Device for obtaining biological tissue

Abstract

The invention provides a device for obtaining biological tissue. The device includes a two-dimensional array of hollow tubes. The two-dimensional array of hollow tubes includes: a first row of a plurality of hollow tubes; a second plurality of hollow tubes, and the second plurality of hollow tubes are adjacent to the first row of hollow tubes; and a third row of a plurality of hollow tubes adjacent to the second row of hollow tubes. Each hollow tube includes at least one tip at a distal end of the hollow tube. The inner diameter of the at least one hollow tube is less than about 1 mm, and the distal end portion of each of the hollow tubes is configured to be inserted into a biological tissue donor site to remove a portion of tissue from the biological tissue donor site when each of the hollow tubes is removed from the donor site. The device is configured to independently actuate each of the first, second and third rows of hollow tubes to insert the respective row of hollow tubes into the biological tissue donor site.

Description

[0001] This application is a divisional application of an application filed on April 21, 2016 (entered the Chinese national phase on December 22, 2017), with national application number 201680036951.1 (international application number PCT / US2016 / 028542), and invention name “Method and system for obtaining biological tissue”. Technical Field

[0002]

[0014] Embodiments of the apparatus and methods described herein generally relate to devices for acquiring and placing tissue. Background Art

[0003] Skin or other tissue can be harvested or removed from a body site using hollow instruments including needles, tubes, cannulas, etc. The tissue can be used for a variety of purposes, and in some cases, the tissue can be used as a graft that can be transplanted from one site (e.g., a donor site) to another site (e.g., a recipient site).

[0004] The greater the force required to insert the tube into the tissue site, the greater the likelihood of damage to the tissue being removed from that site and the donor site itself. In situations where it is necessary to maintain the integrity or viability of the tissue or to facilitate tissue removal while applying less force to the donor site, such as when multiple tubes are applied simultaneously to the tissue site, it may be advantageous to use a tube that reduces the force required to insert the tube into the tissue site. Conventional hollow tubes, such as needles, attempt to reduce the force required to insert the tube into the tissue site in various ways. For example, a needle can include a single bevel end or a double bevel end. A double bevel needle can include two tips and two oval heels, one tip and one oval heel on each side of the needle. Alternatively, a needle with zero, one, or more tips can be rotated to remove tissue, or the needle can be formed from a low-friction material or can be at least partially coated with a lubricant. However, tubes associated with these known techniques may exert significant force on the skin when inserting the tube to remove tissue.

[0005] The formation of 1D, 2D, or 3D arrays using currently available hypodermic needles involves the positioning or placement of each needle—that is, each individual needle must be handled and positioned at some point in the process by which the array is to be formed. This handling and positioning requires a significant amount of labor, which in turn is expensive in terms of time and money. BRIEF DESCRIPTION OF THE DRAWINGS

[0006] The various objects, features and advantages of the present disclosure may be more fully appreciated with reference to the following detailed description when considered in conjunction with the accompanying drawings, in which like reference numerals identify like elements. The following drawings are for illustration purposes only and are not intended to limit the present invention.

[0007] Figure 1A It is a side view of a double-bevel needle.

[0008] Figure 1B is a side view of a double-bevel needle according to aspects of the present disclosure.

[0009] Figure 1C According to aspects of the present disclosure Figure 1B Side view of a double-bevel needle rotated 90 degrees.

[0010] Figure 1D is a side view of another embodiment of a double bevel needle according to aspects of the present disclosure.

[0011] Figure 1E The ellipse and the equation for the ellipse are shown.

[0012] Figure 2 is a top view of a needle array according to an embodiment of the present disclosure.

[0013] Figure 3 and Figure 4 A stamping and rolling technique for manufacturing needles according to embodiments of the present disclosure is described.

[0014] Figure 5A A pick and place folding method for manufacturing needles according to aspects of the present disclosure is depicted.

[0015] Figure 5B A pick and place folding method for manufacturing a needle array according to aspects of the present disclosure is depicted.

[0016] Figure 6A and Figure 6B are photographs of a needle array at various stages of a pick and place folding method for manufacturing needles according to aspects of the present disclosure.

[0017] 7A to 7D Depicted are graft devices including tissue stabilizers and methods of operating the same, according to embodiments of the present disclosure.

[0018] Figures 8A to 8H An apparatus for vibration actuation of a needle according to an embodiment of the present disclosure is shown. Summary of the Invention

[0019] In one aspect, the present disclosure relates to a double-bevel needle. In some embodiments, the double-bevel needle may include: a hollow tube having a proximal end, a distal end, a first lateral side, and a second lateral side opposite the first lateral side; a first needle tip located at the distal end of the hollow tube; a second tip located at the distal end of the hollow tube; a first bevel located on each of the first and second lateral sides, the first bevel having a first bevel angle relative to a longitudinal axis of the tube; and a second bevel located on each of the first and second lateral sides, the second bevel having a second bevel angle relative to the longitudinal axis of the tube, wherein the first and second bevels each form a portion of an elliptical portion having an inner cutting edge and terminating at the first and second needle tips at the distal end of the tube, the second bevel angle being smaller than the first bevel angle, the second bevel being located near the proximal end of the first bevel, and the inner cutting edge converging to a narrow heel.

[0020] In some embodiments, the heel may comprise a portion of the tube where a tangent to the inner cutting edge is between -45 and -90 degrees with the axis of the tube. In some embodiments, the heel may comprise a portion of the tube where a tangent to the inner cutting edge is between +45 and +90 degrees with the axis of the tube. In some embodiments, the narrowness may comprise a width of the heel that is less than approximately 15% of the inner diameter of the tube. In some embodiments, the narrowness may comprise a width of the heel that is less than approximately 10% of the inner diameter of the tube. In some embodiments, a third bevel may be positioned orthogonal to the first and second bevels. In some embodiments, a fourth bevel may be positioned opposite the third bevel and orthogonal to the first and second bevels. In some embodiments, the third and fourth bevels provide a sharp needle tip. In some embodiments, the sharp needle tip may be a needle tip having a single sharp cutting edge. In some embodiments, the first bevel is curved. In some embodiments, the second bevel may be curved. In some embodiments, a pin may be positioned within the central lumen of the hollow tube. In some embodiments, the device can include a third tip located at the distal end of the tube.

[0021] In one aspect, the present disclosure relates to a method for manufacturing an array of needles. In some embodiments, the method may include providing a sheet material; stamping a needle design from the sheet material, wherein the needle design may include a plurality of needles to be formed and a carrier and the needles, wherein the needles may include at least one narrow heel portion and at least one needle tip portion; processing the stamped needle design; and rolling the stamped, processed needle design to form an array of needles having at least one sharp tip portion and at least one narrow heel portion, wherein the needles remain attached to the carrier.

[0022] In some embodiments, the needle may include two pointed portions. In some embodiments, the needle may include two heels. In some embodiments, each heel may include a narrow heel. In some embodiments, processing may include sharpening. In some embodiments, sharpening may include etching. In some embodiments, sharpening may include grinding. In some embodiments, sharpening may include electropolishing. In some embodiments, the inner diameter of the needle may be less than about 1 mm. In some embodiments, the inner diameter of the needle may be less than about 0.8 mm. In some embodiments, the material may include steel. In some embodiments, the material may include plastic. In some embodiments, the method includes forming a needle array having multiple rows of needles and multiple carriers. In some embodiments, the array may include approximately 300 needles. In some embodiments, the method may include removing the carrier from the row of needles. In some embodiments, the method includes forming the multiple rows of needles into a two-dimensional needle array.

[0023] In one aspect, the present disclosure relates to a method for harvesting biological tissue. In some embodiments, the method includes: providing a device having a plurality of rows of hollow tubes and a plurality of pins, each of the hollow tubes having at least one tip located at a distal end of the hollow tube, the plurality of rows forming a two-dimensional array of hollow tubes, each of the pins being disposed within a central lumen of each of the hollow tubes; positioning the two-dimensional array of hollow tubes adjacent to an upper surface of biological tissue; securing the device to the biological tissue; advancing the two-dimensional array of hollow tubes into the biological tissue to cut a portion of the biological tissue away from surrounding tissue, such that the distal ends of the pins are positioned adjacent to the upper surface of the biological tissue; and simultaneously raising the two-dimensional array of hollow tubes and the pins such that the biological tissue is retained within each of the hollow tubes.

[0024] In some embodiments, securing may include attaching the device to the biological tissue using a strap. In some embodiments, securing may include locking the device into a base on the strap. In some embodiments, the strap may include one base. In some embodiments, the strap may include multiple bases. In some embodiments, securing may include positioning the tissue stabilizing housing adjacent to the biological tissue. In some embodiments, securing may include attaching the device to the biological tissue using an adhesive. In some embodiments, securing may include attaching the device to the biological tissue using a clamp. In some embodiments, the method may include measuring the amount of force applied by the device to the biological tissue. In some embodiments, the method may include notifying a user when an optimal amount of force has been applied. In some embodiments, the method may include measuring the angle at which the device is applied to the biological tissue. In some embodiments, the method may include notifying the user of the angle. In some embodiments, the biological tissue may include skin tissue and adipose tissue.

