Device for treating fistulas

Abstract

The present invention relates to devices and related methods for treating fistulas, such as anal or rectovaginal fistulas. Typically, the devices include a seton and an elongate body of tissue growth-promoting matrix material, the elongate body adapted to be positioned within the fistula tract. In one aspect of the invention, the elongate body includes a plurality of protrusions positioned on at least one outer surface of the elongate body. In another aspect of the invention, the devices include one or more attachment points positioned along the length of the elongate body, the one or more attachment points configured to connect the elongate body to an additional seton.

Description

[Technical Field]

[0001] The present invention relates to devices and related methods for treating fistulas, such as anal or rectovaginal fistulas. Typically, the devices include a seton and an elongate body of tissue growth-promoting matrix material, the elongate body adapted to be positioned within the fistula tract. In one aspect of the invention, the elongate body includes a plurality of protrusions positioned on at least one outer surface of the elongate body. In another aspect of the invention, the devices include one or more attachment points positioned along the length of the elongate body, the one or more attachment points configured to connect the elongate body to an additional seton. [Background technology]

[0002] An anal fistula, otherwise known as an anorectal fistula, is an abnormal passageway that forms between the wall of the anal canal and the skin around the anus, typically the perianal skin. An anal fistula usually results from an infection in the anal glands located within the anal canal. When the anal glands become infected, an abscess can form deep under the skin around the anus, requiring surgical drainage. After drainage, a canal can form between the drainage site and the wall of the anal canal, resulting in an anal fistula. The fistula causes symptoms of intermittent discharge and generally does not heal without medical treatment or surgical intervention. Anal fistulas are also a common feature of inflammatory bowel disease, particularly ulcerative colitis and Crohn's disease.

[0003] "Lay-open" fistulotomy is a traditional surgical procedure for treating anal fistulas and involves dividing the tissue between the fistula and the skin to encourage tissue regeneration and therefore healing of the fistula. A disadvantage associated with this procedure is that it causes discomfort and scarring and usually results in some level of incontinence.

[0004] An alternative procedure may involve the use of a seton, which is passed through the fistula track with the use of a fistula probe. The seton is typically a string, preferably made of silicone or rubber, that is threaded through the eye of the fistula probe. The probe is then passed through the fistula track, pulling the seton so that it extends the entire length of the fistula. When the probe reaches the wall of the anal canal, the probe is passed through the anus so that the two loose ends of the seton can be tied together to form a loop and thus form a "seaton stitch," and then removed from the seton. The seton stitch is typically either left in place long-term, helping to drain any secretions from the fistula, or tightly tied to create a gentle form of fistulotomy, i.e., division of the tissue at the surface of the fistula.

[0005] If a seton stitch is left in place for an extended period of time to help drain any secretions from the fistula, results can vary. Particularly if the fistula is narrow and / or the secretions are viscous, drainage is often inadequate, prolonging and / or worsening any infection. Persistent infection makes definitive treatment difficult and less successful.

[0006] An entirely new procedure for the treatment of fistulas is described in Patent Application No. WO 2011 / 151659. The procedure uses Seton stitches to anchor a tissue growth promoting substance, such as a fibrin plug, within the fistula. The procedure thereby allows and encourages the fistula to heal internally, rather than simply draining it. Furthermore, the procedure avoids the major drawbacks associated with fistulotomy, as discussed above. It can therefore be seen that the new procedure represents a major advance in the clinical treatment of fistulas.

[0007] Also described in patent application WO2011 / 151659 are devices suitable for use in the new procedure. For example, in one embodiment, a device is described that includes a fistula plug secured to a seton, with the seton being passed through a hole in the center of the fistula plug. In another embodiment, a fistula plug is described that is sutured to the seton. Additional devices for use in the new procedure are described in patent application WO2014 / 023962 (Patent Document 2).

[0008] However, there is a need for additional devices that better anchor tissue growth promoting materials within the fistula tract, allow end users to treat complex fistulas more easily, and / or are cost-effective to manufacture.

[0009] The present invention seeks to provide a device that meets some or all of the aforementioned needs. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] International Publication No. 2011 / 151659 [Patent Document 2] International Publication No. 2014 / 023962 Summary of the Invention [Means for solving the problem]

[0011] According to a first aspect of the present invention, there is provided a device suitable for treating a fistula, the fistula comprising a fistula tract, the device comprising a seton and an elongate body of tissue growth-promoting matrix material, the elongate body adapted to be positioned within the fistula tract, the elongate body comprising a plurality of protrusions positioned on at least one outer surface of the elongate body.

[0012] In one embodiment of the first aspect of the present invention, the elongate body has a longitudinal axis. Typically, one or more of the plurality of protrusions are positioned on the outer surface parallel or substantially parallel to the longitudinal axis of the elongate body. More typically, two or more of the plurality of protrusions are positioned on the outer surface parallel or substantially parallel to the longitudinal axis of the elongate body.

[0013] The plurality of protrusions may be positioned on a single outer surface of the elongate body, or on two or more outer surfaces. Typically, each outer surface on which the plurality of protrusions is positioned is parallel or substantially parallel to the longitudinal axis of the elongate body. For example, in one embodiment, the elongate body comprises a first outer surface and a second outer surface, both of which are parallel or substantially parallel to the longitudinal axis of the elongate body, and the first plurality of protrusions is positioned on the first outer surface and the second plurality of protrusions is positioned on the second outer surface.

[0014] In one embodiment, each outer surface on which each of the plurality of protrusions is located includes between 2 and 200 protrusions. More typically, each outer surface on which each of the plurality of protrusions is located includes between 5 and 100 protrusions or between 10 and 60 protrusions. Even more typically, each outer surface on which each of the plurality of protrusions is located includes between 30 and 50 protrusions.

[0015] The plurality of protrusions may be uniformly or non-uniformly distributed across each outer surface on which they are located. The plurality of protrusions may be distributed across all or a portion of each outer surface on which they are located. Typically, the plurality of protrusions are substantially uniformly distributed across substantially all of each outer surface on which they are located.

[0016] In one embodiment, the distance (d p) is 0.1 to 20 mm. Typically, the distance between the maximum values ​​of adjacent protrusions (d p ) is 0.2 to 10 mm. More typically, the distance between the maximum values ​​of adjacent protrusions (d p ) is 0.5 to 5 mm. Even more typically, the distance between the maximum values ​​of each adjacent protrusion (d p ) is 1 to 3 mm.

[0017] In one embodiment, each protrusion of the plurality of protrusions has a height of 0.1 to 5 mm. More typically, each protrusion of the plurality of protrusions has a height of 0.5 to 3 mm. Even more typically, each protrusion of the plurality of protrusions has a height of 0.8 to 1.5 mm. As will be understood, as referred to herein, the height of a protrusion is the maximum distance (h) that the protrusion extends from the adjacent minimum of the surface, as measured perpendicular to the surface on which the protrusion is formed. p ) refers to

[0018] In one embodiment, each protrusion of the plurality of protrusions has a width of 0.1 to 10 mm. More typically, each protrusion of the plurality of protrusions has a width of 0.5 to 5 mm. Even more typically, each protrusion of the plurality of protrusions has a width of 1 to 3 mm. As will be understood, as referred to herein, the width of a protrusion is the maximum distance that the protrusion extends between two adjacent minima (w), as measured parallel to the surface on which the protrusion is formed. p ) refers to

[0019] Each protrusion of the plurality of protrusions may have the same or different dimensions. Typically, each protrusion of the plurality of protrusions has substantially the same dimensions. More typically, each protrusion of the plurality of protrusions has the same dimensions.

[0020] Each protrusion of the plurality of protrusions may have the same or different shapes. For example, each protrusion of the plurality of protrusions may be rounded, dome-shaped, cylindrical, conical, square or rectangular, or triangular, triangular prism, or pyramidal. Typically, each protrusion has at least one tip. In one embodiment, each protrusion of the plurality of protrusions is conical, triangular, triangular prism, or pyramidal. Typically, each protrusion of the plurality of protrusions has substantially the same shape. More typically, each protrusion of the plurality of protrusions has the same shape.

[0021] In one embodiment, each minimum between adjacent lobes is not pointed or V-shaped. For example, each minimum between adjacent lobes may be curved or rounded, for example, forming a concave curve between the maxima of each adjacent lobe.

[0022] The elongate body may be in the form of a cylinder, a cone, or a prism. The prism shape may be regular or irregular. For example, the elongate body may be in the form of a cylinder, a cone, a triangular prism, a square prism, a rectangular prism, a pentagonal prism, or a hexagonal prism. In such embodiments, one or more of the plurality of protrusions are typically positioned on one or more of the side surfaces of the cylinder, cone, or prism. Any edges or corners formed between the end face of the cylinder, cone, or prism and one or more of the side surfaces may optionally be chamfered.

[0023] The plurality of protrusions may be formed from the same or a different material as the elongate body of tissue growth-promoting matrix material. Typically, the plurality of protrusions are formed from one or more biodegradable materials, such as those discussed below. Typically, the plurality of protrusions are formed from the same material as the elongate body.

[0024] In one embodiment, the elongate body and the plurality of protrusions are of unitary construction.

[0025] The elongate body may be defined as having a longitudinal axis (x) and two further axes (y) and (z) that are perpendicular to each other and to the longitudinal axis (x). When so defined, the maximum length of the elongate body as measured along the x-axis exceeds both the maximum width and maximum height of the elongate body as measured along the y and z-axes, respectively.

[0026] Typically, the maximum length of the elongate body, as measured along the x-axis, is 2 to 30 times greater than the greater of the maximum width and maximum height of the elongate body, as measured along the y- and z-axes, respectively. More typically, the maximum length of the elongate body is 5 to 15 times greater than the greater of the maximum width and maximum height of the elongate body. More typically, the maximum length of the elongate body is 8 to 12 times greater than the greater of the maximum width and maximum height of the elongate body.

[0027] In one embodiment, the maximum length of the elongate body as measured along the x-axis is between 10 and 200 mm. Typically, the maximum length of the elongate body is between 30 and 150 mm. More typically, the maximum length of the elongate body is between 50 and 100 mm.

[0028] In one embodiment, the greater of the maximum width or height of the elongate body, as measured along the y and z axes, respectively, is between 3 and 20 mm. Typically, the greater of the maximum width or height of the elongate body is between 4 and 15 mm. More typically, the greater of the maximum width or height of the elongate body is between 5 and 10 mm.

[0029] In one embodiment, the elongate body is an elongate sheet of tissue growth-promoting matrix material. In such an embodiment, the elongate sheet may be defined such that when laid flat, it has a longitudinal axis (x) and two additional axes (y) and (z) that are perpendicular to each other and perpendicular to the longitudinal axis (x). Typically, when laid flat, the y axis is parallel to the plane of the sheet and the z axis is perpendicular to the plane of the sheet. When so defined, the maximum length of the elongate sheet as measured along the x axis exceeds the maximum width of the elongate sheet as measured along the y axis, and the maximum width of the elongate sheet as measured along the y axis exceeds the maximum height (i.e., thickness) of the elongate sheet as measured along the z axis.

[0030] Typically, the maximum length of the elongated sheet, as measured along the x-axis, is 2 to 30 times greater than the maximum width of the elongated sheet, as measured along the y-axis. More typically, the maximum length of the elongated sheet is 5 to 15 times greater than the maximum width of the elongated sheet. More typically, the maximum length of the elongated sheet is 8 to 12 times greater than the maximum width of the elongated sheet.

