Patent Description:
Surgeons currently use acellular tissue matrix products such as ALLODERM® and STRATTICE™, both dermal acellular matrices produced by LIFECELL® CORPORATION (Branchburg, NJ), for treatment of a variety of different structural defects. For example, such products can be useful in abdominal wall repair (e.g., complex hernia repair), breast reconstruction, orthopedic surgery, and neurosurgical applications.

Such tissue matrix products are often provided as flexible sheets of material that can replace, augment, or alter existing tissues. For some applications, however, it may be desirable to include holes or openings in the sheets, for example, to permit more rapid fluid flow across the sheets or to provide sites for securing surgical anchors such as sutures, clips, or staples.

<CIT> discloses a hernia implant consisting of a collagen membrane which is gained from biological starting material and is provided with a plurality of drainage openings.

The openings are formed in a pattern comprised of a repeating motif of openings.

<CIT> and <CIT> disclose perforated multilayer membranes useful as artificial skin.

Accordingly, the present application provides tissue matrix products having preformed holes or perforations. The holes or perforations are provided in a configuration that provides the desired functionality without sacrificing other properties such as strength and suture retention.

According to certain embodiments, a tissue matrix product is provided. The product can include a flexible sheet comprising a tissue matrix, wherein the flexible sheet includes a group of holes passing through the tissue matrix, wherein the holes are formed in a pattern comprised of a repeating motif of five holes.

In other embodiments, a tissue matrix comprising a flexible sheet comprising a tissue matrix is provided. The flexible sheet includes a group of between <NUM> and <NUM> holes passing through the tissue matrix, wherein the flexible sheet comprises a rectangular shape having a width between <NUM> and <NUM> and a length between <NUM> and <NUM>, and the holes have a maximum dimension between about <NUM> and <NUM>, and wherein the holes are arranged in a pattern such that a uniaxial tensile strength measured in any direction along the sheet is at least <NUM>% of the uniaxial tensile strength of the sheet without the group of holes.

In other embodiments, a tissue matrix including a flexible sheet comprising a tissue matrix is provided. The flexible sheet includes a group of between <NUM> and <NUM> holes passing through the tissue matrix, wherein the flexible sheet comprises a rectangular shape having a width between <NUM> and <NUM> and a length between <NUM> and <NUM>, and the holes have a maximum dimension between about <NUM> and <NUM>, and wherein the holes are arranged in a pattern such that a straight line drawn obliquely across a top or bottom surface of the tissue matrix can pass through no more than three of the holes.

Also described are methods of treatment including the disclosed products.

Reference will now be made to exemplary embodiments, examples of which are illustrated in the accompanying drawings.

The invention relates to a tissue matrix product as defined in claim <NUM>.

Reference will now be made in detail to various embodiments of the disclosed devices, examples of which are illustrated in the accompanying drawings.

In this application, the use of "or" means "and/or" unless stated otherwise. Furthermore, the use of the term "including", as well as other forms, such as "includes" and "included", is not limiting. Any range described herein will be understood to include the endpoints and all values between the endpoints.

The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

The present disclosure relates generally to devices for surgical procedures and systems and methods relating to such devices. The devices can be used for tissue augmentation, repair or regeneration of damaged tissue, and/or correction of tissue defects. As such, the devices and methods discussed herein can be suitable for a wide range of surgical applications, such as, for example, abdominal wall repair, prophylactic treatment of post-operative complications (e.g., to prevent hernia, dehiscence, or other post-operative abdominal complications), hernia treatment (e.g., any abdominal or visceral hernia, such as a hiatal hernia, inguinal hernia, parastomal hernia, or midline abdominal hernia). The devices disclosed herein can also be used to treat other tissue sites, including, for example, breasts, connective tissue (tendons, ligaments, or fascia), and to assist in any structural defect correction or prevention.

The devices and associated methods discussed herein can include a flexible sheet of biologic material, such as an acellular tissue matrix. Such tissue matrix materials are used for a variety of surgical applications and have become an important tool for treating or preventing many problems associated with trauma, post-operative complications, and/or structural defects due to aging, disease, congenital or acquired defects, or iatrogenic problems.