[0025] In another aspect, the present disclosure relates to a device for harvesting biological tissue. In some embodiments, the device may include: a plurality of rows of hollow tubes and a plurality of pins, each hollow tube including at least one tip located at a distal end of the hollow tube, the plurality of rows forming a two-dimensional array of hollow tubes, each of the pins being disposed within a central lumen of each of the hollow tubes; an attachment device for securing the device to a donor site; and a force sensor for detecting a force applied by the device to the donor site.

[0026] In some embodiments, the attachment device may include a strap. In some embodiments, the strap may include a base to receive the device into the strap. In some embodiments, the strap may include multiple ports to receive the device into the strap at various locations along the strap. In some embodiments, the attachment device may include one of an adhesive or a clamp. In some embodiments, the biological tissue may include skin tissue and adipose tissue. In some embodiments, the device may include a sensor for measuring the angle at which the device is applied to the donor site. In some embodiments, the device may include an alarm to notify the user that the device is being applied at an unacceptable angle.

[0027] In one aspect, the present disclosure relates to a method for harvesting biological tissue. In some embodiments, the method may include: providing a device having a plurality of rows of hollow tubes, each hollow tube including at least one tip located at a distal end of the hollow tube, the plurality of rows forming a two-dimensional array of hollow tubes; positioning the two-dimensional array of hollow tubes adjacent to an upper surface of biological tissue; vibrating at least one hollow tube; while vibrating the at least one hollow tube, advancing the hollow tube into the biological tissue to cut a portion of the biological tissue away from surrounding tissue; and raising the hollow tube such that the biological tissue remains within the hollow tube.

[0028] In some embodiments, each of the hollow tubes includes two tips located at a distal end of the hollow tube. In some embodiments, the vibration may include: impacting each hollow tube with an impact plate. In some embodiments, each hollow tube can move independently of the impact plate. In some embodiments, the hollow tube can vibrate at a resonant frequency of the impact plate. In some embodiments, the hollow tube can vibrate at a non-resonant frequency of the impact plate. In some embodiments, the actuator can cause the impact plate to impact the hollow tube. In some embodiments, the actuator can be physically coupled to the impact plate. In some embodiments, the actuator can be energetically coupled to the impact plate. In some embodiments, the biological tissue can include skin tissue and fat tissue.

[0029] Another aspect of the present disclosure relates to a device for harvesting biological tissue. In some embodiments, the device may include: a plurality of rows of hollow tubes, each hollow tube including at least one tip located at a distal end of the hollow tube, the plurality of rows forming a two-dimensional array of hollow tubes; an impact plate surrounding each hollow tube; and an actuator coupled to the impact plate, wherein the actuator causes the impact plate to impact the hollow tubes and vibrate the hollow tubes.

[0030] In some embodiments, each of the hollow tubes may include two tips located at the distal end of the hollow tube. In some embodiments, the actuator may be physically coupled to the impact plate. In some embodiments, the actuator may be energetically coupled to the impact plate. In some embodiments, a transducer may energetically couple the actuator to the impact plate. In some embodiments, the actuator may be a solenoid. In some embodiments, the actuator may be an electromechanical actuator, a pneumatic actuator, a fluid actuator, a mechanical actuator, or a magnetostrictive actuator. In some embodiments, each hollow tube may move independently of the impact plate. In some embodiments, the hollow tube may vibrate at a resonant frequency of the impact plate. In some embodiments, the hollow tube may vibrate at a non-resonant frequency of the impact plate. In some embodiments, the impact plate may be metal. In some embodiments, the biological tissue may be skin tissue and adipose tissue. DETAILED DESCRIPTION

[0031] The present disclosure relates to a device and method for extracting micro-sized columns of skin tissue from a donor site and depositing and / or spreading the harvested tissue onto a wound. The deposited tissue aids in the healing of the wound site. The device can harvest from a donor site of approximately 1 square inch using hundreds of needles. In some embodiments, the needles used to harvest tissue can have a narrow heel to provide easier insertion into the donor site. In some embodiments, the needles can be manufactured using a stamping and rolling method, while in other embodiments, the needles can be manufactured using a bending method. In other embodiments, each individual needle can be sharpened, cut, and assembled into an array. In some embodiments, all needles can be inserted into the donor site simultaneously, while in other embodiments, selected groups of needles can be inserted sequentially. In some embodiments, the needles can vibrate when entering the donor site and / or inserting the harvested tissue into the wound. In some embodiments, the needles can rotate while being inserted into the donor site.

[0032] Multi-pointed coring needle with narrow heel

[0033] Figure 1AThe figure is a side view of a double-bevel needle 100. Needle 100 can be a barrel or tube 102 and can include one or more tips, for example, two tips 104 and 106, which can be formed by grinding or cutting the needle at an angle on both sides relative to the longitudinal axis of tube 102 to form bevels 108. Hollow tube 102 can be formed from metal or any other structurally rigid material. Bevels 108 form what is herein referred to as an elliptical heel 114. The heel is defined as the section where the tangent of the needle's cutting edge is angled from -45 degrees to -90 degrees and from +45 degrees to +90 degrees to the needle axis. A single-bevel needle may have one beveled side. A double-bevel needle may have one bevel on one side and a second bevel on the opposite side. The angle of the bevels forming the needle tip can vary; although in one example, it is approximately 30 degrees, other larger or smaller angles may be used. For example, the angle can be in the range of approximately 10 degrees to 35 degrees. Needle tips 104 and 106 can each have a flat cutting edge 110, 112, the length of which is equal to the wall thickness of tube 102. In this embodiment, when the needle is inserted into tissue, the sharp tips 104, 106 can enter the tissue with relatively low force due to the sharpness of the tips 104, 106 of needle 102, but the elliptical heel 114 formed where the proximal ends of the two tips converge within the needle body can result in a higher insertion force due to the elliptical heel 114 contacting and entering the tissue at an obtuse angle. In cases where multiple needles are simultaneously applied to tissue, such as in a needle array, the force required to insert the array can be increased relative to the number of needles in the array, significantly inhibiting the user from inserting the array at the tissue site or causing significant pain during insertion. In cases where it is desirable to maintain tissue integrity or viability, the additional force required to insert the heel of the needle can damage the tissue at the donor site as well as the tissue being removed.

[0034] Figure 1B is a side view of a double-bevel needle according to various aspects of the present disclosure. Figure 1C According to various aspects of the present disclosure Figure 1B A side view of a double-bevel needle rotated 90 degrees. Figure 1AThe needle shown in FIG differs in that it has a double bevel on each side of the needle, for a total of four bevels. The use of double bevels on each side results in a significantly narrower heel 122. The narrower heel 122 can provide a sharper cutting edge than needles of the prior art, resulting in less tissue damage and pain when the needle is inserted into the donor site. According to an embodiment of the present disclosure, the cutting edge of the needle described begins at one of the needle tips and travels back toward the heel 122, continuing through the heel 122 and returning upward to the other tip. To harvest tissue with minimal impact on surrounding tissue and minimal pain to the patient, the cutting edge should be sharp. Sharp, as used herein, means that the tube material is as thin as possible along the cutting edge. For example, the cutting edge of the cutting edge may be a single point or a linear portion that is shorter than the wall thickness of the tube. Furthermore, as used herein, narrow refers to the width of the heel, while sharp refers to the width of the cutting edge, i.e., the sharpness of the blade. Narrowness is defined as a width of the heel that is about 15% or 10% or less of the inner diameter of the cannula or needle. Although the present disclosure describes needles having a double bevel on each side to form each heel, the disclosed narrow heels can be achieved with more than two bevels or with curved bevels. The disclosed embodiments achieve a narrow heel without requiring an excessive distance between the heel and the tip. Therefore, the bevel angle should be as small as possible where the bevel intersects the inner diameter of the tube. In some embodiments, as small as possible refers to an acceptable length from the heel to the tip. A smaller angle will provide a narrower heel, but will also result in a longer distance from the heel to the tip. The intended use of the needle can determine the acceptable length. For skin harvesting, the distance can be kept below about 2 mm.

[0035] Reference Figure 1E , in order to obtain a "narrow" heel, the present disclosure attempts to make c (the distance from the center to one of the foci of the ellipse, i.e., the bevel) as long as possible without making the tip of the needle too long, and to make the ratio of a to c as close to 1 as possible. This is because when the device is coring, the needle is pushed into the tissue. Therefore, as the tissue moves up and away from the heel, the direction of travel creates a cutting effect, just like a knife. When the base of the heel is reached, the cutting edge is perpendicular to the direction of push, which requires more force to cut through the tissue. The "narrow heel" keeps the angle between the cutting edge and the axis of the needle less than 45 degrees (as close to the heel as possible) for as long as possible. This will maintain the cutting effect for as long as possible.

[0036] like Figure 1B and Figure 1C As can be seen in FIG, the distal end of the tube 102 can be shaped to form tips 110, 112. Figure 1CAs shown in FIG, a first bevel 124 and a second bevel 120 are formed on the front and back of the distal end of the tube 102. The second bevel 120 forms the tip 110, 112 or the point of the needle. The first bevel 124 and the second bevel 120 combine to form a narrow heel 122.

