Patent Publication Number: US-9850013-B2

Title: Loading devices and methods for percutaneous perforation closure systems

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of U.S. Provisional Patent Application Ser. No. 61/789,584, filed Mar. 15, 2013, the entire content of which is hereby incorporated by reference. 
    
    
     TECHNICAL FIELD 
     The present invention relates generally to closure systems, devices, and methods for use in surgical procedures. 
     BACKGROUND 
     Minimally invasive procedures are continually increasing in number and variation in part because such techniques offer an immediate advantage over more traditional, yet highly invasive surgeries. Endoscopic surgery, for example, uses one or more scopes inserted through small incisions for diagnosing and treating disease. In particular, endovascular surgery gives access to many regions of the body, such as the heart, through major blood vessels. Typically, the technique involves introducing a surgical instrument percutaneously into a blood vessel, such as, for example, the femoral artery. The currently emerging percutaneous endovascular procedures include aortic valve replacement, mitral valve repair, abdominal and thoracic aneurysm repair and tricuspid valve replacement. Other procedures requiring access to the femoral artery include coronary, carotid and cerebral angiographic procedures. 
     Other examples of a minimally invasive procedure include NOTES (Natural Orifice Translumenal Endoscopic Surgery) based surgery, e.g. transgastric, transvesical, and transcolonic approaches. 
     A key feature of these minimally invasive surgical procedures is the forming of a temporary pathway, usually an incision or dilated perforation, to the surgical site. For example, in the emerging percutaneous endovascular procedures, an access site (e.g. incision, puncture hole, or perforation) ranging from approximately 10 to 30 French units is formed as a temporary pathway to access the target site. Various instruments, such as procedural sheaths, guidewires and catheters, are inserted through the access site, as well as specialized medical instruments, such as, balloon catheters and stents. 
     Currently, these large (10 to 30 French (F)) puncture holes (or perforations) or access sites are routinely created after surgical cut down to the blood vessel and post procedure are closed via cut-down surgical repair. This method is very invasive and fraught with complications. Accordingly, the rapid development of percutaneous endovascular surgery, of which interventional radiology and cardiology are a major component, has led to the need for instrumentation to minimize the risk of complications associated with closing the access site after a procedure. 
     SUMMARY 
     In accordance with example embodiments of the present invention, a device for folding an implant having a wing into a an overlapped configuration is provided. The device includes: a funnel body comprising a first portion configured to receive and protect the implant when the wing of the implant is in a relaxed state, a second portion proximal to the first portion and configured to engage and fold opposite first and second side portions of the wing of the implant in a predetermined direction when the implant is retracted proximally from the first portion of the funnel body and into the second portion of the funnel body, and an overlap guide configured to direct the path of a first one of the side portions of the wing such that the first and second side portions of the wing are overlapped in a predetermined manner and to prevent respective edges of the first and second side portions of the wing from butting into each other as the first and second side portions of the wing are guided into the overlapping configuration during proximal retraction of the implant relative to the funnel body. 
     The overlap guide may include a channel configured to receive one of the side portions of the wing to provide an offset between the side portions of the wing such that the edges of the side portions do not butt into each other as the side portions are folded into the overlapping configuration. 
     The overlap guide may include a rib configured to engage one of the side portions of the wing to provide an offset between the side portions of the wing such that the edges of the side portions do not butt into each other as the side portions are folded into the overlapping configuration. 
     The overlap guide may include a cutout slot in the funnel body. 
     The overlap guide may include a flexible tab. 
     The overlap guide may include a scoop. 
     The overlap guide may include one or more convex walls. 
     The overlap guide may include a tear-drop profile providing offset surfaces to direct respective side portions of the implant. 
     The overlap guide may include a dimple. 
     The funnel body may include an elliptical inner profile. 
     The funnel body may include four distinct zones including a first zone corresponding to the first portion of the funnel body, a second zone corresponding to the second portion of the funnel body, a third zone corresponding to the overlap guide of the funnel body, and a fourth zone corresponding to the location of a loading cannula that is separable from the loading funnel. 
     The device may further include a loading cannula separable from the loading funnel and configured to receive the implant from the loading funnel after the implant has been converted to its overlapped configuration via proximal movement of the implant through the loading funnel. 
     At an interface between the loading funnel and loading cannula, an internal diameter of the loading funnel may be less than the internal diameter of the loading cannula such that the implant does not catch on a proximal edge of the loading cannula as the implant is moved proximally into the loading cannula. 
     The second portion of the device may include sloped surfaces configured to engage the side portions of the wing in a manner that forces the side portions to be folded in a predetermined direction. 
     In accordance with example embodiments of the present invention, a method of loading an implant having a flexible wing into a loading cannula, includes: retracting the implant proximally through the device according to any of the preceding claims until the implant is disposed in the loading cannula; and separating the loading cannula from the loading funnel. 
     In accordance with example embodiments, a device for sealing an aperture in a tissue includes: (a) an implant configured to seal the aperture when positioned adjacent to the aperture; and (b) a delivery shaft configured to engage the implant to allow the implant to be maneuvered into sealing engagement with a distal surface of the tissue, the delivery shaft comprising: (i) a retaining sleeve comprising a locking projection engagable with the locking recess of the implant to secure the implant to the delivery shaft, and (ii) a release sleeve axially slideable relative to the retaining sleeve between a first axial position in which the release sleeve is configured to maintain locking engagement between the locking recess of the implant and the locking projection of the retaining sleeve, and a second axial position in which the release sleeve permits the locking projection of the retaining sleeve to disengage the locking recess of the implant. 
     The release sleeve may include an interlocking projection configured to engage an interlocking recess of the implant when the release sleeve is in the first axial position and to disengage the interlocking recess when the release sleeve is moved from the first axial position to the second axial position. 
     The interlocking projection may be one of plurality of interlocking projections configured to engage a respective plurality of interlocking recesses of the implant. 
     The projection may be biased toward a flared position such that movement of the release sleeve from the first axial position to the second axial position causes the interlocking projection to flare away from and out of engagement with the interlocking recess of the implant. 
     The device may further include: a handle coupled to the delivery shaft; and an actuator moveable between a first position and second position relative to the handle, wherein the device is configured such that (a) movement of the actuator from the first position to the second position causes a change in the position of two components of the implant relative to each other and (b) movement of the actuator from the second position to the first position causes the delivery shaft to release the implant. 
     The implant may be formed of a polymer adapted to remain shelf stable and functional for sealing after terminal sterilization. 
     The polymer may be adapted to remain shelf stable and functional for sealing after terminal sterilization using at least one of (a) ethylene oxide, (b) electron-beam, (c) gamma irradiation, and (d) nitrous oxide. 
     The polymer may be biodegradable. 
     The polymer may comprise Polydioxanone, Poly-L-lactide, Poly-D-lactide, Poly-DL-lactide, Polyglycolide, ε-Caprolactone, Polyethylene glycol, or combinations of these. 
     The polymer may comprise polydioxanone. 
     The device may be configured to seal a perforation in a hollow vessel. 
     The implant may include an intraluminal portion configured to form a seal with the perforation by contacting an intraluminal surface of the hollow vessel. 
     The implant may include an extra-luminal portion configured to extend outside the hollow vessel, the delivery shaft being configured to engage the implant via the extra-luminal portion. 
     The implant may include a flexible wing extending outwardly from a base portion. 
     The device may be configured to be guided over a guidewire. 
     The implant may be formed at least in part of a material having an inherent viscosity in a range from 0.5 to 7.0 dl/g. 
     The implant may include a flexible wing having a diameter greater than a diameter of the aperture in the tissue. 
     The implant may include a distal foot portion, a flexible wing, and a recessed surface disposed in the distal foot portion and into which the flexible wing is positioned and crimped to provide an effective fluid seal between the foot portion and the flexible wing. 
     The crimping may be achieved using at least one of (a) mechanical, (b) chemical, and (c) thermal methods. 
     The implant may include: a flexible wing; and a foot including a distal portion configured to be disposed distally of the flexible wing when the implant is positioned to seal the aperture and a proximal neck configured to extend away from the aperture and proximally away from the aperture. 
     The distal portion of the foot may have a length this is greater than a diameter of the aperture. 
     The proximal neck may be flexible relative to the distal portion of the foot. 
     The proximal neck may extend distally along an axis relative to an upper surface of the distal portion of the foot at an angle that is within the range from 10° to 70°. 
     The distal portion of the foot may be configured to reinforce the flexible wing to facility sealing of the aperture. 
     The implant may include a base portion and a pin moveable relative to the base portion between a first position and a second position, wherein the pin in the second position is configured to extend outwardly from the base to provide a safety against the base being fully pushed or pulled distally through the aperture to be sealed. 
     The implant may include a guide channel configured to receive a guide wire. 
     The pin may be configured to block the guide channel when the pin is in the second position. 
     The pin may be configured to leave the guide channel open when the pin is the second position. 
     The base may include a cavity configured to allow sealing of the guide channel via coagulation after removal of a guidewire from the guide channel. 
     The device may further include: a loading funnel configured to fold the implant into an elongated folded configuration to permit the wing to pass through a procedural sheath when the delivery shaft maneuvers the implant into a location of the aperture to be sealed. 
     The loading funnel may include: a tapered portion configured to progressively fold the implant into the folded configuration when the implant is maneuvered through the tapered portion in a proximal direction; and a narrowed portion configured to receive the implant with the flexible wing in the folded configuration when the implant is maneuvered further in the proximal direction and proximally beyond the tapered portion. 
     The tapered portion may include a frustoconical conical portion and the narrowed portion comprises a cylindrical portion. 
     The frustoconical portion and the cylindrical portion may be non-concentric. 
     The narrowed portion may include a cannula configured receive the implant with the wing in the folded configuration and that can be detached from the remainder of the loading funnel. 
     The device may further include a packaging having a proximal and a distal end, wherein: the delivery shaft, the implant, and the loading funnel are disposed in the packaging such that the delivery shaft extends distally through the narrowed portion of the funnel and into the tapered portion, where the delivery shaft is coupled to the implant; and the loading funnel is held in the packaging such that proximal movement of the delivery shaft relative to the package causes, sequentially, (a) proximal movement of the implant through the tapered portion to progressively fold the implant into the folded configuration, (b) proximal movement of the implant into the cannula, and (c) separation of the cannula, with the implant disposed therein, from the remainder of the loading funnel. 
     The implant may be held in the tapered portion by the delivery shaft a location. 
     The device may further include a handle coupled to the delivery shaft. 
     The cannula may be configured to access multiple forms of introducer sheaths. 
     In accordance with example embodiments, a method of using the device includes: loading the implant in to the cannula at the time of a surgery in which the implant is used; and inserting the cannula into a proximal access of a procedural sheath in order to introduce the implant in the folded configuration into the procedural sheath. 
     The method may further include feeding a proximal end of the guidewire through the implant and the delivery shaft prior to inserting the cannula into the proximal access of the procedural sheath, such that the distal end of the guidewire extends through the aperture to be closed by the implant. 
     In accordance with example embodiments, a device includes: a sealing member configured to seal the aperture when positioned adjacent to the aperture; and a delivery device releasably coupleable to the sealing member such that the delivery device is configured to position the sealing member adjacent to the aperture, wherein the sealing member comprises a passageway configured to receive a guidewire to guide the sealing member to the aperture, the sealing member configured to seal the passageway after complete removal of the guidewire from the passageway. 
     The sealing member may include a base portion and a moveable member that is moveable between a first position and a second position relative to the base portion. 
     The sealing member may be configured such that movement of the moveable member from the first position to the second position causes occlusion of the passageway in order to seal the passageway after removal of the guidewire from the passageway. 