For some surgical procedures, it may be desirable to include holes or openings in the tissue matrix. For example, in some cases, it is desirable to place a drainage tube near a surgical site to allow drainage of fluids, e.g., to prevent formation of seromas or other fluid accumulations. Drainage of fluid from opposite sides of implantable tissue matrices, however, can be improved by providing holes or fluid passages through the matrices so that a drainage device located on one side will collect fluids from both sides of the device.

In addition, properly designed holes or openings can be useful for securing the tissue matrices. For example, some tissue matrix materials are designed to be strong and potentially relatively thick. Accordingly, fixation of such devices to surrounding tissues using conventional means such as sutures, staples, or clips, can sometimes be challenging and/or time consuming. Therefore, tissue matrices with preformed holes that can be used for fixation using sutures or other means are desirable.

On the other hand, holes or openings in tissue matrices should be configured to prevent unacceptable changes in other materials properties. For example, a group of holes in a flexible sheet of tissue matrix must be sized, shaped, and positioned such that the tissue matrix does not experience an unacceptable degradation in important mechanical properties such as tensile strength, elasticity, burst strength, and/or suture retention strength. Accordingly, the present application provides improved tissue matrix products that include a group of holes or perforations that are specially configured to provide the aforementioned advantages without causing unacceptable alterations in other material properties. As used herein, "holes" and "perforations" are used interchangeably and will generally refer to any opening that passes through a flexible sheet of material from one side to the other.

According to embodiments, the present application provides tissue products for use in surgical procedures. The tissue products can include a flexible sheet <NUM> (<FIG>) comprising a tissue matrix, wherein the flexible sheet includes a group of holes <NUM> passing through the tissue matrix <NUM>. The holes <NUM> can be placed on the sheet in a specifically designed pattern. According to the invention, the holes are placed using a repeating motif <NUM> (<FIG>).

As used herein "motif" will be understood to refer to any repeatable pattern of holes. Further, the motif need not be repeated exactly, but can be varied (e.g., by changing dimension of holes or spacing of holes), so long as one or all of the goals discussed herein are met.

According to other examples, the present application provides tissue products including a flexible sheet <NUM> comprising a tissue matrix and a group of holes <NUM>. The holes <NUM> are sized and positioned on the flexible sheet of tissue matrix <NUM> to maintain a desired tensile strength of the sheet, as compared to a sheet without the group of holes <NUM>.

According to other examples, the present application provides tissue products including a flexible sheet <NUM> comprising a tissue matrix and a group of holes <NUM>. The group of holes are positioned such that the number of holes that are aligned along an oblique axis of the sheet is minimized or kept below a certain level. For example, in one embodiment, the holes <NUM> are arranged in a pattern such that a straight line <NUM>, <NUM> (<FIG>) drawn obliquely across a top or bottom surface of the tissue matrix can pass through no more than three of the holes <NUM>.

The devices disclosed herein can be used for treating a variety of different anatomic sites. For example, <FIG> illustrates methods of treatment of an abdominal wall using tissue matrix products <NUM> of the present application. The methods of treatment are described in more detail below, but in general, the device <NUM> can be used to treat portions of the abdominal wall <NUM>, while using the group of holes <NUM> to allow fluid flow through the devices or to provide a site for fixation using sutures or other fixation means. Furthermore, as discussed below, the devices <NUM> can be implanted at a variety of different locations to support various anatomic structures and/or treat a variety of different conditions.

<FIG> illustrate an exemplary tissue matrix product <NUM> including holes or perforations, according to certain embodiments. The products <NUM> illustrated in each of <FIG> are identical but include different reference numerals and markings to facilitate discussion of various features of the product <NUM>.

The tissue matrix product <NUM> is illustrated as a two-dimensional view of a flexible sheet of material. Accordingly, it should be appreciated that the flexible sheet will have a length <NUM> and width <NUM>, and a thickness (not shown). The length <NUM>, width <NUM>, and thickness can be selected based on the desired surgical indication, e.g., to provide a sufficient surface area (measured in terms of the length <NUM> and width <NUM>) and structural stability (e.g., based on strength, tensile properties, suture retention, burst strength, etc.). For dermal tissue matrix materials, the thickness can vary, but may be between, for example, <NUM> to <NUM>, <NUM> to <NUM>, or <NUM> to <NUM>.

