Pre-prepared tissue grafts with attachment points

Abstract

The present invention provides tissue grafts having pre-fabricated attachment points (mounting points). [Solution] One or more pre-fabricated attachment points include pre-fabricated markings and / or pre-fabricated suture holes. The membrane tissue graft may be in the shape of a tube. Alternatively, the membrane tissue graft may be in the shape of a rectangle and can be used in nerve repair by wrapping around a severed or damaged nerve. The membrane tissue graft is suitable for repairing severed nerves that have a short gap of less than 5 mm between the severed ends, or nerves that do not have a gap. Therefore, a damaged or severed nerve can be repaired by implanting a membrane tissue graft onto it.

Description

Technical Field

[0001] This application claims the benefit of U.S. Provisional Application No. 62 / 656,735, filed Apr. 12, 2018, the content of which is incorporated herein by reference. This application relates to tissue grafts, and more particularly to tissue grafts having a prefabricated attachment point.

Background Art

[0002] Membrane tissue grafts are often used as a matrix for tissue repair or regeneration, particularly soft tissue repair or regeneration. Typically, such tissue grafts are adhered or sutured onto damaged tissue. Once implanted, the tissue graft can protect the damaged tissue and assist in tissue growth and repair. The tissue graft can even be incorporated into the repaired tissue and become part of the repaired / regenerated tissue.

[0003] Certain membrane tissue grafts are relatively mechanically robust and provide mechanical properties suitable for reinforcing soft tissue grafts. Suturing materials, particularly needles, suitable for microsurgical applications in nerve repair are not always suitable for securing a mechanically strong tissue-based membrane. For example, needles having a larger diameter and tip may be required to prevent needle bending in a membrane tissue graft. However, microsurgical procedures are better performed using thinner taper point needles that can cause less tissue trauma during use, so the use of such needles can be disadvantageous.

[0004] Certain other membrane tissue grafts have relatively weak mechanical properties to facilitate use as a cushioning or lubricating material. In such cases, the properties of the graft can be such that tearing or splitting occurs mainly due to the placement of the suture thread. Such splits or tears can easily propagate through the material and cause mechanical failure.

[0005] Certain membrane tissue grafts may be formed into tubes, conduits, or other forms to support and enhance microsurgical repairs, such as the repair of damaged nerves. Due to the specialized needs of microsurgical repairs, the parameters of sutures and suture needles may be important for the surgical procedure. [Overview of the Initiative] [Problems that the invention aims to solve]

[0006] Therefore, there is a need for a membrane tissue graft that can be sutured with any type of suture without damaging the graft, the suture needle, or the underlying tissue, while preserving the bulk mechanical properties of the graft. [Means for solving the problem]

[0007] This disclosure provides membrane tissue grafts designed to avoid, reduce, or minimize suturing difficulties. In some embodiments, the membrane tissue graft includes one or more pre-fabricated attachment points.

[0008] The membrane tissue graft may contain one or more of the following characteristics. The membrane tissue graft may have a thickness of 25 microns to 3 millimeters. The membrane tissue graft may contain natural materials. Natural materials may be selected from porcine small intestine submucosa, amniotic membrane / chorionic membrane, reconstituted denatured collagen, collagen, elastin, thrombin, fibronectin, starch, poly(amino acids), gelatin, alginate, pectin, fibrin, oxidized cellulose, chitin, chitosan, tropoelastin, hyaluronic acid, fibrin-based materials, collagen-based materials, hyaluronic acid-based materials, glycoprotein-based materials, cellulose-based materials, silk, and combinations thereof. The membrane tissue graft may also contain synthetic materials. The synthetic material can be selected from silicone resin, stretched polytetrafluoroethylene (ePTFE), polyethylene terephthalate tetraphthalate (Dacron), polyurethane aliphatic polyester, poly(amino acid), poly(propylene fumarate), copro(ether ester), polyalkylene oxalate, polyamide, tyrosine-derived polycarbonate, poly(iminocarbonate), polyorthoester, polyoxaester, polyamide ester, polyoxaester containing an amine group, poly(anhydride), polyphosphazene, and mixtures thereof. The membrane tissue graft may contain one or more bioactive components that facilitate the repair of damaged tissue. One or more pre-fabricated attachment points may include one or more pre-fabricated suture holes. One or more pre-fabricated attachment points may be located near the outer edge of the membrane tissue graft. The membrane tissue graft may be in the shape of a tube, and one or more pre-fabricated attachment points may be located along the edges of the two ends of the tube. The membrane tissue graft may be rectangular, and one or more pre-fabricated attachment points may be located along two opposite sides of the rectangular membrane tissue graft, or they may not be located along the other two opposite sides. One or more pre-fabricated attachment points may be located along the edge of the membrane tissue graft, at a distance of approximately 0.5 mm to approximately 10 mm from the edge.

[0009] One or more pre-fabricated attachment points are placed on the membranous tissue graft and may include one or more markings configured to increase the visibility of the one or more pre-fabricated attachment points. The membranous tissue graft may be tubular in shape, and one or more markings may be placed along the edges of two ends of the tubule. The membranous tissue graft may also be rectangular, and one or more markings may be placed along two opposite sides of a rectangular membranous tissue graft, but not necessarily along the other two opposite sides. One or more markings may be placed along the edges at a distance of approximately 0.5 mm to approximately 10 mm from the edges of the tissue graft. One or more markings indicate the orientation (degree of orientation) of the membranous tissue graft. One or more markings may be placed to assist the user in positioning the tissue at a measured distance within the membranous tissue graft. One or more pre-fabricated attachment points may include one or more pre-fabricated suture holes and one or more markings.

[0010] In another embodiment, a method for repairing a damaged and / or severed nerve is provided. This method may include the step of implanting a membrane tissue graft, which includes one or more pre-fabricated attachment points, into the damaged and / or severed nerve. The damaged and / or severed nerve may have a gap ranging from about 0 mm to about 5 mm.