[0031] Typically, the maximum width of the elongated sheet, as measured along the y-axis, is 5 to 50 times larger than the maximum height or thickness of the elongated sheet, as measured along the z-axis. More typically, the maximum width of the elongated sheet is 10 to 30 times larger than the maximum height or thickness of the elongated sheet. More typically, the maximum width of the elongated sheet is 15 to 20 times larger than the maximum height or thickness of the elongated sheet.

[0032] In one embodiment, the maximum length of the elongate sheet as measured along the x-axis is between 10 and 200 mm. Typically, the maximum length of the elongate sheet is between 30 and 150 mm. More typically, the maximum length of the elongate sheet is between 50 and 100 mm.

[0033] In one embodiment, the maximum width of the elongate sheet as measured along the y-axis is between 3 and 20 mm. Typically, the maximum width of the elongate sheet is between 4 and 15 mm. More typically, the maximum width of the elongate sheet is between 5 and 10 mm.

[0034] In one embodiment, the maximum height or thickness of the elongate sheet as measured along the z-axis is 0.1 to 2 mm. Typically, the maximum height or thickness of the elongate sheet is 0.2 to 1 mm. More typically, the maximum height or thickness of the elongate sheet is 0.3 to 0.5 mm.

[0035] Typically, the elongated sheet of tissue growth-promoting matrix material is substantially rectangular, trapezoidal, or oval in shape. More typically, the elongated sheet of tissue growth-promoting matrix material is substantially rectangular or trapezoidal in shape. Most typically, the elongated sheet of tissue growth-promoting matrix material is substantially rectangular in shape. When the elongated sheet is substantially rectangular or trapezoidal in shape, the corners of the rectangle or trapezoid may optionally be rounded or chamfered.

[0036] When the elongate body is an elongate sheet of tissue growth-promoting matrix material, in one embodiment, the plurality of protrusions are located on at least one outer edge surface of the elongate sheet. As will be understood, the term "outer edge surface," when used in reference to an elongate sheet, refers to the outer surface formed in at least one dimension that is parallel or substantially parallel to the thickness of the sheet (i.e., the z-axis as defined above).

[0037] Typically, one or more of the plurality of protrusions are positioned on the outer edge surface that is parallel or substantially parallel to the longitudinal axis of the elongated sheet. In such embodiments, the outer edge surface can be viewed as extending in the directions of the x and z axes, as defined above. More typically, two or more of the plurality of protrusions are positioned on the outer edge surface that is parallel or substantially parallel to the longitudinal axis of the elongated sheet.

[0038] The plurality of protrusions may be positioned on a single outer edge surface of the elongated sheet, or on two or more outer edge surfaces. Typically, each outer edge surface on which the plurality of protrusions is positioned is parallel or substantially parallel to the longitudinal axis of the elongated body. For example, in one embodiment, the elongated sheet comprises a first outer edge surface and a second outer edge surface, both of which are parallel or substantially parallel to the longitudinal axis of the elongated sheet, and the first plurality of protrusions is positioned on the first outer edge surface and the second plurality of protrusions is positioned on the second outer edge surface.

[0039] In one embodiment, the elongate sheet does not have any protrusions on any surface that is parallel or substantially parallel to both the x-axis and the y-axis, i.e., any surface that is parallel or substantially parallel to the plane of the sheet when the sheet is laid flat.

[0040] When multiple protrusions are located on at least one outer edge surface of the elongated sheet, the multiple protrusions may be formed by cutting the outer edge of the elongated sheet to form the multiple protrusions. For example, the elongated sheet may be cut to have one or more castellated or serrated outer edges. Typically, the elongated sheet is cut to have one or more serrated outer edges.

[0041] Thus, in an exemplary embodiment of a first aspect of the present invention, there is provided a device suitable for treating a fistula, the fistula comprising a fistula tract, the device comprising: a seton; and an elongated sheet of tissue growth-promoting matrix material, the elongated sheet being adapted to be positioned within the fistula tract, the elongated sheet having a first outer edge surface and a second outer edge surface, both of which are parallel or substantially parallel to a longitudinal axis of the elongated sheet when laid flat, a first plurality of protrusions formed by serrations on the first outer edge surface, and a second plurality of protrusions formed by serrations on the second outer edge surface.

[0042] According to a first aspect of the invention, the seton may be affixed to an elongate body or elongate sheet of tissue growth promoting matrix material.

[0043] In one embodiment, the seton is threaded through the elongate body or sheet of tissue growth-promoting matrix material. Typically, the seton is threaded through the elongate body or sheet in a direction parallel or substantially parallel to the longitudinal axis of the elongate body or sheet. Typically, the seton is threaded through the elongate body or sheet in a direction coaxial or substantially coaxial to the longitudinal axis of the elongate body or sheet.

[0044] The elongate body or elongate sheet may be defined such that it has a first end and a second end, with a longitudinal axis extending from the first end to the second end. Typically, when a seton is threaded through the elongate body or elongate sheet of tissue growth-promoting matrix material, a portion of the seton extends beyond at least the first or second end of the elongate body or elongate sheet. More typically, a first portion of the seton extends beyond the first end of the elongate body or elongate sheet, and a second portion of the seton extends beyond the second end.

[0045] When the seton is threaded through the elongate body or elongate sheet of tissue growth-promoting matrix material, the seton is typically affixed to the elongate body or elongate sheet to prevent the elongate body or elongate sheet from sliding along the seton. For example, the seton may be affixed to the elongate body or elongate sheet using glue, knots, thermal bonding, and / or welding. In one embodiment, the seton is affixed to the elongate body or elongate sheet via one or more knots to prevent the elongate body or elongate sheet from sliding along the seton when the seton is threaded through the elongate body or elongate sheet. Typically in such embodiments, the seton is affixed to the elongate body or elongate sheet via a first knot located proximal to a first end of the elongate body or elongate sheet, the seton is threaded through the elongate body or elongate sheet such that a first portion of the seton extends beyond the first end of the elongate body or elongate sheet and a second portion of the seton extends beyond the second end, and the seton is affixed to the elongate body or elongate sheet via a second knot located proximal to a second end of the elongate body or elongate sheet.

[0046] In one embodiment, the seton is attached to the elongated sheet via a first knot located proximal to a first end of the elongated sheet, the seton is threaded through the elongated sheet such that a first portion of the seton extends beyond the first end of the elongated sheet and a second portion of the seton extends beyond the second end, the seton is attached to the elongated sheet via a second knot located proximal to the second end of the elongated sheet, the elongated sheet is rolled or folded at each of the first and second ends, and the first and second knots are tied such that the loops of each knot encircle a respective rolled or folded portion of the elongated sheet.

[0047] In another embodiment, the elongated sheet may be formed from a first layer and a second layer of tissue growth-promoting material, the first and second layers being affixed to one another to form the elongated sheet, with the seton sandwiched between the first and second layers, thereby creating a seton through which the elongated sheet of tissue growth-promoting material is threaded. The first layer, second layer, and seton may be affixed to one another using, for example, glue, knots, heat bonding, and / or welding.

[0048] In further embodiments, the seton is attached to one side of the elongate body or elongate sheet of tissue growth-promoting matrix material. For example, the seton may be attached to one side of the elongate body or elongate sheet using glue, knots, thermal bonding, and / or welding. Typically, in such embodiments, the seton is attached to one side of the elongate body or elongate sheet such that the seton extends in a direction parallel or substantially parallel to the longitudinal axis of the elongate body or elongate sheet. Typically, in such embodiments, a portion of the seton extends beyond at least the first or second end of the elongate body or elongate sheet. More typically, a first portion of the seton extends beyond the first end of the elongate body or elongate sheet, and a second portion of the seton extends beyond the second end.

[0049] In another embodiment, the seton is attached to one end of an elongate body or elongate sheet of tissue growth-promoting matrix material. In a further embodiment, when an elongate body or elongate sheet has a first end and a second end and a longitudinal axis extending from the first end to the second end, the first seton is attached to the first end of the elongate body or elongate sheet, and the second seton is attached to the second end of the elongate body or elongate sheet. When a seton is attached to one or both ends of the elongate body or elongate sheet, the seton may be attached using, for example, glue, knotting, thermal bonding, and / or welding. In one embodiment, the seton is attached to one end of the elongate body or elongate sheet of tissue growth-promoting matrix material via a knot. In a further embodiment, a seton is attached via a knot to one end of an elongated sheet of tissue growth-promoting matrix material, the elongated sheet is rolled or folded, and the knot is tied so that the loop of the knot surrounds a respective rolled or folded portion of the elongated sheet. For example, a first seton may be attached via a first knot to a first end of the elongated sheet, and a second seton may be attached via a second knot to a second end of the elongated sheet, the elongated sheet being rolled or folded at each of the first and second ends, and the first and second knots being tied so that the loop of each knot surrounds a respective rolled or folded portion of the elongated sheet.

[0050] According to a second aspect of the present invention, there is provided a device suitable for treating a fistula, the fistula comprising a fistula tract, the device comprising a seton and an elongate body of tissue growth-promoting matrix material, the elongate body adapted to be positioned within the fistula tract, the device comprising one or more attachment points positioned along the length of the elongate body, the one or more attachment points configured to connect the elongate body to a further seton.

[0051] Each attachment point may be provided in the form of a loop, ring, clip, connector, or other means configured to connect the elongate body to an additional seton. Each attachment point may be of the same type or different. Typically, each attachment point is of the same type.

[0052] In one embodiment of the second aspect of the invention, each attachment point is provided in the form of an attachment loop. In other words, the device comprises one or more attachment loops positioned along the length of the elongate body, the one or more attachment loops configured to connect the elongate body to an additional seton. Typically, the one or more attachment loops are configured to allow an additional seton to be fastened to the device via the one or more loops.

[0053] As used herein, unless otherwise stated, the term "loop" does not include discontinuous or interrupted loops.

[0054] Each attachment loop may have the same or different dimensions. Typically, each attachment loop has substantially the same dimensions. More typically, each attachment loop has the same dimensions.

[0055] In one embodiment, each attachment loop has an inner circumference of 3 to 30 mm. Typically, each attachment loop has an inner circumference of 5 to 20 mm. More typically, each attachment loop has an inner circumference of 6 to 15 mm.

[0056] In one embodiment of the second aspect of the invention, the device comprises 2 to 50 attachment points or loops positioned along the length of the elongate body. Typically, the device comprises 5 to 30 attachment points or loops positioned along the length of the elongate body. More typically, the device comprises 10 to 20 attachment points or loops positioned along the length of the elongate body.

[0057] In one embodiment of the second aspect of the present invention, the elongate body comprises a first end and a second end, with a longitudinal axis extending from the first end to the second end.

[0058] Typically, one or more of the attachment points or loops are located on an outer surface that is parallel or substantially parallel to the longitudinal axis of the elongate body, and more typically, two or more of the attachment points or loops are located on an outer surface that is parallel or substantially parallel to the longitudinal axis of the elongate body.

[0059] The attachment points or loops may be located on a single outer surface of the elongate body, or on two or more outer surfaces. Typically, each outer surface on which an attachment point or loop is located is parallel or substantially parallel to the longitudinal axis of the elongate body. For example, in one embodiment, the elongate body comprises a first outer surface and a second outer surface, both of which are parallel or substantially parallel to the longitudinal axis of the elongate body, and one or more attachment points or loops are located on the first outer surface and one or more attachment points or loops are located on the second outer surface.

