or substrate external to the site. For example, MTCs can be deposited directly from the flowing liquid onto a porous dressing, and the dressing with MTCs can then be applied directly to a wound site. The delivery arrangement and substrate can be moved relative to one another such that MTCs are deposited over a particular region of the dressing/substrate during the harvesting procedure. In still further exemplary embodiments of the present disclosure, the porous dressing can be provided as part of the filter arrangement.

The fluid characteristics can be selected to provide a gentle environment for the MTCs, to prevent contamination, and/or to promote their viability and growth. The fluid can be temperature-controlled using conventional thermal control systems. The fluid can contain a variety of substances, including saline, growth factors, buffers, etc. Various sensors and controllers can optionally be provided, e.g., to monitor and/or control such parameters as fluid temperature and flow rate, fluid composition, pressure at various locations within the apparatus, etc..

An actuator such as a solenoid, a motor with a rotary/linear converter, or the like can be provided to direct the needles into the donor tissue and then withdraw them. Such actuators can be controlled using a conventional power source and controller arrangement.

According to additional exemplary embodiments of the present disclosure, a lower portion of the exemplary apparatus can be shaped to create a recess between the tissue surface and a lower surface of the apparatus. One or more ducts can be provided in communication with this enclosed space, and a source of low pressure can be connected to the ducts to pull the tissue surface upward, thereby stretching and stabilizing the tissue to facilitate penetration by the needles. An elevated pressure can optionally be connected to the ducts after penetration by the needles to push the tissue back down. In certain embodiments, the needles can be held stationary with respect to the lower surface of the apparatus, and an alternating low and high pressure can be applied to pull the tissue onto the needles and then pull it away from them.

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 drawings and appended claims.

Further objects, features and advantages of the 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. Similar features may thus be described by the same reference numerals, which indicate to the skilled reader that exchanges of features between different embodiments can be done unless otherwise explicitly stated. 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. It is intended that changes and modifications can be made to the described embodiments without departing from the true scope of the present disclosure.

The present disclosure relates to a method and apparatus for harvesting microscopic tissue columns (MTCs) that uses one or more hollow needles to extract the MTCs from a tissue donor site. An apparatus can be provided that includes one or more hollow harvesting or 'coring' needles.

An illustration of a side perspective view of an exemplary hollow harvesting needle <NUM> is provided in <FIG>. The inner diameter of the needle <NUM> can be selected to approximately correspond to a particular diameter of a tissue sample or MTC to be removed from the donor site as described herein. For example, <NUM>, <NUM> or <NUM> gauge biopsy needles (e.g., having an inner diameter of <NUM>, <NUM> and <NUM>, respectively) or the like can be used to form the tube. In general, needles having a gauge size between <NUM> and <NUM> or the equivalent can be used for cosmetic applications such as skin resurfacing. In general, the inner diameter of such needle <NUM> (e.g., the diameter of the central lumen) can be, e.g., between about <NUM> and about <NUM>, or preferably between about <NUM> and <NUM>. Such smaller inner diameters can be used to separate and remove MTCs having a similar width from surrounding tissue. MTCs having such small widths may exhibit desirable viability, for example, because nutrients can more readily be transported directly to more cells in the MTC from surrounding environment. A hollow needle or tube <NUM> having a slightly larger or smaller inner diameter can also be used in further embodiments, e.g. based on the type of tissue being harvested, if larger or smaller MTCs are desired. For example, larger diameters may be used to harvest samples from tissues or organs other than skin that may be more tolerant of damage and/or for which visible scarring is not problematic.

The harvesting needle <NUM> shown in <FIG> includes a distal end that can be formed as a plurality of piercing arrangements (e.g., including points) <NUM>. A side view of a distal end of the needle <NUM> is shown in <FIG>. For example, the two exemplary points <NUM> shown in <FIG> can be formed by grinding flat bevels on opposite sides of the needle <NUM> at an angle α relative to the long axis of the needle, as shown in <FIG>. The angle α can be, e.g., between about <NUM>° and about <NUM>°, or between about <NUM>° and <NUM>°. Such narrow tip angles can facilitate penetration of the needle <NUM> into tissue and a severing of tissue within the lumen of the needle <NUM> from adjacent tissue as the needle <NUM> is advanced. In further exemplary embodiments, the distal end of the harvesting needle <NUM> can be provided with three or more points <NUM>, e.g., by forming three or more angled flat bevels at different orientations, and optionally at different angles.