[0011] Details of one or more exemplary embodiments are described in the accompanying drawings and the following description. Other possible exemplary features and / or possible exemplary advantages will become apparent from the description, drawings, and claims. Some embodiments may not have those possible exemplary features and / or possible exemplary advantages, and such possible exemplary features and / or possible exemplary advantages may not be necessary in some embodiments. [Brief explanation of the drawing]

[0012] [Figure 1] Examples of one or more pre-fabricated attachment points (e.g., one or more pre-fabricated etchings and one or more pre-fabricated suture holes) in an exemplary membrane tissue graft of the present disclosure are shown. [Figure 2] The diagram shows exemplary shapes and forms of suture holes. In each embodiment, the filled area toward the center indicates a hole or cut. The white area around the hole indicates an optional etching. Additionally, the shaded area surrounding the white area indicates an optional reinforcement area. [Figure 3] The present invention illustrates one or more pre-fabricated attachment points, in particular one of various configurations of one or more pre-fabricated holes or suture holes placed on a membrane tissue graft, consistent with embodiments of the present disclosure. [Figure 4] The present invention illustrates one or more pre-fabricated attachment points, in particular one of various configurations of one or more pre-fabricated holes or suture holes placed on a membrane tissue graft, consistent with embodiments of the present disclosure. [Figure 5] The present invention illustrates one or more pre-fabricated attachment points, in particular one of various configurations of one or more pre-fabricated holes or suture holes placed on a membrane tissue graft, consistent with embodiments of the present disclosure. [Figure 6] The present invention illustrates one or more pre-fabricated attachment points, in particular one of various configurations of one or more pre-fabricated holes or suture holes placed on a membrane tissue graft, consistent with embodiments of the present disclosure. [Figure 7] The present invention illustrates one or more pre-fabricated attachment points, in particular one of various configurations of one or more pre-fabricated etchings or markings placed on a membrane tissue graft, consistent with embodiments of the present disclosure. [Figure 8] The present invention illustrates one or more pre-fabricated attachment points, in particular one of various configurations of one or more pre-fabricated etchings or markings placed on a membrane tissue graft, consistent with embodiments of the present disclosure. [Figure 9] The present invention illustrates one or more pre-fabricated attachment points, in particular one of various configurations of one or more pre-fabricated etchings or markings placed on a membrane tissue graft, consistent with embodiments of the present disclosure. [Figure 10] The present invention illustrates one or more pre-fabricated attachment points, in particular one of various configurations of one or more pre-fabricated etchings or markings placed on a membrane tissue graft, consistent with embodiments of the present disclosure. [Figure 11] Examples of the membrane tissue grafts of this disclosure in nerve repair protector tissue grafts are shown. [Figure 12] Examples of the membrane tissue grafts of this disclosure in nerve repair connector tissue grafts are shown. [Modes for carrying out the invention]

[0013] In some specific exemplary embodiments, the present disclosure may provide a membrane tissue graft comprising one or more pre-fabricated attachment points (e.g., pre-fabricated suture holes and surrounding features to enhance visibility and / or reinforce the suture points).

[0014] In certain exemplary embodiments, the tissue grafts of the Disclosure may be in the form of tubes designed to be implanted on damaged tissue, such as a damaged nerve. In other embodiments, the tissue grafts of the Disclosure may be in the form of sheets designed to be implanted on the surface of damaged tissue, such as a damaged nerve.

[0015] Suture holes in tissue grafts of several embodiments consistent with this disclosure can facilitate the suturing of tissue grafts to damaged tissue, such as damaged nerves. The visibility of suture holes can be increased using etching or other methods.

[0016] In some exemplary embodiments, the tissue grafts of the present disclosure are suitable for repairing damaged nerves, such as severed nerves that have no gaps or gaps between the severed nerve ends, for example, gaps of less than approximately 5 mm. Accordingly, methods for using the tissue grafts of the present disclosure are also described. These methods include, for example, methods for repairing damaged or severed nerves by implanting the tissue grafts of the present disclosure into the damaged or severed nerve. Tissue grafts consistent with the present disclosure may be used for other purposes.

[0017] Tissue grafts are typically adhered or sutured to damaged tissue. The membrane tissue graft and / or the damaged tissue can be damaged due to problems associated with suturing (e.g., needle buckling or dulling by a relatively mechanically tough tissue-based membrane), which can cause more extensive trauma to the underlying nerve tissue and can be damaged due to the pressure exerted on the graft after suturing, being torn during suturing or tearing, etc.).

[0018] In certain embodiments, to assist an individual such as a medical professional in repairing tissue, the present disclosure can provide a membrane tissue graft having one or more pre-made attachment points (e.g., markings such as suture holes and / or etchings designed to increase the visibility of the suture holes).

[0019] Referring to the examples of FIGS. 1-12, in some embodiments, the "membrane tissue graft" as used herein generally refers to a relatively thin graft suitable for transplantation into a subject in a surgical or other medical procedure. The membrane tissue graft (e.g., membrane tissue graft 102) can be made from any of a variety of synthetic and / or natural materials. The membrane tissue graft (e.g., membrane tissue graft 102) can have a thickness of, for example, about 25 microns to 3 mm, 100 microns to 2.75 mm, 200 microns to 2.5 mm, 300 microns to 2 mm, or 500 microns to 1.5 mm. In one embodiment, the thickness is about 100 microns. However, it is understood that the membrane tissue graft can have any thickness within the scope of the present disclosure.