     The delivery device may be configured to move the moveable member from the first position to the second position. 
     In one aspect of example embodiments of the invention, an implantable device for sealing a surgical perforation is provided. In accordance with example embodiments, this device is polymer-based. For example, the device may be formed of a biodegradable polymer. The resulting biodegradable polymer may be biocompatible and bioresorbable with the ability to degrade when implanted in-vivo. 
     A biodegradable polymer can have crystalline and amorphous regions and are therefore, in general, semi-crystalline in nature. Degradation of a biodegradable polymer such as initiates in the amorphous regions, with the crystalline regions also degrading but at a slower rate relative to the amorphous regions. Without wishing to be tied to a theory, degradation of a polymer such as Polydioxanone (PDO) occurs along the polymer back bone by hydrolysis of the ester bonds. This non-specific ester bond scission occurs randomly along the polymer chain with water penetration initially cutting the chemical bonds and converting the long polymer chains into natural monomeric acids found in the body, such as lactic acid. Such monomeric acids are then phagocytized by the enzymatic action of special types of mononuclear and multinuclear white blood cells. The polymer is thus degraded into non-toxic, low molecular weight residues that are capable of being eliminated from the body by normal metabolic pathways, e.g. via exhalation and/or excretion. Such a pathway thereby enables reference to the breakdown of such polymers in-vivo through terminology such as absorbable, bioabsorbable, degradation, biodegradation, resorbtion, bioresorbtion, etc. 
     In another aspect, the biodegradable polymer may be shelf stable even after terminal sterilization, e.g. using ethylene oxide, gamma irradiation, e-beam irradiation, nitrous oxide, etc. for in vivo use. In accordance with example embodiments, the biodegradable polymer is designed to withstand terminal sterilization, such as ethylene oxide sterilization, and still maintain long-term shelf life stability and product functionality. Terminal sterilization, such as by ethylene oxide, can have a dramatic effect on the structural stability of polymers as they are either degraded into low molecular weight species or cross linked into complex polymeric systems, which can negatively alter the post-sterilization polymer properties. Accordingly, in order to provide a post sterilization, shelf-stable, biocompatible polymeric implant; the polymer, in accordance with example embodiments of the present invention, is able to survive the terminal sterilization procedure and still maintain functionality. 
     It has been found that post-sterilization stability is achievable by using polymers with an inherent viscosity [IV] (which is a method of evaluating the relative molecular weight of the polymeric system) that is of a sufficient starting range to endure a drop in IV post-sterilization and still meet the required implant design requirements. Without wishing to be tied to a theory, it is believed that polymers are susceptible to degrade into lower molecular weight species during terminal sterilization, thereby affecting the inherent viscosity of the implant during storage. By starting with a polymer system with an IV value in its upper range pre-sterilization, it is possible to have a sterile system, post-sterilization with an IV lower than that of the starting system but that is designed to meet the required shelf-life stability. This IV value is typically in the range of 0.5-7.0 dl/g. 
     Additionally, in accordance with example embodiments, the use of a specific and defined atmosphere for storage of the implant pre- and post-sterilization further adds to increasing the post-sterilization shelf-life stability of the polymer in question. One such method is the use of a controlled atmosphere, specifically one where excessive moisture is reduced via a vacuum or low moisture containing dried gases such as nitrogen, argon, etc. Furthermore, the use of packaging materials with a low moisture vapor transmission rate, for example orientated polypropylene (OPP), Polyethylene terephthalate (PET), Linear low-density polyethylene (LLDPE), polyethylene (PE), foil-based packaging materials (e.g. aluminium), or combinations thereof, in combination with a low moisture environment can further aid in enhancing the stability of the polymeric material post-sterilization. 
     Further features and aspects of example embodiments of the present invention are described in more detail below with reference to the appended Figures. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1A  shows a perspective view of a closure device with an alternative extra-luminal pin and situated on a guidewire extending into an artery, the artery shown in cross-section. 
         FIG. 1B  shows a perspective view of the closure device of  FIG. 1A  with an alternative extra-luminal pin and situated on a guidewire extending into the artery of  FIG. 1A , the artery shown in cross-section. 
         FIG. 1C  shows a front view of the closure device of  FIG. 1A  engaging the artery, the artery shown in cross-section. 
         FIG. 2A  shows a perspective view of the closure device of  FIG. 1A  when not engaged with the artery, disposed on a guidewire, and with an extra-luminal pin in a retracted position. 
         FIG. 2B  shows a perspective view of the closure device of  FIG. 2A  when not engaged with the artery, and with the extra-luminal pin in a deployed position. 
         FIG. 2C  shows a right side view of the closure device shown in  FIG. 2A . 
         FIG. 2D  shows a right side view of the closure device shown in  FIG. 2B . 
         FIG. 3A  shows a right side view of a foot core of the closure device shown in  FIG. 1A . 
         FIG. 3B  shows a front view of the foot core shown in  FIG. 3A . 
         FIG. 3C  shows a perspective view of the foot core shown in  FIG. 3A . 
         FIG. 3D  shows a cross-sectional perspective view of the foot core shown in  FIG. 3A . 
         FIG. 4A  shows a perspective view of another foot core. 
         FIG. 4B  shows a front view of the foot core shown in  FIG. 4A . 
         FIG. 4C  shows a cross-sectional perspective view of the foot core shown in  FIG. 4A . 
         FIG. 4D  shows a bottom view of the foot core shown in  FIG. 4A . 
         FIG. 4E  shows a perspective view of the foot core shown in  FIG. 4A  and a wing element. 
         FIG. 4F  shows a right side view of the foot core and wing element shown in  FIG. 4E . 
         FIG. 5A  shows a perspective view of another foot core. 
         FIG. 5B  shows a front view of the foot core of  FIG. 5A . 
         FIG. 6A  shows a wing element of the device of  FIG. 1A  in a flat state. 
         FIG. 6B  shows the wing element of  FIG. 6A  in a folded or curved state. 
         FIG. 7A  shows a cross-sectional right side view of a closure system incorporating the closure device shown in  FIG. 1A . 
         FIG. 7B  shows a cross-sectional right side view of the closure device shown in  FIG. 7A  in a released state. 
         FIG. 7C  shows a perspective view of the extra-luminal pin element. 
         FIG. 7D  shows a perspective view of another extra-luminal pin element. 
         FIG. 8A  shows a left side view of another closure system. 
         FIG. 8B  shows a left side view of the closure system of  FIG. 8B  after deployment of an extra-luminal pin arrangement. 
         FIG. 9A  shows a left side view of another closure system. 
         FIG. 9B  shows a left side view of the closure system of  FIG. 9A  after deployment of an extra-luminal pin. 
         FIG. 10A  shows a left side view of another closure system. 
         FIG. 10B  shows a left side view of the closure system of  FIG. 9A  after deployment of an extra-luminal pin. 
         FIG. 11A  shows a left side view of another closure system. 
         FIG. 11B  shows a left side view of the closure system of  FIG. 11A  after deployment of an extra-luminal pin. 
         FIG. 12A  shows a left side view of another closure system. 
         FIG. 12B  shows a left side view of the closure system of  FIG. 12A  after deployment of an extra-luminal pin. 
         FIG. 13A  shows another foot core. 
         FIG. 13B  shows another foot core. 
         FIG. 14  shows another foot core. 
         FIG. 15A  shows a foot core having a flexible neck. 
         FIG. 15B  shows another foot core having a flexible neck. 
         FIG. 16  shows a foot core that does not include a wing-receiving recess. 
         FIG. 17A  shows an implant that utilizes a wing-retention collar. 
         FIG. 17B  shows the implant of  FIG. 17B  with the collar mounted. 
         FIG. 17C  is an enlarged partial view of the implant of  FIG. 17B . 
         FIG. 18  is a sectional side view of a foot core and an intra-luminal pin. 
         FIG. 19  shows an implant. 
         FIG. 20  is a perspective view of a cross-sectioned implant of  FIG. 19 . 
         FIG. 21  is a perspective view of a cross-sectioned implant of  FIG. 19  with an extra-luminal pin in a deployed position. 
         FIG. 22A  shows a foot core of the implant of  FIG. 19 . 
         FIG. 22B  shows a flexible wing of the implant of  FIG. 19 . 
         FIG. 22C  shows an extra-luminal pin of the implant of  FIG. 19 . 
         FIG. 23  is a side view of the implant of  FIG. 19 . 
         FIG. 24  is a front view of the implant of  FIG. 19 . 
         FIG. 25  is a back view of the implant of  FIG. 19 . 
         FIG. 26  is a top view of the implant of  FIG. 19 . 
         FIG. 27  is a bottom view of the implant of  FIG. 19 . 
         FIG. 28A  shows a front perspective view of a foot core. 
         FIG. 28B  shows a rear perspective view of the foot core of  FIG. 28A . 
         FIG. 28C  shows a top view of the foot core of  FIG. 28A . 
         FIG. 28D  shows a bottom view of the foot core of  FIG. 28A . 
         FIG. 28E  shows a perspective view of the bottom of the foot core of  FIG. 28A . 
         FIG. 29  is a partial sectional view the flexible wing of the implant of  FIG. 19 . 
         FIG. 30  shows a side view of a procedural sheath. 
         FIG. 31A  shows a right side view of a delivery system for implanting the closure device of  FIG. 1A . 
         FIG. 31B  is an enlarged view of section A of  FIG. 31A . 
         FIG. 32  is a cross-sectional perspective view of the closure device attached to a distal tip of the delivery system of  FIG. 31A . 
         FIG. 33A  is an exploded perspective view showing a retaining sleeve, foot core, and extra-luminal pin of the system of  FIG. 31A . 
         FIG. 33B  shows a perspective view of the components shown in  FIG. 33A  in an assembled state with a wing and guidewire. 
         FIG. 33C  shows the assembly of  FIG. 33B  together with a release sleeve. 
         FIG. 34A  shows a perspective view of the retaining sleeve of the system of  FIG. 31A   
         FIG. 34B  shows a partial side view of the foot core of the closure device of  FIG. 1A , corresponding to the extra-luminal section of the foot core. 
         FIG. 34C  shows a cross-sectional side view of an interlocking connection between the retaining sleeve, foot core, and release sleeve of the system of  FIG. 31A . 
         FIG. 35  shows a side view of interior components of the handle of the delivery system of  FIG. 31A . 
         FIG. 36  shows a perspective view of a loading funnel. 
         FIG. 37  shows the funnel of  FIG. 36 , the closure device of  FIG. 1A , and a shaft of the delivery system of  FIG. 31A . 
         FIG. 38  shows the components shown in  FIG. 37  with the closure device disposed within the funnel. 
         FIG. 39A  shows a perspective view of another loading funnel. 
         FIG. 39B  shows a cross-sectional perspective view of the loading funnel of  FIG. 39A . 
         FIG. 39C  shows a perspective view of the loading funnel of  FIG. 39A . 
         FIG. 40A  shows a perspective view of another loading funnel. 
         FIG. 40B  shows an exploded view of the loading funnel of  FIG. 40A . 
         FIG. 41A  shows a perspective view of another loading funnel. 
         FIG. 41B  shows a cross-sectional partial perspective view of the loading funnel of  FIG. 41A . 
         FIG. 42A  shows an exploded perspective view of the loading funnel of  FIG. 41A . 
         FIG. 42B  shows a further exploded perspective view of the loading funnel of  FIG. 41A . 
         FIG. 43A  shows a perspective view of a split funnel body. 
         FIG. 43B  shows a perspective view of a splittable funnel body with a notched wall. 
         FIG. 43C  shows a side view of the funnel body of  FIG. 43B . 