[0037] Continue to refer to Figure 1C In order to form the first bevel 120, the front and back of the distal end of the tube 102 may be ground or cut at a certain angle relative to the axis of the tube 102 to form a bevel structure at the distal end of the tube 102. Figure 1C The exemplary tip angle shown in FIG is about 30 degrees, which corresponds to an angle α of about 15 degrees relative to the axis of the tube. Although angle α is about 15 degrees in this example, angle α can be greater or less than 15 degrees. For example, angle α can be in the range of about 10 degrees to about 18 degrees.

[0038] The second bevel angle 124 on each side of the tube 102 is generally less than the first bevel 120 and forms a Figure 1B The second bevel 124 may be angled at 6 degrees relative to the longitudinal axis of the tube 102 and may form a compact, narrow ellipse that approximates the tip of the heel 122 on each side of the needle, as shown in FIG. Figure 1B As seen in the front view.

[0039] In one embodiment, the second bevel 124 can be formed by grinding or cutting the front and back portions of the distal end of the tube 102 at an angle β relative to the axis of the tube 102. This second angle β is smaller than the first angle α to form a narrow elliptical portion approaching the tip at the heel 122 of the needle tip. Although the second angle β is approximately 6 degrees in this example, the angle β can vary while being smaller than the first angle α. In alternative embodiments, the needle can be formed with more than two bevel angles. For example, three or more bevel angles can be formed on each side of the tube, with the bevel decreasing as the angle moves further away from the distal end of the tube. In another alternative embodiment, two or more angles can be formed on each side of the tube by forming a curved surface with varying angles along the length of the tube. In some embodiments, a narrow heel can be achieved with only one bevel per needle side. However, a single bevel would need to be a small angle all the way to the needle tip, which could significantly increase the distance from the heel to the tip of the bevel.

[0040] Continue to refer to Figure 1B and Figure 1C, the tube 102 has two pointed ends 110, 112 which may be formed by grinding opposite sides of the tube at a first bevel angle α relative to the long axis of the tube 102. The two pointed ends 110, 112 have inner cutting edges 111, 113 which converge at or almost at the tip at the heel 122 of the needle tip. The inner cutting edges 111, 113 are formed by the inner wall surface of the tube, the inner cutting edges 111, 113 being exposed by the first bevel 120. A tube with two pointed ends 110, 112 will have four inner cutting edges, two being associated with the respective pointed ends. Although in Figure 1B The cutting edges 111, 113 on the front of the tube 126 are shown, but the corresponding cutting edges on the back of the tube 102 are not shown. In some embodiments, the inner cutting edges can be further sharpened by applying additional bevels to the inner wall surface or the outer wall surface or to the inner wall surface and the outer wall surface. Further sharpening the inner wall edge allows the tube to pass through tissue with a lower force cutting motion. The narrow tip at the heel 122 is indicated by the reference Figure 1C By narrowing the cutting edges 111, 113 to a point or nearly a point at the heel 122, the cutting edge of the needle can continue to cut tissue as the needle is inserted, and the force required to insert the needle into the tissue is reduced compared to a double-bevel needle without a sharp heel. Figure 1A The difference is that in Figures 1B to 1D In the embodiment shown in FIG, only a small section of the cutting edge at the apex of the ellipse will be pushed vertically into the tissue. By minimizing the area of ​​the apex and forming the apex at a certain angle, the force required to insert the tube into the tissue is reduced, and the tube can cut the tissue along the length of the inner cutting edges 111, 113 when the tube is inserted into the tissue.

[0041] Figure 1D is a side view of another embodiment of a double bevel needle according to various aspects of the present disclosure. Figure 1DAs further shown in FIG, a third bevel 144 and a fourth bevel 146 can optionally be disposed in a direction orthogonal to the first bevel 120 and the second bevel 124. These additional bevels are characterized by an angle λ, which represents the angle at which each of the lateral sides of the tube 102 can be ground or cut at said angle relative to the longitudinal axis of the tube 102. In an exemplary embodiment, the angle λ can be approximately 6 degrees, but the angle λ can be larger or smaller, for example, between about 3 degrees and about 9 degrees. These bevels 144, 146 can be provided to reduce the size or width of the sharp edge of the tip 136, 138 formed at the end of the tube 102 to further facilitate insertion of the tube 102 into the tissue of the donor site. The depth of the bevel can vary. For example, the bevel can be shallow, leaving a flat cutting edge at the tip 136, 138, or the bevel can be deeper, such that the tip is formed as shown. Figure 1D The angle of the bevel can also vary. The tips or extensions 136, 138 are formed by an angle λ, where the angle λ is as shown in FIG. Figure 1D The tips or extensions 136, 138 shown in FIG, 1 , having a narrow angle formed at their tips, may be inserted into tissue with less force than a tip formed at an angle greater than λ, although the force may be applied over a longer distance and / or for a longer time to achieve full insertion of the tube 102 into the tissue than a tip formed at an angle greater than λ and thus having an angled tip region of shorter length.

[0042] although Figures 1B to 1DThe exemplary embodiment shown in discloses a tube with two tips and two heels, but other embodiments may include tubes with any number of tips and heels greater than one. For example, in another exemplary embodiment, a tube may be provided with three tips or extensions disposed at the distal end of the tube. This exemplary configuration can be formed, for example, by grinding three portions of the tube at a first angle α relative to the long axis of the tube, wherein the three portions may be spaced approximately 120 degrees apart around the circumference of the tube. In yet another exemplary embodiment, a tube may be provided that includes more than three tips or extensions disposed at the distal end of the tube, for example, a tube having four, five, six, seven, eight, or more tips. In this configuration, one or more of the heels may be formed using a second angle that is smaller than the first angle α, thereby forming one or more sharp heels as described herein. The second angle may be different for each heel located on the tube. If the angle of each tip or extension remains constant, the initial force required for the tube to penetrate tissue may be approximately proportional to the number of tips. While providing a greater number of tips or extensions at the distal end of the tube can improve the mechanical stability of the tube and / or geometric control over the tissue being severed, it can require greater force to penetrate the tissue. However, where the needle tips are sharper due to a smaller angle, a system with a greater number of needle tips can actually have a lower overall force than existing systems with fewer blunt needle tips.

[0043] The various geometries and tips described herein can be used in any exemplary embodiment of the present disclosure, for example, in the exemplary embodiments of the various devices and methods described herein. For example, the hollow tube can be provided with a bevel angle α of less than about 15 degrees, for example, about 12 degrees. Such acute tip angles can provide a sharp tip of the tip or extension that can more easily penetrate biological tissue or matrix material. A narrower tip angle α, for example, about 6 degrees, may be preferred for obtaining and / or inserting micrografts in denser or tougher tissue or matrix materials, wherein the narrower tip of the tip or extension can be configured to more easily cut through tissue or matrix material when the tube is inserted into the tissue or matrix material. A secondary bevel having an angle λ such as Figure 1D The exemplary tip of the tip or extension shown in can further facilitate insertion of the distal end of the tube into various materials by providing a smaller and more pointed tip of the tip or extension. However, a sharper and / or narrower tip of the tip or extension—for example, a tip with a small tip angle α and / or a tip with a secondary bevel having an angle λ—can also be more susceptible to wear, bending, or other deformation when the tube is repeatedly inserted into tissue or matrix. Therefore, the tip geometry selected for a particular application can be selected based on the type of material or tissue with which the device will be used and the expected lifespan of the tube.

[0044] The inner diameter of the tube can be selected or configured to roughly correspond to the specific diameter of the tissue portion to be removed from the donor site, such as a micrograft. According to an exemplary embodiment, the inner diameter of the tube can be less than about 1 mm. For example, an 18-gauge biopsy needle or a 20-gauge biopsy needle (e.g., having an inner diameter of 0.838 mm and an inner diameter of 0.564 mm, respectively) can be used to form the tube. Biopsy tubes with larger gauges (and smaller inner diameters) can also be used. Based on the interaction between the tubes, the width or diameter of the tissue to be harvested can be slightly smaller than the inner diameter of the device used to harvest the tissue.

[0045] Living tissue can be provided with nutrients via diffusion transport over a distance of approximately 0.1 mm. Thus, tubes according to the present disclosure can be configured to extract exemplary micrografts having at least one dimension less than approximately 0.6 mm, such as less than approximately 0.3 mm or, for example, less than approximately 0.2 mm, that can exhibit improved viability, etc., to survive and that can grow when used for transplantation. Such exemplary micrografts can be better able to receive nutrients (e.g., including oxygen) when placed in a recipient site prior to tissue revascularization.

[0046] Tubes according to the present disclosure can also be configured to extract larger micrografts, for example, micrografts having a width of about 1 mm to 2 mm, which can also benefit from this diffusion transport of nutrients and can also be more likely to survive than significantly larger portions of the grafted tissue (e.g., conventional full-thickness grafts, blade-thickness grafts, or mesh grafts). These larger sizes can be preferred for harvested tissue that is heterogeneous, for example, tissue that may include certain structures that can be preserved within a single micrograft. For example, skin tissue has certain structures such as hair follicles, sebaceous glands, etc., and harvesting slightly larger micrografts from the skin can help preserve these tissue structures during harvest and transplantation. On the other hand, smaller micrografts, for example, micrografts having a width of less than about 0.6 mm or about 0.2 mm, can be suitable for relatively homogeneous tissue such as muscle tissue, where there are few or no larger structures in the tissue to be preserved.