[0060] In one embodiment, each outer surface having one or more attachment points or loops located thereon includes 1 to 25 attachment points or loops. More typically, each outer surface having one or more attachment points or loops located thereon includes 3 to 15 attachment points or loops. Even more typically, each outer surface having one or more attachment points or loops located thereon includes 5 to 10 attachment points or loops.

[0061] The elongate body of the second aspect of the present invention may be defined as having a longitudinal axis (x) and two further axes (y) and (z) that are perpendicular to each other and to the longitudinal axis (x). When so defined, the maximum length of the elongate body as measured along the x-axis exceeds both the maximum width and maximum height of the elongate body as measured along the y and z-axes, respectively.

[0062] Typically, the maximum length of the elongate body, as measured along the x-axis, is 2 to 30 times greater than the greater of the maximum width and maximum height of the elongate body, as measured along the y- and z-axes, respectively. More typically, the maximum length of the elongate body is 5 to 15 times greater than the greater of the maximum width and maximum height of the elongate body. More typically, the maximum length of the elongate body is 8 to 12 times greater than the greater of the maximum width and maximum height of the elongate body.

[0063] In one embodiment, the maximum length of the elongate body as measured along the x-axis is between 10 and 200 mm. Typically, the maximum length of the elongate body is between 30 and 150 mm. More typically, the maximum length of the elongate body is between 50 and 100 mm.

[0064] In one embodiment, the greater of the maximum width or height of the elongate body, as measured along the y and z axes, respectively, is between 3 and 20 mm. Typically, the greater of the maximum width or height of the elongate body is between 4 and 15 mm. More typically, the greater of the maximum width or height of the elongate body is between 5 and 10 mm.

[0065] In one embodiment, the elongate body is an elongate sheet of tissue growth-promoting matrix material. In such an embodiment, the elongate sheet may be defined such that when laid flat, it has a longitudinal axis (x) and two additional axes (y) and (z) that are perpendicular to each other and perpendicular to the longitudinal axis (x). Typically, when laid flat, the y axis is parallel to the plane of the sheet and the z axis is perpendicular to the plane of the sheet. When so defined, the maximum length of the elongate sheet as measured along the x axis exceeds the maximum width of the elongate sheet as measured along the y axis, and the maximum width of the elongate sheet as measured along the y axis exceeds the maximum height (i.e., thickness) of the elongate sheet as measured along the z axis.

[0066] Typically, the maximum length of the elongated sheet, as measured along the x-axis, is 2 to 30 times greater than the maximum width of the elongated sheet, as measured along the y-axis. More typically, the maximum length of the elongated sheet is 5 to 15 times greater than the maximum width of the elongated sheet. More typically, the maximum length of the elongated sheet is 8 to 12 times greater than the maximum width of the elongated sheet.

[0067] Typically, the maximum width of the elongated sheet, as measured along the y-axis, is 5 to 50 times larger than the maximum height or thickness of the elongated sheet, as measured along the z-axis. More typically, the maximum width of the elongated sheet is 10 to 30 times larger than the maximum height or thickness of the elongated sheet. More typically, the maximum width of the elongated sheet is 15 to 20 times larger than the maximum height or thickness of the elongated sheet.

[0068] In one embodiment, the maximum length of the elongate sheet as measured along the x-axis is between 10 and 200 mm. Typically, the maximum length of the elongate sheet is between 30 and 150 mm. More typically, the maximum length of the elongate sheet is between 50 and 100 mm.

[0069] In one embodiment, the maximum width of the elongate sheet as measured along the y-axis is between 3 and 20 mm. Typically, the maximum width of the elongate sheet is between 4 and 15 mm. More typically, the maximum width of the elongate sheet is between 5 and 10 mm.

[0070] In one embodiment, the maximum height or thickness of the elongate sheet as measured along the z-axis is 0.1 to 2 mm. Typically, the maximum height or thickness of the elongate sheet is 0.2 to 1 mm. More typically, the maximum height or thickness of the elongate sheet is 0.3 to 0.5 mm.

[0071] Typically, the elongated sheet of tissue growth-promoting matrix material is substantially rectangular, trapezoidal, or oval in shape. More typically, the elongated sheet of tissue growth-promoting matrix material is substantially rectangular or trapezoidal in shape. Most typically, the elongated sheet of tissue growth-promoting matrix material is substantially rectangular in shape. When the elongated sheet is substantially rectangular or trapezoidal in shape, the corners of the rectangle or trapezoid may optionally be rounded or chamfered.

[0072] The attachment points or attachment loops may be evenly or unevenly distributed across each outer surface on which they are located.

[0073] In one embodiment of the second aspect of the invention, the attachment points or loops are evenly or substantially evenly distributed along the entire length of the elongate body. For example, the attachment points or loops may be located in a first line along the length of the first outer surface of the elongate body and a second line along the length of the second outer surface of the elongate body, with the attachment points or loops in each line being evenly or substantially evenly distributed along the entire length of the elongate body.

[0074] When the elongate body is an elongate sheet of tissue growth-promoting matrix material, in one embodiment, one or more of the attachment points or loops are located on a surface that is parallel or substantially parallel to the x- and y-axes, i.e., any surface that is parallel or substantially parallel to the plane of the sheet when the sheet is laid flat. Typically, in such embodiments, one or more of the attachment points or loops are located on a first surface that is parallel or substantially parallel to the x- and y-axes, and one or more of the attachment points or loops are located on a second surface that is parallel or substantially parallel to the x- and y-axes. Thus, for example, one or more of the attachment points or loops may be located on a first side of the elongate sheet and one or more of the attachment points or loops may be located on a second side of the elongate sheet.

[0075] In accordance with a second aspect of the present invention, the seton may be affixed to an elongate body or elongate sheet of tissue growth promoting matrix material.

[0076] In one embodiment, the seton is threaded through the elongate body or sheet of tissue growth-promoting matrix material. Typically, the seton is threaded through the elongate body or sheet in a direction parallel or substantially parallel to the longitudinal axis of the elongate body or sheet. Typically, the seton is threaded through the elongate body or sheet in a direction coaxial or substantially coaxial to the longitudinal axis of the elongate body or sheet.

[0077] The elongate body or elongate sheet may be defined such that it has a first end and a second end, with a longitudinal axis extending from the first end to the second end. Typically, when a seton is threaded through the elongate body or elongate sheet of tissue growth-promoting matrix material, a portion of the seton extends beyond at least the first or second end of the elongate body or elongate sheet. More typically, a first portion of the seton extends beyond the first end of the elongate body or elongate sheet, and a second portion of the seton extends beyond the second end.

[0078] When the seton is threaded through the elongate body or elongate sheet of tissue growth-promoting matrix material, the seton is typically affixed to the elongate body or elongate sheet to prevent the elongate body or elongate sheet from sliding along the seton. For example, the seton may be affixed to the elongate body or elongate sheet using glue, knots, thermal bonding, and / or welding. In one embodiment, the seton is affixed to the elongate body or elongate sheet via one or more knots to prevent the elongate body or elongate sheet from sliding along the seton when the seton is threaded through the elongate body or elongate sheet. Typically in such embodiments, the seton is affixed to the elongate body or elongate sheet via a first knot located proximal to a first end of the elongate body or elongate sheet, the seton is threaded through the elongate body or elongate sheet such that a first portion of the seton extends beyond the first end of the elongate body or elongate sheet and a second portion of the seton extends beyond the second end, and the seton is affixed to the elongate body or elongate sheet via a second knot located proximal to a second end of the elongate body or elongate sheet.

[0079] In one embodiment, the seton is attached to the elongated sheet via a first knot located proximal to a first end of the elongated sheet, the seton is threaded through the elongated sheet such that a first portion of the seton extends beyond the first end of the elongated sheet and a second portion of the seton extends beyond the second end, the seton is attached to the elongated sheet via a second knot located proximal to the second end of the elongated sheet, the elongated sheet is rolled or folded at each of the first and second ends, and the first and second knots are tied such that the loops of each knot encircle a respective rolled or folded portion of the elongated sheet.

[0080] In another embodiment, the elongated sheet may be formed from a first layer and a second layer of tissue growth-promoting material, the first and second layers being affixed to one another to form the elongated sheet, with the seton sandwiched between the first and second layers, thereby creating a seton through which the elongated sheet of tissue growth-promoting material is threaded. The first layer, second layer, and seton may be affixed to one another using, for example, glue, knots, heat bonding, and / or welding.

[0081] In further embodiments, the seton is attached to one side of the elongate body or elongate sheet of tissue growth-promoting matrix material. For example, the seton may be attached to one side of the elongate body or elongate sheet using glue, knots, thermal bonding, and / or welding. Typically, in such embodiments, the seton is attached to one side of the elongate body or elongate sheet such that the seton extends in a direction parallel or substantially parallel to the longitudinal axis of the elongate body or elongate sheet. Typically, in such embodiments, a portion of the seton extends beyond at least the first or second end of the elongate body or elongate sheet. More typically, a first portion of the seton extends beyond the first end of the elongate body or elongate sheet, and a second portion of the seton extends beyond the second end.

[0082] In another embodiment, the seton is attached to one end of an elongate body or elongate sheet of tissue growth-promoting matrix material. In a further embodiment, when an elongate body or elongate sheet has a first end and a second end and a longitudinal axis extending from the first end to the second end, the first seton is attached to the first end of the elongate body or elongate sheet, and the second seton is attached to the second end of the elongate body or elongate sheet. When a seton is attached to one or both ends of the elongate body or elongate sheet, the seton may be attached using, for example, glue, knotting, thermal bonding, and / or welding. In one embodiment, the seton is attached to one end of the elongate body or elongate sheet of tissue growth-promoting matrix material via a knot. In a further embodiment, a seton is attached via a knot to one end of an elongated sheet of tissue growth-promoting matrix material, the elongated sheet is rolled or folded, and the knot is tied so that the loop of the knot surrounds a respective rolled or folded portion of the elongated sheet. For example, a first seton may be attached via a first knot to a first end of the elongated sheet, and a second seton may be attached via a second knot to a second end of the elongated sheet, the elongated sheet being rolled or folded at each of the first and second ends, and the first and second knots being tied so that the loop of each knot surrounds a respective rolled or folded portion of the elongated sheet.

[0083] In one embodiment of the second aspect of the present invention, each attachment point or loop is directly secured to the seton. Typically, in such an embodiment, the seton is threaded through an elongate body or elongate sheet of tissue growth-promoting matrix material. For example, each attachment point or loop may be glued, bonded, or welded to the seton. In one embodiment, each attachment point is provided in the form of an attachment loop, and each attachment loop is bonded to the seton. Each attachment loop may be formed from the same or a different material as the seton. Typically, each attachment loop is formed from the same material as the seton.

[0084] In further embodiments of the second aspect of the invention, each attachment point is provided in the form of an attachment loop, with each attachment loop being formed by a seton. Typically, in such embodiments, the seton is threaded through an elongate body or elongate sheet of tissue-growth-promoting matrix material. In one embodiment, the entire inner periphery of each attachment loop is defined by the seton. In another embodiment, the inner periphery of each attachment loop is defined partially by the seton and partially by the tissue-growth-promoting matrix material of the elongate body or sheet.

[0085] When the seton is threaded through an elongate body or elongate sheet of tissue growth-promoting matrix material, the seton may be threaded to follow a path such that the seton extends beyond a first end of the elongate body or elongate sheet to form an attachment loop on the exterior of the elongate body or elongate sheet, passes through the elongate body or elongate sheet, re-enters the elongate body or elongate sheet, and optionally passes through the elongate body or elongate sheet one or more additional times to form one or more additional attachment loops, re-enters the elongate body or elongate sheet, and exits to extend beyond a second end of the elongate body or elongate sheet.