         FIG. 43D  shows a rear view of the funnel body of  FIG. 43B . 
         FIG. 43E  shows a perspective view of a splittable funnel body with a notched wall and lead-in notch. 
         FIG. 43F  shows a side view of the funnel body of  FIG. 43E . 
         FIG. 43G  shows a rear view of the funnel body of  FIG. 43E . 
         FIG. 43H  shows a perspective view of a staged funnel body. 
         FIG. 43I  shows a side view of the staged funnel body of  FIG. 43H . 
         FIG. 43J  shows a perspective view of an offset funnel body. 
         FIG. 43K  shows a side view of the offset funnel body of  FIG. 43J . 
         FIG. 43L  shows a perspective view of the offset funnel body of  FIG. 43J  showing the relative position of an implant prior to loading along a guidewire 
         FIG. 43M  shows a side view of the arrangement of  FIG. 43L . 
         FIG. 44  shows a guidewire being back-loaded to the foot core of the closure device of  FIG. 1A . 
         FIG. 45A  shows insertion of the closure device of  FIG. 1A  being inserted into a loading funnel. 
         FIG. 45B  shows a cap and seal snapped to a funnel body of the loading funnel of  FIG. 45A . 
         FIG. 46A  shows a perspective view of the loading funnel of  FIG. 45B , containing the closure device of  FIG. 1A  being inserted into a hub of the procedural sheath of  FIG. 30 . 
         FIG. 46B  shows a cross-sectional side view of the loading funnel of  FIG. 45B , containing the closure device of  FIG. 1A , inserted into the hub of the procedural sheath of  FIG. 30 . 
         FIG. 47A  shows advancement of the delivery system of  FIG. 31A  and the closure device of  FIG. 1A  down the procedural sheath of  FIG. 30 . 
         FIG. 47B  shows advancement of the closure device of  FIG. 1A  and the distal portion of the delivery system of  FIG. 31A  into an arterial lumen. 
         FIG. 48  shows the procedural sheath of  FIG. 30  being withdrawn from the artery, with the artery shown in sectional side view. 
         FIG. 49A  shows the arrangement of  FIG. 48  with deployment of the extra-luminal pin of the closure device. 
         FIG. 49B  shows the arrangement of  FIG. 49A  with the closure device released from the delivery system. 
         FIG. 50  shows the arrangement of  FIG. 49B  after withdrawal of the procedural sheath and delivery system from the tissue tract. 
         FIG. 51A  shows a rotatable interlocking arrangement. 
         FIG. 51B  shows the interlocking arrangement of  FIG. 51A  in a disengaged state. 
         FIG. 51C  shows another interlocking arrangement in a disengaged state. 
         FIG. 51D  shows another interlocking arrangement in a disengaged state. 
         FIG. 52  shows an exploded view of a handle portion of a delivery system for implanting a closure device. 
         FIG. 53  shows components of the handle portion of the delivery system of  FIG. 52 . 
         FIG. 54A  shows a cross-sectional view of the handle portion of the delivery system of  FIG. 52  in an initial state with a guidewire in place. 
         FIG. 54B  shows a cross-sectional view of the handle portion of the delivery system of  FIG. 52  with the guidewire being removed. 
         FIG. 54C  shows a cross-sectional view of the handle portion of the delivery system of  FIG. 52  after removal of the guidewire. 
         FIG. 54D  shows a cross-sectional view of the handle portion of the delivery system of  FIG. 52  after removal of the guidewire and depression of a lock member. 
         FIG. 54E  shows an enlarged partial cross-sectional view of a lock member of the handle portion of the delivery system of  FIG. 52  with the lock portion in a locked position. 
         FIG. 54F  shows a cross-sectional view of the handle portion of the delivery system of  FIG. 52  at the onset of distal actuation of a thumb slider. 
         FIG. 55A  shows a cross-sectional view of the handle portion of the delivery system of  FIG. 52  with the thumb slider moved to a distal position. 
         FIG. 55B  shows an enlarged partial cross-sectional view of the handle portion of the delivery system of  FIG. 52  with the thumb slider moved to the distal position. 
         FIG. 56 a    shows an enlarged partial cross-sectional view of the handle portion of the delivery system of  FIG. 52  with the thumb slider in a proximal position. 
         FIG. 56B  shows an enlarged partial cross-sectional view of the handle portion of the delivery system of  FIG. 52  with the thumb slider moved to the distal position. 
         FIG. 57A  shows a cross-sectional view of the handle portion of the delivery system of  FIG. 52  at the onset of proximal actuation of the thumb slider. 
         FIG. 57B  shows a cross-sectional view of the handle portion of the delivery system of  FIG. 52  with the thumb slider returned to the proximal position after both distal actuation and subsequent proximal actuation. 
         FIG. 57C  shows a cross-sectional view of the handle portion of the delivery system of  FIG. 52  with the thumb slider moved to distal position a second time. 
         FIG. 58  shows a packaged surgical closure device product. 
         FIGS. 59 and 60  show a loading funnel of the product of  FIG. 58 . 
         FIG. 61  shows an exploded view of components of a delivery system and a closure device. 
         FIG. 62  shows components of a device after removal from a packaging tray of  FIG. 58 . 
         FIG. 63  shows a cross-sectional view of a loading funnel. 
         FIGS. 64 to 69  sequentially illustrate an implant being retracted into an overlapped configuration and into a loading cannula. 
         FIGS. 70 to 77  sequentially illustrate, from a front view, an implant being reacted into an overlapped configuration and into a loading cannula. 
         FIG. 78  shows the loading cannula and implant after being separated from the loading funnel. 
         FIG. 79  shows a loading funnel having a rib. 
         FIG. 80  shows a cross-sectional view of the loading funnel of  FIG. 63  with a proximally disposed loading cannula. 
         FIG. 81  shows a loading funnel with a slot and a flexible tab. 
         FIG. 82  shows a loading funnel with an inboard scoop. 
         FIG. 83  shows a loading funnel with an elliptical inner profile. 
         FIG. 84  shows a loading funnel with convex walls. 
         FIG. 85  shows a loading funnel with a trajectory inboard scoop. 
         FIG. 86  shows a loading funnel having a dimple. 
         FIG. 87  shows a loading funnel having a dimple that forms an elongated ramp surface. 
         FIG. 88  shows a loading funnel having a loading funnel with a smooth ramp surface over the full length of travel. 
         FIG. 89  shows a loading funnel with a tear-drop inner profile. 
         FIG. 90  shows a loading funnel with an exaggerated tear-drop inner profile. 
     
    
    
     DETAILED DESCRIPTION 
     Various example embodiments are described in detail herein. These embodiments generally share certain features in common. Accordingly, the various embodiments each share common features, except to the extent indicated otherwise. As such, for the sake of conciseness, the description of the common features is not repeated in connection with the description of each described embodiment. Further, features that are the same or analogous among the various embodiments are, in connection with some embodiments, given like reference numbers, but followed by a letter associated with the particular embodiment. For example, if an embodiment has an element  7 , the corresponding or analogous element in further embodiments would be designated  7   a ,  7   b ,  7   c , and so on. For convenience, the description of these features is not repeated in connection with each embodiment; rather, it should be understood that the description of these features in connection with other embodiment(s) applies unless indicated otherwise. 
     As described herein, example embodiments of the present invention provide surgical closure systems, devices, and methods. As such, provided systems, devices, and methods are useful for closing a perforation (i.e., a hole, puncture, tear, rip, or cut, etc.) in any hollow vessel associated with a mammalian surgical procedure. One of ordinary skill in the art will appreciate that the systems, devices, and methods are useful for closing a perforation in any lumen of a mammal, including, for example, the gastrointestinal tract (e.g. the stomach, intestines, colon, etc.), heart, peritoneal cavity, esophagus, vagina, rectum, trachea, bronchi, or a blood vessel. 
     Although certain figures and embodiments relate to use of systems and devices for closure of a perforation associated with vascular surgery, one of ordinary skill in the art will appreciate that components of a provided device are not size dependent (i.e., are scalable) and are therefore useful for closure of any perforation in a lumen of a mammal. 
     Some embodiments of the present invention are directed to a closure system, device, and method of percutaneous closure of an arteriotomy following an endovascular/intra-arterial procedures. 
     One of ordinary skill in the art will recognize that many mammalian lumina are comprised of one or more friable tissues. Thus, a common difficulty associated with surgical closure of a perforation in such lumina is that suture material, used in typical closure systems, tends to cause tears in the friable tissue. Such tearing of the luminal tissue impedes healing and causes scarring. Indeed, such tearing of the friable tissues of the internal lumina of blood vessels can lead to scarring, dislodgment of tissue particles, blockage, or even eventual death of the patient. In view of the fragile nature of luminal tissues, an aspect of example embodiments of the present invention is to provide systems, devices, and methods that allow cseal to be formed closure of a tissue perforation in a reliable manner with minimal trauma to the luminal tissue, for example, by providing a sutureless seal. 
     With regards to the arterial wall morphology, in the context of example embodiments directed to closing arterial perforations, the fibrous adventitial layer of an artery (i.e., the outer layer) is relatively tough, whilst the intimal and endothelial layers are friable. Because of the morphology of the arterial wall, an arteriotomy may be circumferential in nature and perpendicular to the longitudinal axis of the artery. 
     Closure Device 
     Referring to  FIG. 1A , a percutaneous Vascular Closure Device (VCD)  5  is configured to provide relatively large vascular closures. An example of an intended application of this device  5  is the percutaneous closure of 12-30 F arteriotomies following endovascular/intraarterial procedures. In clinical practice, commonly targeted arteries may include, for example, the common femoral artery, the subclavian artery, axillary artery, ascending aorta, brachial artery, and other vessels used for endovascular access. At the conclusion of the interventional procedure, the implant or device  5  is percutaneously delivered into the artery  2  via a procedural sheath  100  (illustrated, e.g. in  FIG. 30 ) over a guidewire  150 . 
     The device  5 ′ shown in  FIG. 1B , differs from the device  5  only in that the device  5 ′ employs an extra-luminal pin  80   a  that differs from an extra-luminal pin  80  of the device  5 . In particular, referring to  FIGS. 7C and 7D , the extra-luminal pin  80   a  has a slot  85   a  to facilitate the pin  80   a  being moved into its distal or deployed position, as described in further detail herein, while the guidewire  150  remains in situ, whereas the extra-luminal pin  80  is configured to prevent full distal extension of the extra-luminal pin  80  when the guidewire  150  remains in situ. Aside from this difference, as well as the presence of the guidewire in certain views, the devices  5  and  5 ′ should be considered identical. Moreover, for the sake of conciseness, the description of the device  5  is considered interchangeable with the device  5 ′, except to the extent indicated otherwise. 
       FIGS. 1A to 1C  illustrate final closure dynamics of the device  5 ,  5 ′ in situ in a sectioned artery  2 , with  FIG. 1A  showing the device  5  after removal of the guidewire  150 . The implant device  5 ,  5 ′ includes a body or foot core  20 , a flexible wing  60 , and the extra-luminal pin  80 ,  80   a.    