[0020] In some embodiments, the membrane tissue graft (e.g., membrane tissue graft 102) can be composed of natural materials such as porcine small intestinal submucosa, amnion / chorion, or reconstituted denatured collagen. Also, the membrane tissue graft (e.g., membrane tissue graft 102) can be made from synthetic materials. In a preferred embodiment, the membrane tissue graft (e.g., membrane tissue graft 102) can be non-immunogenic to the recipient.

[0021] Suitable synthetic materials for use in membrane tissue grafts include, but are not limited to, silicone membranes, stretched polyethylene terephthalate (ePTFE), polyethylene tetrafuslate (Dacron), polyurethane aliphatic polyesters, poly(amino acids), poly(propylene fumarate), copro(ether esters), polyalkylene oxalates, polyamides, tyrosine-derived polycarbonates, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamide esters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, and mixtures thereof.

[0022] Natural polymers suitable for use in membrane tissue grafts include, but are not limited to, collagen, elastin, thrombin, fibronectin, starch, poly(amino acids), gelatin, alginate, pectin, fibrin, oxidized cellulose, chitin, chitosan, tropoelastin, hyaluronic acid, fibrin-based materials, collagen-based materials, hyaluronic acid-based materials, glycoprotein-based materials, cellulose-based materials, silk, and combinations thereof.

[0023] A combination of one or more natural and / or synthetic materials can also be used. In particular, any combination of the natural and / or synthetic materials disclosed in the preceding paragraph can be used.

[0024] As used herein, “nerve graft” generally refers to a graft implanted in a recipient to repair a damaged nerve or other tissue of the nervous system. Nerve grafts may be made from synthetic materials, natural materials, or combinations thereof. The various materials used to prepare the membrane tissue grafts described above may also be used in the preparation of nerve grafts.

[0025] In exemplary embodiments, the membrane tissue graft may include porcine submucosal extracellular matrix ("ECM"). In some specific exemplary embodiments, the tissue graft may include an ECM in the form of a sheet that can be wrapped around damaged tissue, such as a damaged nerve. An example of such a membrane tissue graft is the improved AxoGuard NerveProtector® described in Example 1 below.

[0026] In further embodiments, the membrane tissue graft may include an ECM in the form of a tube suitable for joining severed nerves, having short gaps or no gaps, preferably with gaps of less than 5 mm between the severed ends. An example of such a membrane tissue graft is the improved AxoGuard NerveConnector® described in Example 2 below.

[0027] In another embodiment, the membranous tissue graft may include minimally processed human umbilical cord membrane, which can be used, for example, as reabsorbable soft tissue covering separate tissue layers. An example of such a tissue graft is Avive Soft Tissue®, which has been improved according to embodiments of the present invention.

[0028] In some embodiments, membrane tissue grafts (e.g., membrane tissue graft 102) may be used in conjunction with tendon wraps (covering tendons) and repairs. For example, embodiments of membrane tissue can enhance repair with wraps, assist in anti-adhesion, and / or assist in detension. Membrane tissue grafts may also be used in conjunction with other types of tissue, including blood vessels, intestines, muscles (e.g., heart, skeleton, and smooth muscle), nervous tissue (e.g., nerves, brain, and spinal cord), connective tissue, epithelial tissue, and the like.

[0029] In certain embodiments, the membrane tissue grafts of the present disclosure may contain one or more bioactive components that facilitate the repair of damaged nerves. Non-limiting examples of such bioactive compounds include xenogeneic or autologous growth factors, proteins (including matrix proteins), peptides, antibodies, enzymes, platelets, glycoproteins, hormones, cytokines, glycosaminoglycans, nucleic acids, analgesics, viruses, viral particles, cells, nonsteroidal anti-inflammatory drugs, cells and cell components, or immunosuppressive therapies. In certain embodiments, bioactive components suitable for use in the membrane tissue grafts of the present disclosure include interleukins, metalloproteinase tissue inhibitors, epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, vascular endothelial growth factor, and transforming growth factors. In a preferred embodiment, the bioactive growth factor includes neurotrophic growth factors such as brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), neurotrophic factor (NGF), neutrophil-3 (NT-3), ciliary neurotrophic factor (CNTF), or leukemia suppressor factor (LIF).

[0030] As used herein, “pre-fabricated” generally refers to forming components or features before the membrane tissue graft is used in relation to tissue repair. For example, in some embodiments, one or more pre-fabricated attachment points (e.g., one or more pre-fabricated attachment points 104) may be formed or fabricated during the manufacture of the membrane tissue graft. In this way, one or more pre-fabricated attachment points 104 (e.g., pre-fabricated holes 106 and / or one or more pre-fabricated etchings 108) can be formed or defined before the membrane tissue graft 102 is used in relation to tissue repair. In some embodiments, the membrane tissue graft 102 may be manufactured without one or more pre-fabricated attachment points 104 (e.g., pre-fabricated holes 106 and / or pre-fabricated etchings 108), but may have one or more pre-fabricated attachment points 104 (e.g., pre-fabricated holes 106 and / or one or more pre-fabricated etchings 108) fabricated before the membrane tissue graft is packaged and / or transported. In this way, the membrane tissue graft 102 may include one or more pre-fabricated attachment points 104 (e.g., pre-fabricated holes 106 and / or one or more pre-fabricated etchings 108) at the time the membrane tissue graft 102 is provided to the consumer.

[0031] As used herein, “suture hole” or “hole” generally refers to a pre-formed hole or incision in a membranous tissue graft. For example, a surgeon can use a pre-formed suture hole (e.g., pre-formed hole 106) to suture a tissue graft to a target site. A pre-formed suture hole (e.g., pre-formed hole 106) avoids the need to perforate the membranous tissue graft during surgery, thus reducing the possibility of damaging the suture needle with the potential for subsequent tissue damage, and allowing any suture / needle combination to be used with equal ease. Furthermore, referring to the example in Figure 2 and several embodiments, the suture holes (e.g., pre-made holes 106) can be any of the various shapes or combinations of shapes, such as a "+" symbol (e.g., pre-made hole 202), a "-" symbol (e.g., pre-made hole 204), an "x" symbol (e.g., pre-made hole 206), a triangle (e.g., pre-made hole 208), a circle (e.g., pre-made hole 210), a square, a quadrilateral, a semicircle, a wavy line, or a "sawtooth, ratchet" design.