The exemplary points <NUM> and associated beveled edges can facilitate insertion of the distal end of the needle <NUM> into donor-site tissue and removal of MTCs therefrom. For example, the distal end of the harvesting needle <NUM> can be configured to penetrate the tissue, so that a portion of tissue (an MTC) will be cut away from the surrounding tissue by the needle tips <NUM> and adjacent beveled edges, such that the MTC will be located in the hollow lumen of the needle <NUM>. The needle <NUM> can be formed of metal or another structurally rigid material, e.g., hypodermic stainless steel tubing or the like. For example, the needles <NUM> can be formed from a small biopsy needle or a similar structure. A portion of the needle <NUM> can optionally be coated with a lubricant or low-friction material, such as Teflon®, to further facilitate passage of the needle <NUM> through the donor site tissue. In certain exemplary embodiments of the present disclosure, a rotating motion can be applied around the longitudinal axis of the needle <NUM> during insertion to facilitate penetration of the needle <NUM> into the tissue and/or separation and removal of an MTC from the surrounding tissue.

Exemplary harvesting needles <NUM> were formed by grinding angled bevels into opposite sides of a surgical steel hypodermic needle to form two points, as illustrated schematically in <FIG>. The bevel angle α was about <NUM>°. Thin wall hypodermic needles of <NUM> and <NUM> gauge, and regular-wall needles of <NUM> and <NUM> gauge were used. These exemplary needles <NUM> were inserted into samples of pig and human skin tissue to a depth of the subcutaneous fat layer, and the penetration force was measured. The width of the resulting harvested MTCs was also measured. Data for this study is summarized in Table I below.

In general, the width of a harvested MTC was observed to correspond closely with the inner (lumen) diameter of the harvesting needle <NUM>. Insertion force of any needle into human tissue was about <NUM>-<NUM>% of the force needed to insert the same needle into pig skin tissue. For typical needle sizes that may be used to harvest skin tissue in humans, the force measured to insert a single needle <NUM> was about <NUM>-<NUM> N. If a plurality of needles <NUM> are inserted simultaneously, the total force required would, to a first approximation, be about 5N multiplied by the number of needles <NUM> being inserted. Such force data can be used, e.g., to estimate the force requirements for devices having a plurality of harvesting needles <NUM>, and can also set limits on how many such needles <NUM> can be inserted using a reasonable degree of force.

A cross-sectional view of a diagram of an apparatus <NUM> in accordance with certain exemplary embodiments of the present disclosure is shown in <FIG>. The exemplary apparatus <NUM> shown in <FIG> can include a housing <NUM> with a fluid conduit <NUM> provided therein. One or more harvesting needles <NUM> can be coupled to the housing <NUM>. The fluid conduit <NUM> can be provided with at least one fluid inlet <NUM> and at least one fluid outlet <NUM>. The fluid conduit <NUM> can be configured or structured such that a fluid can flow therethrough; e.g., the direction of fluid flow is indicated by the arrows in <FIG>. A proximal end of the needle lumen can be in a fluid communication with the conduit <NUM>. For example, the fluid can flow past a proximal end of the harvesting needle <NUM>, as shown in <FIG>.

In one exemplary procedure to harvest MTCs <NUM> from a donor tissue <NUM>, as illustrated in <FIG>, the exemplary apparatus <NUM> can be manipulated such that the distal end of one or more of the harvesting needles <NUM> penetrate the tissue <NUM> to a particular depth. The depth can be selected and/or controlled, e.g., by providing or adjusting a particular distance between the bottom of the housing <NUM> and the distal end of the one or more needles <NUM>. For example, a penetration depth can be selected that extends the distal end of one or more of the harvesting needles <NUM> through the entire local thickness of the dermis to about the depth of the subcutaneous fat layer, or optionally slightly into this fat layer. Inserting the needles <NUM> through the entire thickness of the dermis can provide an MTC <NUM> that has the full length of the dermis. Further, such exemplary depth can facilitate a separation of the MTC <NUM> from the surrounding tissue, because the proximal end of the needle <NUM> can cut the MTC <NUM> away from the adjacent dermal tissue, and the MTC <NUM> can then be fully detached by tearing a small amount of subcutaneous fat at the bottom of the MTC <NUM>. Such fatty tissue may be more easily separable than denser dermal tissue. After the needle <NUM> is withdrawn from the donor site tissue <NUM>, an MTC that was separated from the surrounding tissue <NUM> can remain within the lumen of the needle <NUM>.