     All implant device components (e.g., the foot core  20 , the flexible wing  60 , and the extra-luminal pin  80 ,  80   a  in the illustrated examples of  FIGS. 1A to 1C ) are manufactured from synthetic absorbable materials, although other suitable non-synthetic and/or non-absorbable materials may be used instead of, or in addition to, these synthetic absorbable materials. The flexible wing  60 , the foot core  20 , and the extra-luminal pin  80 ,  80   a  may each be manufactured from any suitable material, e.g. Polydioxanone (PDO), Poly-L-lactide (PLLA), Poly-D-lactide (PDLA), blend of D-lactide and L-lactide, i.e. poly-DL-lactide (PDLLA), Polyglycolide (PGA), blend of Poly-L-lactide and Polyglycolide (PLGA), ε-Caprolactone, Poly (ethylene glycol) (PEG), magnesium alloy, 3-hydroxypropionic acid, Polyanhydrides, poly(saccharide)materials or combinations of these. It should be appreciated, however, that any one or more of the components of the implant device  5 ,  5 ′ may be formed of any suitable material. Moreover, some or all of the components of the device  5  may be made of the same or different materials relative to each other. The flexible wing may be manufactured as a thin sheet, it may also be made of a woven material, e.g. using electrospinning, weaving and knitting processes. 
       FIGS. 1A to 1C  represent each of these components in situ. The arteriotomy seal is achieved in large part by the hydraulic haemodynamic pressure, which acts on the flexible wing  60  to force the flexible wing  60  against the luminal surface and conform to the luminal topography to seal around the arteriotomy. 
       FIGS. 2A to 2D  show the assembled implant  5  showing three components—foot core  20 , flexible wing  60 , and extra-luminal pin  80 . Although the example illustrated in  FIGS. 2A to 2D  consists of three pieces, it should be appreciated that more or few pieces may be provided. For example, the flexible wing  60  may be integrally formed with the foot  20  as a single, monolithic piece. 
     As illustrated in  FIGS. 2A and 2C , a guidewire  150  extends through the implant  5 .  FIGS. 2B and 2D  show the implant  5  after proximal retraction of the guidewire  150  and subsequent extension, or deployment, of the extra-arterial pin  80  to its distal, or deployed, position relative to the foot core  20 . 
       FIGS. 2A and 2C  show the implant  5  with the extra-luminal pin  80  in a retracted or undeployed state, and  FIGS. 2B and 2D  show the extra-luminal pin  80  in a distally extended or deployed state. 
     The implant  5  is inserted into the artery  2  through a procedural sheath  100  illustrated in  FIG. 30  and over the guidewire  150 , which extends through the sheath  100  and into the intra-arterial space. 
     Referring, for example, to  FIGS. 3A to 3D , the foot core  20  includes both an intra-luminal section  25  which is configured to be maintained in the interior of the artery  2 , or other tissue structure, when the implant  5  is in situ, and an extra-luminal section  40  which passes through the arteriotomy across the arterial wall when the implant  5  is in situ. The intra-luminal section  25  and the extra-luminal section  40  are separated at a recess  22 , which is configured to receive the wing  60  such that a cylindrical recessed surface  23  is maintained inside a circular central cut-out or aperture  65  in the wing  60 . The aperture  65  is illustrated, for example, in  FIGS. 6A and 6B . 
     It is noted that since some illustrated examples are provided in the context of an arteriotomy, the terms “intra-luminal” and “extra-luminal” may be referred to as “intra-arterial” and “extra-arterial” in the context of the illustrated embodiments, it being understood that the arteriotomy-closure application is non-limiting and the closure of any suitable tissue aperture may be performed by example embodiments of the present invention. 
     The extra-luminal section  40  of the foot core  20  is provided in the form of a neck  42  which extends from the intra-luminal section  25  at an angle, e.g. selected from a range from 10° to 70°, and has five primary functions: 
     1. Secure the flexible wing  60  within the recessed section  22 . This recessed section  22  also provides an effective seal between the flexible wing  60  and foot core  20 . In the example illustrated, e.g. in  FIGS. 1A to 1C , the flexible wing  60  is free to rotate within this recess  22 . It should be understood, however, that the engagement of the wing  60  in the recess  22  may be provided such that the wing  60  is not rotatable within the recess  22 . 
     2. Secures and allows release of the entire implant to a delivery system via interlock recesses  45  in the neck  42 . This functionality is described in further detail elsewhere herein. 
     3. Houses the extra-luminal pin  80  and secures it when deployed to its final position. 
     4. Houses a guidewire channel or conduit  50 . The guidewire channel  50  is illustrated, e.g. in  FIG. 3D . 
     5. The 10°-70° incline on the neck in combination with the extra-luminal pin  80 , or  80   a , also provides, e.g. for safety purposes, protection against the implant being pushed off the luminal surface by application of extracorporeal pressure above the implantation site or due to patient movements. 
     The intra-luminal section  25  of the foot core  20  has a primary function to provide a rigid scaffold to support the flexible wing  60 . The underside of the intra-luminal section  25  may be concave in cross-section to reduce its profile within the artery  2  and has a hollow entry portion or port  52  of the guidewire channel  50  adjacent the neck  42 , shown in the sectioned foot core  20  of  FIG. 3D . 
       FIGS. 4A to 4F  show another foot core  20   a . This configuration has a circular intra-luminal portion  25   a  in plan view and a concave surface  30   a  which is concave in cross-sectional profile within the artery  2 . 
     It should be appreciated that many variations of the intra-luminal portion may be provided, only a limited number of which are shown herein. For example,  FIGS. 5A to 5B  show another foot core  20   b  having an intra-luminal portion  25   b  that is generally rectangular in plan view and includes a concave bottom surface. 
     The flexible wing  60 ,  FIGS. 6A and 6B , is a thin disc sized to be larger than the arteriotomy diameter (arteriotomy diameter is equivalent to the outer diameter of the delivery/procedural sheath  100 ). The central hole  65  and disc portion are circular in shape, in plan view. It should be understood, however, that other geometries may be provided for the hole and/or the disk portion of the wing  60 . The central hole  65  is sized to accept recessed cylindrical surface  23  within the foot core  20 &#39;s flexible-wing retention recess  22  shown, e.g. in  FIGS. 3A and 3B , and is free to rotate relative to the foot core  20  about the concentric axis of the recessed cylindrical surface  23 . 
       FIG. 6A  shows the flexible wing  60  in its flat and relaxed state, and  FIG. 6B  shows the flexible wing  60  in its curved state, which corresponds to the final configuration within the artery  2 . The curvature of the wing  60  shown in  FIG. 6B  corresponds to the curvature of the interior of the artery to which the wing  60  conforms in its final implanted state. When implanted, the wing  60  is pressed against the artery interior wall by hemodynamic hydraulic pressure exerted by the blood in the artery  2 . Although the wing  60  is flat, or planar, in its relaxed state, it should be appreciated that the wing  60  may be curved or have any other suitable geometry in its relaxed state. 
     Referring, e.g. to  FIGS. 1A to 1C , the flexible wing  60  is positioned within the artery  2  against the luminal surface  3  adjacent the arteriotomy and held in this position with the aid of the hemodynamic hydraulic pressure it acts as the primary seal around the arteriotomy to control bleeding. Referring to  FIG. 1C , the wing  60  is illustrated slightly pulled away from the luminal surface  3  only to facilitate illustration. 
     In addition to elastically deforming to conform to the luminal surface  3  of the artery  2 , the flexible wing  60  also elastically deforms to fit within the procedural sheath  100  for delivery into the artery  2 . This is achieved by rolling the wing  60  into a cylinder-like configuration. Once within the artery  2 , and beyond the procedural sheath  100 , the flexible wing  60  intrinsically recovers towards its flat state to allow the hemodynamic hydraulic pressure in the artery  2  to conform the wing  60  to the shape of the arterial luminal and surface topography  3 . In this regard, the elasticity of the wing  60  allows the wing  60  deform locally at differing areas of the luminal surface  3  of the artery  2 . This allows the wing  60  to conform to local irregularities along the surface  3  to ensure that the arteriotomy is adequately sealed despite such irregularities. 
     The flexibility of the wing  60  is not just important in a lateral configuration to facilitate collapse during delivery, but it is also important to flex in a longitudinal plane. Flexibility in both lateral and longitudinal planes is important to ensure an effective seal around the arteriotomy of arteries in differing disease states with different surface topographies and varying anatomical configurations. Longitudinal flex is facilitated by the configurations shown, e.g. in  FIGS. 2A-5D , by the flexible wing  60  and the foot core  20  being separate and distinct parts that are non-fixedly mated together. For example, since the wing  60  is not fixed to the foot  20 , it is able to separate from the upper surface of the relatively rigid intra-luminal portion  25  of the foot core  20  at regions where the topography of the arterial surface  3  deviates or is disposed at a greater distance from the upper surface of the intra-luminal portion  25  than at adjacent regions of the surface  3 . 
     Although the wing  60  has a circular outer periphery, it should be understood that the wing  60  may be provided with any suitable geometry. Further, although the wing  60  has a uniform thickness, it should be understood that the wing  60  may be provided with a thickness that varies at different regions of the wing  60 . For example, the wing  60  could have a thickness in its central region that is greater than a thickness toward the circumferential periphery of the wing  60 . 
       FIGS. 7A and 7B  shows an assembled implant  5  in cross section.  FIG. 7A  shows the implant  5  in a state where the guidewire  150  would be in situ, as illustrated, e.g. in  FIG. 32 , or subsequent to removal of the guidewire  150 .  FIG. 7B  shows the deployed implant  5 . 
     The extra-luminal pin  80  is a safety feature of the closure system to prevent the implant being pushed off the luminal surface by application of extracorporeal pressure above the implantation site or due to patient movements. The extra-luminal pin  80  in the illustrated example does not generally contribute to or form part of the sealing function of the implant  5 . The implant  5  will seal the arteriotomy in the absence of the extra-luminal pin  80  in accordance with some example embodiments. The extra-luminal pin  80  is deflected parallel to the artery  2  wall as it is advanced, as illustrated, e.g. in  FIG. 7B . This deformation of the extra-luminal pin  80  helps secure it in its post deployment position. The pin  80  is also maintained in this position via a press fit between the proximal portion  82  of the pin and the proximal recess  47  of the foot core  20  into which the proximal portion  82  is pressed. 
     Depending on implant design and requirements, the extra-luminal pin  80  may also be used to occlude the guidewire hole within the foot core  20  when deployed, e.g. in a configuration such as illustrated in  FIGS. 7A and 7B , the pin  80  being illustrated in isolation in  FIG. 7C . When deployed, as illustrated, e.g. in  FIG. 7B , an enlarged proximal portion  82  of the extra-luminal pin  80  blocks the guidewire channel  50 . In its proximal or retracted position, the pin  80  allows the guidewire  150  to pass through channel  83  in the enlarged proximal portion  82 . When the pin  80  is moved into its distal or deployed position, the channel  83  does not align with the channel  50  in the foot core  20 , thereby blocking the channel  50 . In the proximal or retracted position, the guidewire is able to pass through both channels  50  and  83  since the channels  50  and  83  are sufficiently axially spaced apart. 
     It should be understood, however, that any other suitable mechanism may be provided for closing the guidewire channel  50 . For example, again referring to  FIGS. 7A and 7B , the formation of coagulated blood in the conically shaped entry portion  52  of the guidewire channel  50 . The coagulated blood would then be pressed and locked into the narrowing conical geometry of the entry portion  52  by the hydraulic pressure exerted by the blood in the artery  2 . To facilitate coagulation of the blood in the entry portion  52 , the guidewire  150  may be left in place for, e.g. several minutes (e.g. 4 to 5 minutes). The presence of the guidewire may, during this period, induce sufficient clotting of the blood to form the closure in the entry portion  52 . Then, upon retraction of the guidewire  150 , the coagulated blood would compress and collapse to fill the void left by the removal of the guidewire  150 . 
     Although the illustrated entry portion  52  of the guidewire channel  50  is conical, it should be appreciated that any suitable geometry may be provided. Referring to  FIG. 7D , an alternative extra-luminal pin  80   a  is shown with an additional slot  85   a  to facilitate the pin  80   a  being moved into its distal or extended position whilst the guidewire  150  remains in place. 
