Patent Publication Number: US-2018049731-A1

Title: Closing device for tissue openings

Description:
This application is a continuation-in-part and claims the benefit of priority of U.S. application Ser. No. 14/748,992 and PCT US2015/037378, both filed on Jun. 24, 2015, which each claim the benefit of priority of U.S. Provisional Application Ser. No. 62/018,986, entitled “Expandable Mesh with Locking Feature,” filed Jun. 30, 2014. This application is also a continuation-in-part and claims the benefit of priority of U.S. application Ser. No. 15/099,068, entitled “Systems and Methods for Facilitating Closure of Bodily Openings,” filed Apr. 14, 2016, which is a continuation of U.S. application Ser. No. 13/096,433 filed Apr. 28, 2011, which claims the benefit of priority of U.S. Provisional Application Ser. No. 61/343,435, filed Apr. 29, 2010, and 61/379,243, filed Sep. 1, 2010. This application is also a continuation-in-part and claims the benefit of priority of U.S. application Ser. No. 15/602,457, entitled “Closing Device for Tissue Openings,” filed May 23, 2017. All of the above-listed applications are incorporated herein by reference in their entireties. 
    
    
     BACKGROUND 
     The present embodiments relate generally to medical devices, and more particularly, to an expandable mesh that may be used in a variety of procedures. For example, the present application discloses structure and methods for closing internal tissue openings, including a closure with two connected mesh structures that may be used to close a minimally-invasive surgical opening in the heart or other organ. 
     There are many instances in which it may be desirable to deliver an expandable mesh into a human or animal body. By way of example, and without limitation, such expandable meshes may be used to treat perforations in tissue or bodily walls that are formed intentionally or unintentionally. 
     Perforations in tissue or bodily walls may be formed intentionally or unintentionally. For example, an unintentional abdominal hernia may be formed in the abdominal wall due to any of a number of reasons, or intentional perforations may be formed, for example, during surgical procedures such as translumenal procedures. Attempts to seal perforations have been attempted by coupling a graft member to tissue. The graft material may completely overlap with the perforation, and the edges of the graft material may at least partially overlap with tissue surrounding the perforation. The graft material then may be secured to the surrounding tissue in an attempt to effectively cover and seal the perforation. In order to secure the graft material to the surrounding tissue, sutures commonly are threaded through the surrounding tissue. However, such manual suturing techniques may be time consuming and/or difficult to perform. 
     There is a hernia repair method commonly referred to as a “mesh plug” or “plug and patch” repair technique, in which a surgeon uses a mesh plug to fill the perforation. Potential advantages include fewer sutures and less tissue dissection. However, a mesh plug alone may not effectively cover the entire area of the perforation, or alternatively, the mesh plug may shrink, become loose, or poke into adjacent tissue. 
     Minimally-invasive surgical procedures have been developed for placement of medical devices inside a patient or other therapeutic or diagnostic purposes, as a way of reducing trauma to a patient. In such procedures, holes are made and accessed by catheters or similar devices, and treatment devices are passed through the catheters to the site of interest. When the procedure or a part of it is concluded, the access catheter is removed and the hole repaired. 
     Devices and methods have been described for suturing such holes to close them. However, such devices and methods are commonly very difficult to use in such limited spaces. To avoid sutures, devices have been developed to plug or cover such holes, to allow the hole to heal naturally or incorporate some or all of such plugs into the tissue. Such items have been effective, but may be difficult to place, particularly when both sides of a hole must be closed. 
     SUMMARY 
     The present embodiments provide a system for facilitating closure of a bodily opening. In one embodiment, the system comprises an anchor having a deployed state dimensioned for engaging tissue surrounding the opening, a first tether coupled to the anchor and extending proximally therefrom, and may include a graft member comprising a first bore disposed therein. The anchor may comprise a width that is larger than a width of the opening such that the anchor is disposed securely within or distal to the opening. The first tether is dimensioned to be disposed through the graft member, such that the graft member can be advanced distally over the first tether. The graft member may be secured to the anchor. 
     In one embodiment, the anchor comprises a plug of material including a plurality of filaments. The plug of material may comprise a diamond shape as initially prepared, in a pre-deployment state it can be positioned in a catheter or other delivery tube and take on a cylindrical shape, and have a deployed state having an increased width relative to the pre-deployment state. As the anchor emerges from the delivery tube, it will relax and begin to take the initial diamond shape, and will flatten as it is pulled against a tissue opening, as will be discussed further below. In an alternative embodiment, the anchor comprises a plurality of deployable members that are biased radially outward in the deployed state. 
     Particular embodiments provide an expandable mesh comprising a first coupling element, a second coupling element, and an intermediate portion disposed between the first coupling element and the second coupling element. Proximal retraction of the first coupling element relative to the second coupling element causes the intermediate portion to flare out to an enlarged width. Distal extension of the second element while maintaining position of the first coupling element can also be used to accomplish flaring to an enlarged width. 
     In one embodiment, the first coupling element comprises a first tube and the second coupling element comprises a second tube. In one example, the first tube, the second tube, and the intermediate portion each originate from the same mesh material. In one example the intermediate portion comprises untreated mesh material, and the first and second tubes are formed from treating the mesh material in a manner that maintains a tubular shape of the first and second tubes. At least one of the first tube or the second tube may be formed by melting or heat-shrinking the mesh material. 
     The expandable mesh may comprise a delivery state in which the first and second tubes lack an axial overlap, and further may comprise an expanded state in which the first and second tubes at least partially axially overlap. In one embodiment, a distal end of the first tube transitions into a first end of the intermediate portion, and a second end of the intermediate portion transitions into a distal end of the second tube. 
     The expandable mesh may comprise first and second ends. In one example, the expandable mesh may have a first state in which the first end is positioned proximal to the second end, and an everted second state in which the second end is positioned proximal to the first end. 
     The first and second tubes may be dimensioned to be secured together using a friction fit when the first tube is proximally retracted relative to the second tube. In one embodiment, one of the first and second tubes comprises a constant diameter along its length, while the other of the first and second tubes comprises a tapered shape. In an alternative embodiment, both the first and second tubes comprise tapered shapes, wherein the first tube is dimensioned to be disposed at least partially within the second tube when the first tube is proximally retracted relative to the second tube. 
     A system may be used with the expandable mesh. The system may comprise a first tether secured to the first coupling element, wherein proximal retraction of the first tether causes proximal retraction of the first coupling element relative to the second coupling element. Further, the system may comprise a graft material having a first bore formed therein, dimensioned for advancement over the first tether to permit the graft material to be advanced relative to the first coupling element. 
     The system may comprise a second tether coupled to the anchor, where the first tether is disposed through a first bore in the graft member and the second tether is disposed through a second bore in the graft member. The graft member may be advanced over the first and second tethers toward the anchor, and the first and second tethers are tied together to secure the graft member to the anchor. 
     Advantageously, an enhanced anchor and graft member attachment may be achieved to better treat the opening. For example, the anchor is capable of expanding to securely engage the opening. Additionally, the expanded anchor is secured to the graft member in a manner that may reduce the rate of migration of the anchor. 
     The devices disclosed as anchors or mesh elements can be part of systems or devices for closing tissue openings. For example, particular embodiments are disclosed of a closure device including a distal collapsible mesh element, a proximal collapsible mesh element, and a tether or stem that connects and is used to pull the two mesh elements together, sandwiching a hole to be sealed. The distal mesh element has two ends that are inverted into the mesh body interior. The mesh fibers at each of the ends are fused together or otherwise narrowed with a bonding or fusing operation such as shape-setting with heat, such as in the shape of tubes as noted above. Radiopaque markers (e.g. cylindrical markers) may be embedded in the fused ends. In particular embodiments, these ends are both inverted into the body of the distal mesh element. The distal end of the distal mesh element is used to anchor the distal end of the tether or stem. The proximal end of the distal mesh may be covered (internally or externally) with a material to seal and/or promote healing (e.g. small intestine submucosa [SIS]). 
     The proximal mesh element has a distal end that is inverted into the body of the proximal mesh element. The end is fused in an identical or similar manner to the ends of the distal mesh element and may also have a radiopaque marker. The distal end of the proximal mesh element may also be covered (internally or externally) with a material to seal and/or promote healing. In particular embodiments, the proximal end of the proximal mesh element is also fused or otherwise narrowed and incorporates a radiopaque marker, but is not inverted, as it is then able to fit into a relatively smaller delivery catheter or tube. It will be understood that the proximal end could be inverted in some embodiments. The proximal fused or narrowed end serves as an eventual conduit for the tether. 
     The tether has a distal end, which may be enlarged (e.g. with a bead, node or knot) and may be fixed to the distal end of the distal mesh element, has a cross-sectional enlargement (e.g. a bead, node or knot) at or near its proximal end. The tether also has a loop feature in particular embodiments that is a part of or adjacent to that proximal enlargement to allow attachment to a trigger or control line. Such a line may be a wire (e.g. of biocompatible metal), filament (e.g. a suture) or other line of a material that can be effectively used for pulling or controlling parts of the device. The line is used to pull the tether through the proximal end of the proximal mesh element as a delivery tool or device pushes and compresses the proximal mesh element. The proximal enlargement is pulled through the fused proximal end of the proximal mesh element and provides a lock or stop for the proximal mesh element once tension on the tether is released. 