The fluid flowing through the conduit <NUM> can reduce pressure at the proximal end of the needle <NUM>, which can facilitate removal of the MTC <NUM> from the lumen of the needle <NUM>. The MTC <NUM> can be entrained in the flowing liquid, and carried through the conduit <NUM> and into a chamber <NUM>. The flowing fluid can be withdrawn from the fluid outlet <NUM>, which can be provided as part of the chamber <NUM>. MTCs that have been harvested as described herein can remain in the chamber <NUM>. One or more optional vents <NUM> can be provided in an upper portion of the chamber <NUM> (or conduit <NUM>, if no chamber is provided) to allow any air entrained during the harvesting procedure to escape from the conduit pathway, e.g., to prevent the chamber <NUM> from filling with air. For example, a small amount of air may be sucked in through the needle <NUM> along with an MTC <NUM> when the needle <NUM> is withdrawn from the donor tissue <NUM>.

In some exemplary embodiments of the present disclosure, the conduit <NUM> can form a closed loop for the fluid flow or otherwise recirculate fluid flowing through the apparatus <NUM>. For example, the fluid inlet <NUM> and outlet <NUM> shown in <FIG> can be connected to the outlet and inlet, respectively, of a fluid pump arrangement (not shown) or the like.

The pump arrangement can be or include an external pump or similar device configured to circulate fluid through the conduit <NUM>. The fluid can be provided from one or more reservoirs, and the pump arrangement and the conduit <NUM> can be configured, connected or structured such that the fluid leaving the chamber <NUM> via the outlet <NUM> can be discarded. In further exemplary embodiments of the present disclosure, the fluid exiting the outlet <NUM> can be recirculated through the conduit <NUM>, e.g., in a closed-loop configuration. One or more sensors (e.g. pressure or flow rate sensors - not shown) can optionally be provided in the apparatus to facilitate control of the circulating fluid. In certain exemplary embodiments of the present disclosure, the pump arrangement can be or include a peristaltic pump. The flowing fluid can facilitate the removal of the MTCs <NUM> through the hollow needle <NUM> and into the fluid path, where the MTCs <NUM> are surrounded by a gentle fluid environment.

A "trap" or filter arrangement <NUM> can be provided in the apparatus to remove harvested MTCs <NUM> from the circulating fluid and hold them for subsequent transfer or further processing. For example, an optional filter arrangement <NUM> can be provided in the chamber <NUM>, e.g., near the outlet <NUM>, to retain harvested MTCs within the chamber during the exemplary tissue harvesting procedure, as shown in <FIG>. The filter arrangement <NUM> can include, e.g., a chamber or an enlarged region provided in the fluid circulation path of the conduit <NUM>. The filter arrangement <NUM> can also include a permeable filter element, e.g. a mesh, woven or porous material, basket, trap, or the like such that the circulating fluid flows at least partially through the chamber <NUM> and the filter element.

A pore size or permeability of the filter arrangement <NUM> can be selected to facilitate the fluid flow therethrough while preventing the MTCs <NUM> from doing so. For example, the pore size can be less than about <NUM> microns, e.g., about <NUM> microns or less. Such exemplary pore sizes can facilitate the flow of the circulating fluid through the filter arrangement <NUM> with a relatively little restriction, while being small enough to trap and retain the MTCs <NUM> that can be suspended in the flowing fluid. Accordingly, the harvested MTCs <NUM> can be retained in the trap while the fluid can flow therethrough, and exit from the filter arrangement <NUM>, e.g., through the outlet <NUM>.

According to certain exemplary embodiments of the present disclosure, the filter arrangement <NUM> can include a porous dressing with holes or pores sufficiently small to trap MTCs <NUM> while facilitating or allowing the fluid to flow through it. The dressing can be 'populated' with MTCs after the exemplary harvesting procedure, and it can be removed from the apparatus and applied directly onto a wound site. Such dressing as the filter element can be used with any of the various embodiments described herein.

In certain exemplary embodiments of the present disclosure, a source of low pressure (not shown) can optionally be provided in communication with the conduit <NUM>, e.g., to reduce pressure in the fluid conduit <NUM> and further facilitate fluid flow and/or removal of MTCs <NUM> from the harvesting needle <NUM>. For example, the chamber <NUM> can be configured or structured to provide a headspace for a gas, such as air, above the filter arrangement <NUM>. The source of low pressure can include, e.g., a vacuum pump, a low-pressure line or the like. The low-pressure source can be in fluid communication with this headspace, e.g., via a tube or hose connected to an opening in the chamber <NUM>, such as the vent <NUM> shown in <FIG>. Other similar or equivalent exemplary configurations can also be provided to generate a reduced pressure in the conduit <NUM> according to further exemplary embodiments of the present disclosure.