[0086] In an exemplary embodiment of the second aspect of the present invention, a device is provided that is suitable for treating a fistula, the fistula comprising a fistula tract, the device comprising: a seton; and an elongated sheet of tissue growth-promoting matrix material, the elongated sheet being adapted to be positioned within the fistula tract, the elongated sheet having a first end and a second end, a longitudinal axis extending from the first end to the second end, the seton extending beyond the first end of the elongated sheet and being repeatedly threaded from the first side to the second side of the elongated sheet and then back to the first side to form a plurality of attachment loops positioned on alternating sides along the length of the elongated sheet, the seton optionally being threaded from the first side to the second side of the elongated sheet and exiting to extend beyond the second end of the elongated sheet, the plurality of attachment loops being configured to attach the elongated sheet to one or more additional setons.

[0087] Typically in such exemplary embodiments, a first side of the elongated sheet forms a surface that is parallel or substantially parallel to the x and y axes when the sheet is laid flat, and a second side of the elongated sheet forms an opposing surface that is parallel or substantially parallel to the x and y axes when the sheet is laid flat.

[0088] Typically in such exemplary embodiments, the seton is attached to the elongated sheet via a first knot located proximal to a first end of the elongated sheet, and the seton is attached to the elongated sheet via a second knot located proximal to a second end of the elongated sheet. Typically, the elongated sheet is rolled or folded at each of the first and second ends, and the first and second knots are tied such that the loops of each knot encircle a respective rolled or folded portion of the elongated sheet.

[0089] In one embodiment, the device of the first aspect of the present invention is also a device according to the second aspect of the present invention. Thus, in one embodiment, there is provided a device suitable for treating a fistula, the fistula comprising a fistula tract, the device comprising a seton and an elongate body of tissue growth-promoting matrix material, the elongate body adapted to be positioned within the fistula tract, the elongate body comprising a plurality of protrusions positioned on at least one outer surface of the elongate body, the device comprising one or more attachment points positioned along the length of the elongate body, the one or more attachment points configured to connect the elongate body to a further seton.

[0090] In an exemplary embodiment, a device suitable for treating a fistula, the fistula comprising a fistula tract, the device comprising: a seton; and an elongated sheet of tissue growth-promoting matrix material, the elongated sheet adapted to be positioned within the fistula tract, the elongated sheet having first and second ends and first and second outer edge surfaces, a longitudinal axis extending from the first end to the second end when the elongated sheet is laid flat, both the first and second outer edge surfaces being parallel or substantially parallel to the longitudinal axis of the elongated sheet when laid flat, and a first plurality of protrusions on the serrated portion of the first outer edge surface. a second plurality of protrusions formed by serrations on the second outer edge surface, the seton extending beyond a first end of the elongated sheet and being threaded repeatedly from the first side to a second side of the elongated sheet and then from the second side back to the first side of the elongated sheet, optionally being threaded from the first side to the second side of the elongated sheet and exiting to extend beyond the second end of the elongated sheet to form a plurality of attachment loops positioned on alternating sides along the length of the elongated sheet, the plurality of attachment loops being configured to attach the elongated sheet to one or more additional setons.

[0091] Typically, the devices of the first and second aspects of the present invention are configured so that the device can be formed into a loop that is long enough to pass through the fistula tract and meet outside the fistula tract. Preferably, the loop includes part or all of the seton and part or all of the elongate body or elongate sheet. Preferably, the loop may also act to anchor the elongate body or elongate sheet within the fistula tract.

[0092] In one embodiment of the first or second aspect of the present invention, the elongate body or elongate sheet is flexible. Optionally, the elongate body or elongate sheet is also resilient, for example, so that the elongate body or elongate sheet can be deformed from a substantially linear or substantially planar position, respectively, to a non-linear or non-planar position by the application of a force, but will return to the substantially linear or substantially planar position upon removal of the applied force.

[0093] The tissue growth-promoting matrix material of the first or second aspects of the invention may be defined as a substance or structure that can act as a scaffold onto and / or through which tissue can grow. Typically, tissue can grow both onto and through the scaffold.

[0094] In one embodiment of the first or second aspect of the invention, the tissue growth-promoting matrix material comprises a microscopic scaffold, i.e., the scaffold structure is not visible to the naked eye. In another embodiment of the first or second aspect of the invention, the tissue growth-promoting matrix material comprises a macroscopic scaffold, i.e., the scaffold structure is visible to the naked eye. The tissue growth-promoting matrix material may also comprise a mixture of macroscopic and microscopic scaffolds. For example, a macroscopic scaffold may be made from, coated with, or embedded in a microscopic scaffold.

[0095] In one embodiment of the first or second aspect of the invention, the tissue growth-promoting matrix material comprises a scaffold, the scaffold comprising a plurality of fibers. The fibers may be woven or non-woven. The fibers may be interconnected in an ordered or disordered structure. In one embodiment of the first or second aspect of the invention, the tissue growth-promoting matrix material comprises a scaffold, the scaffold comprising a plurality of fibers, the fibers being interconnected in a non-woven, disordered structure.

[0096] In alternative embodiments, the scaffold may comprise a porous structure, such as a sponge-like structure, which may be microscopic or macroscopic.

[0097] When a scaffold comprises a plurality of fibers, the fibers typically have an average diameter of 0.1 to 50 μm, more typically, the fibers have an average diameter of 1 to 10 μm, and even more typically, the fibers have an average diameter of 1.5 to 4 μm.

[0098] When the fibers are interconnected in an ordered or disordered structure, typically the fibers are interconnected to form a porous structure. For example, the tissue growth-promoting matrix material may include a scaffold, the scaffold including a plurality of fibers, the fibers interconnected in a non-woven, disordered, porous structure. When the fibers are interconnected to form a porous structure, typically the average pore size is 1 to 100 μm. More typically, the average pore size is 2 to 35 μm. Even more typically, the average pore size is 8 to 25 μm.

[0099] The average fiber diameter and average pore size may be determined using a scanning electron microscope. Suitable methodologies are described in Hixon et al., Electrospinning, Vol. 1, 2017, pp. 31-45. As used herein, unless otherwise specified, the term "pore size" refers to the longest internal dimension (i.e., longest internal linear span) of a given pore, and the term "average pore size" refers to the arithmetic mean of the pore sizes of at least 10 randomly selected pores.

[0100] The tissue growth-promoting matrix material may be constructed from biological or non-biological materials, or a mixture of biological and non-biological materials. Preferably, the material promotes and / or is remodelable for tissue remodeling. Preferably, the material promotes angiogenesis.

[0101] In a preferred embodiment of the present invention, the tissue growth-promoting material is biocompatible. As used herein, the term "biocompatible material" refers to a material that does not have unacceptable adverse effects on the subject (e.g., a human or other animal) being treated. Preferably, the biocompatible material does not have unacceptable adverse effects on the subject being treated when it remains in contact with the subject for at least two weeks, more preferably at least four weeks, and most preferably at least six weeks.

[0102] In one embodiment of the present invention, the tissue growth-promoting matrix material is constructed from biological materials and / or synthetic equivalents thereof. Typically in such embodiments, the biological materials and / or synthetic equivalents thereof are fibrous. Typically in such embodiments, the tissue growth-promoting matrix material comprises a scaffold, the scaffold comprising a plurality of fibers, the fibers being constructed from biological materials and / or synthetic equivalents thereof.

[0103] The biological material may be xenogeneic, allogeneic (e.g., cadaveric), autologous, or a mixture thereof. Typically, when the tissue growth-promoting matrix material is constructed from biological material, the biological material is preferably processed and / or purified so that it is acellular.

[0104] Suitable substances that may provide a scaffold for tissue growth include fibrin, collagen such as type I, II, III, IV, or V collagen, other extracted collagenous extracellular matrix (ECM) materials such as submucosal tissue (e.g., intestinal submucosa, bladder submucosa, or uterine submucosa), fascial tissue, renal capsule membrane tissue, dermal tissue (e.g., dermal collagen), dura mater, pericardial tissue, serosa, peritoneum, basement membrane layer, amniotic membrane, omentum peritoneum, and the like.

[0105] As used herein, "fibrin" refers to a polymer formed from fibrin monomers, which are themselves formed by the treatment of fibrinogen with thrombin.

[0106] Other suitable materials that may provide a scaffold for tissue growth include fibrous biological materials or their synthetic equivalents that have been crosslinked using crosslinking agents such as dialdehydes, polyepoxides, dichloroalkanes, and the like to give materials such as, for example, albumin crosslinked with glutaraldehyde. Crosslinking may also be achieved by reaction of chemical groups within the fibrous biological materials or their synthetic equivalents, such as by dehydration, formation of disulfide bridges, and the like.

[0107] In exemplary embodiments of the present invention, the tissue growth-promoting matrix material is constructed from a biodegradable material, such as a biodegradable polymer. The biodegradable material may be a single biodegradable material or a blend or combination of one or more biodegradable materials. Similarly, the biodegradable polymer may be a single biodegradable polymer or a blend or combination of one or more biodegradable polymers. Typically, in such embodiments, the tissue growth-promoting matrix material includes a scaffold, the scaffold includes a plurality of fibers, and the fibers are constructed from a biodegradable material.

[0108] Alternatively, or in addition, the tissue growth-promoting matrix material may be constructed from non-biodegradable materials, such as non-biodegradable polymers.

[0109] As used herein, a "biodegradable material" refers to a material that degrades upon contact with a biological fluid or system, such as blood plasma, skin, or a sphincter. Similarly, a "biodegradable polymer" refers to a polymer that undergoes hydrolysis upon contact with a biological fluid or system, such as blood plasma, skin, or a sphincter. A "fully biodegradable" polymer refers to a polymer in which at least one covalent bond in every connection between constituent monomer units is capable of undergoing hydrolysis upon contact with a biological fluid or system. After or during degradation, the material or polymer is preferably absorbed into the body, i.e., the biodegradable material or polymer is also bioabsorbable.

[0110] In contrast, a "non-biodegradable" material or polymer refers to a material or polymer that does not substantially degrade or undergo hydrolysis upon contact with biological fluids or systems.

[0111] In one embodiment of any aspect of the invention, a "biodegradable" material or polymer degrades or undergoes hydrolysis in response to contact with an aqueous solution having a pH of 5 to 9, typically 6 to 8, more typically about 7.

[0112] Typically, a "biodegradable" material or polymer undergoes degradation or hydrolysis upon contact with biological fluids or systems at a rate such that it takes an average of at least 10 days for the material or polymer to degrade into its constituent non-biodegradable segments and / or monomeric units. More typically, it takes an average of at least 20, at least 30, at least 40, or at least 50 days for the material or polymer to degrade into its constituent non-biodegradable segments and / or monomeric units. Most typically, it takes an average of at least 60 days for the material or polymer to degrade into its constituent non-biodegradable segments and / or monomeric units.

[0113] Typically, a "biodegradable" material or polymer undergoes degradation or hydrolysis upon contact with biological fluids or systems at a rate such that it takes, on average, fewer than 400 days for the material or polymer to degrade into its constituent non-biodegradable segments and / or monomeric units. More typically, it takes, on average, fewer than 200 days for the material or polymer to degrade into its constituent non-biodegradable segments and / or monomeric units. Most typically, it takes, on average, fewer than 100 days for the material or polymer to degrade into its constituent non-biodegradable segments and / or monomeric units.