[0032] In some embodiments, suture holes may be located near the outer edge of the membranous tissue graft. In some embodiments, suture holes may be located around the entire circumference of the membranous tissue graft. Also, referring to the example in Figure 3 and some embodiments, suture holes (e.g., pre-fabricated holes 306) may be located along the outer edges of opposing regions of the membranous tissue graft (e.g., membranous tissue graft 302). For example, if the tissue graft is rectangular, suture holes may be located along two opposite sides of the rectangle, but not on the other two opposite sides. Similarly, if the tissue graft is circular, suture holes may be located along a portion of the circumference opposite the center.

[0033] Referring again to the example in Figure 3, in some embodiments, the membranous tissue graft (e.g., membranous tissue graft 302) may be in the form of a tube, and suture holes (e.g., pre-fabricated holes 306) may be located along the edges of the two ends of the tube. Such a graft may be used in nerve repair to connect damaged or severed nerves, and the two edges of the tube may be sutured to the two severed ends of the damaged or severed nerve. While an example of using the graft in this example for nerve repair has been provided, it is understood that membranous tissue grafts may be for any type of tissue repair. For example, in some embodiments, membranous tissue grafts may be used in conjunction with tendon repair.

[0034] Referring to the example in Figure 4 and several embodiments, the membranous tissue graft (e.g., membranous tissue graft 402) may be rectangular in shape, and suture holes (e.g., pre-fabricated holes 406) may be located along two opposite sides of the rectangle. Such a membranous graft can be used in nerve repair by wrapping a severed or damaged nerve such that the sides of the rectangle with suture holes surround the severed portion of the nerve, and these sides are sutured to the two ends of the severed nerve. While examples of wrapping a rectangular membranous tissue graft around a nerve are provided, it is understood that the membranous tissue graft can be wrapped around any tissue. For example, in some embodiments, a rectangular membranous tissue graft can be wrapped around a tendon. Also referring to the example in Figure 5 and several embodiments, suture holes (e.g., pre-fabricated holes 506) may be located around the entire circumference of the rectangular membranous tissue graft (e.g., membranous tissue graft 502). Furthermore, referring to the example in Figure 6 and several embodiments, suture holes (e.g., pre-fabricated holes 606) may be present throughout a rectangular membranous tissue graft (e.g., membranous tissue graft 602). While Figure 6 shows rows and columns of suture holes, it will be understood that suture holes (e.g., pre-fabricated holes 606) may be arranged in any pattern or configuration within the scope of this disclosure.

[0035] In some embodiments, suture holes may be located along the edge of the membrane tissue graft at a distance of about 0.5 mm to about 10 mm, for example, about 1 mm to about 3 mm, and in some embodiments, about 1 mm. However, it is understood that within the technical scope of this disclosure, the suture holes may be located at any distance from the edge of the membrane tissue graft.

[0036] Referring again to the example in Figure 1, in some embodiments, “etching” as used herein generally refers to a site or location within a membrane tissue graft where a portion of the material forming the membrane tissue graft is removed to create an area having a different surface roughness from the surrounding material and thus visually distinguishable from the rest of the membrane tissue graft. In some embodiments, the site of etching (e.g., one or more pre-fabricated etchings 108) does not have to include holes penetrating the membrane tissue graft. For example, in some embodiments, pre-formed etchings (e.g., one or more pre-fabricated etchings 108) may be used as guidance to highlight the location of holes used by a surgeon to properly position the graft on the recipient tissue and / or to suture the graft. Furthermore, etchings (e.g., one or more pre-fabricated etchings 108) may be used as guidance marks to indicate other surgically relevant information, such as the distance between nerve endings within a nerve conduit. Thus, the terms “etching” and “marking” may be used interchangeably within the scope of this disclosure. In some embodiments, the etching (e.g., one or more pre-fabricated etchings 108) can be of various shapes or combinations of shapes, such as squares, triangles, semicircles, etc.

[0037] In certain embodiments, etching or marking may be located near, or positioned near, the outer edge of the tissue graft. However, it is understood that etching may be located around the entire circumference of the tissue graft. Alternatively, etching may be located, or present only along the periphery of opposite sides of the tissue graft. For example, if the tissue graft is rectangular, etching may be located along two opposite sides of the rectangle, but not along the other two opposite sides. Similarly, if the tissue graft is circular or elliptical, etching may be located along a portion of the circumference opposite the center.

[0038] Referring also to the example in Figure 7 and several embodiments, the membranous tissue graft (e.g., membranous tissue graft 702) may be in the form of a tube, and etchings (e.g., one or more pre-fabricated etchings 708) may be present, i.e., positioned along the edges of the two ends of the tube. Such a membranous graft may be used in nerve repair to connect damaged or severed nerves, and the two edges of the tube may be sutured to the two severed ends of the damaged or severed nerve.