[0047] In embodiments where a tube as described herein is used to harvest micrografts, the width or diameter of the hole created at the donor site during harvesting (the width or diameter of the hole may correspond roughly to the diameter of the portion of the micrograft being harvested) may be less than about 2 mm or less than about 1 mm. In certain exemplary embodiments of the present disclosure, the tube may be configured to extract micrografts having a diameter or width of less than about 0.6 mm, less than about 0.3 mm, or about 0.2 mm. The size of the exemplary hole at the donor site may be selected, for example, based on the effect of forming a small lesion area in the donor site that can heal quickly and / or be scarless, and based on the portion of the formed tissue that can be small enough to promote viability when transplanted or placed in growth medium, and the size of the exemplary hole at the donor site is large enough to form a sufficient amount of graft tissue and / or capture tissue structures that may be present in the donor tissue. The advantageous sharp heel design described herein can further minimize damage to the donor site tissue by limiting the amount of force required to insert the tube into the donor site, thereby reducing tissue morbidity.

[0048] Other aspects of the cannula, tube or needle with properties described herein can also be realized. In one embodiment, the cannula can be used to obtain or extract graft tissue. In this embodiment, the cannula is configured to remove tissue from the donor site and help to place the tissue at the recipient site. The placement of tissue at the recipient site can be performed by inserting the cannula into the recipient site, or by discharging the tissue from the cannula and depositing or placing the tissue at the recipient site, or otherwise distributing the tissue at the recipient site. The recipient site can be another location of the individual identical to the donor site or a different individual, or the recipient site can be another material such as a matrix. In some cases, the matrix can be a biocompatible matrix that can form a graft or larger copy of the donor tissue, as described in U.S. Patent Application No. 13 / 102,711, the entire contents of which are incorporated herein by reference. The entire contents of U.S. Patent Application No. 12 / 936,173 are also incorporated herein by reference.

[0049] In some embodiments, the tube may further include a collar, stop, or the like disposed on the inner or outer surface of the tube, or the tube may be attached to a device that holds the tube such that the device limits the depth of insertion of the tube. In some embodiments, the stop may include a sensor, camera, or other mechanism that prevents the tube from extending beyond a specific depth. In one embodiment, the stop or other mechanism may be attached to the tube at a specific distance from the end of the tip, or the distance may be adjustable, for example, over the length of movement of the stop along the axis of the tube. In one example, the stop may be positioned on the tube to allow the tube to be inserted up to the dermis / fat layer of the skin.

[0050] In one example, a tube can be inserted into tissue at a donor site, and the tip and cutting edge can sever a portion of the tissue from surrounding tissue as the tube penetrates the donor site tissue. The tube can be inserted to a specific depth, for example, until a stop contacts the surface of the donor site. A portion of the tissue can be present within the lower portion of the tube. This tissue can remain within the tube and can be separated from the donor site using the tube when the tube is removed from the donor site to form a micrograft. An exemplary micrograft so formed can include both epidermal tissue and dermal tissue. For example, the micrograft can be removed from the donor site by removing the tube including the micrograft from the donor site without rotating the tube about its axis and without suction. A tip or extension provided on the tube can facilitate this removal of the micrograft tissue from surrounding tissue at the donor site.

[0051] Micrografts or other tissue can be removed from the tube in various ways. For example, by applying pressure through an opening at the proximal end of the tube. This pressure can be mechanical, hydraulic, pneumatic, or the like. For example, pressure can be applied by blowing into the opening, by squeezing a flexible bulb attached to the proximal end of the tube, or by opening a valve connected to a high-pressure source such as a small pump. In other embodiments, tissue can be removed from the tube using a pin positioned within the tube to push the graft out of the tube. Alternatively, tissue, such as micrografts, can be harvested by inserting the tube into multiple locations at the donor site. Each micrograft within the tube can then push any micrografts above it toward the proximal end of the tube, which can be open or connected to a container configured to store micrografts for transport. Once the tube is substantially filled with harvested tissue, each additional insertion of the tube into the donor site can help push the uppermost micrograft within the tube out of the proximal end or into a container or other collection device. Other mechanisms, such as vibration, can also be used to remove micrografts from the tube.

[0052] In embodiments where the cannula is inserted and / or penetrated into a recipient site to remove tissue, the exemplary configuration of the distal portion of the tube, including the reduced dimension from the heel to the tip or near the tip, allows the cutting surface to be angled with the tissue for as long as possible, which benefits the recipient site in addition to the advantages achieved at the donor site. For example, when the cannula is inserted into the recipient site, trauma at the recipient site is reduced for the same reasons discussed above with respect to the donor site.

[0053] In an alternative embodiment, the cannula can be used in combination with a piercing cannula. In this embodiment, the cannula can be disposed within the piercing cannula and advanced through the piercing cannula to deposit tissue at the recipient site. The piercing cannula can also include at least one narrow heel as described in the present disclosure.

[0054] Many advantages can be achieved by the devices of the present disclosure over conventional cutting or piercing tubes or cannulas. In one embodiment, a device can be provided that includes a plurality of tubes, each of the plurality of tubes having a sharp heel as described in the present disclosure. The plurality of tubes can be mechanically attached or coupled to a base to form a tube array. In this configuration, multiple portions of tissue can be harvested from a donor site simultaneously or nearly simultaneously by a single insertion of the tube array into the donor site. The array can be formed in a variety of configurations, including a linear array or any form of pattern along the base. The spacing of the tubes in the pattern can be regular, slightly irregular, or varied, which can both facilitate insertion of the array at the donor site and avoid forming a pattern at the donor site. The spacing of the needle array can be selected to facilitate insertion and, in some embodiments, also to avoid collateral damage to surrounding tissue, such as tearing.

[0055] Typically, a greater number of tubes in an array corresponds to a greater force required to simultaneously insert the tubes into tissue or matrix, which may be undesirable if the force is too great. However, when the needles with narrow heels discussed in the present disclosure are assembled into a needle array to be inserted into a donor site to harvest tissue, the amount of force required to insert the array into the patient is disproportionately reduced compared to a conventional needle array without narrow heels. The apparatus of the present disclosure also creates substantially less donor site trauma than would be achieved using conventional instruments, resulting in less trauma at the donor site and greater patient comfort. These unexpected advantages allow for larger arrays with tens or hundreds of needles, resulting in tools that can harvest larger areas of tissue while minimizing donor site morbidity and patient pain. The distribution of the needle array can reduce tissue damage and provide cleaner coring of the donor site.

[0056] For example, Figure 2 is a top view of a needle array 200 according to an embodiment of the present disclosure. The array 200 is circular and includes 316 needles and has an area of ​​approximately 1 square inch. Figure 2 In the example of FIG. 1 , a 21-gauge regular-wall hypotube needle with a pin having an outer diameter of approximately 0.018 inches was used. The needles were spaced 0.056 inches apart from the center, and the diameter of the circle was approximately 1.13 inches. This configuration of needles can result in the acquisition of an area corresponding to 10% of the acquisition site, that is, the total cross-sectional area of ​​316 tissue columns is equal to 0.1 square inches, which is 10% of 1 inch. The needle density in the array can range from about 1% to as high as about 20%, for example, a density of 10%.

[0057] The circular array is formed by assembling multiple rows of needles in horizontal or vertical rows. The design is modular and the configuration can have any shape or size using rows of various sizes depending on the module. In some embodiments, all needles can be actuated simultaneously, for example, to be inserted into tissue. In other embodiments, each group or section of the needles can be actuated sequentially. For example, the array can be divided into quadrants, and each quadrant can be actuated sequentially. Sequentially can mean actuating each row in a linear order (e.g., row 1, row 2, row 3) or a nonlinear order (e.g., row 1, row 10, row 3). Alternatively, each row of needles can be actuated separately and sequentially. Finally, each individual needle can be actuated separately and sequentially. In some embodiments, the circular needle array can be divided into multiple pie-shaped wedges, such as three, four, five, six or more wedges, and each wedge can be actuated sequentially. In some embodiments, two or more arrays can be actuated simultaneously, and other arrays can be actuated individually or in groups until all needles are actuated. In some embodiments, one row is actuated at a time, for example, 20 rows are actuated individually in sequence, while in other embodiments, two, three, four or more rows may be actuated at a time. An advantage of sequentially actuating segments of the array is that insertion of the segments onto the donor site may require less force than inserting the entire array, which may result in less trauma to the donor site. In some embodiments, a solenoid is used to drive the array. Multiple actuations using the solenoid allow for sequential insertion, row by row. In some embodiments, two solenoids may be used, each firing in opposite directions to prevent recoil of the device and also to reduce the force applied to the donor site, thereby reducing damage to surrounding tissue.