[0114] Biodegradable polymers suitable for use in the present invention include, but are not limited to, polyesters such as polylactic acid (polylactide), polyglycolic acid (polyglycolide), polycaprolactone, polycaprolactone diol, and polycaprolactone triol; polyanhydrides such as poly(sebacic acid), poly(adipic acid), poly(fumaric anhydride), poly(stilbene dicarboxylic anhydride), and poly[1,6-bis(p-carboxy-phenoxy)hexane]; polyphosphoesters such as poly[1,4-bis(hydroxyethyl)-terephthalate-alt-ethyloxyphosphate]; polyphosphazenes such as poly(bis(1,4-dioxapentyl)phosphazene), poly(bis(4-carboxyphenoxy)phosphazene), and poly-[bis(1-(ethoxycarbonyl)-2-phenylethylamino)phosphazene]; polypropylene oxides; Examples of suitable polymers include polyethers such as oxides and polyethylene glycols, polycarbonates, polycyanoacrylates, polydioxanone, poly(1,5-dioxapan-2-one), polyamino acids, polyamides, polyhydroxybutyrate, polyhydroxyvalerate, polyesteramides, polyvinylpyrrolidone, polyurethanes, polyalkylene succinates, poly(malic acid), polyalkylene oxalates, polyorthocarbonates, polyorthoesters, polyamines, polyhydroxycellulose, polyvinyl alcohol, polyacetals, polyketals, and other synthetic polymers such as cyclodextrins, albumin, chitin, chitosan, collagen, dextran, fibrin, fibrinogen, gelatin, polysaccharides, carrageenan, tragacanth, acacia, xanthan gum, and poly(alginate), and any combination thereof.

[0115] Biodegradable polymers can also include copolymers of any of the above, including alternating copolymers, periodic copolymers, random copolymers, and block copolymers. Examples of such copolymers are poly(lactic acid-co-glycolic acid), poly(lactide-co-glycolide), poly(lactide-co-caprolactone), poly(lactide-co-caprolactone-co-glycolide), poly[(lactide-co-ethylene glycol)-co-ethyloxyphosphate], poly[(1,6-bis(p-carboxyphenoxy)hexane)-co-sebacic acid], poly(hydroxybutyric acid-co-hydroxyvaleric acid), poly[1,4-bis(hydroxyethyl)terephthalate-alt-ethyloxyphosphate]-co-1,4-bis(hydroxyethyl)terephthalate-co-terephthalate, poly(ethylene glycol), poly(ethylene glycol)-poly(caprolactone) methyl ether block copolymer, poly(ethylene glycol)-polylactide methyl ether block copolymer, poly(ethylene glycol) methyl ether-poly-lactide block copolymer, poly(ethylene oxide)-polycaprolactone block copolymer, poly(ethylene oxide)-polylactide block copolymer, polycaprolactone-polytetrahydrofuran-polycaprolactone block copolymer, polylactide-poly(ethylene glycol)-polylactide block copolymer, polyoxyethylene-polypropylene block copolymer, and any combination thereof.

[0116] Suitable non-biodegradable polymers for use in the present invention include celluloses such as cellulose ethers, ethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxyethyl methyl cellulose, methyl cellulose, cellulose acetate, and derivatives thereof, and copolymers thereof. Other suitable non-biodegradable polymers include polyalkylenes, polyacrylates, polymethacrylates, polypyrrolidones, polyoxyethylenes, polyoxyethylene-polypropylene copolymers, polymethyl methacrylates, polybutyl methacrylates, polysiloxanes, shellacs, acrylic and methacrylic acid-based polymers, and copolymers thereof.

[0117] In exemplary embodiments of the first and second aspects of the present invention, the tissue growth-promoting matrix material includes a scaffold, the scaffold including a plurality of fibers, and the fibers are constructed from a biodegradable polymer. Typically, in such embodiments, the fibers are constructed from a biodegradable and bioabsorbable polymer. For example, the fibers may optionally be constructed from a biodegradable polyester selected from the group consisting of polylactic acid (polylactide), polyglycolic acid (polyglycolide), polycaprolactone, polycaprolactone diol, polycaprolactone triol, and copolymers thereof. More typically, in such embodiments, the fibers are composed of a biodegradable polyester selected from the group consisting of polylactic acid (polylactide), polyglycolic acid (polyglycolide), and copolymers thereof. Most typically, the fibers are constructed from a polylactic acid, such as poly-L-lactic acid (PLLA).

[0118] In one aspect of the above embodiment, the tissue growth-promoting matrix material comprises a scaffold, the scaffold comprising a plurality of fibers, the fibers interconnected in a non-woven, disordered, porous structure, the fibers constructed from a biodegradable polymer such as any of those listed in the paragraph above. Typically, in such an aspect of the embodiment, the tissue growth-promoting matrix material is prepared by electrospinning a solution of the polymer to form the scaffold. Such electrospinning procedures are described, for example, in Patent Application No. WO 2007 / 132186, the contents of which are incorporated herein by reference in their entirety.

[0119] Optionally, the tissue growth-promoting matrix material of the first or second aspect of the present invention may be coated or impregnated with one or more tissue growth-promoting agents and / or one or more other pharmaceutical agents. Exemplary tissue growth-promoting agents include growth factors such as basic fibroblast growth factor (FGF-2), transforming growth factor beta (TGF-β), epidermal growth factor (EGF), cartilage-derived growth factor (CDGF), platelet-derived growth factor (PDGF), insulin-like growth factors I and II (IGF-I and IGF-II), interferons (e.g., interferon α, β, γ), and the like. Other pharmaceutical agents may be selected from the group consisting of anti-inflammatory agents, antibacterial agents, immunomodulatory agents, or combinations thereof. Examples of suitable agents are listed on pages 13-19 of Patent Application No. WO2011 / 151659, the contents of which are incorporated herein by reference in their entirety.

[0120] In any embodiment of any aspect of the invention, it is preferred that the seton and / or the device as a whole be made from a biocompatible material. For example, the seton may be formed from a flexible material such as rubber, silicone, silk, flexible plastics such as polypropylene, and the like. Typically, the seton is made from a flexible plastic.

[0121] In one embodiment of the first or second aspect of the present invention, the seton is formed from one or more biodegradable materials, such as a biodegradable polymer. Examples of suitable biodegradable polymers are listed above. Typically, the seton is formed from one or more biodegradable and bioabsorbable polymers. Typically, the seton is optionally formed from one or more biodegradable polyesters selected from the group consisting of polylactic acid (polylactide), polyglycolic acid (polyglycolide), polycaprolactone, polycaprolactone diol, polycaprolactone triol, and copolymers thereof.

[0122] In one embodiment of the first or second aspect of the present invention, the seton comprises a braided cord coated with at least one coating. Typically, in such an embodiment, the seton comprises a braided cord constructed from a first biodegradable polymer and at least one coating, the coating including a second biodegradable polymer and, optionally, a fatty acid, a fatty acid ester, or a salt thereof. Typically, both the first and second biodegradable polymers are biodegradable polyesters, optionally selected from the group consisting of polylactic acid (polylactide), polyglycolic acid (polyglycolide), polycaprolactone, polycaprolactone diol, polycaprolactone triol, and copolymers thereof. The first and second biodegradable polymers may be the same or different. Typically, the first and second biodegradable polymers are different. In one embodiment, the first biodegradable polymer is selected from the group consisting of polylactic acid (polylactide), polyglycolic acid (polyglycolide), and copolymers thereof, and the second biodegradable polymer is selected from the group consisting of polyglycolic acid (polyglycolide), polycaprolactone, polycaprolactone diol, polycaprolactone triol, and copolymers thereof. Typically, the first biodegradable polymer is a copolymer of glycolide and lactide, more preferably glycolide and L-lactide. Typically, such a copolymer contains about 80-95 mol% glycolide and about 5-20 mol% L-lactide. Most preferably, the copolymer contains about 90 mol% glycolide and about 10 mol% L-lactide. Typically, the second biodegradable polymer is a copolymer of glycolide and caprolactone. Typically, the fatty acid, fatty acid ester, or salt thereof is a lactic ester of a fatty acid or a salt thereof. More typically, the fatty acid, fatty acid ester, or salt thereof is a stearoyl-lactylate or a salt thereof, such as stearoyl-2-lactylate. Most typically, the fatty acid, fatty acid ester, or salt thereof is calcium stearoyl-2-lactylate.A coated braided cord comprising a copolymer of glycolide and lactide as the first biodegradable polymer, a copolymer of glycolide and caprolactone as the second biodegradable polymer, and calcium stearoyl-2-lactylate as the fatty acid, fatty acid ester, or salt thereof is commercially available under the trade name Polysorb and may be used as a seton in accordance with the first or second aspects of the present invention.

[0123] Typically, the seton and / or any portion of the elongate body or elongate sheet to be positioned within the stoma does not contain exposed metal. More typically, the seton and / or any portion of the elongate body or elongate sheet to be positioned within the stoma does not contain metal. Most typically, a device of the first or second aspects of the invention does not contain metal.

[0124] The seton has an elongated shape. Typically, in any embodiment of any aspect of the present invention, the total length of the seton and elongated body or elongated sheet (e.g., when the seton is threaded through the elongated body or elongated sheet) is 100 to 1,000 mm. More typically, the total length of the seton and elongated body or elongated sheet is 200 to 800 mm. Even more typically, the total length of the seton and elongated body or elongated sheet is 400 to 600 mm.

[0125] In one embodiment, the seton is generally polygonal in cross section (e.g., generally rectangular, pentagonal, hexagonal, heptagonal, or octagonal). In another embodiment, the seton is generally circular in cross section.

[0126] Typically, the cross section of the seton has a maximum width or diameter of 0.05 to 6 mm. More typically, the cross section has a maximum width or diameter of 0.1 to 4 mm. Typically, the cross section of the seton has a minimum width or diameter of 0.2 to 2 mm. More typically, the cross section has a minimum width or diameter of 0.3 to 0.5 mm.

[0127] A third aspect of the invention provides a method of manufacturing a device according to the first and / or second aspects of the invention, the method comprising the step of affixing a seton to an elongate body or elongate sheet.

[0128] In one embodiment of the third aspect of the invention, the method is a method of manufacturing a device according to the first aspect of the invention. Typically, in such an embodiment, the method includes forming a plurality of protrusions on at least one outer surface of the elongate body and affixing the elongate body to a seton. More typically, the method includes cutting an elongate sheet of tissue growth-promoting matrix material from a larger sheet of tissue growth-promoting matrix material such that the elongate sheet is formed with one or more castellated or serrated outer edges, and affixing the elongate sheet to the seton.

[0129] In one embodiment of the third aspect of the invention, the method is a method of manufacturing a device according to the second aspect of the invention. Typically in such an embodiment, the step of affixing the seton to the elongate body or elongate sheet comprises threading the seton in and out of the elongate body or elongate sheet to form one or more of the attachment loops.

[0130] In an exemplary embodiment of the third aspect of the invention, the method comprises: (i) optionally, cutting elongated sheets of tissue growth-promoting matrix material from a larger sheet of tissue growth-promoting matrix material such that the elongated sheets are formed with one or more castellated or serrated outer edges extending in a direction parallel or substantially parallel to the longitudinal axis of the elongated sheet; (ii) folding the elongate sheet in alternating directions to create accordion folds, the accordion folds extending in a direction perpendicular or substantially perpendicular to the longitudinal axis of the elongate sheet; (iii) passing the seton through the concertinaed elongated sheet, optionally with the aid of a needle, so that the seton passes through the elongated sheet multiple times; (iv) extending the concertinaed elongate sheet along the length of the seton; (v) optionally, tying or otherwise securing the seton to the elongate sheet to prevent the elongate sheet from sliding along the seton; Includes.