[0039] Referring to the example in Figure 8 and several embodiments, the membrane tissue graft (e.g., membrane tissue graft 802) may be rectangular, and etching (e.g., one or more pre-fabricated etchings 808) may be present along two opposite sides of the rectangle, but not along the other two opposite sides. Such a graft can be used for nerve repair by wrapping around a severed or damaged nerve, so that the sides of the rectangle with etching surround the nerve, and these sides can be sutured to the two severed ends of the nerve. While examples of wrapping a membrane tissue graft around a nerve are provided, it is understood that the membrane tissue graft can be wrapped around any tissue. For example, in some embodiments, the membrane tissue graft can be wrapped around a tendon. Also referring to the example in Figure 9 and several embodiments, etching (e.g., pre-fabricated etchings 908) may be present around the entire circumference of a rectangular membrane tissue graft (e.g., membrane tissue graft 902). Furthermore, referring to the example in Figure 10 and several embodiments, etching (e.g., pre-fabricated etching 1008) may be present throughout a rectangular membrane tissue graft (e.g., membrane tissue graft 1002). While Figure 10 shows rows and columns of etching, it will be understood that etching (e.g., pre-fabricated etching 1008) may be arranged in any pattern or configuration within the scope of this disclosure.

[0040] In some embodiments, the etching may be present as a ring along the edge of the membrane tissue graft at a distance of about 0.2 mm to about 1.5 mm, in some embodiments about 0.5 mm to about 1.25 mm, and in some embodiments about 1 mm. The etching may be pre-formed in relation to a pre-formed hole having a width between 50 microns and 1 mm, preferably about 100 microns.

[0041] Referring to the example in Figure 11 and several embodiments, the etched marks (e.g., pre-fabricated etching 1108) are located in the central portion of the membrane tissue graft (e.g., membrane tissue graft 1102) and can guide the placement of the membrane tissue graft in the correct position. One embodiment of the etching marks includes a "dash" of approximately 200 microns × 1 millimeter, which can assist the surgeon in the placement of tissue at measured distances within the membrane tissue graft. For example, one or more etchings can assist the surgeon in placing nerve ends within the membrane tissue graft at measured distances within the membrane tissue graft (e.g., measured distances within membrane tissue graft 1102). In some embodiments, one or more markings can facilitate the placement of multiple tissue ends at measured distances from each other. For example, one or more markings or etchings can assist the surgeon in determining when tissue or nerve ends are within a membrane tissue graft, for example, within 1 millimeter of each other (e.g., within membrane tissue graft 1102, at measured distances from each other, at each end). However, it is understood that one or more markings may be placed to assist the surgeon in determining when multiple tissue ends are within any measured distance from each other and / or from the ends of the membrane tissue graft.

[0042] In some embodiments, a membrane tissue graft may include one or more pre-fabricated attachment points (e.g., one or more pre-fabricated attachment points 104), which may include at least one of one or more pre-fabricated holes (e.g., one or more pre-fabricated holes 106) and one or more etchings (e.g., one or more pre-fabricated etchings 108). For example, referring again to the example in Figure 11, a membrane tissue graft 1102 (e.g., a nerve repair protector tissue graft) may include one or more pre-fabricated holes 1106 and one or more pre-fabricated etchings 1108. In this way, when a surgeon uses one or more pre-fabricated holes 1106 to repair tissue using the membrane tissue graft 1102, they are guided by the orientation of one or more pre-fabricated etchings 1108. In this embodiment, a predetermined spacing is shown between pre-fabricated attachment points of 2 millimeters. However, it is understood that within the scope of this disclosure, any spacing can be used between pre-fabricated attachment points (e.g., pre-fabricated holes 1106 and / or pre-fabricated etchings 1108).

[0043] Furthermore, referring to the example in Figure 12 and several embodiments, the membrane tissue graft 1202 (e.g., a nerve repair connector tissue graft) includes one or more pre-fabricated holes 1206. Referring again to the example in Figure 2, in some embodiments, etching (e.g., etchings 212, 214, 216, 218, 220) can be placed around suture holes (e.g., pre-made holes 202, 204, 206, 208, 210) to increase the visibility of the holes, for example, by using a ring of etched areas surrounding the holes. In such embodiments, by improving the visibility of the holes indicated by etching, the surgeon can suture the membrane tissue graft by suturing through the holes. Alternatively, visual contrast can be provided in a similar manner by using reinforcing areas that include thickened areas (e.g., reinforcing areas 222, 224, 226, 228, 230) of the material forming the tissue graft or substitute material. The reinforcing areas (e.g., reinforcing areas 222, 224, 226, 228, 230) may also include supporting materials such as adhesive or rings of supporting fibers or wires surrounding the holes. The reinforcement area can be any shape surrounding the hole, such as circular, elliptical, oblong, square, triangular, or rectangular.

[0044] In some embodiments, etching and / or suture holes may include additional markings to further enhance the visibility of the etching and / or suture holes. The markings may be positioned and designed to indicate the orientation of the membrane tissue graft. For example, markings in a particular asymmetrical region of a rectangular membrane tissue graft may be used to indicate two surfaces of the membrane tissue graft due to the asymmetrical positioning of the markings.

[0045] In some embodiments, the etching and / or suture holes of the membrane tissue grafts of the present disclosure can facilitate the suturing of the membrane tissue grafts to damaged tissue, such as damaged nerves. Accordingly, methods for using the membrane tissue grafts of the present disclosure, for example, for repairing damaged tissue (e.g., damaged or severed nerves or damaged tendons), are also described.

[0046] In some exemplary embodiments, the disclosure may provide methods for repairing damaged nerves, particularly damaged or severed nerves that have no gap or have a gap between the severed nerve ends, e.g., less than about 5 mm. In these methods, a membrane tissue graft in the form of a tube may be sutured to the severed ends of the damaged nerve. The implantation of such a tissue graft may allow the body's natural healing process to repair the severed nerve by isolating and protecting the severed nerve during the healing process. For example, patient cells may be incorporated into the extracellular matrix to reconstruct and form a tissue similar to neuroepithelium.

[0047] In certain other cases of nerve injury where the damaged nerve has no gap, or has a small gap, for example less than about 5 mm, a rectangular membranous tissue graft is wrapped around the damaged nerve, and such a membrane is sutured to the damaged nerve.