The tissue matrices used to produce the products <NUM> described herein can include a variety of different materials. For example, an acellular tissue matrix or other tissue product can be selected to allow tissue ingrowth and remodeling to assist in regeneration of tissue normally found at the site where the matrix is implanted. For example, an acellular tissue matrix, when implanted on or into subdermal tissue, fascia, mammary tissue, or other tissue, may be selected to allow regeneration of the tissue without excessive fibrosis or scar formation. In certain embodiments, the devices can be formed from ALLODERM® or STRATTICE™ (LIFECELL® CORPORATION, BRANCHBURG, NJ) which are human and porcine acellular dermal matrices, respectively. Alternatively, other suitable acellular tissue matrices can be used. For example, a number of biological scaffold materials as described by Badylak et al. , or any other similar materials, can be used. The devices described herein can be produced from a variety of different human or animal tissues including human, porcine, ovine, bovine, or other animals tissues.

As stated above, the products <NUM> can include a group of holes <NUM> that can be sized and positioned to provide a number of desired properties. As illustrated in <FIG>, the product <NUM> includes a total of thirty holes, but a range in the number of holes can be used, as discussed further below. Further, as shown in <FIG>, the holes <NUM> can be positioned such that a perimeter region <NUM> is formed in which no holes <NUM> are present. The perimeter region <NUM> can be sized to allow an area for passage of sutures or other connection devices and/or to provide a non-perforated section for fixation to tissue such as fascia. Suitable sizes may include <NUM>-<NUM>, <NUM>-<NUM>, about <NUM>, <NUM>-<NUM>, or values in between. Larger or smaller perimeter regions <NUM> can be used.

To provide the desired functional properties, the group of holes <NUM> can be positioned in specialized patterns. For example, according to the invention, the group of holes <NUM> are positioned using a repeating motif <NUM>. The motif <NUM> can be selected to allow formation of a desired number of holes <NUM> without unacceptable changes in certain material properties such as strength or elasticity.

A suitable motif <NUM> is illustrated in <FIG>, <FIG>, <FIG>, and <FIG>. As shown, the motif <NUM> can include five holes <NUM>. In one embodiment the motif <NUM> has a rectangular shape with a hole <NUM> positioned at each corner of the rectangle and one hole <NUM> positioned at the center of the rectangle. Further, as illustrated in <FIG>, the rectangular shape can have a range of suitable sizes, including a width <NUM> and a length <NUM> (the length being double the distance <NUM> measured along an edge of the rectangle from a corner hole <NUM> to the center hole <NUM>). In various embodiment the width can be between about <NUM> and <NUM>, or between about <NUM> and <NUM>; the length between about <NUM> and <NUM>, between about <NUM> and <NUM>; and the distance <NUM> between about <NUM> and <NUM>. In one embodiment, the width is about <NUM> and the length <NUM> about <NUM>, but the width and length can be varied (e.g., scaled at the same ratio or otherwise varied in accordance with the goals described herein).

The motif <NUM> can be distributed across the sheet of tissue matrix <NUM> in a variety of patterns. For example, as shown, the motif <NUM> may be arranged in multiple columns <NUM>, <NUM>, <NUM>, and in rows <NUM>, <NUM>, and, <NUM>. The number of columns <NUM>, <NUM>, <NUM>, and rows may be varied based on the size of the product <NUM> and the specific number of holes <NUM> desired. For example, the device of <FIG> includes three columns, but suitable devices may include between <NUM> and <NUM> columns, or any specific number in between. In addition, each column or row need not include all five holes of a motif. For example, as shown in <FIG>, the motifs at some positions, e.g., column <NUM>, rows <NUM> and <NUM>, have four holes of the motif <NUM>, and the motif at the top and bottom of column <NUM> have only three holes (holes <NUM> and <NUM> are not part of the motif <NUM> and are discussed below).

The distances between each column <NUM>, <NUM>, <NUM>, and rows <NUM>, <NUM>, <NUM> can be selected to produce desired hole spacing. For example, according to the invention, the distance between two columns and the size of the motifs <NUM> are selected to provide a spacing pattern that reduces linear alignment of holes <NUM> along various directions of the sheet. In so doing, the mechanical strength of the products <NUM> is maintained.