[0131] Typically, in steps (ii) and (iii), sharp folds or sharp creases in the elongate sheet are avoided.

[0132] A fourth aspect of the present invention provides a device according to the first and / or second aspects of the present invention for use in medicine. Typically, the device is for use in treating a fistula, such as an anal fistula or a rectovaginal fistula. Typically, treatment involves inserting the device into the fistula tract. Typically, treatment involves forming the device into a loop that passes through the fistula tract and meets outside the fistula tract. More typically, the loop acts to anchor an elongate body or elongate sheet within the fistula tract.

[0133] According to a fifth aspect of the present invention, there is provided a method of treating a fistula, comprising the use of a device according to the first and / or second aspects of the present invention. Typically, the fistula is an anal fistula or a rectovaginal fistula. Typically, the method comprises inserting the device into the fistula tract. Typically, the method comprises forming the device into a loop that passes through the fistula tract and meets outside the fistula tract. More typically, the loop acts to anchor an elongate body or elongate sheet within the fistula tract.

[0134] As used herein, "fistula" refers to any abnormal passage or communication throughout the body between two epithelial surfaces, including those that arise naturally, e.g., as a result of infection; those that arise as a result of injury, e.g., as a result of an impalement injury; and those that are artificial, e.g., as a result of surgery or body piercing.

[0135] In one embodiment of any aspect of the invention, the fistula to be treated comprises: (i) Body piercing or skin fistula; (ii) anal or anorectal fistulas, which may be anatomically classified as intersphincteric, transsphincteric, suprasphincteric, or extrasphincteric; (iii) rectovaginal fistulas, such as anovulval, anovaginal, rectovulval, rectovaginal, or rectovaginal vestibular fistulas, which may be anatomically classified as subsphincteric, transsphincteric, or suprasphincteric; (iv) rectoprostatic fistula; (v) gastrointestinal fistulas, such as tracheoesophageal, gastrocutaneous, ileocutaneous, colonic, rectocutaneous, colovaginal, or gastrointestinal vascular fistulas; (vi) a urinary fistula, such as a urethrocutaneous, urethrovaginal, urethrovesical, vesicovaginal, rectovesical, or rectourethral fistula; or (vii) Fistulas comprising any combination of the foregoing fistulas, such as rectovesical-vaginal fistulas; is selected from.

[0136] Typically, the fistula is complete (i.e., both ends open onto a mucosal or external surface of the body). A complete fistula can be external (i.e., between a hollow organ and an external surface of the body) or bimucosal (i.e., both ends open onto a mucosal surface of the body).

[0137] In one embodiment, the fistula is simple (i.e., it does not include any blind ducts and includes only one opening at each end of the duct). Optionally, however, the fistula includes blind ducts and / or is complex (i.e., it includes more than two openings due to division of the duct). An example of a complex fistula is a horseshoe fistula (two ends of the fistula duct open on the external surface of the body and the third end opens into a hollow organ such as the anal canal).

[0138] In one embodiment of the fourth or fifth aspect of the invention, the fistula to be treated is complex and the device is according to at least the second aspect of the invention. In such an embodiment, the treatment or method typically comprises: (i) securing a further seton to an attachment point or attachment loop of the device of the second aspect of the invention, optionally the further seton forming part of an additional device according to the first and / or second aspects of the invention; (ii) inserting the combined device and the further seton (or additional devices) into the branched tract of the complex fistula tract so that one or more elongated bodies or elongated sheets are positioned within the branched fistula tract, and so that a first end of a seton of the device emerges from a first opening at the first end of the branched fistula tract, a second end of a seton of the device emerges from a second opening at the second end of the branched fistula tract, and one end of the further seton emerges from a third opening at the third end of the branched fistula tract; (iii) securing two or more of the emerged ends of the seton to one another, for example, by tying the emerged ends together in one or more knots; Includes.

[0139] Typically, the fistula to be treated is selected from an anal fistula or a rectovaginal fistula. More typically, the fistula is an anal fistula.

[0140] Typically, the patient to be treated in any of the foregoing aspects of the invention is a human. Typically, the patient to be treated is in need of such treatment. Optionally, the patient may also be suffering from ulcerative colitis, such as Crohn's disease.

[0141] For the avoidance of doubt, where practicable, any embodiment of a given aspect of the invention may occur in combination with any other embodiment of the same aspect of the invention. In addition, where practicable, it will be understood that any preferred or optional embodiment of any aspect of the invention shall also be considered a preferred or optional embodiment of any other aspect of the invention. [Brief explanation of the drawings]

[0142] Embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0143] [Figure 1] FIG. 1 shows a perspective view of a device according to the present invention comprising a seton and an elongated sheet of tissue growth-promoting matrix material.

[0144] [Figure 2] FIG. 2 shows a perspective view of the device according to FIG. 1 illustrating the longitudinal axis and various dimensions of the device.

[0145] [Figure 3] FIG. 3 shows a perspective view of the device according to FIG. 1 in a non-linear position.

[0146] [Figure 4] FIG. 4 shows a top view of the device according to FIG.

[0147] [Figure 5] FIG. 5 shows a side view of the device according to FIG.

[0148] [Figure 6] FIG. 6 shows an enlarged top view of a distal portion of the elongate sheet of the device of FIG.

[0149] [Figure 7] FIG. 7 shows an enlarged top view of the distal portion of the elongate sheet of the device of FIG. 1, but with the castellated protrusions.

[0150] [Figure 8] FIG. 8 shows an enlarged side view of a distal portion of the elongate sheet of the device of FIG.

[0151] [Figure 9] FIG. 9 shows a side view illustrating a method of manufacturing the device of FIG.

[0152] [Figure 10] FIG. 10 shows a schematic diagram of the device of FIG. 1 positioned within a simple anal fistula.

[0153] [Figure 11] FIG. 11 shows a perspective view of a device of the present invention attached via an attachment loop to a further device of the present invention.

[0154] [Figure 12] FIG. 12 shows a schematic diagram of the attached device of FIG. 11 positioned within a complex anal fistula.

[0155] Figure legend 101 devices 102 Seton 102a First Part of Seton 102b Seton's second part 102c Seton section 103 Long, thin sheets of tissue-ingrown matrix material 104 first plurality of protrusions 105 second plurality of protrusions 106 first end of elongated sheet 107 second end of elongated sheet 108 First Knot 109 Second Knot 110 First double-thickness region 111 Second double-thickness region 112 First side of elongated sheet 113 Second side of the elongated sheet 113a Side of a long, narrow sheet 114 Position on a narrow sheet 115 Position on a narrow sheet 116 Position on a narrow sheet 117 Mounting Loop 118 Mounting Loop 119 Mounting Loop 120 mounting loop 121 Mounting loop 122 Mounting loop 123 Position on a narrow sheet 124 Inner circumference of mounting loop 125 folds 126 folds 127 Compressed Strip Sheet 128 mounting loop 129 Mounting Loop 130 probes 131 Fistula tube 132 First Opening 133 Second Opening 134 Anal canal 135 knots 136 First device attachment loop 137 Complex Fistula 138 First Opening 139 Second Opening 140 Third Opening 141 Anal canal 142 Fistula bifurcation 143 First Probe 144 Second Probe 145 knots 201 More Devices 202 Further Device Seton 203 Further Devices: Elongated Sheets of Tissue-Growth-Promoting Matrix Material 204 Knots 205 Multiple protrusions of further devices 236 Attachment loop for further devices 704 Castle wall protrusion 705 Castle wall protrusion 901 needle DETAILED DESCRIPTION OF THE INVENTION

[0156] The devices of the present invention are particularly useful for treating fistulas, such as anal or rectovaginal fistulas. Depending on the fistula to be treated, it may be desirable and / or necessary to pretreat the fistula prior to use of the devices of the present invention comprising an elongated body of tissue growth-promoting matrix material. For example, if the fistula is severely infected, it may be desirable to insert a drainage seton according to the prior art methods discussed above. The drainage seton may optionally incorporate antibiotics and / or anti-inflammatory agents to help reduce the level of infection. Alternatively, it may be preferable to insert a device comprising a fistula stent, such as the device described in WO 2014 / 023962.

[0157] After a period of time, the drainage seton or fistula stent may be removed prior to insertion of a device comprising an elongated body of tissue growth-promoting matrix material according to the present invention.

[0158] Optionally, prior to insertion of a device according to the invention, the fistula tract is cleaned, for example using a jet of water and / or a suitable brush.

[0159] 1, 4, and 5, a device 101 according to an embodiment of the present invention is shown comprising a seton 102 and an elongated body 103 of tissue growth-promoting matrix material. The elongated body can be viewed as being in the form of a rectangular prism and is provided by a sheet of tissue growth-promoting matrix material. Thus, the elongated body may be viewed as an elongated sheet 103 of tissue growth-promoting matrix material.

[0160] 2, when laid flat and unrolled, the device and elongated sheet may be viewed as having a longitudinal axis, x, extending lengthwise through the seton 102 and elongated sheet of tissue growth-promoting matrix material 103. As shown, the device may also be viewed as having a y-axis that is perpendicular to the longitudinal x-axis and parallel to the plane of the sheet, and a z-axis that is perpendicular to both the x-axis and y-axis.

[0161] As will be understood, as used herein, all references to the longitudinal axis and associated orientations and dimensions refer to the device when laid flat in an unfolded position, as illustrated in Figures 1 and 2. Unless otherwise stated, dimensions are measured in such position. However, it should be understood that both the seton 102 and the elongated sheet of tissue growth-promoting material 103 are flexible and can adopt a wide variety of positions, such as that shown in Figure 3.

[0162] As discussed in the Summary of the Invention, the dimensions of elongate body or sheet 103 and seton 102 may vary depending on the fistula to be treated. However, typically, the maximum length l of elongate sheet 103 as measured along the x-axis is 1. 1 (See FIG. 4) is about 75 mm, the maximum width w (See FIG. 4) of the elongated sheet as measured along the y-axis is about 7.5 mm, and the maximum height or thickness h (See FIG. 5) as measured along the z-axis is about 0.4 mm. Similarly, the seton 102 typically has a maximum width or diameter d (See FIG. 4) of about 0.35 mm, and the seton extends over the entire length l of the device 101. 2 is selected to be approximately 475 mm (see FIG. 4). In the embodiment shown, the seton is generally circular in cross section, although it should be understood that other cross-sectional shapes are also possible.

[0163] In the illustrated embodiment, the tissue growth-promoting matrix material of the elongated sheet 103 comprises a scaffold, which includes a plurality of fibers interconnected in a non-woven, disordered structure. The fibers are formed from poly-L-lactic acid (PLLA), a biodegradable, biocompatible, and bioabsorbable polymer. The matrix material was purchased from Neotherix Limited and formed by electrospinning a solution of the polymer in 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) to produce a material with a fiber diameter of 2-3 μm and an average pore size of approximately 10 μm. As discussed above, while the use of other tissue growth-promoting matrix materials is possible, the use of electrospun biodegradable polymers, such as those exemplified, allows for excellent tissue growth-promoting properties due to their large surface area and porosity, which promote both tissue ingrowth and drainage, while the polymer fibers degrade over time, are absorbed by the body, and are eventually excreted.