[0048] The implantation of the membranous tissue grafts described herein may protect damaged nerves and reinforce nerve reconstruction. Suture holes may be useful for the use of any suture, particularly when a suture needle is not mechanically suitable for the membranous tissue graft. The membranous tissue graft is designed to protect and isolate, and may separate and protect the damaged nerve from surrounding tissue during the healing process. Patient cells are incorporated into a minimally processed extracellular matrix to reconstruct and form a tissue similar to the epineurium.

[0049] (definition) As used herein, the singular form (one) is intended to include the plural form unless the context explicitly indicates otherwise. Furthermore, to the extent that the terms “include,” “have,” “equip,” or their variations are used in either the detailed description and / or the claims, these terms are intended to be as comprehensive as the term “include.” “Equip,” “essentially equip,” and “consist of” are interchangeable.

[0050] The phrase "essentially consisting of" indicates that the claims include embodiments that involve a particular material or step, and embodiments that do not substantially affect the fundamental and novel features of the claims.

[0051] The term "approximately" means within an acceptable margin of error for a particular value as determined by those skilled in the art, which depends in part on how the value is measured or determined, i.e., the limits of the measurement method. In the context of the sizes of various parameters of membrane tissue grafts in this disclosure, where the term "approximately" is used, these parameters are within a 0-10% variation (margin of error) around the stated value (X ± 10%).

[0052] In this disclosure, ranges are described concisely to avoid having to define a length and describe each and all values ​​within that range. Any suitable value within a range may be chosen as the upper, lower, or terminal value of the range, where appropriate. For example, the range 0.1–1.0 represents the terminal values ​​of 0.1 and 1.0, as well as the intermediate values ​​of 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, and 0.9, as well as all intermediate ranges contained within 0.1–1.0, such as 0.2–0.5, 0.2–0.8, and 0.7–1.0. Values ​​with at least two significant figures are assumed within a range; for example, the range 5–10 represents all values ​​between 5.0 and 10.00, as well as all values ​​between 5.00 and 10.00, including the terminal value.

[0053] Where the scope is used herein, combinations and partial combinations of the scope (e.g., a partial scope within the disclosed scope), and specific embodiments within them are intended to be expressly included.

[0054] All patents, patent applications, provisional applications, and publications referenced or cited herein are incorporated herein by reference in their entirety, including their drawings and tables, unless they conflict with the express disclosure herein.

[0055] The following are examples illustrating the procedures for carrying out embodiments of the present disclosure. These embodiments should not be considered limiting. (Example 1) AxoGuard NerveConnector® (AxoGen, Inc.) improved according to an embodiment of the present invention. Referring again to the example in Figure 12, in some embodiments, the AxoGuard NerveConnector® can provide minimally processed porcine extracellular matrix for ligation support junction of severed or damaged nerves. Several embodiments of the AxoGuard NerveConnector® are described in the brochure entitled “Nerve Repair Solution,” AxoGen Inc (2015). This brochure is incorporated in its entirety herein. To be included.

[0056] In this embodiment, the AxoGuard NerveConnector® may be improved according to embodiments of the present invention by providing one or more attachment points (e.g., etching and / or suture holes). Such improved AxoGuard NerveConnector® may be suitable for treating severed nerves such as severed nerves that have no gap or have a gap between the severed nerve ends, e.g., a gap of less than about 5 mm. The improved AxoGuard NerveConnector® may be in the shape of a tube designed to be implanted into the damaged nerve. The improved AxoGuard Nerve Connector® may have dimensions of 1.5 mm × 10 mm, 2 mm × 10 mm, 3 mm × 10 mm, 4 mm × 10 mm, 5 mm × 10 mm, 6 mm × 10 mm, 7 mm × 10 mm, 1.5 mm × 15 mm, 2 mm × 15 mm, 3 mm × 15 mm, 4 mm × 15 mm, 5 mm × 15 mm, 6 mm × 15 mm, or 7 mm × 15 mm. However, it is understood that the improved AxoGuard NerveConnector® may have any dimensions within the scope of the present invention.

[0057] In some embodiments, the improved AxoGuard NerveConnector® may have etched and / or sutured holes along the edges of the two ends of the tube. (Example 2) AxoGuard NerveProtector® (AxoGen, Inc.) improved according to an embodiment of the present invention. AxoGuard NerveProtector® provides minimally processed porcine extracellular matrix for wrapping or protecting severed or damaged nerves. Specific aspects of AxoGuard NerveProtector® are described in the catalog “Nerve Repair Solution, AxoGen Inc (2015)”. This brochure is entirely as described herein. It will be incorporated into it.

[0058] Referring again to the example in Figure 11, this example may be improved according to embodiments of the present invention by providing one or more attachment points (e.g., etching and / or suture holes). Such improved AxoGuard NerveProtector® may be suitable for wrapping and protecting severed nerves, such as severed nerves that have no gaps or gaps between the severed nerve ends, less than about 5 mm. The improved AxoGuard NerveProtector® can be rectangular in shape when wrapping around a damaged or severed nerve in tubes having sizes of 2 mm × 20 mm, 3.5 mm × 20 mm, 5 mm × 20 mm, 7 mm × 20 mm, 10 mm × 20 mm, 3.5 mm × 40 mm, 5 mm × 40 mm, 7 mm × 40 mm, or 10 mm × 40 mm. However, it is understood that the improved AxoGuard NerveProtector® can have any dimensions within the scope of this disclosure.

[0059] The improved AxoGuard Nerve Connector® can have etching or suture holes along the two sides that surround the nerve and form the two ends of the tube when the improved AxoGuard Nerve Connector® is wrapped around a severed nerve or other tissue.