Of note, as shown in <FIG>, the distance between holes of two columns (Lr) differs from the distance (Lm) between the holes <NUM> at bottom corners of a motif <NUM>. This variation in distance cause the motifs <NUM> of two different columns <NUM>, <NUM> to fall out of alignment, so that the motif is not simply repeated, and the alignment of holes is reduced along oblique axes (<NUM>, <NUM>-<FIG>).

The products <NUM> described herein can have a variety of shapes and sizes. For example, each of the flexible sheets of tissue matrix illustrated in <FIG>, <FIG>, and <FIG> are rectangular, which provides a simple shape for use in abdominal wall procedures. Furthermore, a rectangular shape can be trimmed or reshaped based on a specific patient's needs or surgeon's preferences. It will be appreciated, however, that other shapes can be used including circular, oval, square, triangular, bi-convex, or asymmetric shapes.

The size and shape of each of the holes <NUM> can also be varied. Generally, however, the holes <NUM> are sized and shaped to preserve the mechanical properties of the sheet of tissue matrix <NUM>, while allowing fluid flow or passage of sutures or other anchors through the holes. For example, the holes can be sized such that they have a maximum dimension between about <NUM> and <NUM>, between about <NUM> and <NUM>, between <NUM> and <NUM>, between <NUM> and <NUM>. mm, between <NUM> and <NUM>, about <NUM>, or any values within the aforementioned ranges.

Further, the holes <NUM> can be shaped to maintain sheet mechanical properties. For example, to prevent excess force due to tensile forces of sutures passed through a hole <NUM> or high stress points from stretching, each hole can have a rounded border (e.g., oval, circular, rounded but asymmetric). In one embodiment, all holes <NUM> are circular and have a diameter between about <NUM> and <NUM>, between about <NUM> and <NUM>, between <NUM> and <NUM>, between <NUM> and <NUM>. mm, between <NUM> and <NUM>, about <NUM>, or any values within the aforementioned ranges.

In some cases, the size of the holes, position of holes, and other mechanical properties of the tissue matrix <NUM> are selected to maintain a uniaxial tensile strength of the tissue matrix <NUM>. For example, the product can be configured such that a uniaxial tensile strength (as measured along an axis parallel to the length of the tissue matrix <NUM>) is at least <NUM>%, at least <NUM>%, at least <NUM>%, at least <NUM>%, at least <NUM>%, or at least <NUM>%, or any values in between versus the uniaxial tensile strength of a sheet not having the holes <NUM>.

The hole size and shape as well as other sheet properties (e.g., thickness) can be configured to provide holes that will maintain suture retention strength if sutures or other fixation devices are passed through a hole. For example, the suture retention strength of each hole <NUM> can be configured such that it is at least <NUM>%, at least <NUM>%, at least <NUM>%, at least <NUM>%, at least <NUM>%, at least <NUM>% or approximately <NUM>% of the suture retention strength of a region of the same tissue matrix without a hole <NUM>.

Suture retention can be measured using a simple technique. Specifically, a suture or suture analog (e.g., a steel wire) can be passed through the tissue to form a loop, and tension can be applied until the material tears. The amount of force (Newtons) needed to tear the tissue is the suture retention strength. The suture retention strength can be measured by passing the suture through one of the holes <NUM> to measure the suture retention when a hole is used.

In various embodiments, the holes <NUM> are positioned to minimize or control the number of holes that are linearly aligned along various directions. For example, in certain embodiments, the holes <NUM> are positioned such that the number of holes that are linearly aligned along an oblique axis <NUM>, <NUM> of the flexible sheet <NUM> is kept below a certain value.

As used herein "oblique axis" will be understood to refer to a direction along the flexible sheet that is parallel to the flat top or bottom surfaces of the sheet (when the flexible sheet is laid on a flat surface) but is not parallel to an axis <NUM> directed along the length <NUM> or an axis <NUM> directed along the width <NUM> of the flexible sheet <NUM>.

In some examples the number of holes that can be linearly aligned along an oblique axis is two or fewer, three or fewer, four or fewer, or five or fewer. According to the invention, the number of the holes linearly aligned along an oblique axis is kept below five.