[0164] In the described embodiment, the seton 102 comprises a braided cord having an outer coating. The braided cord is formed from a poly(lactide-co-glycolide) (PLGA) copolymer having an approximately 10 mol% lactide content and an approximately 90 mol% glycolide content. The outer coating is formed from a poly(caprolactone-co-glycolide) copolymer mixed with calcium stearoyl-2-lactate. Again, the copolymer is biodegradable, biocompatible, and bioabsorbable. Such setons are commercially available as sutures under the trade name Polysorb. While the use of setons made from other materials is envisioned, such coated braided cords offer the advantages of strength and flexibility while being sufficiently smooth to facilitate their use and biodegradable to avoid the need for subsequent surgical removal.

[0165] 1, it can be seen that the elongated body or sheet 103 comprises a first plurality of protrusions 104 positioned on a first outer edge surface substantially parallel to the longitudinal axis x of the elongated sheet, and a second plurality of protrusions 105 positioned on a second outer edge surface also substantially parallel to the longitudinal axis x of the elongated sheet. Typically, about 40 protrusions are provided in the first plurality of protrusions 104 and about 40 protrusions are provided in the second plurality of protrusions 105. The protrusions are integral with the elongated sheet 103 and are provided in the form of serrations, which are formed by appropriately cutting the outer edge of the elongated sheet. As illustrated in FIG. 6, the distance d between the maximum of each adjacent protrusion is p is typically about 2 mm, and the width or maximum distance that each protrusion extends between two adjacent minima (w p ) is typically about 2 mm, and the height or maximum distance that each protrusion extends from the adjacent minimum on the surface (h p ) is typically about 1 mm.

[0166] When the device is inserted into the fistula tract, the protrusions 104, 105 may act to grip or bite into the inner wall of the fistula. Thus, the protrusions may act to both prevent rotational movement and prevent lateral or lateral movement of the elongate body or sheet 103 within the fistula tract, preventing the elongate body or sheet 103 from sliding out of the fistula tract. The protrusions help maintain the elongate body or sheet 103 in a single position relative to the surrounding tissue of the fistula tract, thereby encouraging tissue ingrowth.

[0167] As will be appreciated, the protrusions need not be triangular or sawtooth shaped, but may be, for example, castellated, as illustrated by protrusions 704 and 705 in Figure 7. Other shapes are described in the Summary of the Invention above. Advantageously, however, each protrusion includes at least one tip, which may serve to better grip or bite into the inner wall of the stoma.

[0168] As illustrated in Figures 6 and 7, the minimum between adjacent protrusions 105, 705 is in the form of a V-shape (Figure 6) or a square outline with sharp or pointed interior corners (Figure 7). However, it may be desirable to ensure that each minimum between adjacent protrusions is not sharp or V-shaped. For example, each minimum between adjacent protrusions may be curved or rounded, e.g., to form a concave curve between the maxima of each adjacent protrusion. Tear-promoting points are thereby minimized.

[0169] As best shown in Figures 1, 4, and 5, the seton 102 is threaded through the elongated sheet 103 so that a first portion 102a of the seton 102 extends beyond a first end 106 of the elongated sheet 103, a second portion 102b of the seton 102 extends beyond a second end 107, and the seton 102 spans the entire length of the elongated sheet 103. In use, the elongated sheet 103 is placed within the fistula tract, and the first and second portions 102a, 102b are tied together outside the fistula tract to form a loop or seton stitch. Such a configuration means that the fixation relies entirely on the robust seton cord for strength, and not on a potentially weaker material such as a tissue-growth-promoting matrix material. A more robust fixation is thereby achieved.

[0170] Elongated sheet 103 is folded over at a first end to create a double-thickness region of sheet 110. A first knot 108 is tied using a seton around folded portion 110 of the elongated sheet. Similarly, elongated sheet 103 is folded over at a second end to create another double-thickness region of sheet 111. A second knot 109 is tied using a seton around folded portion 111 of the elongated sheet. As will be appreciated, the two knots prevent elongated sheet 103 from sliding along seton 102. Also, by folding or rolling the elongated sheet, a more robust connection is formed, allowing a surgeon or medical professional to forcefully pull either the first or second portion (102a or 102b) of the seton with little risk of tearing elongated sheet 103. The same folding or rolling also minimizes the risk of the elongated sheet 103 tearing while in situ due to the routine strains and stresses imparted by patient movement.

[0171] In the illustrated embodiment, the elongated sheet 103 of tissue growth-promoting matrix material is substantially rectangular in shape (see particularly the top view of device 101 in FIG. 4), with the corners of the rectangle at first end 106 and second end 107 each forming a right angle. However, it may be desirable to ensure that the corners of the rectangle are rounded or chamfered, thus aiding in insertion of the device into the fistula tract.

[0172] 5, tracing the path of the seton 102 from the first knot 108, it can be seen that the seton is threaded from the first side 112 to the second side 113 of the elongated sheet 103 at location 114, then back through the second side 113 at location 115, then back through the first side 112 at location 116, and so on down the length of the elongated sheet. In doing so, it can be seen that a plurality of attachment loops 117, 118, 119, 120, 121, 122 are formed and positioned on alternating sides along the length of the elongated sheet in a direction substantially parallel to the longitudinal x-axis. As shown, it can be seen that the seton 102 finally passes from the first side 112 to the second side 113 through the elongated sheet 103 at location 123 before tying the second knot 109. However, this is not critical, and the final pass through the elongated sheet may equally be from the second side to the first side. It should be understood that, as illustrated in Figures 5, 8, and 9, the seton 102 is shown loosely threaded to best illustrate its path through the elongated sheet 103 and the attachment loops 117, 118, etc. In practice, however, the seton 102 and elongated sheet 103 will typically be tightened prior to completing the tying of the first knot 108 and the second knot 109 so that the seton lies flat against the surfaces 112, 113 of the elongated sheet 103.

[0173] In the embodiment shown, the distances between locations 114, 115, 116, etc. where the seton passes through the elongated sheet are approximately equally spaced. As a result, attachment loops 117, 118, 119, 120, 121, 122, etc. are substantially evenly distributed along the entire length of the elongated sheet and are each substantially the same size. However, it should be understood that alternative spacings can be used to vary the distribution and size of the attachment loops. Similarly, in the embodiment shown in FIG. 1, there are seven attachment loops on the first side and eight attachment loops on the second side of the elongated sheet, thus resulting in a total of 15 attachment loops positioned along the length of the elongated sheet. However, again, it should be understood that the number of attachment loops on each side and total can vary.

[0174] A plurality of attachment loops 117, 118, 119, 120, 121, 122 are configured to attach the elongated sheet to one or more additional setons. As shown in most detail in FIG. 8, the inner perimeter of attachment loop 117 is formed in part by seton portion 102c and in part by side portion 113a of elongated sheet 103. Accordingly, in relation to attachment loop 118, the inner perimeter is illustrated by a thick line 124. The inner perimeter is advantageously selected so that additional setons can be passed through the attachment loops and attached relatively easily by an end user, while preventing substantial lateral movement of the attached additional setons. To achieve this, an inner perimeter of 10 mm is typical.

[0175] Turning now to the manufacture of the device of FIG. 1 , it should be understood that this is typically done at a factory prior to delivery to a surgeon or other end user. The elongated sheet 103 may be cut from a larger sheet of tissue growth-promoting matrix material. Typically, the serrated or castellated portions are cut at the same time the elongated sheet is cut from the larger sheet, thus allowing for the cutting of multiple elongated sheets with little waste, particularly if the same cut is used to form the serrated or castellated portions on more than one elongated sheet. Cutting methods are not limited and may include, for example, die cutting, laser cutting, or the use of scissors.

[0176] In a particularly efficient manufacturing method illustrated in FIG. 9 , the elongated sheet 103 may be folded in alternating directions to create accordion folds, with accordion folds 125, 126 extending perpendicular or substantially perpendicular to the longitudinal axis x of the elongated sheet. The accordion-folded sheet may then be compressed to provide a compressed elongated sheet 127. A seton 102 may then be passed through the compressed elongated sheet 127 in a direction substantially parallel to the x-axis as shown in FIG. 9( b). As shown, a needle 901 is used to assist in passing the seton through the compressed elongated sheet 127; however, it should be understood that other means of forming holes, such as perforation or drilling, are also possible. The compressed elongated sheet 127 may then be extended in the opposite direction along the length of the seton 102, as shown in FIG. 9( c). Once stretched, an elongated sheet 103 having multiple attachment loops 128, 129 formed by the seton 102 is provided, as shown in FIG. 9(d). The two ends of the elongated sheet may then be folded, and the seton secured at first and second knots about each end, as previously described. In such a manner, multiple attachment loops may be created via a single operation, facilitating automated or bulk manufacturing.

[0177] When folding and compressing elongate sheet 103, it may be desirable to ensure that creases 125, 126 or folds are not sharp. For example, the creases or folds may be formed around temporary support rollers (not shown) that are placed on the inside of folds or creases 125, 126 during folding and compressing steps (a)-(c). Permanent creases in elongate sheet 103 will thereby be avoided.

[0178] Alternatively, an accordion-folded elongate sheet may be formed by compressing the elongate sheet 103 between an upper mold and a lower mold. Typically, the upper and lower molds are shaped with corresponding mating surfaces to allow the accordion fold to be formed when the elongate sheet 103 is sandwiched between the two molds. For example, the mating surfaces may be configured to cause the elongate sheet to adopt a shape that approximates that of a sine wave extending in a direction parallel to the longitudinal axis x of the elongate sheet. Sharp folds or creases in the elongate sheet may thereby be avoided.

[0179] A longitudinal guide passage may be formed through multiple component passages in the two dies. The longitudinal guide passage may be configured so that, when the elongated sheet 103 is sandwiched between the two dies, a puncture instrument, such as a needle or drill, may be passed through the guide passage to form a series of holes in the elongated sheet extending along the length of the sheet. The upper and lower dies may then be removed, and the seton 102 may be threaded through the holes to form attachment loops 128, 129. Alternatively, the upper and lower dies may each be subdivided into at least two sections that interlock around the component passage. In such an embodiment, a puncture instrument may be attached to the seton 102 and threaded through the elongated sheet 103 along the longitudinal guide passage. The upper and lower die sections may then be separated, leaving the seton 102 threaded multiple times through the elongated sheet 103 to form attachment loops 128, 129, as shown, for example, in FIG. 9(d). The seton 102 and elongated sheet 103 may then be pulled tight and the seton may be secured to the seton using, for example, a knot as described above.

[0180] The devices of the present invention may be used to treat simple or complex fistulas, particularly simple or complex anal or rectovaginal fistulas. Typically, the devices of the present invention may be inserted while the patient is awake, for example, using local anesthesia. However, the devices may also be inserted under general anesthesia.

[0181] For the treatment of a simple fistula, a single device according to the present invention is typically used. Referring to Fig. 10(a), a patient is shown with a fistula tract 131 extending from a first opening 132 located on the exterior surface of the patient's buttocks or perianal skin to a second opening 133 located inside the anal canal 134. A surgeon or medical professional may feed a device 101, comprising a seton 102 and an elongated sheet 103, through the first opening 132 and into the fistula tract 131 with the aid of a probe 130. The probe and the first end of the seton are then manipulated through the fistula tract 131, out the second opening 133, and out of the patient via the anal canal 134, as shown by the arrows in Fig. 10(a). In such a manner, the elongated sheet 103 may be positioned within the fistula tract 131, with a first end of the seton extending from the second opening 133 and out of the anal canal 134, and a second end of the seton extending out of the first opening 132. The probe may then be removed and the two ends of the seton may be tied together at a knot 135 to secure the elongated sheet 103 within the fistula tract via a seton stitch, as illustrated in FIG. 10(b).