     The delivery tool delivers the mesh elements in a stacked manner. The closure device is stacked within the tool with the distal mesh element residing in a distal peel-away catheter (e.g. 14 French), and the proximal mesh element residing in a sheath (e.g. 12 French). An access sheath, e.g. for pericardial access, having an anchoring balloon is (or has previously been) placed through a tissue hole to be closed. When the tool is inserted through the access sheath, which is anchored by its balloon on the distal side of the hole, the peel-away catheter is removed so that the distal mesh element sits within the sheath through the hole and is pushed by the sheath holding the proximal mesh element. The distal mesh element is pushed out of the sheath through the hole to a site distal to the hole to be sealed. The tether is then slightly retracted which serves to compress the distal mesh element against the distal end of the access sheath. The distal mesh element is thereby expanded. After deflating the balloon, the two sheaths are pulled back through the hole, which pulls the distal mesh element against the tissue and seals the hole. 
     In embodiments in which one or both sheaths include a fluid pathway, a contrast medium may be moved through that pathway to the site to allow visualization (e.g. by fluoroscopy) so as to check the seal created by the distal mesh element. After confirming a seal, and confirming that the sheath tips are on the proximal side of the hole, the proximal mesh element is pushed out of its sheath with a smaller inner tube or sheath (e.g. 9 French), alone or with further retraction of the sheath that held the proximal mesh element. Tension is maintained on the tether or stem via the control line throughout to ensure that the distal mesh element maintains a seal of the hole. The inner tube or sheath continues to push the proximal end of the proximal mesh element so as to advance that proximal end over the control line and ultimately over the proximal enlargement on the tether or stem, locking the mesh elements together. A final contrast injection can be made to confirm the seal of the hole, and an end of the control line is released to allow it to unloop from the tether or stem end. 
     In particular embodiments, the tether or stem may have multiple enlargements (e.g. knots, beads or nodes) to allow variable amounts of tightening of the mesh elements together. The proximal end of the proximal mesh element may have reliefs cut into it to allow some expansion as enlargement(s) of the tether or stem are pulled through that proximal end, and/or have a tapered hole to favor unidirectional movement of the tether or stem enlargement(s) through. Other gripping, attachment or reversion preventers or minimizers may be used, such as a barb, claw or corkscrew in the proximal end of the proximal mesh element to engage the tether or stem. A handle of the delivery device or tool may have one or more actuators or other mechanisms to promote performing deployment steps in the proper order and to minimize the chance of premature deployment or release of any component during the procedure. 
     As examples, a closure for an opening in tissue can include a first closure element, the first closure element having a first mesh enclosure, the first mesh enclosure having a first distal narrowed end and a second proximal narrowed end and a central volume. Each of the first and second ends are inverted so as to be within the central volume of the first mesh enclosure, and each of the first and second ends are surrounded by respective external surfaces of the first mesh enclosure. A second closure element has a second mesh enclosure with a third distal narrowed end and a fourth proximal narrowed end and a central volume. The third end is inverted so as to be within the central volume of the second mesh enclosure, and each of the third and fourth ends are surrounded by respective external surfaces of the second mesh enclosure. A tether joins the first and second closure elements in an initial configuration prior to delivery of the closure elements to the opening. The tether has first and second enlarged ends, wherein the tether extends through the first, second and third narrowed ends so that the first enlarged end of the tether is outside the first closure element adjacent or engaging the first end and the second enlarged end of the tether is within the central volume of the second closure element. The first closure element is adapted to engage a distal side of the tissue having the opening, and the second closure element is adapted to engage a proximal side of the tissue, and the tether is adapted to pass through the opening. 
     The mesh for the closure elements and the material for the tether or stem are preferably bioresorbable. As the closure elements are formed or prepared, a heat-annealing or shape-set process may be performed on them so that even though compressed or otherwise fitted within a delivery device, the closure elements naturally expand when deployed from the delivery device. 
     A sheet of bioresorbable material (e.g. the graft, seal or healing material referred to herein) may be fixed to the first closure element adjacent or over the second narrowed end. Such a sheet can be fixed to an external or internal surface or portion of the first mesh enclosure, or to an internal or external surface or portion of the second mesh enclosure, or to both mesh enclosures. The enlarged ends of the tether can be or include a bead or a knot. A control line or wire is looped through the second enlarged end of the tether, and may pass through the fourth narrowed end. The closure device is preferably initially fitted within a delivery device. The ends of the first closure element may be aligned with each other, and/or the ends of the second closure element may be aligned with each other. In other embodiments, the ends of the first closure element may be laterally offset with respect to each other, or one of those ends may be larger in diameter than the other. 
     An example of a device for closing an opening in tissue can include a delivery device having a first peel-away catheter, a second tube within the first peel-away catheter, and a pusher tube within the second tube, along with a closure device as disclosed herein fitted within the delivery device. For instance, a first closure element may be within the first peel-away catheter and a second closure element within the second tube. A control line may be looped through the second enlarged end of the tether. A control cannula may extend through the pusher tube, with the control line extending through the control cannula. The control line can extend from the control cannula and returns to the control cannula from the second enlarged end of the tether, so that a free end of the control line is within the control cannula. 
     Unlike available systems which use a single mesh construct or container with two collapsible disks to form distinct regions, particular embodiments described herein use two independent mesh constructs linked by a suture or other filament. The mesh constructs do not share any mesh or surface area This provides several advantages. For example, only a suture with its small diameter, rather than a much larger expanding-diameter mesh portion, sits between the independent mesh constructs to tether them together for delivery. The small suture diameter means there is little or no distention of the hole to be closed. Further, if the hole is not straight (e.g., substantially perpendicular to the adjacent tissue surface(s)), but is instead diagonal or crooked with respect to adjacent surface(s), the suture will not tend to deform the hole or its opening(s). As another example, the independent meshes allow spacing between each to be adjusted, particularly when the meshes are flattened in use as described below. This allows for such embodiments to accommodate a range of thicknesses of tissue through which the hole extends. As another example, with two independent mesh constructs each can conform to their respective surfaces independently. If the opposing (e.g. inside and outside) tissue surfaces are not parallel or are angled with respect to each other, for example where the tissue through which the hole extends is of variable thickness near or around the hole, each mesh construct can conform to its respective tissue surface independently. Neither mesh pulls on the other in such a configuration, lessening the likelihood of damage to the tissue. 
     Whether denoted as a “plug,” “anchor,” “mesh,” “closure member” or similar term, what is intended is a device for closing a hole in tissue. Other systems, methods, features and advantages of the invention will be, or will become, apparent to one with skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, features and advantages be within the scope of the invention, and be encompassed by the following claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The invention can be better understood with reference to the following drawings and description. The components in the figures are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. Moreover, in the figures, like referenced numerals designate corresponding parts throughout the different views. 
         FIGS. 1-5  are side-sectional views illustrating exemplary method steps that may be used to facilitate closure of an opening using a system according to a first embodiment comprising an anchor and a graft member. 
         FIG. 6  is a side view of a mesh disposed over a first mandrel. 
         FIG. 7  is a side view of the mesh after formation of a first tube. 
         FIG. 8  illustrates eversion of a portion of the mesh, with the first tube depicted in a side view and other mesh material shown in a side-sectional view. 
         FIGS. 9-10  illustrate exemplary method steps, with first and second tubes depicted in a side view and other mesh material also shown in a side view. 
         FIG. 11  illustrates the mesh in a delivery state, with the mesh shown in a side view and an insertion tool shown in a side-sectional view. 
         FIG. 12  illustrates deployment of the mesh, with the first tube depicted in a side view, and the second tube, other mesh material and the insertion tool shown in side-sectional views. 
         FIGS. 13-14  illustrate advancement of a graft member over a first tether coupled to the mesh, with the first tube depicted in a side view, and the second tube, other mesh material and the insertion tool shown in side-sectional views. 
         FIGS. 15A-15C  are side views of alternative first and second tube configurations. 
         FIG. 16  is a perspective view of an embodiment of a closure device described herein. 
         FIG. 17  is a side view of an embodiment of a mesh portion prior to being formed into a part of the embodiment of  FIG. 16 . 
         FIG. 18  is a side part-cross-sectional view of a portion of the embodiment of  FIG. 16 . 
         FIG. 19  is a side part-cross-sectional view of a portion of the embodiment of  FIG. 16  with an alternative joining member. 
         FIG. 20  is a side part-cross sectional view of an alternative closure element that can be used in the embodiment of  FIG. 16 . 
         FIG. 21  is a side part-cross sectional view of an alternative closure element that can be used in the embodiment of  FIG. 16 . 
         FIG. 22  is a side part-cross sectional view of an alternative closure element that can be used in the embodiment of  FIG. 16 . 
         FIG. 23  is a side part-cross-sectional view of a delivery device with the embodiment of a closure device of  FIG. 16  fitted within it, in an initial stage of insertion into a patient. 
         FIG. 24  is a view of the embodiment of  FIG. 23  in a later stage of deployment compared to  FIG. 23 . 
         FIG. 25  is a view of the embodiment of  FIG. 23  in a later stage of deployment compared to  FIG. 24 . 
         FIG. 26  is a view of the embodiment of  FIG. 23  in a later stage of deployment compared to  FIG. 25 . 
         FIG. 27  is a view of the embodiment of  FIG. 23  in a later stage of deployment compared to  FIG. 26 . 
         FIG. 28  is a schematic representation of a portion of the delivery device embodiment shown in  FIG. 23 . 
         FIG. 29  is a side part-cross-sectional view of a portion of the delivery device embodiment of  FIG. 23  with additional structure. 
         FIG. 30  is a side part-cross-sectional view of a portion of the delivery device embodiment of  FIG. 23  with additional structure. 
     