[0060] The examples and embodiments described herein are for illustrative purposes only, and various modifications or changes in light thereof are proposed to those skilled in the art, but should be understood to be within the scope of the spirit and scope of this application and the appended claims. Furthermore, any constituent element or limitation of any invention or embodiment disclosed herein may be combined with any and / or all other elements or limitations disclosed herein (individually or in any combination) or any other invention or embodiment, and all such combinations are intended within the scope of the present invention, without limiting them.

[0061] (Note) The technical concepts that can be understood from the above embodiments and modified examples are described below. [Item 1] It comprises one or more pre-fabricated attachment points. Membrane tissue grafts.

[0062] [Item 2] The membrane tissue graft described in item 1, Having a thickness of 25 microns to 3 millimeters Membrane tissue grafts.

[0063] [Item 3] The membrane tissue graft described in item 1, Contains natural materials Membrane tissue grafts.

[0064] [Item 4] The membrane tissue graft described in item 3, The aforementioned natural materials are selected from porcine small intestine submucosa, amniotic membrane / chorionic membrane, reconstituted denatured collagen, collagen, elastin, thrombin, fibronectin, starch, poly(amino acids), gelatin, alginate, pectin, fibrin, oxidized cellulose, chitin, chitosan, tropoelastin, hyaluronic acid, fibrin-based materials, collagen-based materials, hyaluronic acid-based materials, glycoprotein-based materials, cellulose-based materials, silk, and combinations thereof. Membrane tissue grafts.

[0065] [Item 5] The membrane tissue graft described in item 1, Includes synthetic materials Membrane tissue grafts.

[0066] [Item 6] A membrane tissue graft as described in item 5, The synthetic material is selected from silicone resin, stretched polytetrafluoroethylene (ePTFE), polyethylene terephthalate tetraphthalate (Dacron), polyurethane aliphatic polyester, poly(amino acid), poly(propylene fumarate), copro(ether ester), polyalkylene oxalate, polyamide, tyrosine-derived polycarbonate, poly(iminocarbonate), polyorthoester, polyoxaester, polyamide ester, polyoxaester containing an amine group, poly(anhydride), polyphosphazene, and mixtures thereof. Membrane tissue grafts.

[0067] [Item 7] The membrane tissue graft described in item 1, Contains one or more bioactive ingredients that facilitate the repair of damaged tissue. Membrane tissue grafts.

[0068] [Item 8] The membrane tissue graft described in item 1, The one or more pre-fabricated attachment points include one or more pre-fabricated suture holes. Membrane tissue grafts.

[0069] [Item 9] The membrane tissue graft described in item 1, The one or more pre-fabricated attachment points are positioned near the outer edge of the membrane tissue graft. Membrane tissue grafts.

[0070] [Item 10] The membrane tissue graft described in item 1, The membrane tissue graft is tubular in shape, and the one or more pre-fabricated attachment points are arranged along the edges of the two ends of the tubular tissue. Membrane tissue grafts.

[0071] [Item 11] The membrane tissue graft described in item 1, The aforementioned membrane tissue graft is rectangular, The one or more pre-fabricated attachment points are positioned along two opposite sides of the rectangular membrane tissue graft, but not along the other two opposite sides. Membrane tissue grafts.

[0072] [Item 12] The membrane tissue graft described in item 1, The one or more pre-fabricated attachment points are positioned along the edge of the membrane tissue graft, at a distance of 0.5 mm to 10 mm from the edge. Membrane tissue grafts.

[0073] [Item 13] The membrane tissue graft described in item 1, The one or more pre-fabricated attachment points are placed on the membrane tissue graft and include one or more markings configured to increase the visibility of the one or more pre-fabricated attachment points. Membrane tissue grafts.

[0074] [Item 14] A membrane tissue graft as described in item 13, The membrane tissue graft is tubular in shape, and the one or more markings are positioned along the edges of the two ends of the tubular tissue. Membrane tissue grafts.

[0075] [Item 15] A membrane tissue graft as described in item 13, The aforementioned membrane tissue graft is rectangular, The one or more markings are positioned along two opposite sides of the rectangular membrane tissue graft, but not along the other two opposite sides. Membrane tissue grafts.

[0076] [Item 16] A membrane tissue graft as described in item 13, The one or more markings are positioned along the edge of the tissue graft at a distance of 0.5 mm to 10 mm from the edge. Membrane tissue grafts.

[0077] [Item 17] A membrane tissue graft as described in item 13, The one or more markings indicate the orientation of the membrane tissue graft. Membrane tissue grafts.

[0078] [Item 18] A membrane tissue graft as described in item 13, The one or more markings are positioned to assist the user in positioning the tissue at the measured distance within the membrane tissue graft. Membrane tissue grafts.

[0079] [Item 19] A membrane tissue graft as described in item 18, The one or more markings facilitate the arrangement of multiple tissue ends that are at a measured distance from each other. Membrane tissue grafts.

[0080] [Item 20] The membrane tissue graft described in item 1, The one or more pre-fabricated attachment points include one or more pre-fabricated suture holes and one or more markings. Membrane tissue grafts.

[0081] [Item 21] A method for repairing damaged and / or severed nerves, A method comprising the step of implanting a membrane tissue graft having one or more pre-fabricated attachment points onto the damaged and / or severed nerve.

[0082] [Item 22] The method described in item 21, The damaged and / or severed nerves have gaps ranging from 0 to 5 millimeters. method.

Claims

1. It is a membrane tissue graft, The main body is made of the material, The membrane tissue graft includes one or more pre-fabricated attachment points arranged only along the edges of the main body of the membrane tissue graft, The membrane tissue graft wherein the one or more pre-fabricated attachment points are the only openings in the membrane tissue graft.

2. The aforementioned membrane tissue graft is tubular in shape. The membrane tissue graft according to claim 1, wherein the one or more pre-fabricated attachment points are arranged along the edges of the two ends of the tube.