According to further exemplary embodiments of the present disclosure, the exemplary apparatus <NUM> can include one or more control arrangements (not shown). For example, a pressure sensor can be provided at one or more locations within the apparatus <NUM> to detect, e.g., the pressure within the fluid conduit <NUM> near the harvesting needle <NUM> or a pressure differential across the filter arrangement <NUM> to ascertain if the filter arrangement <NUM> is clogged and may be impeding fluid flow. Such exemplary sensors can be provided in communication with, e.g., a fluid pump arrangement and/or an optional low-pressure source as described herein, to control or adjust the operation of such components and maintain preferred conditions for the apparatus <NUM> during the exemplary operation. Other exemplary sensors that can be provided and can include, for example, temperature sensors to monitor and optionally control the fluid temperature, an optical sensor adjacent to or within the conduit <NUM> to detect a presence of MTCs <NUM> flowing therethough, and/or one or more sensors configured to monitor characteristics of the fluid flowing through the apparatus <NUM>. In further embodiments, a location sensor can be provided on or next to the needle <NUM> or within the apparatus <NUM> to detect a position of the needle <NUM> relative to the bottom surface of the housing <NUM>, e.g., to track or monitor the penetration depth of the needle <NUM> during use. Such exemplary sensors and control arrangements, and/or a low-pressure source, can be used with any of the various embodiments described herein, including those embodiments illustrated in <FIG> and <FIG>.

In still further exemplary embodiments of the present disclosure, a cauterizing arrangement can be provided on one or more needles <NUM>. For example, RF current can be provided to one or more of the harvesting needles <NUM> in the apparatus <NUM>. The cauterizing arrangement can be used to reduce or prevent bleeding during or after the harvesting procedure. For example, RF current can be applied to one or more of the needles <NUM> after the MTCs <NUM> have been withdrawn from the needle lumens, and before the needles <NUM> are fully withdrawn from the tissue <NUM> to avoid damaging the MTCs <NUM> while cauterizing the area around the removed volume of tissue.

According to yet further exemplary embodiments of the present disclosure, one or more control valves (not shown) can optionally be provided at one or more locations in the conduit <NUM>. For example, a valve <NUM> can be provided between the proximal end of the coring needle <NUM> and the chamber <NUM> and/or filter arrangement <NUM>, as shown in <FIG>. The valve <NUM> can be kept open during harvesting of tissue columns <NUM>, to allow and/or facilitate fluid containing such MTCs <NUM> to flow therethrough. The valve <NUM> can be periodically and/or momentarily closed while fluid is circulating, e.g., while the needle <NUM> is not located within the tissue of the donor site <NUM>, which can direct some fluid entering the inlet <NUM> through the coring needle <NUM> and out of the distal end thereof, which can clean and/or unblock the lumen of the needle <NUM>.

The fluid can be selected to provide a gentle environment for the MTCs <NUM>, e.g., to prevent mechanical damage or contamination, and/or to promote their viability and growth. The fluid can be temperature-controlled using conventional thermal control systems. For example, the fluid can be provided from a source reservoir or container, and the temperature and/or other conditions of the fluid reservoir can be controlled using conventional control systems. The fluid can contain a variety of substances including, for example, saline, growth factors, buffers, etc. For example, the fluid can contain supplemental nutrients such as, e.g., amino acids, glucose, electrolytes, and/or oxygen to promote or help maintain viability of the harvested MTCs <NUM>. The fluid can also include or comprise a conventional tissue culture medium, such as Dulbecco's Modified Eagle Medium, F12, or the like. Antibiotics (e.g., penicillin, streptomycin, or the like) and/or antifungal agents (e.g., amphotericin or fluconazole) can optionally be provided in the fluid to help disinfect the MTCs <NUM> after they are removed from the donor site <NUM>.

In the various exemplary embodiments described herein, the MTCs <NUM> can be maintained in a controlled fluid environment from the time they are pulled up from the harvesting needle(s) <NUM> and flow through the conduit <NUM> until they are captured or deposited on the filter arrangement <NUM>, which can also be maintained within the fluid. Accordingly, the MTCs <NUM> are less likely to be damaged or contaminated as compared to, e.g., other tissue removal devices that may expose removed tissue samples to air and/or other non-sterile surfaces.

<FIG> shows a cross-sectional view of a diagram of an apparatus <NUM> in accordance with further exemplary embodiments of the present disclosure. The apparatus <NUM> shown in <FIG> can be operated manually, and it has many features similar to those shown and described for the apparatus <NUM> in <FIG>, e.g., but not limited to, the housing <NUM> with the fluid conduit <NUM>, the harvesting needle(s) <NUM>, the fluid inlet <NUM>, the outlet <NUM>, the upper chamber <NUM>, the optional vent <NUM>, and the filter arrangement <NUM>. Certain differences between the exemplary embodiments of the apparatus <NUM> illustrated in <FIG> and the apparatus shown in <FIG> are described herein.