     Some alternative embodiments to the extra-luminal pin  80  shown, e.g. in  FIG. 7C , are shown in  FIGS. 8A to 12B . 
     Referring to  FIGS. 8A and 8B , provided are a series of protrusions  80   c  that, in the radially extended position of  FIG. 8B , engage the extra-arterial subcuticular tissue to prevent the implant from being pushed forward. The protrusions  80   c  are exposed and allowed to spring into their radially extended position by proximal retraction of an outer shaft sleeve  84   c  configured to radially constrain and cover the protrusions  80   c  when the outer shaft sleeve  84   c  is in the distal position illustrated in  FIG. 8A . 
       FIGS. 9A and 9B  show an extra-luminal pin  80   d  attached to a suture  86   d , which when pulled proximally, flips the pin forward to engage the extra-arterial subcuticular tissue to prevent the implant being inadvertently pushed forward. The suture  86   d  may include a series of knots  87   d  to lock and hold the pin  80   d  in any desired angle between the position shown in  FIG. 9A  and the position shown in  FIG. 9B , depending on, e.g. tissue thickness and/or resistance. The suture  86   d , or any other suture described herein, may be formed of any suitable material. For example, any of the sutures described herein may be formed, in whole or in part, of a bio-absorbable material. 
       FIGS. 10A and 10B  show an arrangement similar to that shown in  FIGS. 9A and 9B . In this arrangement, the extra-luminal pin  80   e  is attached to a suture  86   e ; however the pin  80   e  has a pivot attachment or joint  81   e  to connect to the foot core  20   e . By pulling the suture  86   e , the pin flips forward, via rotation about the pivot attachment  81   e , to engage the extra-arterial subcuticular tissue of the artery  2  to prevent the implant from being pushed forward. The suture  86   e  may include a series of knots  87   e  to lock and hold the pin  80   e  in any desired angle between the position shown in  FIG. 10A  and the position shown in  FIG. 10B , depending on, e.g. tissue thickness and/or resistance. 
       FIGS. 11A and 11B  show an arrangement that is similar to that of  FIGS. 10A and 10B , but without a suture. The pin  80   f  has a pivot joint or attachment  81   f  to the foot core  20   f  activated by movement of an outer shaft sleeve  84   f  to engage the extra-arterial subcuticular tissue of the artery  2  to prevent the implant from being inadvertently pushed forward. The sleeve  84   f  may engage an angled surface of the pin  80   f  to begin rotation of the pin  80   f  about the pivot attachment  81   f . The pin may be moved to the position shown in  FIG. 11B  by any suitable mechanism. For example, the pin  80   f  may be spring biased toward the position shown in  FIG. 11B , with the sleeve  84   f , disengaging a latch, detent, or other mechanism that maintains the pin  80   f  in the position shown in  FIG. 11A . 
       FIGS. 12A and 12B  show an extra-luminal T-bar  80   g  attached to the end of a suture  86   g , which when pulled proximally, engages the T-Bar  80   g  with the extra-arterial subcuticular tissue to prevent the implant from being inadvertently pushed forward. The suture  86   g  may include a series of knots  87   g  to lock and hold the pin  80   g  in any desired angle or position between the position shown in  FIG. 12A  and the position shown in  FIG. 12B , depending on, e.g. tissue thickness and/or resistance. 
       FIGS. 13A to 18  show variations on the configuration of the foot core. 
     The foot core  20   h  of  FIG. 13A  has the intra-luminal portion  25   h  off-set proximally, toward the rear of the neck section  42   h . The intra-luminal portion  25   h  is circular in shape but the extra-luminal portion  40   h  meets the intra-luminal portion  25   h  at a location that is non-concentric to the circular cross-section of the intra-luminal portion  25   h . An advantage to this bias is that during delivery of the implant, specifically, as the delivery device is withdrawn from the artery to position the implant against the arteriotomy, the biased intra-luminal portion  25   h  offers more security or overlap between the intra-luminal portion  25   h  of the foot core  20   h  and the distal wound edge of the arteriotomy to prevent inadvertent pull-out from the artery. 
     The foot core  20   i  of  FIG. 13B  is similar to the foot core  20   h  of  FIG. 13A , but with a larger angle between the intra-luminal section  25   i  and the neck  42   i  of the implant. The larger angle has the advantage of further encouraging the heel of the intra-arterial implant to remain within the artery  2  during withdrawal of the delivery device  90  and positioning the implant against the lumen adjacent to the arteriotomy to prevent inadvertent pull-out from the artery  2 . This assumes a constant withdrawal angle of the delivery device (described in additional detail herein) of 60 degrees. However, a larger angle increases the tolerance on the withdrawal angle and still ensures the implant hooks or otherwise engages the rear wall of the arteriotomy. The increase in angle between the neck  42   i  and intra-luminal foot section  25   i  may be limited by what will reasonably fit through a loading funnel, which is described in further detail elsewhere herein. 
     To increase the flexibility of use, for example, another variation is to make the neck flexible. For example,  FIG. 14  shows a foot core  20   j  with a flexible neck  42   j . The neck  42   j  of the implant transitions from a round cross-section at its distal section to an elliptical cross-section at its proximal end. This allows the neck  42   j  to flex during its insertion through the loading-funnel. 
     Further variations to that shown in  FIG. 14  is to articulate the implant relative to a delivery device as shown in  FIGS. 51A to 51C . These configurations allow articulation between the delivery device and the implant. Securement of the implant to the delivery device is achieved by securing paddles or interlock projections  165   k ,  165   m  of retaining tubes  160   k ,  160   m  of a delivery device in place in corresponding interlock recesses  45   k ,  45   m  and preventing them from moving in a lateral direction by providing an external sleeve, such as, e.g. a release sleeve such as release sleeve  175  described in further detail herein. 
     The configuration of  FIGS. 51A and 51B  differs from that of  FIG. 51C  in that the interlock recesses  45   k  of  FIGS. 51A and 51B  extend laterally entirely though the wall of the neck  42   k , whereas the recess  45   m  of  FIG. 51C  does not. 
     Further variations to impart flexibility to the implant neck is shown in  FIGS. 15A and 15B . Here, the flexibility is imparted via a reduced cross section in at least a portion of the neck  42   n ,  42   p . The configuration of  FIG. 15A  differs from that of  FIG. 15B  in that  FIG. 15A  has a reduced cross-sectional geometry in only a portion its extra-luminal portion, whereas the configuration of  FIG. 15B  has a constant narrow cross sectional geometry along its extra-luminal portion. 
       FIG. 51D  shows a variation on the attachment of the implant to the delivery device. In particular, the interlock projections  165   r  of the retaining sleeve  160   r  have hooked portions that extend laterally inwardly to engage recesses  45   r.    
       FIG. 16  shows a further embodiment of the foot core. This configuration differs in that the foot core  20   t  has no retaining feature to secure the flexible-wing to the foot core  20   t . That is, the foot core  20   t  does not have a recess or any other particular mechanism configured to retain the wing  60  on the foot core  20   t . In this example, the flexible wing  60  may be secured by an interference fit between the foot core&#39;s neck  42   t  and the central opening  65  within the flexible wing  60 . This may facilitate the assembly of the flexible wing  60  onto the foot core  20   t.    
     Referring to  FIGS. 17A to 17C , a further variation of this concept is to assemble the flexible wing  60  onto the neck  42   u  of the foot-core  20   u  and then secure the wing  60  in place by the addition of a through pin or the further assembly of a collar  195   u  with an interference fit between the collar  195   u  and foot core&#39;s neck  42   u . The collar  195   u  may further be secured by one or more projections configured to engage with corresponding one or more recesses in neck section  42   u.    
       FIG. 18  provides another extra-luminal pin  80   w . In this example, an additional feature to secure the extra-luminal pin  80   w  within the foot core  20   w  is to incorporate a taper lock when the enlarged proximal or rear portion  82   w  of the extra-luminal pin  80   w  engages with the foot core  20   w.    
     The conical taper lock between the extra-luminal pin  80   w  and the foot core  20   w  relies, in this example, on the foot core taper being at a lesser angle than the taper on the mating surfaces of the extra-luminal pin  80   w . This taper-lock not only enhances the lock between the two components  80   w ,  20   w  once positioned relative to each other, but also improves the potential fluid seal between the two components with respect to sealing the guidewire channel  50   w.    
     Referring to  FIGS. 19 to 27 , a further closure device or implant  5   y  includes all of the features of the other closure devices, e.g. closure device  5 , except to the extent indicated otherwise. 
     The closure device  5   y  includes a foot core  20   y  having a profile that is “hybrid” in that it shares geometric features with both a round foot core, such as, e.g. the foot core  20   a  shown in  FIG. 4A , and an elongated foot core, such as, e.g. the elongated foot core  20  shown in  FIG. 3C . Referring for example, to  FIG. 27 , the hybrid foot core  20   y  has rounded portions  56   y  and projecting portions  57   y.    
     The rounded portions  56   y  extend around the portion of the foot core  20   y  that extends through the flexible wing  60  to provide increased lateral surface area of the foot core  20   y , adjacent the opening in the wing  60  and the arteriotomy to be sealed. This region of increased lateral surface area provides for a greater sealing between, e.g. the foot core  20   y  and the wing  60 . 
     The projecting portions  57   y  give the intra-luminal portion of the hybrid foot core  20   y  an elongated shape. This elongated shape further limits the ability of the foot core from being inadvertently pulled back through the arteriotomy when the operator is setting the closure device  5   y  in into its implanted position. 
     Thus, the hybrid foot core  20   y  may provide the sealing advantages of a wide or rounded foot core as well as the setting benefits of an elongated foot core. 
     The geometry of the hybrid foot core  20   y  provides support to the artery in both a longitudinal direction and transverse direction. Although the foot core  20   k  has a circular central region, it should be understood that any suitable widened geometry, e.g. oval, square, rectangular and/or polygonal, with rounded and/or sharp corners. This central region provides a flaring out of the profile of the intra-luminal portion of the foot core  20   k  in the region where the neck of the foot core  20   k  passes through the flexible wing  60 . 
     In a manner analogous to that of the device  5  illustrated, e.g. in  FIGS. 7A and 7B , the pin  80   y  may be used to occlude the guidewire hole within the foot core  20   y  when deployed, e.g. in a configuration such as illustrated in  FIG. 21 . When deployed, as illustrated, e.g. in  FIG. 21 , an enlarged proximal portion  82   y  of the extra-luminal pin  80   y  blocks the guidewire port or channel  50   y . In its proximal or retracted position, the pin  80   y  allows the guidewire to pass through channel  83   y  in the enlarged proximal portion  82   y . When the pin  80   y  is moved into its distal or extended position, the channel  83   y  does not align with the channel  50   y  in the foot core  20   y , thereby blocking the channel  50   y . In the proximal or retracted position, the guidewire is able to pass through both channels  50   y  and  83   y  since the channels  50   y  and  83   y  are sufficiently axially spaced apart. 
     Referring, for example, to  FIG. 25 , the channel  83   y  in the pin  80   y  is elongated to allow for increased freedom of movement of the guidewire within the channel  83   y.    
       FIGS. 28A to 28B  show a front perspective view of a foot core  20   z  that differs from the foot core  20   y  in that the lateral portions  56   z  are partially flattened to provide a reduced width. This flattening or facing results in two flat surfaces  58   z . By reducing the width of the foot core  20   z  relative to the foot core  20   y , greater clearance is provided between the foot core  20   z  and the loading funnel  396  or loading cannula  335  described in further detail herein. This allows a larger diameter or thicker flexible wing  60  to be loaded by facilitating more clearance and hence, a larger amount of the flexible wing  60  to overlap within the loading funnel and loading cannula thereby reducing the potential for premature and unfavorable interaction between the footcore and overlapping flexible wing. 