3. The aforementioned membrane tissue graft is rectangular, The membrane tissue graft according to claim 1, wherein the one or more pre-fabricated attachment points are arranged along two or more sides of the rectangular membrane tissue graft.

4. The aforementioned membrane tissue graft is rectangular, The membrane tissue graft according to claim 1, wherein the one or more pre-fabricated attachment points are arranged along two opposite sides of the rectangular membrane tissue graft and are not present along the other two opposite sides.

5. The membrane tissue graft according to claim 1, wherein the one or more pre-fabricated attachment points are arranged along the edge of the membrane tissue graft at a distance of approximately 0.5 mm to approximately 10 mm from the edge.

6. The membrane tissue graft according to claim 1, wherein the material is selected from the group consisting of small intestinal submucosa, amniotic membrane, chorionic membrane, reconstituted denatured collagen, collagen, elastin, thrombin, fibronectin, starch, poly(amino acids), gelatin, alginate, pectin, fibrin, oxidized cellulose, chitin, chitosan, tropoelastin, hyaluronic acid, fibrin-based materials, collagen-based materials, hyaluronic acid-based materials, glycoprotein-based materials, cellulose-based materials, silk, silicone resin, stretched polytetrafluoroethylene (ePTFE), polyethylene terephthalate tetraphthalate (Dacron®), polyurethane aliphatic polyester, poly(propylene fumarate), copro(ether ester), polyalkylene oxalate, polyamide, tyrosine-derived polycarbonate, poly(iminocarbonate), polyorthoester, polyoxaester, polyamide ester, poly(anhydrous), polyphosphazene, and mixtures thereof.

7. It is a membrane tissue graft, One or more pre-fabricated attachment points, Including one or more regions, Each region has a surface roughness different from the surface roughness of other parts of the membrane tissue graft, and one or more of the regions having different surface roughnesses, To increase the visibility of the one or more pre-fabricated attachment points; To guide the placement of the membrane tissue graft into the recipient tissue; The orientation of the membrane tissue graft is determined; To assist in positioning one or more nerve ends at a measured distance within the aforementioned membrane tissue graft; and / or This facilitates the placement of multiple nerve ends within the aforementioned membrane tissue graft at measured distances from one another. A membrane tissue graft, configured for use.

8. The membrane tissue graft according to claim 7, wherein each of the one or more regions is thinner than the membrane tissue graft in the other portion.

9. The membrane tissue graft according to claim 7, wherein each of the one or more regions is formed by removing at least a portion of the material forming the membrane tissue graft.

10. The membrane tissue graft according to claim 7, wherein the one or more pre-fabricated attachment points include one or more pre-fabricated suture holes or cuts.

11. The membrane tissue graft according to claim 7, wherein the membrane tissue graft comprises a natural material.

12. The membrane tissue graft according to claim 11, wherein the natural material is one or more of the following: porcine small intestine submucosa, amniotic membrane / chorionic membrane, reconstituted denatured collagen, collagen, elastin, thrombin, fibronectin, starch, poly(amino acids), gelatin, alginate, pectin, fibrin, oxidized cellulose, chitin, chitosan, tropoelastin, hyaluronic acid, fibrin-based material, collagen-based material, hyaluronic acid-based material, glycoprotein-based material, cellulose-based material, silk, and combinations thereof.

13. The membrane tissue graft according to claim 7, wherein the membrane tissue graft comprises a synthetic material.

14. The membrane tissue graft according to claim 13, wherein the synthetic material is one or more of the following: silicone resin, stretched polytetrafluoroethylene (ePTFE), polyethylene terephthalate tetraphthalate (Dacron®), polyurethane aliphatic polyester, poly(amino acid), poly(propylene fumarate), copro(ether ester), polyalkylene oxalate, polyamide, tyrosine-derived polycarbonate, poly(iminocarbonate), polyorthoester, polyoxaester, polyamide ester, polyoxaester containing an amine group, poly(anhydride), polyphosphazene, and mixtures thereof.

15. The membrane tissue graft according to claim 7, wherein the one or more pre-fabricated attachment points are arranged only along the edge of the membrane tissue graft.

16. The aforementioned membrane tissue graft is tubular in shape. The membrane tissue graft according to claim 15, wherein the one or more pre-fabricated attachment points are arranged along the edges of the two ends of the tube.

17. The aforementioned membrane tissue graft is rectangular, The membrane tissue graft according to claim 15, wherein the one or more pre-fabricated attachment points are arranged along two or more sides of the rectangular membrane tissue graft.

18. The aforementioned membrane tissue graft is rectangular, The membrane tissue graft according to claim 15, wherein the one or more pre-fabricated attachment points are arranged along two opposite sides of the rectangular membrane tissue graft and are not present along the other two opposite sides.

19. The membrane tissue graft according to claim 15, wherein the one or more pre-fabricated attachment points are arranged along the edge of the membrane tissue graft at a distance of approximately 0.5 mm to approximately 10 mm from the edge.

20. The membrane tissue graft according to claim 7, wherein the one or more pre-fabricated attachment points include a plurality of pre-fabricated suture holes located across the edges and central portion of the membrane tissue graft.

21. The membrane tissue graft according to claim 20, wherein the plurality of pre-fabricated suture holes are arranged in rows and columns.

22. The membrane tissue graft according to claim 20, wherein the plurality of pre-fabricated suture holes are of approximately the same size.

23. The membrane tissue graft according to claim 20, wherein at least some of the plurality of pre-fabricated suture holes are of different sizes.

24. The membrane tissue graft according to claim 20, wherein the plurality of pre-fabricated suture holes are spaced apart from each other at regular intervals.

25. The membrane tissue graft according to claim 7, wherein the membrane tissue graft has a thickness of 25 microns to 3 millimeters.

26. The membrane tissue graft according to claim 7, further comprising one or more bioactive components that facilitate the repair of damaged tissue.

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