[0058] Typically, an exemplary tube may include a pin disposed in a central lumen or central opening of the tube. The diameter of the pin may be approximately the same as or slightly smaller than the inner diameter of the tube, such that the pin may translate along the axis of the tube while filling or closing most or all of the lumen of the tube. In some embodiments, the pin may be formed of, or coated with, a low friction material, such as, for example, The pins may be arranged to facilitate movement of the pins within the tubes and / or inhibit accumulation or adhesion of biomaterial to the pins. The distal end of the pins may be substantially flat to facilitate displacement of the micrograft tissue within the tubes as the pins translate. In another exemplary embodiment of the present disclosure, a device may be provided with multiple tubes and multiple pins. All tubes may be capable of translating relative to the pins using a single actuator, or certain of the tubes may be simultaneously and / or sequentially translated using multiple actuators.

[0059] In some embodiments, to harvest tissue, a needle is first inserted to the full specified depth at a location selected for harvesting. In some embodiments, the depth of insertion can be limited by the use of a hub. All needles can be bonded to a "hub" or "stop" (discussed above), and the hub limits the depth because needle penetration stops when the hub hits the skin. In some embodiments, the needle can be inserted into the skin at high speed using a solenoid. In some embodiments, the needle can be inserted using a spring-loaded device or any other device that releases or provides a high-energy impact. When the needle enters the harvesting position, a skin column is formed within the hollow space of the needle. Once the needle has been inserted into the tissue to the appropriate depth and the tissue column is present within the needle, the user removes the device from the harvesting area. The tissue column remains in place within the needle. The user then transports the device, along with the harvested column, to the wound site for deposition. Deposition can be achieved by inserting the tissue column into the wound or wound matrix, or by dripping (spreading) the tissue column onto the wound surface.

[0060] To insert, the user positions the device on the wound and presses the needle array into the wound, wound dressing, or wound matrix. Once the needle with the tissue column is inserted, the needle contracts, thereby keeping the pin tip at the surface of the wound location. This holds the previously acquired tissue column in place while the needle is contracted. The device is then pulled away from the wound location, and the tissue column has been inserted into the wound site. The contraction of the needle pushes the tissue column out of the needle. To disperse, the user positions the device on the wound, contracts the needle, and activates the solenoid (or other actuation method) again, which causes the needle tip to extend downward along the length of the pin and push the tissue column out of the pin. The needle then quickly stops and contracts again, thereby throwing the tissue column out of the tip of the needle.

[0061] Exemplary tubes of the present disclosure may be formed from any sufficiently strong material that is preferably biocompatible or inert with respect to biological tissue, such as, for example, 304 stainless steel, surgical stainless steel, etc. In some embodiments, the tubes may be coated with a lubricant or low friction material such as To further facilitate the passage of the tube through tissue. Bevels and other sharp edges can be formed by cutting, grinding, etching, photolithography, electropolishing, etc. Further finishing treatments such as electropolishing can be applied to the tube 20 to increase the sharpness of the cutting edge, or to provide ME- Chrome coating to increase the strength of the material. This type of finishing treatment can increase cutting effectiveness and / or improve the useful life of the tube.

[0062] The above-described method for harvesting and spreading tissue may be performed using the described narrow-heeled needle or any other type of harvesting device, such as a needle having only one bevel or a double bevel without a narrow heel.

[0063] Method for manufacturing coring needle

[0064] The needles described previously can be manufactured by a variety of methods, including: (1) grinding the individual tubes,

[0065] (2) stamping and rolling techniques and (3) folding methods. The latter two methods will be discussed below.

[0066] Stamping and rolling

[0067] In one embodiment, a stamping and rolling method can be used to form a needle structure from a flat plate material. 1D arrays, 2D arrays, and 3D arrays of needles and related structures can be formed by the stamping and rolling method. For the purposes of this discussion, a 1D array can be defined as an arrangement of needles in which the needle tips are positioned in space in a straight line or curve with equal spacing or a repeating pattern of variable spacing between the needle tips; a 2D array can be defined as an arrangement of needles in which the needle tips are positioned in space in a plane with a repeating pattern of spacing between the needle tips; and a 3D array can be defined as an arrangement of needles in which the needle tips are positioned in space in a three-dimensional surface with a repeating pattern of spacing between the needle tips.

[0068] Currently, hollow needles, and in particular hypodermic needles, are made from cylindrical tubes. This places limitations on the ultimate geometry of the needles based on the manufacturing process used to form the hollow tubes and the structural integrity of the tubes. Furthermore, forming 1D, 2D, or 3D arrays using currently available hypodermic needles involves the positioning or placement of each needle, meaning that at some point in the array formation process, each individual needle must be handled and positioned.

[0069] The described method allows the formation of needles of any geometry that can be conceived from a flat sheet material that is cut and bent, rolled, curved, twisted, or otherwise formed. Furthermore, the described stamping and rolling design allows the arrangement of a plurality of such needles in a regular pattern in space with a high degree of precision and without the need to handle or position the individual needles.

[0070] In the electronics industry, for example, conductive connector pins are typically manufactured from flat metal strips using a process sometimes referred to as "punch and roll." Typically, the metal strip is unwound from a reel and continuously fed into a machine that cuts and forms the components, after which the final components are wound onto a take-up reel. This manufacturing process results in evenly spaced components along the strip. Each connector pin is designed to be easily disconnected from the strip (the unused portion of the strip is called a "carrier"), allowing the loose pins to be incorporated into a plastic connector housing. The carrier, or carrier fabric, is a processed item that is typically discarded in standard punch and roll processing after the formed components are removed from it. However, according to some embodiments, the method of the present invention does not require the pins to be removed from the carrier. Instead, the carrier can be used to hold the pins together in an array and can be an integral part of the pin array. Thus, in some embodiments, the carrier can automatically become part of the array of pins formed during the punch and roll process and can serve the same purpose as carriers that can be added to pins during other array-forming processes.

[0071] The needles disclosed herein can be manufactured using a "stamping and rolling" process, but are not limited to this process. Additionally, it should be noted that in the devices disclosed herein, the carrier can optionally (and advantageously) be designed as an integral part of the final assembly, rather than being discarded.

[0072] Figure 3 and Figure 4 A stamping and rolling technique for manufacturing needles according to embodiments of the present disclosure is described. Figure 3 and Figure 4 As shown, the disclosed stamping and rolling technology may include the following steps:

[0073] 1. Provide plate material; (302) - in Figure 4 Not shown;

[0074] 2. Stamping the needle design into the plate material, (304);

[0075] 3. Processing the stamped needle design; (306) and

[0076] 4. Rolling the stamped needle design to form an array of needles having at least one sharp end and at least one narrower heel, wherein the needles remain attached to the carrier; (308).

[0077] In some embodiments, the needle design may include a plurality of needles to be formed and may include both a carrier and a needle. In some embodiments, the resulting needle may include at least one narrow heel and at least one needle tip. In some embodiments, the above method may be performed using a machine or manufacturing equipment. The machine or other manufacturing equipment may include a processor / software or other non-volatile memory programmed to perform the above steps.

[0078] According to the stamping and rolling technology, several advantages can be achieved. For example, the geometry of the needle can be formed by a flat metal sheet without being restricted by the manufacturing process constraints of the hollow tube, and the stamping and rolling technology can also achieve complex needle geometries. For example, in one embodiment, the design can have a flat structural portion at the top, an open funnel-shaped structure below the top, a substantially closed cylindrical structure in the middle, and a double-pointed structure at the bottom. In addition, these technologies can allow multiple needles to be formed in a manner with precise spacing between the needles, and the number of needles in the 1D array can be any number. In some embodiments, a 1D array of a given length (for example, a length consisting of 20 elements) can be stacked or layered at an additional given length to form a 2D or 3D array. The spacing between the 1D parts of the 2D or 3D array can be controlled by placing material spacers between the layers. Another advantage is that a variety of geometric arrangements of adjacent layers including square grids, triangular grids, hexagonal grids, etc. are possible. For example, any portion of the array may be bonded, potted, or otherwise incorporated into a larger structure intended to provide support, strength, orientation, or other properties to the whole.

[0079] Another advantage of the described manufacturing method is that both surfaces of the planar starting material are readily accessible prior to needle forming to allow for a wide variety of surface treatments including coating, texturing, ribbing, anodizing, etc., and either or both surfaces can include design features on the interior or exterior surfaces of the needle. Furthermore, all edges of the needle are accessible prior to needle forming to allow for a wide variety of edge profiles (e.g., single and multiple tips; abutting, overlapping, interlocking, scalloped, spiraled, etc.) and a wide variety of edge treatments including coining, beveling, serration, sharpening, deburring, electropolishing, etc.

[0080] In some embodiments, for example, a 1D array of a given length can be further bent or shaped back onto itself to form a layered 2D array or 3D array. For example, a 1D array of a given length can be further bent or shaped into, for example, a circle in which the needle tips are radially oriented, or a circle in which the needle tips are oriented perpendicular to the plane of the circle, or a circle generally along an arbitrary curve in space. Thus, in principle, any 3D surface can be populated with needle tips. In some embodiments, the stamping and rolling process can create a single tip, two tips, or three tips. The resulting needles can have any number of tips desired and be stamped into a sheet before rolling. In some embodiments, the needles have no tips at all.