For example, one or more of the harvesting needles <NUM> can be attached or affixed to a hub <NUM>. The hub <NUM> can be provided, e.g., as a shaped disc or in another geometry with one or more harvesting needles <NUM> affixed to it. The hub <NUM> can be configured such that it can fit into a shaped recess in the housing <NUM>, to facilitate removal and replacement of the harvesting needle(s) <NUM> during or between harvesting procedures. A protrusion distance of the harvesting needle(s) <NUM> beyond the bottom surface of the apparatus <NUM>, which can correspond to a penetration depth of the needle(s) <NUM> into tissue, can be adjusted using an adjusting arrangement such as, e.g., a threaded screw coupler provided in the housing, or the like. In certain embodiments, one or more needles <NUM> can be provided with a hub <NUM>, where a desired penetration depth of the needles <NUM> into the tissue of the donor site can be determined or selected based on a predetermined distance between the hub <NUM> and the distal end of the needle(s) <NUM>. A hub <NUM> such as that shown in <FIG>, which can include one or more of the needles <NUM>, can be used with any of the various exemplary embodiments described herein.

The chamber <NUM> can be provided with a removable cap <NUM>, or the like, to facilitate access to the interior of the chamber and removal of MTCs <NUM> that may be trapped or retained by the filter arrangement <NUM>. For example, the exemplary apparatus <NUM> can include the filter arrangement <NUM> provided in the chamber <NUM>, where the filter arrangement <NUM> can be located between an end of the conduit <NUM> and the fluid outlet <NUM>. Such configuration facilitates the flow of fluid containing the harvested MTCs <NUM> through the filter arrangement <NUM> and out of the outlet <NUM>, where the MTCs <NUM> can be retained by the filter arrangement <NUM>. Access to the MTCs <NUM> after they are harvested and trapped can be achieved, e.g., by removing the cap <NUM> from the chamber <NUM>.

According to additional exemplary embodiments of the present disclosure, the filter arrangement <NUM> and optionally the cap <NUM> can be provided, for example, as a sterile cartridge that can be inserted into the chamber <NUM> before harvesting MTCs <NUM>, and can later be removed with the harvested MTCs <NUM>. In still further exemplary embodiments of the present disclosure, the filter arrangement <NUM> can be provided as a removable "basket" or the like that can be inserted into the chamber <NUM>, and removed with trapped MTCs <NUM> after the harvesting procedure is completed.

In an exemplary operation, similar to the exemplary operation of the exemplary apparatus <NUM> described herein, the exemplary apparatus <NUM> can be pressed onto a donor tissue site, such that the distal end of the harvesting needle <NUM> pierces the tissue and separates an MTC <NUM> from the surrounding tissue. The fluid flowing through the conduit <NUM> can facilitate withdrawal of the MTC <NUM> from the proximal end of the harvesting needle <NUM> such that it flows with the fluid through the conduit <NUM>. The flowing fluid can transport the MTC <NUM> to the filter arrangement <NUM>, where the MTC <NUM> can be retained by a mesh or other filter element, while the fluid flows through the filter arrangement <NUM> and exits the outlet <NUM>, where it can optionally be recirculated. The apparatus <NUM> can be withdrawn from the donor site, and inserted into another location to harvest a further MTC <NUM>. This process can be repeated a plurality of times to harvest a number of MTCs <NUM> from the donor site. After a sufficient number of MTCs <NUM> have been harvested, the filter arrangement <NUM> (or a portion thereof) containing the MTCs <NUM> can be removed from the apparatus <NUM> for further handling or processing.

Another exemplary apparatus <NUM> is shown in <FIG> that can include several features in common with the other exemplary apparatuses <NUM>, <NUM>, e.g., the housing <NUM> with the fluid conduit <NUM>, the harvesting needle(s) <NUM>, and the fluid inlet <NUM>. The exemplary apparatus <NUM> illustrated in <FIG> can be provided with a delivery arrangement <NUM> configured to direct at least a portion of the fluid flowing from the inlet <NUM> and through the conduit <NUM> onto a receiving substrate <NUM> (which can be or act as a filter arrangement). The delivery arrangement <NUM> can include rigid and/or flexible tubing, or the like, which can be connected to the conduit <NUM>.

The receiving substrate <NUM> can be or include, e.g., a filter element that can trap MTCs <NUM> while allowing fluid from the conduit <NUM> to flow through or off of the substrate <NUM>. In further exemplary embodiments of the present disclosure, the substrate <NUM> can be or include a permeable or porous dressing material, which can act as a filter element to trap MTCs <NUM> thereon while allowing the fluid to pass through or flow off of the substrate <NUM>. In this exemplary manner, harvested MTCs <NUM> can be directly deposited onto a dressing or the like, and such dressing with the MTCs <NUM> can then be transported or applied directly to a wound site.