     Nevertheless, the foot core  20   z  may provide similar benefits to the rounded portions  56   y  due to the lateral projection of the portions  56   z  relative to the width of the lateral portions  56   z  relative to the width of the projecting portions  57   z . As with the foot core  20   y , this increased width is provided at a location adjacent the location where the extra-luminal portion  40   z  extends through the aperture in the flexible wing  60 . 
     Thus, the foot core  20   z  reduces the width of the lateral projections, but only to an extent that does not substantially affect the sealing between, e.g. the foot core  20   z  and the wing  60 . 
     As with the foot core  20   y , the foot core  20   z  may provide the sealing advantages of a widened or rounded foot core as well as the setting benefits of an elongated foot core. 
     Referring to  FIG. 29 , which is not drawn to scale, the wing  60  includes an anterior surface  61 , which contacts the luminal surface of the artery when implanted, and a posterior surface  64 , which faces the lumen of the artery and the blood flow when implanted. 
     The anterior surface  61  and/or the posterior surface  64  is provided with an altered wettability, i.e., a change in surface energy from the native, e.g. smooth, surface finish. This change in wettability may be provided in the form of electrical charge, surface texture, protein attachment, mechanical scraping, chemical etching, laser etching and/or other etching, shot blasting (using various shot media), plasma discharge, manufacturing process that encourage functional end groups at the surface, and/or any other suitable form. This change in surface energy encourages cell (or thrombocyte) attachment or adhesion directly or via protein attachment, extracellular matrix and/or adhesion molecule to the luminal surface of the flexible-wing or, conversely, discourage cell or protein attachment. In the illustrated example, the wettability of the anterior surface  61  is increased in order to encourage attachment or adhesion. Cellular attachment or platelet aggregation on the luminal surface  61  of the flexible wing  60  aids and expedites sealing as well as anchoring the intra-arterial implant. This change in surface energy also encourages the adhesion, via a change to the surface tension of the modified material, to the surrounding soft tissue. 
     Referring to example embodiment of  FIG. 29 , the anterior surface  61  of the wing  60  is roughened, e.g. abraded, to created grooves or channels  62  having a depth  63  on the order of, for example, 1-100 μm. In some examples, the depth may be on the order of 7-10 μm. It should be understood, however, that the depth  63  may fall within a substantially larger, smaller, and/or different range. The area of abrasion may be continuous or provided in a patterned arrangement. These channels or grooves  62  facilitate cell attachment (e.g. leukocytes, erythrocytes and particularly thrombocytes) and aggregation. As indicated above, this aggregation of cell promotes thrombogenesis which also forms an attachment to the luminal wall of the artery above the wing  60 . This cellular attachment to both the artery wall and anterior surface of the wing  60  may act as a secondary seal. The cellular attachment to the surface  61  of the wing  60  may occur, for example within seconds of the wing  60  being implanted. 
     The posterior surface  64  is relatively flat in the illustrated example. It should be understood, however, that the posterior surface  64  may be provided with a texture in some example embodiments. Further the posterior surface  64  may be provided with any other mechanism of altered wettability, either increased or decreased, as may be suitable. 
     Delivery System for Delivering the Closure Device 
     The closure device  5  is designed to be delivered into the artery  2 , or other suitable location, via the procedural sheath  100  used in the interventional procedure over a guidewire  150  in the illustrated examples. Hence, the delivery sequence may start with the sheath  100  and guidewire  150  in situ within the vessel  2 . The procedural sheath  100  of the illustrated example includes a hub  110  containing a valve and typically a side arm  120 , as illustrated, e.g. in  FIG. 30 . In particular,  FIG. 30 , shows an 18 F introducer sheath  100  having hub  110  with valves and side-arm  120 . 
     The side arm  120  may be used, for example, to inject contrast to confirm the position of the sheath  100  relative to the arteriotomy or pressured saline to prevent the sheath  100  from back filling with blood. The valve assembly within the hub  110  is provided to allow the introduction of devices of varying diameters into the sheath  100  and prevents blood loss through the rear of the sheath  100 . The guidewire  150 , which extends through the longitudinal lumen of the sheath  100 , is provided as a safety feature which allows percutaneous re-access to the arterial lumen as a contingency if needed. 
     Referring to  FIGS. 31A and 31B , a delivery system  1  includes a delivery device  90 . The delivery device  90  has a handle  93  at its proximal end and a flexible shaft  92 , which attaches to the implant  5  at the distal end.  FIGS. 31A and 31B  show the implant attached at distal end of the delivery device and within artery  2 . 
     The shaft  92  includes three flexible concentric slidable tubes  155 ,  160 ,  175 . The inner tube (pusher-tube  155 , illustrated in  FIG. 7A ) is configured to push the extra-luminal pin  80  from its proximal delivery position, as shown, e.g. in  FIG. 2A , to its distal post deployment position, as shown, e.g. in  FIG. 2B . The pusher-tube  155  has an internal diameter sized to accept the guidewire  150 . The middle tube (retaining-sleeve  160 ) and outer tube (release-sleeve  175 ) in combination retain and release the implant which is attached to the distal end of the delivery system as shown in  FIGS. 33A to 33C . 
     Referring to  FIG. 35 , the handle  93  is attached to the proximal end of the shaft  93  and is used to control the relative position of the implant  5 , push the extra-luminal pin  80  and release the implant  5 . As shown in  FIG. 35 , the handle  93  has its right-hand-side external cover removed from the mated left-hand-side cover  94  to expose the internal components of the handle  93 . 
     Handle components: With reference to  FIG. 35 , the thumb button  180  activates the push-tube  155  to push forward the extra-luminal pin  80 . The retaining-sleeve anchor  169  anchors the retaining-sleeve  160  to the handle  93  in a fixed position. The release-sleeve hub  177  connects the release sleeve  175  to a slide switch  185 , which when slid proximally or backwards pulls the release sleeve  177  backwards or proximally relative to the retaining sleeve  160  to release the implant  5 . 
       FIG. 52  shows another handle  200  configured to be mated to the shaft  92  in manner analogous to the handle  93 . The handle  200  includes: a first housing portion  205 , a second housing portion  210 , a guidewire extension tube  215 , a pusher tube hub  220 , a retaining sleeve hub  225 , a release sleeve hub  230 , a lock member  240 , and a thumb slider  250 . 
     The thumb slider  250  is configured to move along a linear guideway formed by housing  203 , which includes the first and second housing portions  205  and  210 . In particular, the thumb slider  250  is configured to move, due to, e.g. manual actuation by the thumb of a human operator, between a first position and a second position. The first position is shown, for example, in  FIGS. 54A to 54F , and the second position is shown, for example, in  FIGS. 55A to 55C . 
     The guidewire  150  runs through the pusher tube  155  and through the handle, including through the guidewire extension tube  215  and out the proximal or rear end of the handle  200 . The guidewire extension tube  215  is supported by support ribs  216  of the housing  203 . 
     The handle  200  is configured such that movement of the thumb slider  250  from the first position to the second position causes the extra-luminal pin  80  of the implant  5  to move from its proximal delivery position as shown, e.g. in  FIG. 2A  to its distal post deployment position as shown, e.g. in  FIG. 2B . 
     The lock member  240  is configured to prevent the deployment of the extra-luminal pin  80  prior to removal of the guidewire  150  from the delivery device. The lock member  240  is configured to be pressed transversely into the housing  203  from a first position illustrated, for example, in  FIG. 54B , to a depressed second position illustrated, for example, in  FIG. 54D  when the user wishes to unlock the thumb slider  250 . 
     Referring to  FIG. 53 , the lock member  240  includes a projection  248  that is received in a corresponding recess  213 , illustrated in  FIG. 52 , of the housing  203 . When the projection  248  is received in the recess  213 , the lock member  240  is prevented from being depressed. In order to depress the lock member  240 , the projection  248  must be moved out of engagement with the recess  213 . This mechanism prevents, or at least reduces the likelihood of, inadvertent depression of the lock member  240  prior to insertion of the guidewire—for example, when the device is removed from its packaging, which is described in additional detail below. 
     In order for the operator to move the projection  248  out of engagement with the recess  213 , the user applies a proximally directed force to the lock member  240 . The lock member  240  includes a pair of slots  241  and  242  that allow a portion  247  between the slots  241  to be bend or flex with respect to the remainder of the lock member  240  when the operator applies the proximally directed force. Since the projection  248  is disposed on the portion  247 , this bending of the portion  247  causes the projection  248  to move out of engagement with the recess  213 , thereby allowing the lock member  240  to be depressed. 
     When the lock member  240  is in the non-depressed first position, a locking tab  244  extends into a space in the thumb slider  250  adjacent a locking surface  252 , such that the interface between the locking tab  244  of the lock member  240  and the locking surface of the thumb slider  250  forms a positive stop to prevent the thumb slider  250  from moving axially away from the lock member  240 . Since the lock member  250  is constrained to the housing  203  in a fixed axial position, the positive stop between the lock member  240  and the thumb slider  250  prevents the thumb slider  250  from being slid forward to its distal position, thus preventing the corresponding actuation of the extra-luminal pin  80  into its deployed position. 
     In order to unlock the thumb slider  250  to allow deployment of the extra-luminal pin  80 , the user depresses the lock member  240  to move the lock member from its first position to its depressed second position, illustrated, for example, in  FIG. 54E . In the depressed position, the locking tab  244  moves out of engagement with the thumb slider  250 , such that the locking surface  252  of the thumb slider  250  does not contact the locking tab  244  of the lock member  240  as the thumb slider  250  is pressed and moved forward or distally to thereby deploy the extra-luminal pin  80 . 
     To prevent the lock member  240  from being depressed prior to removal of the guidewire  150 , the lock member  240  is provided with a through hole  243  through which the guidewire  150  passes during positioning of the implant  5 . When the guidewire  150  extends through the through hole  243 , as illustrated in  FIGS. 54A and 54B , the lock member  240  is prevented from being depressed, since the guidewire  150  engages the through hole  243  to block the lock member  240  from moving laterally with respect to the guidewire and into the depressed position. 
     Although the lock member  240  is provided with a through hole in the illustrated example, it should be understood that any suitable geometry, e.g. a slot, notch, and/or flat surface, may be provided to engage the guidewire  150  and thereby block movement of the lock member  240 . 
       FIG. 54B  shows the guidewire  150  being removed from the device in the direction of the arrow superimposed on the housing  203 , until the guidewire  150  is fully withdrawn as illustrated in  FIG. 54C . After the guidewire  150  is withdrawn, the guidewire  150  no longer extends through the through hole  243 , as illustrated, e.g. in  FIG. 54C . Thus, the lock member  240  is no longer prevented from being depressed. 
     Referring to  FIG. 54E , the lock member  240  includes a projection  246  that engages a first recess  201  when the lock member  240  is in the first position and that engages a second recess  202  when the lock member  240  is in the depressed second position. This engagement allows the lock member  240  to be retained in the respective first and second positions, but allows movement upon application of a force sufficient to overcome the engagement. Thus, the projection  246  and the recesses  201  and  202  function as detent mechanisms. 
     After the lock member  240  is depressed to disengage the lock member  244  from the thumb slider  250 , as illustrated, e.g. in  FIG. 54D , the user may slide the thumb slider  250  distally, in the direction illustrated by the arrow in  FIG. 54F , until the slider reaches its distal second position, as illustrated, for example, in  FIG. 55A . 