    
    
     DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS 
     For the purposes of promoting an understanding of the principles of the disclosure, reference will now be made to the embodiments illustrated in the drawings and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the claims is thereby intended, and alterations and modifications in the illustrated devices and methods, and further applications of the principles of the disclosure as illustrated therein are herein contemplated as would normally occur to one skilled in the art to which the disclosure relates. 
     In the present application, the term “proximal” refers to a direction that is generally towards a physician during a medical procedure, while the term “distal” refers to a direction that is generally towards a target site within a patent&#39;s anatomy during a medical procedure. Thus, “proximal” and “distal” portions of a device or bodily region may depend on the point of entry for the procedure (e.g., percutaneously versus laparoscopically or endoscopically). Additionally, it is noted that when manufacturing a device according to one embodiment, an eversion step is performed whereby a portion that was originally a distal region of the device becomes a proximal region. For clarity, with respect to  FIGS. 6-15C  the region that is originally near a proximal end will be referred to as the first end, while the region that is originally near a distal end will be referred to as the second end. 
     Referring now to  FIGS. 1-5 , systems and methods are described for facilitating closure of a bodily opening according to a first embodiment. The system comprises an anchor or closure member  20 , which has pre-deployment and deployed states. In the pre-deployment state, the anchor  20  comprises a generally diamond shape having a proximal region  22 , a distal region  24 , and side regions  26  and  28 , and further comprising a height h and a width w, as shown in  FIG. 1 . In this example, the anchor  20  may be formed of a plug of material, such as a plurality of filaments  21  that are woven together in a manner that allows compression of the filaments with respect to each other when a sufficient force is applied. In one embodiment, in the pre-deployment state the height h between the proximal and distal regions  22  and  24  may be about the same or greater than the width w between the side regions  26  and  28 . Preferably, the width w of the anchor  20  in the pre-deployment state is greater than a width w o  of an opening  75  formed in tissue  74 . As will be explained further below, by oversizing the width w of the anchor  20  relative to the width w o  of the opening  75 , the anchor  20  may be frictionally held in place within or covering the opening  75 . Moreover, the width w of the anchor  20  may be further increased in the deployed state using an actuator  40 , as explained further in  FIG. 3  below, to further enhance the frictional engagement with the tissue  74  surrounding the opening  75 . 
     The anchor  20  can be fashioned from absorbable and non-absorbable mesh or biologic implant with or without spars of absorbable or non-absorbable material to help it retain its shape and anchorage. The mesh can be shaped like an umbrella or diamond. The deployed expanded shape can be maintained with suture material or a locking mechanism or through the inherent shape and orientation of the spars. In addition, the anchor  20  can be fashioned out of absorbable or non-absorbable spars or a metallic material (e.g., nitinol, stainless steel etc.) shaped as an umbrella, diamond or any shape that expands in diameter after deployment which can be deformed and compressed when placed into the deployment instrument and will then return to its expanded shape after deployment in the defect. In addition, legs of the anchor  20  can have small hooks or tines at the ends to catch on the surrounding tissue. The anchor can be made in multiple sizes for different depth and/or diameter defects. 
     The system further comprises a first tether  30  coupled to the anchor  20  and extending proximally therefrom, as shown in  FIGS. 1-5 . The first tether  30  is sized to be disposed through a first bore  81  in a graft member  80 , thereby enabling distal advancement of the graft member  80  over the first tether  30  towards the anchor  20  after the anchor  20  has been deployed within the opening  75 , as explained further in  FIGS. 4-5  below. Optionally, a second tether  32  similarly may be coupled to the anchor  20 , and disposed through a second bore  82  in the graft member  80 . After distal advancement of the graft member  80  over the first and second tethers  30  and  32  toward the anchor  20 , the first and second tethers  30  and  32  may be tied, thereby securing the graft member  80  in place relative to the anchor  20 , as explained further in  FIG. 5  below. In one example, the first and second tethers  30  and  32  each comprise monofilament sutures, though they can comprise single fibers or woven fibers, may be biodegradable, and have other suitable characteristics to perform the functions herein. 
     Optionally, the system may comprise an actuator  40  for laterally expanding the anchor  20  between the pre-deployment and the deployed states. In one example, the actuator  40  comprises a suture  42  having a distal region comprising a loop member  44 , which may extend around the distal region  24  of the anchor  20  as shown in  FIG. 1 . The loop member  44  is coupled to a tensioning member  46  that is disposed adjacent to the proximal region  22  of the anchor  20 . In use, the tensioning member  46  may be advanced distally over the suture  42  to reduce the overall diameter of the loop member  44 , thereby moving the proximal region  22  towards the distal region  24  to reduce the height h, while increasing the width w between the side regions  26  and  28 , as explained further in  FIG. 3  below. 
     In the example shown, the opening  75  is a hernia located in the tissue  74  of the abdominal wall. While treatment of a hernia is shown for illustrative purposes, it will be apparent that the systems described herein may be used in a wide range of medical procedures, including open, laparoscopic, endoscopic, percutaneous and luminal procedures, and including but not limited to any exemplary procedures described herein. 
     The initial stages of hernia repair may be performed using various techniques, for example, an open technique, a laparoscopic technique, an endoscopic technique, or a percutaneous technique. In an open technique, an incision may be made in the patient, e.g. an abdominal or chest wall and the hernia may be repaired using generally known principles. In a laparoscopic technique, two or three smaller incisions may be made to access the surgical site. A laparoscope may be inserted into one incision, and surgical instruments may be inserted into the other incision(s). In an endoscopic technique, an endoscope may be advanced through a bodily lumen such as the alimentary canal, with an access hole being created through tissue to obtain access to the surgical site. One or more components, such as the insertion tool  70 , may be advanced through a working lumen of the endoscope. The percutaneous approach is similar to the laparoscopic approach, but in the percutaneous approach the insertion tool  70  may be advanced directly through a patient&#39;s skin. In particular, with the components loaded, the insertion tool  70  is advanced directly through the abdominal skin, through the tissue  74 , and may be advanced just distal to the opening  75  and into the peritoneum. In order to optimally visualize the insertion tool  70 , a laparoscopic viewing device may be positioned in the peritoneum, or an endoscope may be translumenally advanced in proximity to the target site, as noted above. Alternatively, the insertion tool  70  and markers disposed thereon may be viewed using fluoroscopy of other suitable techniques. A transluminal approach, e.g. for the heart, may include accessing the vasculature of the patient and advancing tools through the vasculature to the surgical site, e.g. through a catheter. 
     After gaining access to the opening  75  using any of the above-referenced techniques, an insertion tool  70 , such as a catheter or a needle, may be used to deliver one or more of the components of the system. If a needle is used, it may be an endoscopic ultrasound (EUS) or echogenic needle, such as the EchoTip® Ultrasound Needle, or the EchoTip® Ultra Endoscopic Ultrasound Needle, both manufactured by Cook Endoscopy of Winston-Salem, N.C. 
     The anchor  20  is disposed within a lumen of the insertion tool  70 , as illustrated in the dashed delivery state  20 ′ of the anchor, shown in  FIG. 1 . The anchor may be advanced within the lumen of the insertion tool  70 , e.g., using a stylet, and then is ejected from a distal end of the insertion tool  70 . The anchor  20  assumes its pre-deployment state, as shown in  FIG. 1 . At this time, the first and second tethers  30  and  32 , along with the suture  42  of the actuator  40 , each extend proximally through the lumen of the insertion tool  70  for manipulation by a physician. 
     Referring to  FIG. 2 , the anchor  20  is advanced distally by a suitable device, such as a pusher tube, insertion tool, forceps or other grasping instrument. The anchor  20  is positioned within the opening  75 , as shown in  FIG. 2 . Advantageously, the anchor  20  is diamond-shaped in the pre-deployment state, such that the distal region  24  is tapered to facilitate entry into the opening  75 . Since the width w of the anchor  20  preferably is greater than the width w o  of the opening  75  in the pre-deployment state, a force may be applied, e.g., using the pusher tube, insertion tool, forceps or other grasping instrument, to urge the anchor  20  in place so that at least the side regions  26  and  28  securely engage the tissue  74  surrounding the opening  75 , as shown in  FIG. 2 . Alternatively, the anchor  20  may be deployed distal to the opening  75 , in which case the anchor can assume a diameter larger than the opening  75  and provide anchoring functionality just distal to the tissue  74  with the same method steps otherwise being performed as shown herein. 
     Referring to  FIG. 3 , in a next step the actuator  40  is actuated to laterally expand the anchor  20 , thereby further securing the anchor  20  within the opening  75  and/or distal to the opening  75 . In particular, the tensioning member  46  is advanced distally over the suture  42  to reduce the overall diameter of the loop member  44 , thereby moving the proximal region  22  towards the distal region  24  to reduce the height h, while increasing the width w between the side regions  26  and  28  of the anchor  20  to enhance a secure fit between the side regions  26  and  28  of the anchor  20  and the tissue  74  surrounding the opening  75 . An increased width w of the anchor  20  in the deployed state of  FIG. 3  may provide an increased frictional engagement with tissue disposed within the opening  75 . 
     Preferably, the tensioning member  46  comprises a one-way movement feature, such as a cinching or ratcheting mechanism, to prevent proximal movement of the tensioning member  46  relative to the anchor  20  after deployment. Alternatively, the tensioning member  46  may comprise a rubber disc or beaded member, which may frictionally engage an exterior surface of the suture  42 , but may be advanced distally over the suture  40  with a suitable external force. After actuating the actuator  40 , the suture  42  may be cut by a suitable device, such as laparoscopic scissors, leaving the anchor  40  in place as shown in  FIG. 3 . 
     Referring to  FIGS. 4-5 , in a next step the graft member  80  may be advanced distally over the first and second tethers  30  and  32  towards the anchor  20 . Properties of suitable graft members  80  are described in detail below. The graft member  80  comprises first and second bores  81  and  82 , as noted above, which are sized to permit advancement of the graft member  80  over the first and second tethers  30  and  32 , respectively. 
     In use, proximal ends of the first and second tethers  30  and  32  are disposed through the first and second bores  81  and  82  of the graft member  80  outside of the patient, and the graft member  80  is advanced distally relative to the first and second tethers  30  and  32 . The graft member  80  may be delivered through the insertion tool  70 , as depicted by the dashed lines of a graft member  80 ′ in the delivery state in  FIG. 4 . Alternatively, the graft member  80  may be delivered directly through a trocar, e.g., a 5 mm trocar. When ejected from the insertion tool  70  or the trocar, the graft member  80  then is positioned in place relative to the tissue  74  using a suitable grasping device, or a pusher tube or the insertion tool  70  itself, such that the graft member  80  is adjacent to the tissue  74  and covering the opening  75 , as shown in  FIG. 4 . 
     In a next step, a suture tying device may be used to tie the first and second tethers  30  and  32  together in a manner that secures the graft member  80  adjacent to the tissue  74  and the anchor  20 . By way of example, and without limitation, one suitable suture tying device is disclosed in U.S. patent application Ser. No. 12/125,525, filed May 22, 2008, the disclosure of which is hereby incorporated by reference in its entirety. Another suitable suture tying device is disclosed in U.S. patent application Ser. No. 12/191,001, filed Aug. 13, 2008, the disclosure of which is hereby incorporated by reference in its entirety. Upon completion of the tying procedure, the first and second tethers  30  and  32  may be cut by a suitable device, such as laparoscopic scissors, leaving the anchor  40  and the graft member  80  in place as shown in  FIG. 5 . 