[0081] In some embodiments, the 1D needle array can be subjected to secondary processing (e.g., immersion or spray coating, chemical sharpening, welding or secondary closure of seams, etc.) as a monolithic structure, thereby allowing parallel processing of multiple elements. As described herein, stamping and rolling techniques enable the formation of very narrow heels because there are no restrictions on tubular geometries. Since this technique does not involve splitting a cylinder, the heel is not restricted to an elliptical shape. For example, the heel can be formed into an angular shape. Therefore, the narrowness of the heel of a needle made according to these techniques is limited to how narrow it can be made when the flat sheet is sharpened before forming the needle. For example, by forming the heel with the seam of the needle, the heel can be made in the shape of a needle tip rather than a heel with rounded corners.

[0082] Other advantages of the described stamping and rolling method include an accurate, repeatable, and low-cost method for forming complex needle geometries. The various needle geometries can include a single tip or multiple tips of nearly any shape. The described method can form non-cylindrical cross-sections, such as square or any other geometric shape, flared tops (for easier insertion of the needle body, such as into an obturator), and other unusual or special geometries. The disclosed method can also provide textured interior and exterior surfaces of the knitting needle.

[0083] Pick and place folding method for manufacturing

[0084] Another method for manufacturing needles and needle arrays can include a pick-and-place folding method. This method can be used to form 1D arrays, 2D arrays, and 3D arrays of needles and related structures. According to these methods, needles or precursor materials of needles are processed in groups consisting of more than one needle, wherein the processing can include but is not limited to positioning, stacking, installing and fixing. In some embodiments, these methods can be performed using a machine or other manufacturing equipment. By using this method, spacing can be effectively, accurately and precisely established between needles. In some embodiments, the spacing can be regular or patterned and can extend throughout 1D space, 2D space or 3D space.

[0085] The folded tube used in the manufacturing method can be manufactured using various conventional wire forming processes, such as those used for springs and other complex linear structures. These processes include automated versions, which generally consist of (1) pinch rollers that provide a mechanism for continuous feeding of the raw material and (2) computer numerically controlled ("CNC") bending and forming tools that allow continuous lengths of the raw material to be manipulated and formed. The disclosed folding method can use an enhanced automated wire forming process as described in the present disclosure, but is not limited to such a process.

[0086] According to aspects of this method, needles or needle precursor material are processed in groups of more than one needle. As used herein, processing can include, but is not limited to, grinding, welding, brazing, deburring, sharpening, texturizing, and polishing. Groups of needles can be combined or stacked to form larger groups or arrays, optionally with accurate and precise inter-needle spacing.

[0087] Figure 5A and Figure 5B A pick and place folding method for manufacturing a plurality of needles according to aspects of the present disclosure is described. In some embodiments, as Figure 5A and Figure 5B As shown at 502, a length of tubing is bent or curved into an accordion shape. The number of bends can range from a single bend to multiple bends. The cross-sectional integrity and straightness of the bent tubing is maintained within a "critical region" located between the bends. For example, at the bends in the accordion shape, the cross-section of the tubing will be deformed rather than circular. If a round needle is used, the needle should be round, but in some embodiments, the straight section can be long enough so that the bend and any deformed sections near the bend are removed, leaving enough material for the appropriate needle length.

[0088] The bend radius of the bent shape thus facilitates insertion of the component into a needle array spacer or carrier 508, as shown at 504. In some embodiments, the bend radius can be approximately half the desired center-to-center distance between needles, for example, approximately 0.056 inches. In some embodiments, the carrier can be constructed of stainless steel. In other embodiments, the carrier can be constructed of a plastic material. Many different clamping devices can be used to temporarily secure the bent shape in the carrier 508. In some embodiments, such as Figure 5A As shown, the carrier 508 is secured to the tube in a position that does not include the end of the tube. Figure 5BIn the embodiment of the present invention, a carrier 508 can be fixed to one end of the tube. The bend shape can be tightly held by the carrier 508 (for example, by mechanical means such as by an interference fit with a groove or by snapping into a groove), or the bend shape can be permanently fixed to the carrier 508 in various ways including welding, gluing, insert molding, and brazing.

[0089] In some embodiments, the carrier may include locating holes. Locating holes are holes in the carrier that allow the carrier to be connected to other carriers or other objects. In some embodiments, the locating holes can be used to stack a row of needles to form different shapes. In some embodiments, the thickness of the carrier can be important because the spacing between the lines of needles can be further apart or closer when multiple carriers are stacked. Other locating methods, such as shoulders, pins, etc. are also possible. The carriers are designed to give the desired spacing between adjacent tube sections within a group (by the center distance of the grooves of the carrier) and between multiple groups (by the locating holes and the thickness, length and width of the carrier).

[0090] Once the single bending shape (or optionally multiple shapes) is secured within one or more carriers, the bending shape is processed, as shown at 506. Examples of processing may include, but are not limited to, cutting, grinding, sharpening, beveling, texturing, polishing, deburring, forming, bonding, and welding. In some embodiments, the single bending shape or multiple shapes may be processed to form an array or subarray of needles having precise inter-needle spacing and a precise geometric relationship relative to the carrier. During processing, the subassembly comprising the single bending shape (or multiple bending shapes) and the carrier, along with other securing components, is processed as a unitary structure, thereby allowing for parallel processing of multiple needle elements.

[0091] In some embodiments, the subarrays can be stacked or combined to form a larger array. Stacking can be done before or after processing of the subarrays. Figure 2 As discussed, a wide variety of geometric arrangements of adjacent layers are possible, including square grids, triangular grids, hexagonal grids, etc. Any portion of the array may be bonded, potted, or otherwise incorporated into a larger structure intended to provide support, strength, orientation, or other properties to the whole. The same fixing methods (e.g., Figure 5B The invention relates to a method for forming a wire array by using a plurality of methods (as shown) and a forming method to form a wire array, for example, the wire array can be used in combination with a needle array as a precisely matched ejector pin. The wire array and the tube array can be formed in separate steps or in the same step. If formed in the same step, the wire can be threaded through the tube before forming. The combination of the tube and the wire should then be processed together (bending, grinding, etc.), which has the possible advantage of eliminating the need for a later assembly step. Figure 6A and Figure 6B Photos of bent tubing in a carrier and in a processed needle, respectively. In some embodiments, this "folding" method can also be accomplished without bending or folding. For example, long, straight sections of tubing can be placed and bonded to multiple carriers at once. Once these sections are formed, they can be cut separately (one carrier per section) and subsequently sharpened.

[0092] Organizational stability

[0093] In some embodiments, a tissue stabilizer is implemented to apply pressure to the tissue during extraction and stabilize the tissue at the donor site. For example, applying pressure to the donor site with a tissue stabilizer can reduce the amount of force required for the needle or array to penetrate the donor site and thereby can reduce trauma at the donor site. 7A to 7D Depicted are a graft device having a tissue stabilizer and a method of operating the graft device according to embodiments of the present disclosure. 7A to 7D A strap is depicted as a tissue stabilizer. However, in embodiments without a strap, the grafting device can be stabilized by a plastic housing surrounding the needle array. The plastic housing can be constructed of a hard or soft material and can be combined with a softer, flared piece of material that contacts the skin and can be shaped so that in the case of multiple harvests the housing can align with the contours of the previous harvest to minimize the harvest area. The plastic housing pushes against the skin to stabilize the skin and hold the skin in place before and during harvesting. A strap can be used to help hold the plastic housing against the skin. Thus, the device is stabilized by allowing the user to apply pressure and stability to the tissue site, such as an arm, leg, or any other harvesting site. In some embodiments, the device can sense the appropriate force on the leg before allowing the needles to be actuated.

[0094] Figure 7A Depicted at step 700, a disposable package 702 includes a disposable array 704 and a disposable tape 706 and base 708. Disposable array 704 includes needles for harvesting tissue from a donor site. At step 700, disposable tape 706 and base 708 are removed from disposable package 702. At step 710, disposable tape 706 and base 708 are applied to a patient, such as a patient's leg 712. At step 720, the disposable tape can be tightened until indicator 722 indicates that optimal tension has been achieved.

[0095] Figure 7B The disposable package 702 is depicted fully opening to allow the device 732 to enter the disposable array 704. Step 740 shows clicking and locking the device 732 into the disposable array 704. Step 750 depicts placing the device 732 and disposable array 704 into the disposable belt 706.

[0096] Figure 7C The tissue acquisition sequence is depicted. The user presses button 760. The device 732 then maintains the appropriate force during the acquisition without requiring further input or force from the user. The user simply waits until the acquisition sequence is complete. Figure 7D Depicted are removal of the device (step 770), positioning the device on the wound with the harvested tissue (step 780), and spreading the harvested tissue on the wound (step 790). The user can press button 760 to spread the harvested tissue from the needle onto the treatment site, as shown in more detail at 795.

[0097] Although a strap has been shown in the above figures as a means for securing the device to the donor site, other means for securing the device may also be used. For example, in some embodiments, an adhesive or clamp may be used to secure the device. Furthermore, in some embodiments, the angle or verticality of the device may be checked and adjusted before the needle is inserted into the donor site to ensure that the tissue is not harvested at an angle. For example, the device may be held within a range of + / - 10 degrees relative to vertical.