The distal end of the delivery arrangement <NUM> can be positionable such that it traverses a predetermined region of the substrate <NUM> during the harvesting procedure, e.g., while fluid containing MTCs <NUM> flows through the conduit <NUM> and out of the distal end of the delivery arrangement <NUM>. For example, at least a portion of the delivery arrangement <NUM> can be flexible, such that the distal end thereof can be positioned and/or moved over the substrate <NUM> while the housing <NUM> containing the needle(s) <NUM> can be advanced and withdrawn over multiple locations of the donor site to harvest MTCs <NUM>.

In a further exemplary embodiment of the present disclosure, the distal end of the delivery arrangement <NUM> can be held or maintained in a stationary position, and the substrate <NUM> can be controllably moved or translated relative to this distal end such that MTCs <NUM> are deposited over a predetermined area of the substrate <NUM>.

The translation of the distal end of the delivery arrangement <NUM> relative to the substrate <NUM> (or vice versa) can be performed, e.g., using any one of various translation arrangements known in the art. Such positional translators can include, e.g., one or more motors or actuators, various arms, supports, clamps, pivots, or the like, along with any sensors and/or controllers that may be used to control a rate and/or direction of motion, limits of motion or displacement, etc. For example, the relative motion of the distal end of the delivery arrangement <NUM> and the substrate <NUM> can be selected and/or performed such that MTCs <NUM> are deposited in a predetermined spacing, pattern or density on the substrate <NUM>. The deposition geometry can be estimated in a straightforward manner based on the frequency at which the needle <NUM> is inserted into tissue to obtain a new MTC <NUM>, together with the speed and direction of the relative motion between the distal end of the delivery arrangement <NUM> and the substrate <NUM>.

According to a further exemplary embodiment of the present disclosure, another exemplary apparatus can be provided, is shown in <FIG> and <FIG> that can include the harvesting needle(s) <NUM> secured to the hub <NUM>. The apparatus <NUM> shown in <FIG> and <FIG> has many features similar to those shown and described for the apparatus <NUM>, <NUM> and/or <NUM> shown in <FIG>, <FIG> and <FIG>, respectively. These features include, e.g., the housing <NUM> with the fluid conduit <NUM>, the harvesting needle(s) <NUM>, the fluid inlet <NUM> and the outlet <NUM>, the upper chamber <NUM>, the optional vent <NUM>, and the filter arrangement <NUM>. One or more harvesting needles <NUM> can be attached or affixed to the hub <NUM>.

The exemplary apparatus <NUM> can include a base <NUM> that can be slidably engaged with the housing <NUM>, e.g., such that the housing <NUM> can move up and down over a particular distance relative to the base <NUM>. One or more solenoid coils <NUM> can be coupled or affixed to the base <NUM>, and a solenoid core <NUM> can be located at least partially within the solenoid coil <NUM> and mechanically coupled to the housing <NUM>. With such exemplary configuration, the solenoid(s) <NUM> can be configured to move the housing <NUM> and the attached needles <NUM> up and down relative to the base <NUM>, thereby inserting and withdrawing the needles <NUM> from the donor tissue <NUM>. One or more O-rings or similar sealing arrangements can be provided to maintain a fluid-tight seal between the housing <NUM> and the hub <NUM>, and also between the housing <NUM> and the base <NUM> when the housing <NUM> is translated during operation of the apparatus <NUM>. A linear bearing can optionally be provided to maintain support and alignment of the housing <NUM> within the base <NUM> during operation of the apparatus <NUM>.

For example, the apparatus <NUM> of <FIG> shows the solenoids <NUM> which are not activated. In this exemplary state, the harvesting needles <NUM> are retracted so that they are close to but not protruding from, a lower surface of the base <NUM>. In operation, the base <NUM> can be placed on the surface of the donor site tissue <NUM> to be harvested, with the solenoids <NUM> off, as shown in <FIG>. A pump arrangement or the like (not shown) can be activated to supply fluid to the inlet <NUM> and circulate it through the conduit <NUM>, as described herein.