[0182] 10(b), when in place, the protrusions 104, 105 may act to grip or bite into the inner wall of the fistula tract 131. Thus, the protrusions may act to both prevent rotational movement and prevent lateral or lateral movement of the elongated sheet 103 within the fistula tract, such that rotation of the seton stitches prevents the elongated sheet 103 from sliding out of the fistula tract.

[0183] Also, while the elongated sheet is flexible, it may have some elasticity. In use, to aid in feeding the elongated sheet 103 into the fistula tract 131, a surgeon or medical professional will typically form the sheet into a groove or V-shape, with the valleys of the groove or V extending roughly along the same line as the seton, i.e., parallel to the previously defined longitudinal axis of the device. If the sheet is elastic, it will tend to unfold or spread once placed within the fistula tract, thus creating outward pressure against the protrusions into the wall of the fistula tract and thereby promoting fixation. It can also be seen that by forming the elongated sheet 103 into a grooved or V-shaped configuration with the grooves or V-shaped valleys extending along roughly the same lines as the seton, any attempt to rotate the elongated sheet 103 about the seton in place will result in one of the two sets of protrusions 104, 105 digging into the inner wall of the fistula tract 131 in a direction opposite the attempted direction of rotation, regardless of whether the elongated sheet is rotated clockwise or counterclockwise, and regardless of whether the elongated sheet is elastic or not. Thus, it can be seen that the multiple protrusions are very effective in maintaining the tissue growth-promoting matrix material in a fixed position against the inner wall of the fistula tract. As a result, tissue ingrowth is encouraged.

[0184] For the treatment of longer fistula tracts or for the treatment of fistula tracts with non-uniform internal diameters, two or more devices of the invention may be attached together end-to-end, e.g., such that one end of an elongated sheet of a first device of the invention is closely adjacent to or abuts one end of an elongated sheet of a second device of the invention. The elongated sheets of the first and second devices according to the invention may have different widths (w) to accommodate the different internal diameters of a given fistula tract.

[0185] The multiple attachment points or loops make the device particularly suitable for treating complex fistulas. As shown in FIG. 11 , a seton 202 of an additional device 201 according to the present invention may be attached to the attachment loop 136 of the first device 101 according to the present invention via a knot 204. The additional device comprises an elongated sheet 203 of tissue growth-promoting matrix material and a protrusion 205, as previously described. As will be appreciated, although the additional device 201 is attached via the attachment loop 136 shown, the additional device may instead be attached to any one of the additional attachment loops on the first device 101. Also, although not shown, additional devices of the present invention may be attached to the combined attached devices either via the same attachment loop 136, via separate additional loops located on either side of the first device 101, or via an attachment loop 236 located on the additional device 201. In all cases, the dimensions of first device 101, further device 201, and any additional devices may be selected by the end user according to the fistula to be treated. Thus, it should be understood that nearly infinite variations are possible, allowing a surgeon or medical professional to attach any number of devices together in nearly any configuration to match the anatomy and degree of branching of the complex fistula to be treated.

[0186] Turning to Figure 12, the insertion of the combined, bonded devices of Figure 11 into a complex fistula tract is illustrated. Referring to Figure 12(a), a patient is illustrated with a complex fistula tract 137 extending from a first opening 138 located on the exterior surface of the patient's buttocks or perianal skin to a second opening 139 located inside the anal canal 141, and further extending via a bifurcation 142 to a third opening 140 also located on the exterior surface of the patient's buttocks or perianal skin.

[0187] A surgeon or medical professional may feed a first end of the seton 102 of the first device 101 through the anal canal 141 with the aid of a first probe 143 and into the fistula tract 137 via a second opening 139. The first probe and the first end of the seton 102 may then be manipulated through the fistula tract 137 and out of a first opening 138, as shown by the arrows in FIG. 12( a). Similarly, a first end of a seton 202 of an additional device 201 attached to the first device may be fed through the anal canal 141 with the aid of a second probe 144 and into the fistula tract 137 via a second opening 139. The second probe and the first end of the seton 202 may then be manipulated through a bifurcation 142 of the fistula tract 137 and out of a third opening 140, again as shown by the arrows in FIG. 12( a).

[0188] In such a manner, the elongated sheet 103 of the first device is positioned within the fistula tract 137, with a first end of the seton 102 extending from the second opening 139 and out of the anal canal 141, and the second end of the seton 102 extending out of the first opening 138. The additional device 201 is attached to the attachment loop of the first device 101 via a knot 204, as discussed above, and the elongated sheet 203 is positioned to extend through the length of the fistula tract bifurcation 142, such that one end of the seton 202 of the additional device extends out of the third opening 140. After removal of any probes, the two ends of seton 102 and the free end of seton 202 may then be tied together at knot 145 to secure both elongated sheets 103 and 203 within the bifurcation of fistula tract 137 via a seton stitch, as shown in FIG. 12(b).

[0189] As will be appreciated, because the seton 202 of the further device is attached directly to the seton 102 of the first device, in situ the combined seton stitches and the resulting bond between the two elongated sheets 103 and 203 will be extremely robust. The two elongated sheets 102 and 203 may also include a plurality of protrusions 105 and 205 in the form of serrated or castellated edges, thereby assisting in the bond as explained above.

[0190] The described devices and methods may be best adapted by a surgeon or medical professional in view of the particular fistula to be treated. For example, the manner of insertion of the devices of the present invention is not limited to that described in connection with Figures 10 and 12, and other insertion techniques may be readily adopted or envisioned. For example, with reference to Figure 12, first device 101 and second device 201 may be inserted into their respective branches of the fistula tract before the first device is attached to the second device via the attachment loop.

[0191] While embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that the foregoing description is to be considered as merely a description of preferred embodiments. The examples are not intended to limit the scope of the invention. Various modifications and embodiments can be made without departing from the scope and spirit of the invention, which is defined solely by the following claims.

Claims

1. 1. A device suitable for treating a fistula, comprising: the fistula comprises a fistula tract; The device comprises a seton and an elongate body of tissue growth promoting matrix material; the elongate body is adapted to be positioned within the fistula tract; A device wherein the elongate body comprises a plurality of protrusions positioned on at least one outer surface of the elongate body.

2. The device of claim 1 , wherein each outer surface on which the plurality of protrusions are positioned is parallel or substantially parallel to the longitudinal axis of the elongate body.

3. 3. The device of claim 1, wherein each protrusion of the plurality of protrusions has a height of 0.5 to 3 mm and a width of 0.5 to 5 mm.

4. 10. The device of claim 1, wherein each protrusion of the plurality of protrusions is in the shape of a cone, a triangle, a triangular prism, or a pyramid.

5. 10. The device of claim 1, wherein the elongate body and the plurality of protrusions are of unitary construction.

6. 10. A device according to any preceding claim, wherein the elongate body is an elongate sheet of tissue growth promoting matrix material.

7. 7. The device of claim 6, wherein the plurality of protrusions are positioned on at least one outer edge surface of the elongated sheet, the outer edge surface being parallel or substantially parallel to the longitudinal axis of the elongated sheet.

8. 1. A device suitable for treating a fistula, comprising: the fistula comprises a fistula tract; The device comprises a seton and an elongated sheet of tissue growth promoting matrix material; the elongate sheet is adapted to be positioned within the fistula tract; the elongate sheet having a first outer edge surface and a second outer edge surface; the first outer edge surface and the second outer edge surface are both parallel or substantially parallel to the longitudinal axis of the elongate sheet when laid flat; a first plurality of protrusions formed by serrations on the first outer edge surface; a second plurality of protrusions formed by serrations on said second outer edge surface;

9. 1. A device suitable for treating a fistula, comprising: the fistula comprises a fistula tract; The device comprises a seton and an elongate body of tissue growth promoting matrix material; the elongate body is adapted to be positioned within the fistula tract; The device comprises one or more attachment points positioned along the length of the elongate body, the one or more attachment points configured to connect the elongate body to an additional seton.

10. 10. The device of claim 9, wherein the elongate body is an elongate sheet of tissue growth-promoting matrix material.

11. A device according to claim 9 or claim 10, wherein each attachment point is provided in the form of an attachment loop, and optionally each attachment loop has an inner circumference of between 5 and 20 mm.

12. 12. The device of claim 11, wherein the seton is threaded through the elongate body or elongate sheet of tissue growth promoting matrix material, and each attachment loop is secured directly to or formed by the seton.

13. 1. A device suitable for treating a fistula, comprising: the fistula comprises a fistula tract; The device comprises a seton and an elongated sheet of tissue growth promoting matrix material; the elongate sheet is adapted to be positioned within the fistula tract; the elongated sheet has a first end and a second end, a longitudinal axis extending from the first end to the second end; the seton extends beyond a first end of the elongated sheet and is repeatedly threaded from a first side to a second side of the elongated sheet and then from the second side back to the first side of the elongated sheet to form a plurality of attachment loops positioned on alternating sides along the length of the elongated sheet; the seton is optionally threaded from the first side of the elongate sheet back to the second side; the seton exits to extend beyond the second end of the elongate sheet; The device, wherein the plurality of attachment loops are configured to attach the elongate sheet to one or more additional sheetons.

14. the seton is affixed to the elongated sheet via a first knot located proximal to the first end of the elongated sheet, and the seton is affixed to the elongated sheet via a second knot located proximal to the second end of the elongated sheet; Optionally, the elongate sheet is rolled or folded at each of the first end and the second end, and the first knot and the second knot are tied such that the loop of each knot encircles a respective rolled or folded portion of the elongate sheet. The device of claim 13.

15. 10. The device of any preceding claim, wherein the tissue growth-promoting matrix material comprises a scaffold, the scaffold comprising a plurality of fibers, optionally the fibers being interconnected in a non-woven, disordered structure.

16. 16. The device of claim 15, wherein the fibers are constructed from a biodegradable polymer, such as a biodegradable polyester.

17. The device of claim 16, wherein the fibers are constructed from poly-L-lactic acid.

18. 10. The device of claim 1, wherein the seton is formed from one or more biodegradable polymers.

19. 10. A method of manufacturing a device according to any preceding claim, said method comprising the step of affixing said seton to said elongate body or elongate sheet.

20. The method comprises: (i) optionally, cutting elongated sheets of tissue growth promoting matrix material from a larger sheet such that the elongated sheets are formed with one or more castellated or serrated outer edges extending in a direction parallel or substantially parallel to the longitudinal axis of the elongated sheet; (ii) folding the elongate sheet in alternating directions to create accordion folds, the accordion folds extending in a direction perpendicular or substantially perpendicular to the longitudinal axis of the elongate sheet; (iii) passing the seton through the accordion-folded elongate sheet, optionally with the aid of a needle, so that the seton passes through the elongate sheet multiple times; (iv) extending the accordion-folded elongate sheet along the length of the seton; (v) optionally, binding or otherwise securing the seton to the elongated sheet to prevent the elongated sheet from sliding along the seton; 20. The method of claim 19, comprising:

21. A method of treating a fistula comprising the use of a device according to any one of claims 1-19.

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