In addition to the holes <NUM> being provided in a specified pattern, one or more additional holes <NUM>, <NUM> can be included. For example, as shown in <FIG>, one hole <NUM> is located at a bottom <NUM> of the sheet, and another hole <NUM> is located at a top <NUM> of the sheet. The holes <NUM>, <NUM> are provided to identify for a surgeon where the top <NUM> and bottom <NUM> of the sheet are located (i.e., identify the orientation of the sheet so that the surgeon recognizes how the sheet should be aligned when implanted in an abdominal wall). In particular, using the pattern set forth in <FIG>, the sheet <NUM> should be implanted such that the holes <NUM>, <NUM> are generally aligned with an anatomic axis in an superior-inferior (rostral-caudal) direction. It will be appreciated, however, that the holes could be moved to identify a different anatomic direction for different surgical indications.

<FIG> illustrate one embodiment for a flexible sheet of tissue matrix <NUM> with holes <NUM>. The sheets <NUM> illustrated therein, however, may be modified in other ways. For example, <FIG> and <FIG> illustrate tissue matrix products <NUM>', <NUM>" including holes or perforations, but having differing sizes and differing numbers of holes. It should be understood that the size of the products and number of holes may be adjusted based on the size of the patient, the condition to be treated, or other factors determined by a surgeon.

The specific number of holes <NUM> in the devices <NUM>, <NUM>', <NUM>" illustrated can be varied. For example, a sheet can include between <NUM> and <NUM> holes passing through the tissue matrix, between <NUM> and <NUM> holes, between <NUM> and <NUM> holes, between <NUM> and <NUM> holes, between <NUM> and <NUM> holes, or other values in between. Further the sheets can be rectangular and have a width between <NUM> and <NUM>, between <NUM> and <NUM>, between <NUM> and <NUM>, or any ranges in between. In addition the devices <NUM>, <NUM>', <NUM>" can have a length between <NUM> and <NUM>, between <NUM> and <NUM>, or between <NUM> and <NUM>.

The products described herein are generally described with reference to acellular tissue matrices, but it will be appreciated that the tissue matrices can be pre-treated with exogenous cells or other therapeutic components prior to or after implantation. Accordingly, the devices can include tissue matrix products from which substantially all native cellular material has been removed, but which include exogenous cellular sources such as stem cells, fibroblasts, platelets, blood cells, or other cell sources.

The devices described herein can be used in a variety of different surgical operations, including in operations for treatment of abdominal wall issues. For example, <FIG> illustrates implantation of devices <NUM> at a variety of different positions within an abdominal wall. Although one of skill in the art will recognize that a certain procedure may require only one of the devices <NUM> of <FIG>, each of the illustrated implantation locations (as well as others) may be desirable, depending upon the specific procedure being performed. The illustrated implantation locations would be recognized by surgeons and can include onlay <NUM>, inlay <NUM>, retromuscular <NUM>, preperitoneal <NUM>, or intraperitoneal <NUM>, but additional sites can be used.

In some examples, the device <NUM> may also be implanted next to a drainage device <NUM>, such as a drainage bulb, which may include a tube that passes to a surgical location <NUM> near an implanted device.

Furthermore, the devices <NUM> can be implanted during open, laparoscopic, or using any suitable surgical approach. The holes <NUM> can be used to receive sutures, clips, staples, or other fixation devices that facilitate positioning and securing the device and/or surrounding tissues in place.

Claim 1:
A tissue matrix product, comprising:
a flexible sheet (<NUM>, <NUM>', <NUM>") comprising a tissue matrix, wherein the flexible sheet includes a group of holes (<NUM>) passing through the tissue matrix, wherein the holes (<NUM>) are formed in a pattern comprising a repeating motif (<NUM>) of five holes, the motif including a rectangular shape with a hole (<NUM>) positioned at each corner of the rectangular shape and one hole (<NUM>) positioned at a centre of the rectangular shape, the motif repeating in at least two columns (<NUM>, <NUM>, <NUM>),
wherein a size of the motif and a spacing between the columns is selected to keep the number of the holes linearly aligned along any oblique axis (<NUM>, <NUM>) below five, and
the flexible sheet of tissue matrix with the group of holes (<NUM>) has a uniaxial tensile strength measured in any direction along the sheet that is at least <NUM>% of the uniaxial tensile strength of a sheet without the group of holes.