     Advantageously, using the anchor  20 , the first and second tethers  30  and  32 , and the graft member  80  in combination, along with the techniques described, an enhanced anchor and graft member attachment may be achieved to comprehensively treat the opening  75 . In this example, the anchor  20  is capable of expanding to fill the opening  75 , potentially resulting in better tissue ingrowth and lower rates of recurrence. Moreover, the anchor  20  is secured within the opening  75  in an expanded, secure manner that may reduce anchor migration. Further, the coupling of the anchor  20  to the graft member  80  provides an enhanced seal relative to a plug alone, and the secure attachment of the anchor  20  to the graft member  80  may further reduce the rate of migration of the anchor  20 . 
     The graft member  80  may comprise any suitable material for covering the opening  75  and substantially or entirely inhibiting the protrusion of abdominal matter. In one embodiment, the graft member  80  may comprise small intestinal submucosa (SIS), such as BIODESIGN® SURGISIS® Tissue Graft, available from Cook Biotech, Inc., West Lafayette, Ind., which provides smart tissue remodeling through its three-dimensional extracellular matrix (ECM) that is colonized by host tissue cells and blood vessels, and provides a scaffold for connective and epithelial tissue growth and differentiation along with the ECM components. The graft member  80  may be lyophilized, or may comprise a vacuum pressed graft that is not lyophilized. In one example, the graft member  80  would be a one to four layer lyophilized soft tissue graft made from any number of tissue engineered products. Reconstituted or naturally-derived collagenous materials can be used, and such materials that are at least bioresorbable will provide an advantage, with materials that are bioremodelable and promote cellular invasion and ingrowth providing particular advantage. Suitable bioremodelable materials can be provided by collagenous ECMs possessing biotropic properties, including in certain forms angiogenic collagenous extracellular matrix materials. For example, suitable collagenous materials include ECMs such as submucosa, renal capsule membrane, dermal collagen, dura mater, pericardium, fascia lata, serosa, peritoneum or basement membrane layers, including liver basement membrane. Suitable submucosa materials for these purposes include, for instance, intestinal submucosa, including small intestinal submucosa, stomach submucosa, urinary bladder submucosa, and uterine submucosa. The graft member  80  may also comprise a composite of a biomaterial and a biodegradeable polymer. Additional details may be found in U.S. Pat. No. 6,206,931 to Cook et al., the disclosure of which is incorporated herein by reference in its entirety. 
     While the exemplary embodiments herein have illustrated the use of one or more systems for covering an opening  75  formed in the abdominal wall, the systems disclosed herein may be useful in many other procedures. Solely by way of example, the systems may be used to treat perforations in a visceral wall, such as the stomach wall. Further, the systems  20  may be used to secure a graft member to tissue for reconstructing local tissue, and the like. 
     An example of a mesh device usable as an anchor or closure device  20  is shown in  FIG. 6 . Referring to that figure, a mesh  520  having a first end  522  and a second end  524  is provided. The mesh  520  may be disposed over a first mandrel  590  having an outer diameter D 1 , such that the first end  522  is initially disposed proximal to the second end  524 . The mesh  520  can be fashioned from absorbable or non-absorbable mesh or biologic implant. By way of example, and without limitation, the mesh material may comprise polypropylene, polyethylene, glycolide/L-lactide copolymer, PTFE, nylon, polyurethane, PEEK, PLGA, PGA, polycaprolactone, carbothane, polydioxanone, or any copolymer of the aforementioned list. 
     Referring to  FIG. 7 , in a next step, the first end  522  of the mesh  520  is made to form a first coupling element  530 . In this example, the first coupling element  530  is in the form of a first tube  530 . However, it will be appreciated that the first coupling element  530  may take a form different than a tubular shape. For reference purposes below, the first coupling element  530  will be referenced as a first tube  530 , although it is not intended to limit the shape of the first coupling element  530  to tubular form. 
     Since the first tube  530  is formed around the first mandrel  590 , the first tube  530  comprises an inner diameter that is only slightly larger than the outer diameter D 1  of the first mandrel  590 . Further, the first tube  30  comprises an outer diameter D A , as shown in  FIG. 7 . 
     The first tube  30  is formed such that it comprises a length X 1 , as shown in  FIG. 7 . In a presently preferred embodiment, the length X 1  is less than half of the overall length of the mesh  520 , where the overall length is measured between the most proximal and distal endpoints of the mesh  520  in a flattened state of  FIG. 6 . Preferably, the length X 1  of the first tube  530  is between about 5.0 percent and about 33.0 percent of the overall length of the mesh  520  in the flattened state. In this manner, the length X 1  of the first tube  530  can most effectively cooperative with a subsequently formed second tube  40  and an intermediate portion  550 , as will be explained further below. 
     In one exemplary technique, the first end  522  of the mesh  520  may be secured as the first tube  50  by melting or heat-shrinking the mesh material upon itself along the first end  522 . In alternative embodiments, the first end  522  of the mesh  520  may be secured as the first tube  530  using a separate biocompatible adhesive, one or more biocompatible sutures, or other mechanisms that can maintain the structural integrity of the tubular shape for the purposes explained below. 
     Referring now to  FIG. 8 , in a next step, the mesh  520  may be at least partially everted by moving the second end  524  proximally beyond the first end  522 . In this manner, the second end  524  is brought radially over and around the first tube  50 , as shown in  FIG. 8 . Therefore, in this eversion step, the second end  524  of the mesh  520  that was originally a distal region of the device has become a proximal region. 
     Referring to  FIGS. 9-10 , the second end  524  then is made into a second coupling element  540 , for example, in a manner similar to which the first end  522  was made into the first coupling element  530 . In this example, the second coupling element  540  is in the form of a second tube  540 . However, it will be appreciated that the second coupling element  540  may take a form different than a tubular shape. For example, the second coupling element  540  may comprise a solid inner diameter, and still may engage an inner surface of the first coupling element  530  using a friction fit, as explained below. For reference purposes below, the second coupling element  540  will be referenced as a second tube  540 , although it is not intended to limit the shape of the second coupling element  540  to tubular form. 
     In one embodiment, the mesh  520  is disposed over a second mandrel  92  having an outer diameter D 2 , as shown in  FIG. 9 . Upon manufacture, the second tube  40  comprises an inner diameter D B , as shown in  FIG. 10 , which is only slightly larger than the outer diameter D 2  of the second mandrel  592 . Like the first tube  530 , the second tube  540  may be secured in the tubular manner by melting or heat-shrinking the mesh material upon itself along the second end  524 , or alternatively, by using a separate biocompatible adhesive, one or more biocompatible sutures, or other mechanisms that can maintain the structural integrity of the tubular shape for the purposes explained below. 
     The outer diameter D A  of the first tube  530  is dimensioned to engage the inner diameter D B  of the second tube  540  using a friction fit, as explained further in  FIG. 12  below. To accomplish the friction fit, the outer diameter D A  of the first tube  530  may be approximately equal to the inner diameter D B  of the second tube  40 , thereby allowing the outer diameter D A  of the first tube  530  to snugly engage the inner diameter D B  of the second tube  540 . In the embodiment of  FIGS. 6-14 , the first and second tubes  530  and  540  are depicted as being generally cylindrical with constant diameters along their lengths. In the alternative embodiments of  FIGS. 15A-15C  below, various alternative configurations of the first and second tubes  530  and  540  are described. 
     Referring still to  FIGS. 9-10 , the second end  524  of the mesh  520  is secured in the tubular manner such that the second tube  540  comprises a length X 2 . In one embodiment, the length X 2  is less than half of the overall length of the mesh  250 , where (as noted above) the overall length is measured between the most proximal and distal endpoints of the mesh  520  in a flattened state of  FIGS. 6-7 . Preferably, the length X 2  of the second tube  540  is between about 10.0 percent and about 38.0 percent of the overall length of the mesh  520  in the flattened state. 
     An intermediate portion  550  of the mesh  520 , which is neither part of the first tube  30  nor the second tube  540 , remains after formation of the first and second tubes  530  and  540 . The intermediate portion  550  of the mesh  520  may comprise the original mesh material, e.g., untreated by heat or other techniques used to form the tubes  530  and  540 , and spans from the distal end  534  of the first tube  530  to the distal end  544  of the second tube  540 , as shown in  FIG. 9 . 
     The intermediate portion  550  of the mesh  520  includes the everted portion of the mesh, as shown in  FIGS. 9-10 , and may comprise between about 29.0 percent to about 85.0 percent of the overall length of the mesh  520 , i.e., the total length of the mesh  520  minus the lengths of the first and second tubes  530  and  540 . The desired length of the intermediate portion  550  of the mesh  520  may be selected based on a particular application, for example, closure of a bodily opening of a certain diameter. As will be explained further with respect to  FIGS. 12-14 , the intermediate portion  550  of the mesh  520  will flare radially outward to a width w to perform its intended purpose. As will be understood, the final deployed width w of the device is related to the overall length of the intermediate portion  550 , i.e., if the length of the intermediate portion  550  is relatively large then the device can flare to a relatively large width w, whereas if the length of the intermediate portion  550  is relatively small then the device can flare to a relatively small width w. 
     Further, it is noted that an axial spacing X 3  is provided between the first and second tubes  530  and  540 , as shown in  FIGS. 9-10 . The spacing X 3  provides a distance for retraction of the first tube  530  relative to the second tube  540 , as explained further in  FIG. 12  below. By varying the spacing X 3 , the deployed width w of the intermediate portion  550  may be varied accordingly. For example, if a relatively large axial spacing X 3  is provided, then the first tube  530  must be retracted a relatively long distance before securely engaging the second tube  540 , and during this relatively long distance the intermediate portion  550  has additional time and length to flare out to a greater width w. 
     Referring to  FIGS. 10-11 , a first tether  560  is coupled to the first tube  530 , either on an inner or outer surface of the first tube  530 . The first tether  560  extends proximally from the first tube  530 , is disposed through the second tube  540 , and extends further proximally along a length of an insertion tool  570  for actuation by a physician. A distal region of the first tether  560  may be coupled to the first tube  530  using an adhesive, mechanical member or other suitable techniques. 
     In a delivery state, the mesh  520  is housed within a lumen  572  of the insertion tool  570 , as shown in  FIG. 11 . The insertion tool  570  may comprise a catheter, needle or other suitable insertion member, as noted above. 
     The insertion tool  570  may be advanced to a target site using various known techniques, depending on the desired treatment modality. For example, and without limitation, in one embodiment the mesh  520  may be used to treat an opening  575  of a hernia within tissue  574  of the abdominal wall, as depicted in  FIG. 12 . While treatment of a hernia is explained for illustrative purposes with respect to certain embodiments, it will be apparent that the systems described herein may be used in a wide range of medical procedures, as previously noted, including but not limited to repair of cardiac tissue, e.g. a right atrial appendage or any other exemplary procedures described herein. 
     The initial stages of the hernia repair may be performed using various techniques, with examples noted above. After gaining access to the opening  575  or target site using any of the above-referenced techniques, the insertion tool  570  may be used to deliver the mesh  520 . The mesh  520  may be advanced within the lumen  572  of the insertion tool  570 , e.g., using a stylet, and then may be positioned such that the second tube  540  is aligned near the distal end  573  of the insertion tool  570 . At this time, a majority of the intermediate portion  550  of the mesh  520  may be disposed distally beyond the distal end  573  of the insertion tool  570 . As will be appreciated, the distal end  573  of the insertion tool  570 , and any of the first and second tubes  530  and  540 , may comprise radiopaque markers or features that facilitate visualization of relative components positions by a physician during such delivery. 
     Referring to  FIG. 12 , in a next step, the first tether  560  is retracted proximally to cause the first tube  530  to be retracted proximally relative to the second tube  540 . Optionally, a stylet may be provided within the lumen  572  of the insertion tool  570  to abut the proximal end  542  of the second tube  540  to hold it steady during retraction of the first tether  560  and coupled first tube  530 . This causes the first tube  530  to engage the second tube  540 , as depicted in  FIG. 12 . 