     This distal movement of the thumb slider  250  results in deployment of the extra-luminal pin  80 . As with the handle  93 , the handle  200  achieves the actuation of the extra-luminal pin  80  from its delivery position to its deployed position by distally pushing the pusher tube  155 . In particular, the proximal end of the pusher tube  155  is attached to the pusher tube hub  220 , which is in turn coupled to the thumb slider  250 . Thus, as the thumb slider  250  moves distally or forward, the pusher tube hub  220  is also moved distally or forward, thereby also moving the pusher tube  155  forward to push the extra-luminal pin  80  from its proximal position to its extended deployed position. 
     Referring to  FIGS. 52 and 53 , the pusher tube hub  220  includes grooves  221  that receive respective corresponding linear guide ribs or projections  206  in the housing  203  to function as a linear slide. One of the guide ribs  206  is illustrated as part of the first housing portion  205 , the second housing portion  210  being essentially identical, but mirrored, with respect to the first housing portion  205 . The pusher tube hub  220  also includes a projection  222  that is received in a corresponding recess or groove  251  of the thumb slider  250  to constrain the projection  222  and thereby transfer proximal and distal motion of the thumb slider  250  to the pusher tube hub  220 . 
     As the thumb slider  250  and the pusher tube are pushed distally relative to the housing  203 , the retaining sleeve  160  and the release sleeve  175  remain stationary with relative to the housing. Thus, the pusher tube  155  is pushed relative to the retaining sleeve  160  and the release sleeve  175 , and therefore also relative to the implant  5  supported by the retaining sleeve  160  and the release sleeve  175 . 
     The retaining sleeve  160  is maintained in its stationary position relative to the housing  203  by being mounted in a retainer hub compartment  207  of the housing  203 , as illustrated, for example, in  FIGS. 52 and 54A . In the illustrated example, the retaining sleeve is maintained in a stationary position relative to the housing  203  during all stages of operation of the surgical system. It should be understood however, that the retaining sleeve may be configured to move relative to the housing during one or more stages of operation of the system. 
     The release sleeve  175  is maintained in its stationary position relative to the housing  203  during the forward movement of the thumb slider  250  by distal and proximal stops of the housing  203  that engage the release sleeve hub  230  to constrain distal and proximal movement, respectively. The distal stop is formed by a projection or wall  209  of the housing  203 , as illustrated, e.g. in  FIG. 55B , while the proximal stop is formed by a hub lock  208  of the housing  203 , as illustrated, e.g. in  FIGS. 56A and 56B . 
     Referring to  FIG. 53 , a front face  231  of the release sleeve hub  230  contacts the distal stop and projections  232  contact the proximal stop. In the illustrated example, two projections  232  engage a pair of respective hub locks  208 ; however, it should be understood than any number of projections  232 , including a single projection  232  may be provided to engage any number of hub locks  208 , including a single hub lock  208 . 
     After deployment of the intra-luminal pin  80 , the next procedural step is to release the implant  5  from the delivery device. In order to do so in the illustrated example, the user needs to move the release sleeve  175  proximally relative to the retaining sleeve  160 . The mechanism for releasing the implant  5  upon the relative motion between the release sleeve  175  and the retaining sleeve  160  is described in further detail elsewhere in the present description. 
     In order to move the release sleeve  175  proximally relative to the retaining sleeve  160 , which remains stationary relative to the housing  203 , (a) the proximal lock, which is the hub lock  208  in the illustrated example, must be disengaged from the release sleeve hub and (b) the thumb slider  250  engages the release sleeve hub  230  such that proximal movement of thumb slider  250  relative to the housing  203  causes corresponding movement of the release sleeve hub  230 , and therefore also the release sleeve  175 , relative to the housing  203  and the retaining sleeve  160 . 
     Referring to  FIGS. 53, 56A, and 56B , the thumb slider  250  includes a pair of cam sliders  253  that engage the respective hub locks  208  as the thumb slider  250  approaches its distal second position. In particular, the distal advancement of the ramped or sloped surfaces  254   a  of the cam sliders  253  causes the hub locks  208  to move laterally and clear of the projections  232  of the release sleeve hub  230 . Continued distal advancement of the thumb slider  250  causes the hub locks  208  to slide along flat surfaces  254   b  of the respective cam sliders  253  to maintain the hub locks  208  in their disengaged positions. 
     The hub locks  208  may be configured as cantilevered projections from the housing  203  that flex in the lateral direction in the manner of a leaf spring, while maintaining sufficient rigidity in the axial direction to resist proximal movement of the release sleeve hub  230  when engaged therewith. Moreover, any other suitable proximal locking mechanism may be provided. 
     After the hub locks  208  are moved out of alignment with the projections  232  of the release sleeve hub  230 , a clip member  255 , which slides over a ramped or sloped surface  233  of the release sleeve hub  230 , latches with the release sleeve hub  230  by engaging with distally facing latch surface  234  of the release sleeve hub  230 . 
     After latching of the thumb slider  250  to the release sleeve hub  230 , the operator moves the thumb slider  250  proximally to a proximal third position in the direction of the arrow shown in  FIG. 57A , to retract the release sleeve hub  230  and the release sleeve  175  to the position shown in  FIG. 57B . Although in the illustrated example, the proximal third position of the thumb slider corresponds to the proximal first position of the thumb slider, it should be understood that the first and third positions may be different. 
     The cam surfaces  254   a  and  254   b  are of sufficient length in the illustrated example to maintain the disengaged position of the hub locks  208  until the proximally directed faces of the projections  232  of the release sleeve hub  230  have proximally cleared the distally facing stop surfaces of the hub locks  208 . 
     When the device is in the state illustrated in  FIG. 57B , the implant  5  is released from the end of the delivery device via the proximal movement of the release sleeve  175  relative to the retaining sleeve  60 . 
     The thumb slider  250  further includes a projection  256  that engages a corresponding recess  212  in the housing  203  when the thumb slider  250  is in the proximal position. This engagement allows the lock member  240  to be retained in the respective first and second positions, but allows movement upon application of a force sufficient to overcome the engagement. Thus, the projection  256  and the recess  212  function as a detent mechanism. 
     Prior to withdrawal of the distal end of the delivery device, the thumb slider  250  may be again moved distally, to a fourth position, as illustrated in  FIG. 57C . Moving the thumb slider  250  to the distal fourth position causes the release sleeve  175  to move distally with respect to the retaining sleeve  160 , which causes the distal end of the release sleeve  175  to at least partially cover the interlocking projections  165  of the retaining sleeve  160 , which are illustrated, for example, in  FIG. 33A . Re-covering or re-sheating these projections  165  may be advantageous to reduce the risk of trauma to the surrounding tissue as the delivery device is withdrawn from the percutaneous tissue tract. 
     Although in the illustrated example, the distal fourth position of the thumb slider corresponds to the distal second position of the thumb slider, it should be understood that the first and third positions may be different. 
     To facilitate passage of the release sleeve hub  230  distally past the hub locks  208 , the release sleeve hub  230  may be provided with ramped or sloped chamfer surfaces  236 , which are illustrated in  FIG. 53 . These surfaces  236 , which slope downwardly as they extend distally along the release sleeve hub  230 , engage the hub locks  208  as the release sleeve hub  230  is moved distally in order to move raise the hub locks  208  to prevent the hub locks  208  from axially blocking the projections  232  of the release sleeve hub  230 . 
     The shaft  92  is designed to push the implant  5  down the procedural sheath  100  into the artery  2  and allow control of the implant&#39;s relative position by the user from the handle  93 . 
     Implant retention and release: Referring, e.g. to  FIGS. 33A to 33C , to secure the implant  5  on the distal tip of the delivery device  90 , two profiled interlock projections  165  which extend from the retaining sleeve  160  engage into the implant&#39;s matching interlock recesses  45  in the neck  42  of the foot core  20 . To ensure the profiled projections  165  remain engaged with the foot core  20 , a release-sleeve  175  is positioned in a distal or forward location, as illustrated in  FIG. 33C , to prevent the projections  165  from moving laterally outwardly. 
     To release the implant  5  from the distal tip of the delivery device  90 , the release-sleeve  175  is slid back to expose the interlock projections  165  on the retaining-sleeve  160 . The tip of the retaining-sleeve  160  is split longitudinally, via longitudinal splits or notches  167 , to allow lateral movement of the interlocking projections  165 , and the rear shoulders of interlocking recesses  45  on the foot core  20  may be ramped, as illustrated, e.g. in  FIGS. 34A to 34B , to facilitate release of the implant  5  by pulling the delivery device  90  away from the implant  5 . It should be understood, however, that any suitable geometry may be provided, e.g. a perpendicular edge, under-cut, etc, to mate with appropriate geometries of the interlocking projections  165 . 
     Further, mating surfaces of the interlock projections  165  and the interlocking recesses  45  may be provided with one or more radial protrusions that engage with one or more corresponding radial recesses. For example, an interlocking projection  165  may include a plurality of radial protrusions that engage a corresponding plurality of radial recesses of a mated interlocking recess  45 , or the interlocking recess  45  could be provided with the radial protrusions that mate with corresponding radial recesses of the interlocking projection  165 . Further, the interlocking recess  45  could have at least one recess and at least one protrusion, the at least one recess and the at least one protrusion respectively mating with corresponding at least one protrusion and at least one recess of the interlocking recess  45 . These various surface recess/protrusion configurations may provide a high level of securement (e.g. in the axial direction) between the interlocking projections  165  and the interlocking recesses  45 . Moreover, these various surface recess/protrusion configurations may be provided alone or in combination with other interlocking mechanisms between the interlocking projections  165  and the interlocking recesses  45 . 
     Although the interlocking projections  165  extend straight along the length of the retaining sleeve  160 , it should be appreciated that the projections  165  may be flared outwardly, such that retraction of the release sleeve  175  allows the interlock projections  165  to spring outwardly away from their interlocking engagement with the interlock recesses  45 . 
     Referring to  FIG. 36 , the loading funnel  95  is used to compress the flexible wing  60  of the implant into a cylindrical shape to allow it to fit within the procedural sheath  100  for delivery. The loading funnel  95  is also used to insert the compressed implant and delivery system into the procedural sheath  100  through the sheath&#39;s valve, as shown in  FIG. 30 . The loading funnel  95 , in accordance with some exemplary embodiments, is used immediately prior to delivery to avoid storage of the flexible wing  60  in the compressed state and potentially taking a memory set shape in the compressed form. 
     The loading funnel in the illustrated example includes four components namely, the funnel or funnel body  96 , cap  97 , seal  98 , and seal-retainer  99  shown in  FIG. 36 . It should be understood however that the loading funnel may have more or fewer components. 
     The cap  97  and seal  98  are pre-loaded on the shaft  92  of the delivery device  90  proximal to the implant  5 . The funnel  96  is advanced over the implant  5 , large opening end first, to compress the wing  60  into a cylindrical shape as the tapered section of the funnel  96  is advanced over the implant  5 . The funnel  96  is advanced until the implant  5  is resident in the cylindrical section  130  of the funnel  96 .  FIG. 37  shows the relative positions of the funnel body  96 , cap  97 , and seal  98  to the implant  5  and shaft  92  of the delivery device  90  during advancement of the funnel  96  relative to the implant  5 . 
     Once the implant  5  is disposed in the cylindrical section  130  of the funnel  96 , the cap  97  is now attached to the funnel  96 , which forms a seal with the delivery device&#39;s shaft  92 . 
       FIG. 38  shows the relative position of the implant  5  within the funnel  96  after being loaded therein. 