[0098] In some embodiments, the device may have a force sensor. The force sensor can detect the force with which the user applies the device to the skin. Once the user reaches a force that is considered optimal, the device notifies the user that the optimal force has been reached and notifies the user that deployment of the device can begin. The device can use the force sensor to know that sufficient force has been applied before acquisition. Alternatively, if the user is applying force (with or without a belt), the device will check to ensure that the user is pushing hard to successfully penetrate the donor site before acquisition. In some embodiments, the optimal force can be in the range of about 10 pounds to 40 pounds. The device can also measure and monitor force throughout the acquisition sequence and can alert the user when appropriate force has been applied and / or the applied force has dropped below an acceptable level. The alarm can be visual or audio.

[0099] In some embodiments, the belt may include multiple ports for accessing multiple harvesting sites. In these embodiments, a disposable shield may be included in each port on the belt that can be attached to the cartridge after harvesting. The purpose of the disposable shield is to prevent contamination of the donor site if the cartridge comes into contact with the wound during dispensing and then returns to harvest. The user can then discard the disposable shield before re-harvesting at the second and additional ports. The disposable shield also prevents the user from returning to the same port twice, for example, harvesting from the same area twice.

[0100] Vibration-assisted coring

[0101] In some embodiments, vibrating the needle while entering the donor site can help reduce the insertion force of the needle and thus reduce damage to the tissue and pain to the patient. Figure 8A A device 800 for vibration actuation of a needle is depicted. Figure 8A The three states of the same configuration are depicted as a first state 802 / 804, a second state 810 / 812, and a third state 820 / 822. A top view (804, 812, 822) and a side view (802, 810, 820) of each state are shown.

[0102] In some embodiments, device 800 can include an oscillating impact plate 803 surrounding a needle 805 via a contact aperture 806. Impact plate 803 can be supported by one or more plate supports 807, which allow and facilitate lateral or sideways movement of impact plate 803, such that impact plate 803 can impact needle 805 one or more times per oscillation. In some embodiments, impact plate 803 can be set into oscillatory motion and maintained in motion by any of a number of means, including but not limited to piezoelectric, electromechanical, pneumatic, fluidic, mechanical, or magnetostrictive actuators 808. One or more actuators 808 can be employed. The schematic diagram is intentionally not drawn to scale; in practice, the vibration amplitude of impact plate 803 can be as small as a few microns, but it can also be considerably larger. In a first state 802 / 804, actuator 808 actuates oscillating impact station 803 and brings the side of needle 805 into contact with impact plate 803. In the second state 810 / 812, the strike plate 803 has moved away from the actuator 808 and is centered around the needle 805. In the third state 820 / 822, the strike plate 803 is in contact with the opposite side of the needle 805. In some embodiments, the strike plate 803 can be constructed of metal or plastic.

[0103] In this embodiment, the impact plate 803 and the needle 805 are mounted and moved independently. That is, the needle 805 can move independently of the impact plate 803. For example, the needle 805 can be translated in a vertical direction (up or down) through the contact opening 806 without any need to translate the impact plate 803 and its support 807 in a vertical direction. In addition, as Figure 8A As shown in FIG, the energy of actuator 808 is directed into strike plate 803 rather than directly into needle 805. This allows the design and selection of specific vibration characteristics, such as resonant frequency, for the strike plate 803 assembly independent of the needle actuation scheme.

[0104] exist Figures 8B to 8F Five conventional methods of coupling an actuator to a strike plate are shown in FIG. It should be understood that a single actuator and a single needle are shown for illustrative purposes, but that these schemes can be expanded to include multiple actuators and multiple needles, such as Figure 8G shown. Figure 8B The vibration actuation system is depicted in a first state 802, a second state 810, and a third state 820, with an actuator 808 fixed to a fixed base 830 and loosely coupled to a strike plate 803 or a support structure 807 for the strike plate. The free end of the actuator intermittently contacts the strike plate (or a portion of the support structure for the strike plate). The resonant properties of the strike plate and its support structure are independent of the actuator. The contact point of the actuator may therefore affect the displacement amplification. For example, in Figure 8B In the embodiment of the present invention, the actuator makes contact at a point midway between a node of vibration and an anti-node of vibration of the plate support. The motion of the impact plate can thus contact the needle once per oscillation, twice per oscillation (e.g., Figure 8B The energy of the actuator can be transmitted to the contact point via a waveguide 832 or similar transmission element, which can also include a displacement amplifier, as shown in the second figure below.

[0105] Figure 8C A vibration actuation system is depicted in a first state 802, a second state 810, and a third state 820 in an arrangement in which the actuators 808 are fixed to a fixed base 830 and tightly coupled to the impact plate 803 (shown in the top row 836) or the support structure 807 of the impact plate 803 (shown in the bottom row 838). The actuators (or waveguide extensions of the actuators) are attached to the impact plate 803 or the support structure of the impact plate. Non-resonant vibration modes can be excited with greater control than with a loosely coupled solution. The actuators can simultaneously be used as sensors, thus, vibration feedback control becomes possible. In Figure 8C In some embodiments, when the actuator is attached to the strike plate, the actuator does not travel with the strike plate. In some embodiments, the actuator is also attached to a fixture that is substantially heavier than the strike plate (e.g., a handle of the device), such that this other fixture is essentially "stationary." This way, the strike plate moves precisely only in the manner in which the actuator moves, and the frequency and amplitude of the strike plate's vibration can be controlled.

[0106] Figure 8DA vibration actuation system is depicted in a first state 802, a second state 810, and a third state 820 in an arrangement in which actuators 808 are tightly coupled to a strike plate 803 (shown in top row 840) or a support structure for the strike plate 803 (shown in bottom row 842), and the actuators 808 travel with the strike plate 803. In this embodiment, very low-mass solutions are possible, and complex vibration modes are common. In some embodiments, a low-mass solution refers to an actuator that is not attached to a substantially heavier object to stabilize it. In this solution, the actuator is attached only to the strike plate. Complex vibration modes refer to modes that are more complex than simple waveforms, and because the strike plate and actuator move together, complex modes occur when multiple waves interact.

[0107] Figure 8E The vibration actuation system is shown in a first state 802, a second state 810, and a third state 820 in an arrangement in which the actuator 808 is fixed to a fixed base 830 and is energetically coupled 850 to the impact plate 803 or its support structure 807 without physical contact via a transducer 852. Any of several energy transfer methods are possible, including inductive, electrostatic, acoustic, and pneumatic energy transfer methods. Depending on the technology used, the transducer 852 can be a piezoelectric, EMF, magnetoelectric, mechanical, or other type of transducer.

[0108] Figure 8F The vibration actuation system is depicted in a first state 802, a second state 810, and a third state 820 in an arrangement in which actuation is indirectly achieved due to the overall vibration of the assembly 860. The strike plate 803 and associated structure 807 are designed to resonate when the entire assembly is vibrated, such as through the action of a solenoid elsewhere in the assembly or through the action of a spring and ratchet mechanism elsewhere in the assembly. In some embodiments, the vibration of the strike plate 803 can be synchronized with other movements or operations of the assembly. In some embodiments, the vibration of the strike plate 803 can be triggered manually or automatically.

[0109] Operation mode and configuration

[0110] For any of the above schemes, the vibration mode can be selected as resonant or non-resonant. In some embodiments, vibration can be implemented in conjunction with other operations. For example, vibration can be applied intermittently and briefly, as needed, in conjunction with a pulsed energy source, such as a solenoid, that can be applied directly to the needle. In some embodiments, feedback control (for those cases where the actuator is also used as a sensor) can be used to control the duration and duration of the vibration actuation. In addition, the frequency and displacement amplitude can be selected from a wide range: subsonic, sonic, and ultrasonic.

[0111] Vibration assistance can be used to advance, retract, or eject the cored material from the needle. In some embodiments, the contact opening of the impact plate can be shaped to achieve one or more contact points per oscillation. The roughness and / or sharpness of the opening can be configured to influence the quality of the needle's resulting vibration. Furthermore, in some embodiments, the contact position between the impact plate and the needle can be selected to influence the needle's vibration amplitude and vibration mode.

[0112] In some embodiments, the impact plate and its associated structural components can be designed to oscillate due to direct actuation or indirect actuation, and the actuation can be achieved manually or automatically (electronically). Direct actuation includes, but is not limited to, vibration sources such as piezoelectric elements, magnetostrictive elements, electromagnetic solenoids, mechanical springs and ratchets, pneumatic bursts, fluid oscillations, acoustic energy, etc. Indirect actuation includes any vibratory movement of the entire assembly that can be achieved through the action of, for example, a solenoid. Thus, the advancement or retraction of the needle through some mechanical action can be used to simultaneously cause vibratory oscillations of the impact plate, which will then impart vibrations to the needle. Direct actuation schemes include physical contact methods as well as non-contact methods. For example, the actuator can be located remote from the impact plate, and the vibration energy of the actuator can be transmitted to the impact plate or a structural component of the impact plate through direct contact with a flexible waveguide or via electromagnetic induction, magnetostrictive induction, or acoustically through air without contact.

[0113] Figure 8G An oscillating impact plate 803 is depicted for use with a needle array 870 in accordance with some aspects of the present disclosure. The impact plate 803 can be configured to impact on a ID array or a 2D array of needles 870. Any single needle or multiple needles can be moved into or out of the contact aperture at any time.