     As the first tether  560  is proximally retracted and the first tube  530  is retracted proximally relative to the second tube  540 , the intermediate portion  550  of the mesh  520  expands radially outward to the width w, as depicted in  FIG. 12 . Locking of the first and second tubes  530  and  540  relative to one another consequently fixes the width w of the intermediate portion  550 , and therefore the intermediate portion  550  is retained in its deployed state. 
     As explained in detail above, the first and second tubes  530  and  540  may comprise diameters that are dimensioned to securely engage each other with a friction fit, and may comprise constant diameters or tapered shapes to facilitate a secure engagement upon retraction of the first tube  530  relative to the second tube  540 . A secure engagement between the first and second tubes  530  and  540  therefore may be provided. 
     In addition to, or in lieu of, the friction fit noted above, another locking mechanism may be used to securely hold the first and second tubes  530  and  540  relative to each other. For example, and without limitation, an exterior surface of the first tube  530  may engage an interior surface of the second tube  540  using a one-way ratcheting mechanism, which can permit incremental securement to incrementally adjust the width w of the intermediate portion  550  of the mesh  520 . An example of interlocking components  539  and  549  of a ratchet arrangement is shown in the embodiment of  FIG. 15C  below. 
     If the mesh  520  is used to treat the opening  575  of a hernia within tissue  574  of the abdominal wall, the intermediate portion  550  of the mesh  520  may be anchored within the opening  575  of the hernia and/or distal to the opening  575 . If deployed within the opening  575 , the width w of the mesh  520  may be larger than an inner diameter of the opening  575  to secure the mesh  520  within the opening  575  using a friction fit. Alternatively, the mesh  520  may be deployed distal to the opening  575 , as depicted in  FIGS. 12-13 , in which case the mesh  520  can assume a diameter larger than the opening  575  and provide anchoring functionality just distal to the tissue  574 . 
     Referring to  FIGS. 13-14 , in a next step, a graft member  580  may be advanced distally over the first tether  560  towards the mesh  520 . Properties of suitable graft members  580  are described in detail below. The graft member  580  comprises a first bore  581 , which is sized to permit advancement of the graft member  580  over the first tether  560 . 
     In use, the proximal end of the first tether  560  is disposed through the first bore  581  of the graft member  580  outside of the patient, and the graft member  580  is advanced distally relative to the first tether  560 . The graft member  580  may be delivered through the insertion tool  570 . Alternatively, the graft member  580  may be delivered directly through a trocar, e.g., a 5 mm trocar. When ejected from the insertion tool  570  or the trocar, the graft member  580  then is positioned in place relative to the tissue  574  using a suitable grasping device, or a pusher tube or the insertion tool  570  itself, such that the graft member  80  is adjacent to the tissue  574  and covering the opening  575 , as shown in  FIG. 13 . In a next step, a suture tying device may be used to tie a knot for the first tether  60  to hold the graft member  580  in place. 
     Optionally, a second tether (not shown) may be provided in a similar manner to the first tether  560 . In this embodiment, the graft member  580  may comprise a second bore, whereby the first bore  581  of the graft member  580  is advanced over the first tether  560  and the second bore of the graft member  580  is simultaneously advanced over the second tether. In this example, a suture tying device may be used to tie the first and second tethers together in a manner that secures the graft member  580  adjacent to the tissue  574  and the mesh  520 . By way of example, and without limitation, one suitable suture tying device is disclosed in U.S. Pat. No. 8,740,937, the disclosure of which is hereby incorporated by reference in its entirety. Upon completion of the tying procedure, the one or more tethers may be cut by a suitable device, such as laparoscopic scissors, leaving the mesh  520  and the graft member  580  in place as shown in  FIG. 14 . 
     Advantageously, using the mesh  520 , the first tether  560  (and optionally a second tether), and the graft member  580  in combination, along with the techniques described, an enhanced mesh anchoring and graft member attachment may be achieved to comprehensively treat the opening  575 . Further, the coupling of the mesh  520  to the graft member  580  provides an enhanced seal relative to a plug alone, and the secure attachment of the mesh  520  to the graft member  580  may further reduce the rate of migration of the mesh  520 . 
     The graft member  580  may comprise any suitable material for covering the opening  575  and substantially or entirely inhibiting the protrusion of abdominal matter. Particular embodiments are discussed above with respect to graft member  80 . 
     While the exemplary embodiments herein have illustrated the use of an expandable mesh  520  for covering an opening  575  formed in the abdominal wall, the expandable mesh  520  disclosed herein may be useful in many other procedures. Solely by way of example, the expandable mesh  520  may be used to treat perforations in a visceral wall, such as the stomach wall, or could be used to treat heart defects, to prevent a duodenal sleeve from migrating, for securing a graft member to tissue for reconstructing local tissue, or various other procedures that can benefit from such an expandable mesh. 
     Referring to  FIGS. 15A-15C , alternative embodiments are shown in which the first tube  530  and/or the second tube  540  lack constant diameters. In the embodiment of  FIG. 15A , an alternative second tube  540 ′ comprises a tapered shape between proximal and distal ends  542 ′ and  544 ′, wherein the distal end  544 ′ has an inner diameter than is larger than an inner diameter of the proximal end  542 ′. In this embodiment of  FIG. 15A , the inner diameter of the distal end  544 ′ of the second tube  540 ′ may be larger than the outer diameter D A  of the first tube  530  to allow the first tube  530  to be proximally retracted within the distal portion of the second tube  540 , however, the inner diameter of the proximal end  542 ′ of the second tube  540 ′ may be smaller than the outer diameter D A  of the first tube  530  so that the first tube  530  could not be proximally retracted beyond the proximal end  542 ′ of the second tube  540 ′. In this manner, the first tube  530  may frictionally engage a region of the second tube  540 ′ between the proximal and distal ends  542 ′ and  544 ′. 
     In a further alternative embodiment of  FIG. 15B , an alternative first tube  530 ′ may comprise a tapered shape between its proximal and distal ends  532 ′ and  534 ′. A diameter at the proximal end  532 ′ is smaller than a diameter at the distal end  534 ′ to permit retraction into the second tube  540 . 
     In the embodiment of  FIG. 15C , both first and second tubes  530 ″ and  540 ″ are tapered with proximal diameters being smaller than distal diameters. Further, in the embodiment of  FIG. 15C , an exterior surface of the first tube  530 ″ may engage an interior surface of the second tube  540 ″ using a one-way ratcheting mechanism using interlocking components  539  and  549 . Such a one-way ratcheting mechanism can permit incremental securement to incrementally adjust the width w of the intermediate portion  550  of the mesh  520 . In addition to the friction fit and one-way ratcheting mechanism options, it is contemplated that other coupling methods may be used to secure the first and second tubes together, including but not limited to magnetic couplings, knobs or beads that interlock in notches, or other mechanical arrangements. 
     Examples of closure elements are disclosed below, which may use elements or features described above. For example, mesh  520  with ends  530  as described above may be used as (or as part of) the closure elements  720 ,  722  discussed below. 
     Referring generally to the drawings, there are shown embodiments of parts of a system  720  for closing a hole in tissue, for example cardiac tissue. Such a system may include one or both of a closure device  722  and a placement device  724 . As will be discussed further below, closure device  722  is initially placed within placement device  724 . When placement device  724  is adjacent or through a tissue opening, closure device  722  is moved out of placement device  724  to cover the tissue opening, and is fixed in place to permit or promote healing. 
     Closure device  722  in the illustrated embodiment is a two-piece device, having a first or distal closure element  730  and a second or proximal closure element  732 , which can be similar or identical to, in whole or in part, anchor  20  and/or mesh  520  described above. “Distal” and “proximal” in this context are defined as above, referring to relative position with respect to the direction of travel of closure device  722  and/or placement device  724 , “distal” being generally toward or beyond a tissue hole or opening to be closed, and “proximal” being generally toward the operator along that direction of travel. Closure element  730  is intended to engage tissue and cover an opening through it on the distal side of the tissue, i.e. the side beyond a hole through the tissue. Closure element  732  is intended to engage tissue and cover an opening through it on the proximal side of the tissue, i.e. the side approached first by placement device  724 . Closure elements  730  and  732  are linked together prior to insertion into a patient&#39;s body or on or into a delivery device in particular embodiments, as discussed further below. 
     Closure element  730  in the illustrated embodiment is made of a mesh  734 , and in particular embodiments are bioresorbable, non-bioresorbable, and/or of a biologic material. Such materials may be or include those described above with respect to anchor  20  and/or mesh  520 , e.g., polypropylene, polyethylene, glycolide/L-lactide copolymer, PTFE, nylon, polyurethane, PEEK, PLGA, PGA, polycaprolactone, carbothane, polydioxanone, or copolymers of such constituents. Mesh  734  as illustrated includes a number of interstices  736  among a solid but flexible material that are or have the appearance of crossed strand(s) or similar linear member(s)  737 . 
     Closure element  730  has first and second ends  738 ,  740  in the illustrated embodiment which are narrowed or closed. In one example, a sheet or length of mesh  734  is rolled or otherwise formed around an axis into a cylinder or other longitudinally closed shape having opposing open ends  738  and  740 . In such embodiments, mesh  734  has a central volume  742  between ends  738  and  740 . End  738  is narrowed or closed to form a tube (e.g. with a passage), a closed mass, or other tip. For example, narrowing or closing can be accomplished by heat-shrinking a portion of end  738  to form a tube with a passage having a diameter substantially smaller than a nominal diameter of central volume  742 , e.g. one-third to one-tenth of such nominal diameter or smaller. As another example, narrowing or closing can be accomplished by chemically or thermally fusing end  38  to form a closed mass as a tip. Techniques such as those described above and/or in U.S. patent application Ser. No. 14/748,992 may be used. End  40  is similarly narrowed or closed, preferably to form a tube with a small passage through it. Closure element  30  thus has an intermediate portion  44  of mesh  34  longitudinally in between narrowed or closed ends  38  and  40 , with volume  42  being within intermediate portion  44  and bounded by mesh  34 . 
     In particular embodiments, end  738  (and potentially other end(s) of closure elements  730 ,  732 ) is or includes a radiopaque marker. For example, such a marker may be a tube of biocompatible metal (e.g. gold, platinum, tungsten-, zinc-, iron-, and/or magnesium-based metals) or appropriate bioresorbable materials. Exemplary markers have open ends and an interior and exterior, and in some embodiments include a side opening through a side wall. It is encased by mesh  734  of the particular closure element. Such integration is possible where the mesh  734  is able to exist as a fluid mass and can undergo a phase change to a solid mass. With end portion of mesh  734  treated to become a fluid mass (as by heating, chemical curing, or applying electric or magnetic fields), pressure is applied to direct the fluid mass into and around the tubular marker, e.g. in or through the open ends and/or the side opening. The fluid mass then undergoes a phase change to solid (as by cooling) so that the solid mesh material encases the tubular marker. The interior of the marker may be occluded by the mass entirely, or a lumen can be left through the encased marker. In this way, the marker is securely anchored with respect to the mesh  34  while covering any rough edges on the marker. Such markers serve to indicate when the ends of one or both of closure elements  730 ,  732  are pulled together, e.g. to indicate the shape of the compressed or collapsed mesh and indicate if the mesh compression is distorted. 
     Closure element  730  in the illustrated embodiment is double-inverted, meaning that each end  738 ,  740  is inverted so that the narrowed or closed portions point into or are within volume  742 . For example, closure member  730  may be made by forming a sheet of mesh  734  into a tube with open ends (which will become ends  738  and  740 ). In that tube form, there is an exterior surface  746  with edges  747  surrounding an inner space, which will form the volume  742  of closure member  730 . An interior surface  48  faces that volume  742 . Forming an inverted end includes turning the edge  747  into the inner space, so that the edge is inside of a portion of the interior surface  748 . The end is narrowed or closed, as noted above (e.g. by heat-shrinking, chemical treatment), so that the edge remains inside volume  742  of closure  730 . In such an example, a portion of the exterior  746  of the mesh  734  folds over itself, and a curved or folded part of that exterior  746  forms an exterior end  750  of closure  730 , with end  738  inverted into volume  742 . It will be understood that the narrowing or closing of the end(s) can occur prior to or after inversion. As noted, closure element  730  is double-inverted, so that end  40  is also inverted identically or similar to end  738 . 