The solenoids <NUM> can then be activated, such that the cores <NUM> are drawn downward, such that the housing <NUM> with mechanically coupled needles <NUM> are also pulled downward with respect to the base <NUM>, as shown in <FIG>. This exemplary motion can result in the harvesting needles <NUM> protruding beyond a lower surface of the base <NUM>, causing the needles <NUM> to pierce the tissue <NUM> of the donor site and separate MTCs <NUM> from the surrounding tissue <NUM>, as described herein. The MTCs <NUM> can then be withdrawn from the needles <NUM> such that they flow through the conduit <NUM> with the fluid and can be deposited in the filter arrangement <NUM>. The solenoids <NUM> can then be deactivated, such that the housing <NUM> rises relative to the base <NUM> (e.g., using springs or the like to return the housing to a raised position) and the needles <NUM> are withdrawn from the donor site <NUM> and back into the base <NUM>, as shown in <FIG>. This exemplary procedure can be repeated at different locations on the donor site <NUM> to harvest additional MTCs <NUM>. In an exemplary operation, such apparatus <NUM> can be used to harvest the MTCs <NUM> at a frequency between about <NUM> and about <NUM>, e.g., with a time interval between successive penetrations of about <NUM> to <NUM> seconds. Certain exemplary modifications may be developed to allow faster harvesting rates, and slower rates can also be used if desired.

An adjusting arrangement such as, e.g., a screw-type adjuster or a spacer that can be attached to the base <NUM>, can be provided to control the maximum protrusion length of the needles <NUM> from a lower surface of the base <NUM> (thereby controlling a corresponding maximum penetration depth of the needles <NUM> into the donor site tissue <NUM>).

In further exemplary embodiments of the present disclosure, other types of actuators can be used instead of or in addition to the solenoids <NUM>. For example, one or more motors can be provided with a rotary/linear converter to convert rotary motion to a linear motion of the housing <NUM> relative to the base <NUM>, e.g., at a controlled frequency and/or particular excursion distance. Other types of linear actuators can also be used to extend and withdraw the needles <NUM> from the tissue <NUM> beneath the apparatus <NUM>.

The base <NUM> of the exemplary apparatus <NUM> can be structured to include a recess <NUM> that can form an enclosed volume between the tissue surface <NUM> and a lower surface of the base <NUM> adjacent to the needles <NUM>, as shown in <FIG>. Such exemplary recess <NUM> can be formed, e.g., by providing the base <NUM> with a rim or edge that can rest on the donor site tissue <NUM> while a lower surface of the base <NUM> remains a small distance above the tissue surface. One or more vacuum ducts <NUM> can be provided in communication with the enclosed volume. Application of a low-pressure or vacuum source (not shown) to the vacuum duct(s) <NUM> can cause the surface of the donor site tissue <NUM> to be pulled up into the recess <NUM>, as shown in <FIG>.

This exemplary deformation can stretch the surface and provide tension, which may provide several benefits. For example, stretching the tissue surface can mechanically stabilize it such that the needles <NUM> can penetrate the stretched tissue <NUM> more easily than they may penetrate unstretched, resilient tissue. Further, puling the tissue surface upward using low pressure such that it contacts a lower surface of the base <NUM>, as shown in <FIG>, can facilitate an accurate insertion depth of the needles <NUM>. In certain embodiments, the needles <NUM> can be in a fixed position relative to the base <NUM> such that they remain protruding a small distance from the lower surface, as shown in <FIG>.

Instead of forcing the needles <NUM> into the tissue <NUM>, as described herein, the tissue <NUM> can be pulled up onto the needles <NUM> such that they pierce the tissue <NUM>, as shown in <FIG>. The low pressure can then be released to allow the tissue <NUM> to relax and fall off the needles <NUM>, optionally assisted with a positive pressure being applied to the vacuum ducts <NUM>. An exemplary application of low (and/or optionally high) pressure to the vacuum ducts <NUM> can be done, for example, using a conventional pump arrangement or other source(s) of low and high pressure, together with an appropriate valve arrangements to control the application and release of pressure differences in the ducts <NUM>. The timing of such pressure cycles can be coordinated with the activation/deactivation of the solenoids <NUM>. Such exemplary chamber <NUM> with the vacuum ducts <NUM> can also be used with any of the other exemplary embodiments described herein.

According to still further exemplary embodiments of the present disclosure, the surface of the donor site tissue <NUM> can be stretched or stabilized using other procedures, e.g., by manually stretching the surface with fingertips before inserting the needles <NUM>. In yet further exemplary embodiments of the present disclosure, the donor site tissue <NUM> can be pre-cooled or partially frozen prior to insertion of the harvesting needles <NUM>, e.g., using convective or conductive techniques such as a cryospray or contact with a cooled object. The exemplary cooling of the donor site tissue <NUM> can make it more rigid and facilitate insertion of the harvesting needles <NUM>. In still further embodiments a mechanical surface clamp or spreader can be applied around the donor site region to stretch the tissue <NUM> before inserting the needles <NUM>. Such procedures can be performed with any of the exemplary devices and methods described herein.