[0114] Oscillation mode

[0115] Figure 8H Two modes of operation of the vibration actuation system are depicted. Depending on several parameters (number, position and order of actuator elements, shape and mass of the impact plate 803, stiffness and orientation of the flexible support, etc.), the impact plate 803 can oscillate over a wide range of motions, including simple linear motion (shown at 880 on the left) to staged quasi-circular motion (shown at 890 on the right). The linear mode 880 is included in the following example: One actuator 808 is shown moving in a single linear plane. A staged quasi-circular pattern 890 may have three actuators 808, where each actuator may move in separate planes A, B, and C. Figure 8H The vibration in is perpendicular to the axis of the needle; however, Figure 8HThe vibrations in the solenoid do not have to be perpendicular to the axis of the needle. The vibrations can be applied in any direction including the axis of the needle. One way to apply vibrations along the axis of the needle is to send a very short and fast signal to the solenoid, thereby "trembling" the solenoid.

[0116] Stem cells / adipose tissue

[0117] The described micro-grafts can include skin tissue, which can include, for example, epidermal tissue and dermal tissue and / or tissue obtained from other body organs. The micro-grafts can have at least one relatively small size, for example, less than about 1 mm or less than about 0.5 mm, or alternatively about 0.3 mm or less, or about 0.2 mm. This exemplary small size of the micro-graft can simultaneously promote healing of the donor site after acquisition and promote the viability of the micro-graft by allowing greater diffusion nutrition of the micro-graft tissue. Small damaged areas in the donor site caused by the removal of tissue portions can heal rapidly with less or no visible scars. The micro-grafts obtained from skin tissue can include, for example, epidermal tissue and dermal tissue and can also include stem cells that can be located near the dermis / fat layer boundary.

[0118] An exemplary micrograft can have an elongated, generally cylindrical shape. The micrograft can include both epidermal and dermal tissue from an exemplary donor site. For example, an exemplary micrograft can have a length of approximately 3 mm, which can correspond to a typical total depth of skin layers (e.g., epidermal and dermal layers). Different lengths can be used based on the specific skin or tissue characteristics of the donor site. In previous applications, it has been noted that it may be preferable to avoid harvesting a significant amount of subcutaneous tissue, and thus the harvested micrograft can primarily include epidermal and dermal tissue. For example, existing techniques for performing skin grafts remove or scrape off any fat or adipose tissue from the skin graft before applying the graft to the wound site. This is because adipose tissue is generally viewed as a byproduct of the harvesting process, which adversely interferes with the ability of the transplanted skin to access a blood supply at the wound site. Therefore, in existing methods, all adipose tissue is removed from the graft.

[0119] However, according to aspects of the present disclosure, due to the smaller size of the micrograph columns, these columns can typically survive at the wound site via diffusion without having to form a good connection to the blood supply at the wound site. Therefore, since the adipose tissue in the subcutaneous tissue contains stem cells, it may be helpful to include the subcutaneous tissue in the micrograft. Thus, in cases where the depth of the micrograft can extend to the lower part of the dermis and the dermis of the donor site (e.g., near the dermis / fat layer boundary) and even into the dermis / fat layer boundary, the micrograft can include stem cells such as mesenchymal stem cells. When these stem cells are dispersed or inserted into the recipient site, these stem cells can promote the healing and integration of the exemplary micrograft.

[0120] In addition, prior art methods for obtaining adipose-derived stem cells require isolating and purifying stem cells from adipose tissue. See, for example, U.S. Patent No. 6,777,231 to Katz. However, according to aspects of the present disclosure, the healing benefits of stem cells can be achieved without processing, separating or purifying stem cells. The presence of stem cells only within the adipose tissue of the micrograft can lead to the healing and integration of the micrograft. Therefore, it may be beneficial to include at least 5% or 10% adipose, adipose tissue in the micrograft to achieve the advantages of stem cells at the recipient site. Therefore, according to some embodiments of the present disclosure, the micrograft can reach 4mm or 5mm to touch the fat cells in the adipose tissue layer.

[0121] Needle rotation and actuation

[0122] In some embodiments, the individual needles can rotate. This can be achieved by using gears or O-rings or any other means of rotating the entire array of needles. The rotation of the needles allows for lower force coring of the skin as the needles enter the donor site. In some embodiments, the use of rotation allows for better use of the straight cutting, sharp cutting edge of the needles.

[0123] In some embodiments, an electric hammer can be used to drive the needle into the donor site. This electric hammer can have a rotating cam that strikes a plunger to move the needle multiple times per second. In this embodiment, the use of an automatic hammer can drive the needle into the donor site more slowly than a solenoid-type actuation.

[0124] In other exemplary embodiments of the present disclosure, the exemplary methods and apparatus described herein can be applied to tissues other than skin tissue, for example, internal organs such as the liver or heart, etc. Thus, grafts for various tissues can be formed with minimal damage to the donor site and rapid healing of the donor site, while forming transplanted tissue suitable for placement at the recipient site.

[0125] The subject matter described herein can be implemented alone or in combination with a system that facilitates the removal of the assembly from the donor site and / or the dispersal or otherwise placement of the tissue at the recipient site or other site. It should be understood that the disclosed subject matter is not limited to its application to the specific structures and arrangements of components described in the foregoing description or shown in the accompanying drawings. The disclosed subject matter can have other embodiments and can be practiced and executed in various ways. In addition, it should be understood that the wording and terminology used herein are for descriptive purposes and should not be considered as restrictive.

[0126] Therefore, it should be understood by those skilled in the art that the concepts underlying this disclosure can be readily used as the basis for the design of other structures, methods, and systems to achieve the multiple purposes of the disclosed subject matter. Therefore, it is important that the claims be deemed to include such equivalent constructions as long as they do not depart from the spirit and scope of the disclosed subject matter.

[0127] While the disclosed subject matter has been described and illustrated in the foregoing exemplary embodiments, it should be understood that the present disclosure has been made by way of example only and that numerous changes may be made in the details of its implementation without departing from the spirit and scope of the disclosed subject matter.

Claims

1. A device (732) for obtaining biological tissue, the device (732) comprising: A two-dimensional array of hollow tubes (102), the two-dimensional array of hollow tubes (102) comprising: a first row of a plurality of hollow tubes (102); a second row of a plurality of hollow tubes (102), wherein the second row of a plurality of hollow tubes (102) is adjacent to the first row of hollow tubes (102); a third row of a plurality of hollow tubes (102), the third row of a plurality of hollow tubes (102) being adjacent to the second row of hollow tubes (102), wherein each hollow tube (102) comprises at least one tip (14, 106) at a distal end of the hollow tube (102); wherein the inner diameter of the at least one hollow tube (102) is less than about 1 mm, and the distal end of each of the hollow tubes (102) is configured to be inserted into a biological tissue donor site to remove a portion of tissue from the biological tissue donor site when each of the hollow tubes (102) is removed from the donor site; Characterized in that the device (732) is configured to independently actuate each row of hollow tubes in the first row, the second row and the third row to insert the corresponding row of hollow tubes (102) into a biological tissue donor site.

2. The device (732) according to claim 1, wherein: The array comprises a circle.

3. The device (732) according to claim 2, wherein: The area of ​​the circle comprises approximately 6.4516 square centimeters (one square inch).

4. The device (732) according to claim 3, wherein: The donor site comprises an area of ​​approximately 6.4516 square centimeters (one square inch); or Therein, the tissue removed from the donor site comprises approximately 0.64516 square centimeters (0.1 square inches).

5. The device (732) of claim 1, wherein: The array of hollow tubes (102) includes approximately 300 hollow tubes (102).

6. The device (732) according to claim 1, comprising a plurality of pins, each pin being disposed within a central cavity of each hollow tube (102).

7. The device (732) according to claim 1, comprises a stopper to limit the depth of insertion of each hollow tube (102) in the array of hollow tubes (102) into the biological tissue donor site.

8. The device (732) of claim 1, comprising a solenoid, wherein: The solenoid actuates the array of hollow tubes (102) to insert the array of hollow tubes (102) into the biological tissue donor site.

9. The device (732) of claim 1, comprising a spring, wherein: The spring actuates the array of hollow tubes (102) to insert the array of hollow tubes (102) into the biological tissue donor site.

10. The device (732) of claim 1, comprising a first solenoid, wherein: The first solenoid actuates the first row of hollow tubes (102).

11. The device (732) of claim 1, comprising a second solenoid, wherein: The second solenoid actuates in an opposite direction as the first solenoid.

12. The device (732) of claim 1, comprising a force sensor, wherein: The force sensor senses the force with which the device is applied to the biological tissue donor site.

13. The device (732) of claim 1, wherein: Each hollow tube (102) comprises: two tips at the distal end of the hollow tube (102); a narrow heel portion positioned between the two pointed portions, and Wherein, the narrow heel portion comprises less than about 10% of the inner diameter of the hollow tube (102).

14. The device (732) of claim 1, wherein: The inner diameter of the hollow tube (102) is less than about 0.8 mm.

15. The device (732) according to any of the preceding claims, further comprising a housing arranged in a two-dimensional array around the hollow tubes (102) and configured to stabilize the biological tissue donor site.

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