     In particular embodiments, some or all of closure element  730  includes a sheet or mass of therapeutic or healing material  754  (e.g. graft material  80 ,  580  discussed above) which may at least partially block fluid flow and/or assist in tissue growth and contribute or assist the healing process. As an example, a sheet, layer or other portion of SIS (small intestinal submucosa) may be placed to line the inside of mesh  734  (e.g. within volume  742 ) or fixed to an outside portion of mesh  734 . A layer  754  is indicated in  FIG. 16  fixed to the outside of mesh  734  to cover most or all of the surface around end  740 , or at least so that when closure element  730  is flattened as discussed further below, the sheet  754  covers at least part of a tissue opening to be repaired or healed. 
     Closure element  732  is for proximal placement, i.e. on the side of the tissue that is first reached or approached by placement device  724 , and is similar to closure element  730  in particular embodiments. For example, closure element may be identical or essentially identical to closure element  730  as described above, having mesh  734  as a body enclosing a central volume  752 , with first and second ends  758 ,  760  in the illustrated embodiment which are narrowed or closed. In a particular embodiment, closure element  732  is similar to closure element  730  as described above, but has one inverted end  758  and one non-inverted end  760  (see  FIGS. 16, 19 ). End  758  is inverted and closed or narrowed as described above. End  760  is closed or narrowed as described above, but an exterior surface of mesh  734  of closure element  732  is not folded in on itself, and so end  760  does not enter or point into volume  752 . Rather, in this embodiment end  760  points generally away from volume  752 . In a particular embodiment, ends  758  and  760  are aligned along a common longitudinal axis that extends through volume  752 . It will be understood that in other embodiments closure element  732  is double-inverted, like closure element  730 , rather than single-inverted. 
     Closure elements  730  and  732  are joined by a filament or tether  764  in specific embodiments. Tether  764  has two ends  766 ,  768  that are enlarged, as with knots or beads, that are at least slightly larger than any opening through ends  738 ,  740 ,  758 ,  760  of closure elements  730 ,  732 . Additional beads, knots or other enlarged portions may be present between ends  766  and  768  for adjustability in locking closure elements  730 ,  732 . Tether  764  extends through end  738  of closure element  730 , with end  766  of tether  764  outside of volume  742  and within, engaged with or beyond end  738  of element  730 , so as to be fixed or otherwise connected to end  738 . From end  738 , tether  764  passes through both ends  738  and  740  and volume  742  of element  730 . From closure element  730 , tether  764  extends across any gap that may exist between closure elements  730  and  732 , and then passes through end  758  and into volume  752  of closure element  732 . It will be understood that in embodiments in which tether  764  is fixed to end  738  of closure element  732 , other ways of fixation such as adhesives or fusion, could be used to fix tether  764  to end  738  or another part of closure element  730 . In the illustrated embodiment, tether  764  is connected to end  738  at a point within the inner space created by the fold of the inversion of end  738 . Tether  764  is not fixed with respect to end  740  of closure element  730 , but can be moved through end  740 , as by pulling. Likewise, tether  764  is not fixed to end  758  of closure member  732 , but can be moved through ends  758  and end  768  of tether  764  can be forced through end  760  of closure element  732 , as by pulling. Pulling on tether  764  can collapse closure member  730  toward closure member  732  and toward tissue between members  730  and  732 . 
     As will be discussed further below, a tensioning or control line  770  is looped through end  768  of tether  764 , passing into and out of closure element  732  via the opening through end  750  of closure element  732 . In particular embodiments, line  770  passes through a bight, hole or knot in tether  764 . When line  770  is pulled or otherwise placed in tension, it places tension on tether  764  and thereby pulls on end  738  of closure member  730 , pulling or flattening closure member  730  toward tissue and closure member  732 . Control line  770  is also a part of the procedure to flatten closure element  732  with respect to tissue, as will be discussed further below. 
     In an alternative embodiment, a filament in the form of a solid stem  764 ′ is provided in place of tether  764 . Stem  764 ′ in the illustrated embodiment has an elongated body  765 ′ with a flat end  766 ′ and an opposite end  768 ′. In the illustrated embodiment body  765 ′ and ends  766 ′ and  768 ′ are monolithic, e.g. formed or created as a single piece of the same material. Such materials are preferably a bio-resorbable material that has sufficient strength to hold the two closure elements  730 ,  732  together for a time sufficient to allow the closure elements  730 ,  732  to be encapsulated and sealed by bodily tissue. Body  765 ′ includes one or more protrusions  769 ′ to act as stop points or barbs between end  768 ′ and flat end  766 ′. In particular embodiments, protrusions  769 ′ have surfaces facing flat end  766 ′ that are perpendicular to or form an acute angle with a longitudinal axis of body  765 ′, to form stop surfaces as will be discussed further below. End  768 ′ is adapted to be engaged to a suture or control line  770  (as discussed further below), for example having a loop, bight or eye through which control line  770  can extend and/or be attached to body  765 ′. Flat end  766 ′ in a particular embodiment is substantially planar along a surface  771 ′ that adjoins body  765 ′, and convexly curved along a surface  772 ′ opposite surface  771 ′. 
     In this embodiment, stem filament  764 ′ is fixed to or otherwise engaged with closure member  730 . For example, body  765 ′ is inserted through the closed or narrowed end  738  of closure member  730 , with flat end  766 ′ abutting a portion of closure element  730  that is distal of the inverted end  738  so as to anchor stem  764  to the closure element  730 . Body  765 ′ extends through closure element  730  and into or through closure element  732  in an initial condition, and is adapted to extend through and away from end  750  of closure element  732  when placed in the body. In particular embodiments, body  765 ′ can extend through each of ends  738 ,  740 ,  758 ,  760  of the closure elements  730 ,  732 , and in other embodiments body  765 ′ need not pass through one or more of those ends, but can pass through the mesh of one or more parts of closure elements  730 ,  732 . 
     When closure device  722  is initially prepared, end  768  of tether  764  or protrusions  769 ′ of body  762 ′ extend at least through end  738  and into volume  742  of closure element  730 . Control line  770  extends from tether  764  or body  765 ′, and depending on how far tether  764  or body  765 ′ is initially placed through closure element  730  and/or  732 , line  770  extends through closure element  730  and  732 , exiting closure element  732  via narrowed or closed end  760 . As closure elements  730 ,  732  are being placed, they are compressed so that tether  764  or stem  764 ′ holds one or both of them in a compressed state. For example, once closure element  730  is placed (as discussed further below), line  770  may be pulled, so that tether  764  or stem  764 ′ is pulled, and end  766  of tether  764  or one or more protrusions  769 ′ of body  765 ′ are forced through end  760  or another portion of closure element  732 . End  766  of tether  764  or flat end  766 ′ of stem  764 ′ pulls the distal portion (or end  738 ) of closure element  730  toward the proximal portion (or end  740 ) of closure element  730 , compressing closure element  730 . One or more protrusions  769 ′ can engage a proximal portion (or end  740 ) of closure element  730  to prevent re-expansion of closure member  730 . Similarly, further pulling of line  770  can draw body  765 ′ through a distal portion (or end  758 ) of closure element  732  and/or through a proximal portion (or end  760 ) of closure element  732  to compress closure element  732  on itself and/or toward closure element  730 , to finally fix closure device  722  against tissue. Thus, tether  764  or stem  764 ′ passes between and within closure elements  730 ,  732 , with end  766  of tether  764  or flat end  766 ′ of stem  764 ′ on the distal outside of closure element  730 , and at least one protrusion  769 ′ of body  765 ′ on the proximal outside of closure member  732 . 
     The inventors have further found that there is an advantage in some uses of closure device  722  of reducing the compressed, in-use height of one or both of closure elements  730 ,  732 . By “height” in this context is meant the dimension measured outward from the tissue to which the closure elements are applied. To address those cases where space is minimal or where a smaller closure is otherwise indicated, closure element  730  is prepared so that ends  738  and  740  are offset from each other within volume  742 . As seen in  FIG. 20 , ends  738  and  740  are inverted and narrowed or closed as described above but are arranged non-symmetrically, so that each end  738 ,  740  is to one side of the other. This allows closure element  730  to be compressed so that ends  738  and  740  move past each other, with less or no contact or other interference with each other as compared to a configuration as described above in which ends  738 ,  740  are aligned or coaxial. In this embodiment, tether  764  or stem  764 ′ is fixed to end  738 , as discussed above, but does not extend through end  740 . Rather, tether  764  or stem  764 ′ passes through mesh  734  alongside end  740 , and on to closure element  732 , as discussed above. It will be understood that a similar configuration could also or instead be applied to closure element  732 . 
     In another embodiment ( FIG. 21 ), closure element  730  has ends  738  and  740  that are aligned, but with one of the ends  738  or  740  of a larger diameter than the other. For example, end  740  is inverted and narrowed as discussed above, to a given diameter. End  738  is inverted and narrowed as discussed above to a diameter smaller than that of narrowed end  740 . Tether  764  or stem  764 ′ extends through both ends  738  and  740 . When closure element  730  is compressed, end  738  is pulled toward end  740  so that end  738  enters at least partially into end  740 . It will be understood that in other embodiments end  740  may be smaller than end  738 , and that similar configuration(s) could also or instead be applied to closure element  732 . 
     In another embodiment ( FIG. 22 ), closure element  730  is not a double-inverted member, but is instead a single-inverted member like the illustrated embodiment of closure element  732 . Thus, in this embodiment end  738  is inverted as discussed above, but end  740  is not inverted, like end  760  of closure element  732 . One or both of ends  758 ,  760  of closure element  732  have a diameter greater than that of end  740  of closure member  730 , as in the above discussion. Tether  764  or stem  764 ′ passes through each of ends  740  and  758  initially, and in use through end  760 , in this embodiment. When closure elements  730 ,  732  are compressed, end  740  of closure element  732  passes through the tissue hole to be closed or sealed, and may enter one or both of ends  758 ,  760  of closure element  732 . 
     Closure device  722  may be placed in the body in a minimally-invasive manner, e.g. by obtaining percutaneous access to a blood vessel, organ or other part of the body and moving closure device  722  with or through a catheter or other tube to the desired location. It will be understood that closure device  722  may be placed at the desired location in the body via open surgery or other procedures as well. An embodiment for placement device  724  for minimally-invasive placement of closure device  722  is shown schematically in  FIGS. 23-28 . This embodiment of placement device  724  is intended for insertion through a previously placed sheath  800  that allows access to or is placed through a hole H in tissue T to be closed. In this example, sheath  800  extends from within a right atrial appendage (RAA) through hole H in tissue T to the pericardial space, in which balloon  801  of sheath  800  is inflated to anchor sheath  800 . 
     Device  724  includes three tubular members  802 ,  804  and  806  to which a handle  808  is connected, in the illustrated embodiment. As will be discussed further below, device  724  is inserted through delivery sheath  800 , which in one example is a 14 French tubular sheath that has been advanced through and anchored with respect to hole H. In that example, tubular member  802  is a 14 French peel-away tube around and at the distal end of member  804 , which can be a 12 French delivery sheath. Member  806  is a pusher and/or guide cannula, which is slidable within member  804 . Thus, member  804  is initially at least partially inside peel-away member  802 , and member  806  is within member  804 . In particular embodiments, a further tubular member  810 , extending through member  806 , is provided as a guide cannula for control line  770 . Control line  770  extends through member  810 , and in a particular embodiment line  770  is a thin braided stainless steel cable. Line  770  has a proximal end connected to handle  808 , and extends out of the open distal end of member  810 , through end  760  of closure element  732 , looping through tether  764  or stem  764 ′ (as discussed above), and returning through end  760  and into member  810 . In this way, line  770  is doubled initially within member  810 , so that a free end  811  is in member  810  and generally points proximally. Member  804  can fit into sheath  800  while containing closure device  722 . In an initial (pre-usage) configuration, closure element  730  is within member  802 , and closure element  732  is within member  804 , which is immediately or closely adjacent closure element  730 . Pusher member  806  is initially proximal or rearward of closure element  732 . As device  724  is inserted into the delivery sheath  800 , peel-away member  1802  is pulled apart and removed, leaving closure member  730  within sheath  800 , and delivery member  804  (with closure element  732  inside) behind closure element  730  and also within sheath  800 . 