The exemplary apparatuses <NUM>, <NUM>, <NUM>, <NUM> can be provided with various numbers of the harvesting needles <NUM>. For example, in addition to a single one of the needles <NUM>, arrays of <NUM>, <NUM>, <NUM>, <NUM>, <NUM> or more of the needles <NUM> can be used, and they can be affixed to a hub <NUM> to facilitate insertion and removal of the needles <NUM> from the exemplary apparatuses <NUM>, <NUM>, <NUM>, <NUM> as a group. The needles <NUM> can be provided in various geometrical arrangements such as, e.g., a square or triangular pattern. Providing a hub with a larger number of needles can increase the efficiency and speed of harvesting MTCs <NUM>, as more MTCs <NUM> (one per needle <NUM>) can be harvested with each insertion- and-withdrawal cycle of the needles <NUM>. However, a very large number of needles <NUM> can increase the force required to advance all of the needles <NUM> into the donor site tissue <NUM> simultaneously, and can increase the complexity of manufacturing the hub-needle component. According still additional exemplary embodiments of the present disclosure, the hub arrangements can have between about <NUM> and <NUM> needles coupled thereto.

The needles <NUM> can be spaced apart an appropriate distance to facilitate harvesting of a large number of the MTCs <NUM> from a donor site <NUM> while maintaining healthy tissue between the removed tissue samples <NUM> to promote rapid healing of the donor site <NUM>, prevent formation of scars or markings, etc. For example, the spacing between adjacent needles <NUM> can be about <NUM>-<NUM>, or up to about <NUM>. Larger spacings can be used in certain embodiments, but this can require a correspondingly larger width of the overall apparatus to accommodate the larger hub. The MTCs <NUM> can be harvested over a larger area of tissue <NUM> by moving the exemplary apparatuses <NUM>, <NUM>, <NUM>, <NUM> to different locations before each needle insertion procedure.

The exemplary embodiments described herein can include the fluid conduit <NUM> that is substantially vertical. In further exemplary embodiments of the present disclosure, other orientations of the conduit <NUM> can be provided. For example, the conduit can be substantially horizontal, with the inlet <NUM> and the outlet <NUM> can be provided at opposing ends of such a conduit <NUM>, and the proximal ends of the needles <NUM> protruding into the conduit <NUM> such that the liquid flows past this end of the needles <NUM>. Such an exemplary configuration can also provide a simpler, e.g. linear, conduit geometry that may be easier to manufacture and/or clean, may result in fewer pressure drops along the fluid path, etc. Other exemplary orientations of the conduit <NUM> or shapes thereof, such as a curved conduit, can also be provided in still further exemplary embodiments of the present disclosure.

According to still additional exemplary embodiments of the present disclosure, at least two of the needles <NUM> can be separately actuated, e.g., such that they pierce the tissue <NUM> at different times. For example, two or more actuators can be coupled to different ones of the needles. Alternatively, a singular actuator can be provided that is configured to advance different ones of the needles at different times. Such 'staggering' of penetrations can reduce the maximum force needed to advance the needles into the tissue.

Other needle cross-sectional shapes can be used with the various embodiments described herein to harvest the MTCs <NUM> having different geometric characteristics. Although circular cross-sections are most common, needles <NUM> having oval, square, or triangular cross-sections, or combinations thereof in multi-needle devices, can also be used.

In further embodiments of the present disclosure, the methods and apparatus described herein can be applied to other tissues besides skin tissue. Thus, the MTCs <NUM> can be harvested from a variety of organs or tissue structures, which can facilitate rapid healing of a donor site while providing microscopic graft tissue suitable for placement at recipient sites, on scaffolds, within biocompatible matrices, etc..

Claim 1:
An apparatus (<NUM>) for harvesting a plurality of portions of tissue, the apparatus (<NUM>) comprising:
a harvesting needle (<NUM>) configured to penetrate a biological tissue (<NUM>) to a particular depth;
a conduit (<NUM>) configured to facilitate flow of a fluid therethrough, wherein the harvesting needle (<NUM>) is in communication with the conduit (<NUM>);
a filter arrangement (<NUM>) provided at least partially in a path of the fluid;
a base (<NUM>) configured to be placed on a surface of the biological tissue (<NUM>);
wherein when the harvesting needle (<NUM>) is in a retracted state, the harvesting needle (<NUM>) does not protrude from a lower surface of the base (<NUM>); and
wherein when the harvesting needle (<NUM>) is pulled downward, the harvesting needle (<NUM>) protrudes beyond a lower surface of the base (<NUM>).