     Embodiments of system  720  (e.g. placement device  724  and/or one or both of closure elements  730 ,  732 ) can be configured to accommodate passage of a wire guide. For example, such a wire guide may run through each closure element  730 ,  732  and through placement device  724  and into sheath  800  that is in hole H. The wire guide may run alongside or within the pusher member  806 , or may run through a separate lumen through or alongside device  724 . If the wire guide passes through closure elements  730 ,  732 , it may do so through mesh  734  at location(s) other than at one or more of ends  738 ,  740 ,  758 ,  760 . Such a wire guide serves both to help align the closure elements  730 ,  732 , and to provide a navigation pathway that may be left behind in the event that use of system  720  needs to be abandoned and the closure process re-started. In such a case, the wire guide provides a guide path for subsequent closure devices to approach and close hole H. 
     As noted, the illustrated embodiment of sheath  800  includes a balloon  801  at or near a distal end, to anchor delivery sheath  800 . When sheath  800  extends through a hole, to deliver therapeutic devices or compositions or for other purposes, balloon  801  is inflated on the distal side of the hole in order to anchor delivery sheath  800  in place. With sheath  800  so anchored, and all desired procedures via sheath  800  having been performed, the user inserts placement device  724  in its initial configuration into sheath  800  and peels away member  802 , as indicated above. Such insertion and advancing into sheath  800  may be accomplished over a wire guide that passes through or along device  724 . Device  724  without member  802  (i.e. members  804  and  806 , connected to handle  808  and including the features noted above within members  804  and/or  806 ) is then pushed through sheath  800  so that closure element  730  emerges from the distal end of sheath  800 . In particular embodiments, moving delivery member  804  forward from or using handle  808  pushes closure element  730 , so that closure element  730  is pushed outside of sheath  800 . Member  804  and/or handle  808  connected to it is preferably locked to sheath  800  outside the patient&#39;s body, and deployment of closure element  730  can be visualized (e.g. by fluoroscopy). 
     When closure element  730  has emerged from member  804 , distal end  738  is generally away from tissue T through which hole H extends. End  740  is directed toward tissue T, so that exterior end  750  (with folded-over mesh and in some embodiments healing material, as noted above) faces hole H. Tension is maintained on tether  764 , by pulling back at least slightly on member  810  (which may be connected to or locked with members  804  and/or  806 ). Such pulling provides tension via control line  770  to tether  764  and on to end  738  of closure element  730 , flattening closure element  730  against the distal end of sheath  800 . 
     At this point, balloon  801  is deflated to permit withdrawal of sheath  800  from hole H. Sheath  800  and device  724  are withdrawn together until closure element  730  engages the distal surface of tissue T (e.g. the pericardial side of the RAA wall). Again, the user can visualize the site to confirm that closure element  730  is against the tissue and/or to confirm that sheath  800  is out of hole H (e.g. fully on the cardiac side of the RAA wall). The position of member  806  (e.g. with member  810 ) and line  770  is then maintained as member  804  and sheath  800  are withdrawn further to expose and deploy the middle of tether  764 . The user can confirm (e.g. by visualization under fluoroscopy) the spacing between closure element  730  and the distal end of member  804  and/or that the distal end of member  804  is clear of the RAA wall. Again maintaining the position of member  806  (e.g. with member  810 ) and line  770 , member  804  and sheath  800  are further withdrawn to expose and deploy closure element  732  from within member  804 . Visualization of that deployment can be performed. 
     With closure element  732  out of member  804  and its distal end  758  generally facing tissue T, the operator holds the position of line  770  while advancing pusher member  806  against proximal end  760  of closure element  732 . Member  806  pushes end  760  over enlarged end  768  of tether  764 , forcing end  768  through end  760  and flattening closure element  732 . As noted above, enlarged end  768  of tether  764  is larger than an opening through end  760  of closure element  732 , so that once tether end  768  is forced through end  760 , closure device  722  is locked. That is, closure elements  730  and  732  are flattened against their respective sides of tissue T, and tether  764  locks them together, preventing ends of the closure elements from passing over enlarged ends  766 ,  768  of tether  764 . 
     With closure device  722  locked, line  770  is maintained in position while member  810  is withdrawn sufficiently to allow the free end  811  of line  770  to escape the distal end of member  810 . Line  770 , as noted above, is looped so as to have free end  811  within member  810 , and in particular embodiments, free end  811  bends outward when free of member  810 . With free end  811  outside of member  810 , line  770  is withdrawn (e.g. via handle  808 ). Free end  811  is pulled through end  768  of tether  764  and from closure element  732 , and away from the treatment site. The remainder of device  724  (including members  804  and  806 ) and sheath  800  can then be withdrawn, over a wire guide if present. Closure device  722  remains in the above-noted locked condition to allow healing of hole H. 
     An exemplary embodiment of the operational (distal) end of device  724  is shown schematically in  FIG. 28 . Peel-away sheath  802  is shown as outermost, with distal closure element  730  within it. An inner catheter or tube  804  is within peel-away sheath  802 , and its distal end is closely adjacent to closure element  730 . Proximal closure element  732  is within inner catheter or tube  804 . A pusher or guide tube or cannula  806  is within inner catheter or tube  804 , and in particular embodiments a cannula  810  for control line  770  is provided. Control line  770  extends through member  806  and/or member  810 , is threaded through end  768  of tether  764 , and returns to member  806 . Proximally, each of members  804 ,  806  (and member  810  if present) and line  770  are connected to handle  808 . 
     The representation of handle  808  shows pusher catheter  806  connected directly to it, with peel-away sheath  802  and inner catheter or tube  804  around pusher catheter  806 . A lock  820  may connect handle  808  and tube  804  in particular embodiments. The connection of handle  808  and line  770  is not shown in that figure. In the illustrated embodiment, handle  808  includes a body  850  shaped and configured for holding and maneuvering by hand. Three actuators are placed on or in handle  808 . A control line actuator  852  may include a pull ring and a shaft connected to line  770 . Actuator  852  maintains line  770  in position, and by pulling actuator  852 , line  770  is pulled or placed in tension. Additional actuators may be connected to members  804  and/or  806  to permit relative motion of them with respect to each other or other parts of device  724 . It will be understood that one or more actuators can be assembled in series to automate several actions with essentially one motion. 
     One problem that has occurred with placement of delivery sheaths or similar devices through tissue openings is that when the sheath is withdrawn, the friction of the withdrawing sheath can stretch or move the tissue plane through which the opening extends. For example, in an procedure in which a hole is created in the thin wall of the right atrial appendage for a delivery sheath, when the sheath is withdrawn through the hole the appendage wall will tend to invaginate into the right atrium, which is undesirable. To address that problem, an outer sheath  870  may be placed over the delivery sheath ( 800  in the illustrated embodiment) that is anchored by a balloon  801 . While balloon  801  is inflated, sheath  870  is moved to a position so that its distal end is just proximal to the hole (e.g. engaging or closely adjacent to tissue around the hole). When the delivery sheath  800  is withdrawn (following deflation of balloon  801 ), the distal end of sheath  870  supports the wall of the tissue plane through which sheath  800  is withdrawn. 
     Alternatively, delivery sheath  800  may include a lumen (either the same or a different lumen from that containing device  724 ) and a communicating side port  880  located a sufficient distance below balloon  801  to be at least partially below an inner tissue wall surface when balloon  801  is inflated and anchoring on the outer tissue wall surface. A wire  882  fabricated from a shape-memory material (e.g. Nitinol) is within the lumen in an unexpanded or restrained shape or configuration. When withdrawal of sheath  800  is desired, wire  882  is advanced through the lumen and at least partially out of port  880 . As wire  882  emerges from port  880 , it assumes an expanded shape, e.g. an expanding helical shape. Wire  882  presses against the wall of the tissue plane as it is advanced, providing counter support for the tissue as the sheath  800  is withdrawn. 
     It will be understood that port  880  may also be used for other purposes, in addition to or instead of placement of wire  882 . For example, once sheath  800  is in place or close to it, a contrast medium can be injected through the lumen and the side port  880  to help visualize the hole or tissue surrounding it. Similarly, side port  880  may be used as a flush port. 
     The above discussion of closure of a hole in an organ or other tissue is generally applicable to a number of types of openings, whether occurring naturally (e.g. a fistula) or artificially (e.g. through trauma or for passage of a therapeutic or diagnostic device). In particular embodiments, as noted above, the devices and methods described herein can be used for repairing a hole through a right atrial appendage opened for passage of treatment devices to the heart. In such an embodiment, the tissue T is part of the right atrial appendage, separating the appendage&#39;s interior from the pericardial space. 
     While the subject matter herein has been illustrated and described in detail in the exemplary drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only the preferred embodiment(s) have been shown and described and that all changes and modifications that come within the spirit of the disclosure are desired to be protected. It will be understood that structures, methods or other features described particularly with one embodiment can be similarly used or incorporated in or with respect to other embodiments. 
     While various embodiments of the invention have been described, the invention is not to be restricted except in light of the attached claims and their equivalents. Moreover, the advantages described herein are not necessarily the only advantages of the invention and it is not necessarily expected that every embodiment of the invention will achieve all of the advantages described. 
     The following numbered clauses set out specific embodiments that may be useful in understanding the present invention: 
     1. A closure for an opening in tissue, comprising: 
     a first closure element, the first closure element having a first mesh enclosure, the first mesh enclosure having a first distal narrowed end and a second proximal narrowed end and a central volume, each of the first and second ends being inverted so as to be within the central volume of the first mesh enclosure, each of the first and second ends being surrounded by respective external surfaces of the first mesh enclosure; 
     a second closure element, the second closure element having a second mesh enclosure physically separate from the first mesh enclosure, the second mesh enclosure having a third distal narrowed end and a fourth proximal narrowed end and a central volume, the third end being inverted so as to be within the central volume of the second mesh enclosure, each of the third and fourth ends being surrounded by respective external surfaces of the second mesh enclosure; 
     a tether joining the first and second closure elements in an initial configuration prior to delivery of the closure elements to the opening, the tether having first and second enlarged ends, wherein the tether extends through at least the first narrowed end, parallel to and alongside the second narrowed end and into the second closure element, so that the first enlarged end of the tether is outside the first closure element adjacent or engaging the first end and the second enlarged end of the tether is within the central volume of the second closure element and positioned to pass through the fourth narrowed end, 
     wherein the first closure element is adapted to engage a distal side of the tissue having the opening, and the second closure element is adapted to engage a proximal side of the tissue, and the tether is adapted to pass through the opening. 
     2. The closure of clause 1, further comprising a sheet of bioresorbable material fixed to the first closure element adjacent or over the second narrowed end.
 
3. The closure of any of clauses 1-2, wherein the sheet is fixed to an external portion of the first mesh enclosure.
 
4. The closure of any of clauses 1-2, wherein the sheet is fixed to an internal portion of the first mesh enclosure.
 
5. The closure of any of clauses 1-4, further comprising a sheet of bioresorbable material fixed to the second closure element adjacent or over the third narrowed end.
 
6. The closure of any of clauses 1-5, wherein each of the enlarged ends of the tether comprise a bead or a knot.
 
7. The closure of any of clauses 1-6, further comprising a control line looped through the second enlarged end of the tether.
 
8. The closure of clause 7, wherein the control line passes through the fourth narrowed end.
 
9. The closure of any of clauses 1-8, fitted within a delivery device.
 
10. The closure of any of clauses 1-9, wherein the first and second narrowed ends are aligned with each other.
 
11. The closure of any of clauses 1-10, wherein the third and fourth narrowed ends are aligned with each other.
 
12. The closure of any of clauses 1-11, wherein the first and second narrowed ends are laterally offset with respect to each other.
 
13. The closure of any of clauses 1-12, wherein one of the first and second narrowed ends is larger in diameter than the other of the first and second narrowed ends.
 
14. The closure of any of clauses 1-13, wherein at least one of the first and second closure elements are adapted to expand in width during placement as at least one of the enlarged ends of the tether and at least one of the narrowed ends of at least one of the closure elements move with respect to each other.
 
15. A device for closing an opening in tissue, comprising:
 
     a delivery device having a first peel-away catheter, a second tube within the first peel-away catheter, and a pusher tube within the second tube; and 
     the closure device of claim  1  fitted within the delivery device. 
     16. The device of clause 15, wherein the first closure element is within the first peel-away catheter and the second closure element is within the second tube.
 
17. The device of any of clauses 15-16, further comprising a control line looped through the second enlarged end of the tether.
 
18. The device of clause 17, further comprising a control cannula extending through the pusher tube, and wherein the control line extends through the control cannula.
 
19. The device of clause 18, wherein the control line extends from the control cannula and returns to the control cannula from the second enlarged end of the tether, so that a free end of the control line is within the control cannula.
 
     Structures or other features specified in the above clauses may be included singly or in any combination in the inventive devices, along with other structures or features described above with respect to any embodiment.