     Loading funnel configurations: The loading funnel  95  in a very simple form may be a tapered funnel. However, to encourage the flexible wing  60  to fold when loaded into the funnel body  96 , an alternative option is to provide a funnel body  96   a  that includes a protrusion  132   a  along the tapered section  131   a  which extends into the cylindrical section  130   a , as shown in  FIGS. 39A to 39C . With this option, the loading funnel  95   a  is positioned relative to the flexible wing  60  to encourage one side of the wing  60  to be lifted above the opposite leaflet of the wing  60  during insertion. 
     Referring to  FIGS. 40A and 40B , a third option is to have a splitable funnel  96   b  for removal from the shaft  92  of the delivery device  90  once the implant  5  is delivered through the procedural sheath hub  110  and valve. Once the implant  5  is within the procedural sheath  100 , the funnel  95   b  may be withdrawn from the sheath valve, its cap  97   b  then removed, and the funnel body or section  96   b  may then be opened, via separation of two subparts connected at split line  134  to remove the funnel body  96   b  from the shaft  92  of the delivery device  90 . 
     The above-described loading funnel concepts require the cap  97 ,  97   a ,  97   b  to be pre-loaded onto the shaft  92  of the device  1  proximal to the implant  5  and the funnel  96 ,  96   a ,  96   b  to be advance over the implant  5  and shaft  92 . Referring to  FIGS. 41A and 41B , a fourth concept is to have the funnel  95   c  pre-loaded onto the shaft  92 , proximal to the implant  5 , and advance the funnel  95   c  distally over the implant  5  to compress the flexible wing  60  into the cylindrical section  130   c  and into the cannula section  135   c  of the loading funnel  95   c . The tapered section  131   c  and cylindrical section  130   c  of the funnel body  96   c  is completely removable from the cannula  135   c , as illustrated in  FIG. 42A . The loading cannula  130   a  is cylindrical in shape and is used to insert the implant  5  and device  90  through the procedural sheath valve and into the procedural sheath  100  for delivery into the artery  2 . The delivery cannula  130 ,  130   a  and  135   c  may be chamfered at it distal end to assist in penetrating the valve at the rear of the procedural sheath  100 . As illustrated in  FIG. 42A  the funnel body  96   c  has been removed after loading the implant  5  into loading cannula  135   c.    
       FIG. 42B  shows the components of the loading funnel  95   c , including loading cannula  135   c , detachable funnel  96   c , end cap  97   c , seal  98   c , and seal retainer  99   c . The loading cannula  135   c  and detachable funnel  96   c  form the funnel body  95   c  in this example. The proximal end of the delivery cannula  135   c  is adapted to form a seal around the shaft  92  of the device  90  but allow the shaft  92  to axially slide relative to the cannula  135   c . This configuration of loading funnel  95   c  also has the advantage of protecting the implant  5  during storage and handling of the device  90 . 
       FIGS. 43A to 43M  show alternative funnel bodies  96   d ,  96   e ,  96   f ,  96   g , and  96   h . These funnel bodies  96   d ,  96   e ,  96   f ,  96   g , and  96   h  may be used in connection with, for example, the preloaded loading funnel  95   c  shown in  FIG. 41A , in place of funnel body  96   c , or in place of any of the other funnel bodies recited herein. 
     Referring to  FIG. 43A , the detachable funnel section or body  96   d  includes a longitudinal split  140   d  to facilitate removal of the funnel section from the guidewire  150 . This split  140   d  may be a discontinuation of the component to provide a gap, or allow a gap to be formed (e.g. via flexing of the funnel body  96   d ) for the guidewire  150  to pass there through during removal. This split may also be formed by physical removal of a strip of material from the funnel wall, for example as a peelable strip. 
     Referring to  FIGS. 43B to 43D , the funnel body  96   e  includes a weakened or notched section  145   e  that allows the funnel wall, in this example, to have a continuous integral internal surface which can easily be split along the weakened or notched section  145   e . In the illustrated example, the weakened section is provided as a longitudinally extending groove or channel that weakens the structure of the funnel wall. The weakened or notched section  145   e  may be split, for example, by manual exertion of force by an operator. 
     The open split arrangement of  FIG. 43A  and the weakened wall arrangement of  FIGS. 43B to 43D  may, in some examples, be notched at the beginning of the splits or pre-split weakened portions to allow ease of locating the guidewire into the split, e.g. to facilitate relative movement of the guidewire from the inner lumen of the funnel body to the exterior of the funnel body via the split. 
     For example, referring to  FIG. 43E TO 43G , a split funnel body  96   f , which includes features analogous to the split funnel body  140   d  of  FIG. 43A , further includes a notch  142   f , which is continuous with the split  140   f.    
     It should be appreciated that a split or splittable funnel body concept is applicable to any funnel arrangement in the context of the present invention. Further, although the splits or split lines of the illustrated examples are coplanar with the longitudinal axes of the respective funnel bodies, it should be appreciated that the split or split line may be non-coplanar and/or have an irregular path. 
     Moreover, although the illustrated examples include a single split or split line, it should be appreciated that multiple splits or split lines or any combination of splits and split lines may be provided. Further, a respective split line may be split at one or more locations along the length of the split line and weakened so as to be splittable at one or more other locations along the split. 
     Other mechanisms for removing the funnel body may include, for example, cutting or tearing the funnel body, e.g. with a cutting tool, in the presence or absence of predetermined split lines such as the split lines described above. 
       FIG. 43H  shows a perspective view of a staged funnel body  96   h  that may be used in connection with, e.g. any of the funnel arrangements described herein. As shown, the staged funnel body  96   h  includes two distinct tapered or funnel-shaped portions  162   g  and  164   g  separated axially by a constant-diameter (in this example, cylindrical) portion  163   g . Sections  161   g  and  130   g  are at opposed axial ends of the funnel body  96   h  and are, in this example, cylindrical. The staged funnel body  96  provides a progressive folding of the implant in two distinct sections. 
       FIGS. 43J to 43M  show an offset funnel body  96   h , which may be used in connection with, e.g. any of the loading funnel arrangements described herein. In this arrangement, the overall central axis A of the funnel body  96   h  is nonlinear, such that the central axis along the enlarged introduction portion  171   h  is offset with regard to central axis along the narrowed cylindrical portion  172   h , with a transition provided along tapered or funnel-shaped portion  173   h . In this embodiment, the off-set funnel body  96   h  biases the shaft of the delivery device and hence the flexible-wing to the side of the funnel as illustrated. It may be advantageous for the funnel body  96   h  to be at a particular orientation relative to the implant  5  during loading. 
     Although the tapered geometry of the various funnel bodies described herein may in some examples be illustrated as being conical or of a constant taper angle, it should be understood that curved and/or irregular tapers may be provided in addition, or as an alternative, to the illustrated funnel bodies. 
       FIGS. 44 to 50  show a delivery sequence in accordance with exemplary embodiments of the present invention. 
     The delivery of the implant  5  starts with the procedural sheath  100  and guidewire  150  percutaneously positioned in situ. 
     The delivery sequence depends on which variant of loading funnel is used. For example, if any of the loading funnel shown in  FIGS. 36 to 40B  are used, then the first step may be to load the loading funnel onto the guidewire  150 . If, for example, the loading funnel shown in  FIGS. 41A to 42B  is used then this step may be omitted. For simplicity the following sequence describes an exemplary delivery method using the loading funnel  95  shown in  FIGS. 36 to 38 . 
     Step  1 : Back load the guidewire  150  into the foot core  20  and the shaft  92  and handle  93  of the device  90 . This step is generally illustrated in  FIG. 44 . 
     Step  2 : Insert the implant  5  into the funnel  96  to compress the flexible wing  60 , and place the cap  97  and seal  98  (as well as retainer  99 ) onto the rear of loading funnel  96 . This step is generally illustrated in  FIGS. 45A and 45B . 
     Step  3 : Insert the loading funnel  95  (and the other components of the device  90 ), which houses the implant  5 , into the hub  110  and valve  115  at the rear of the procedural sheath  100 . This step is generally illustrated in  FIGS. 46A and 46B . 
     Step  4 : As illustrated in  FIGS. 47A and 47B , the delivery device  90  and implant  5  are advanced down the procedural sheath  100  into the artery  2  to deliver the implant  5  into the arterial lumen (just distal to the procedural sheath tip) of the artery  2 . Alternatively, the implant may be delivered into the arterial lumen by being advanced down the procedural sheath  100  into the artery  2  to deliver the implant  5  just proximal to the procedural sheath tip, then holding the delivery device  90  stationary (once the implant is positioned at the sheath tip) and withdrawing the sheath  100  over the delivery device  90  the required amount to expose the implant  5 . This avoids pushing the exposed implant  5  upstream within the artery  2 . 
     Step  5 : Withdraw the procedural sheath  100  from the artery  2  and position the implant  5  in juxtaposition to the arteriotomy. The implant  5  is now controlling the bleeding from the arteriotomy. This step is generally illustrated in  FIG. 48 . 
     Step  6 : Once confirmed that the implant  5  is correctly positioned and effecting a seal, the guidewire  150  is withdrawn, the extra-luminal pin  80  is deployed, and the implant is released. This step is generally illustrated in  FIGS. 49A and 49B . 
     Step  7 : Withdraw the procedural sheath  100  and delivery device  90  from the tissue tract to leave the implant (foot core  20 , flexible wing  60 , and extra-luminal pin  80 ) implanted to complete the delivery of the implant  5  and sealing of the arteriotomy. This step is generally illustrated in  FIG. 50 . 
     The above delivery sequence steps outline a method of implant deployment, there are many possible variants on this sequence to suit clinical requirements or preferences. For example, it may be advantageous to leave the guidewire  150  in situ through the implant after implant release, to maintain arterial percutaneous access, and remove the guidewire  150  when judged clinically appropriate. In this regard, it is noted that, as indicated above, in some embodiments, e.g. the version having extra-luminal pin  80   a , the guide wire may remain in place even after deployment of the pin. 
     Referring to  FIGS. 59 and 60 , the loading funnel/cannula assembly  395  includes a loading cannula  335  and an offset loading funnel  396  analogous to the loading funnel  96   h  shown, for example, in  FIG. 43J . Referring to the exploded view of  FIG. 60 , the cannula  335  includes a cannula tube  336 , a cannula cap  397 , a cannula seal  398 , and a cannula seal retainer  399  that function in a manner analogous to other like components described herein, e.g. the components of the assembly illustrated, e.g. in  FIG. 42B . 
     Closure Product and Packing 
       FIG. 58  shows a packaged product  300 , that includes a surgical device  301  packaged in a protective tray  400 . The surgical device  301  includes the same features of the other analogous example devices described herein, except to the extent indicated otherwise. 
     The surgical device  301  includes, inter alia, the handle  200  as described in additional detail herein, and a loading funnel/cannula assembly  395 , which is analogous to other loading funnel/cannula arrangements described herein. 
     As illustrated in  FIG. 58 , the surgical device  301  is held in a recess  405  shaped to closely match the geometry of the surgical device  301  by tabs or projections  410 . 
     The product  300  is configured such that the device  301  is removable from the tray  400  by proximally pulling the device  301  from the tray  400 . In this example, the offset loading funnel  396  is retained in the tray as the remainder of the device  301  is withdrawn proximally from the tray. 
     To remove the device from the tray, the operator grips handle  200  protruding from the proximal end of the tray  400 , e.g. between the thumb and fingers. While holding the tray  400  in the opposite hand or supporting the tray on a suitable surface for stability, the user may withdraw the device  301  proximally in a straight smooth continuous motion until the device  301  is completely free of the tray. Since the funnel  396  is retained in the tray  400  as the remainder of the device  301  is withdrawn, the implant  2  held by the device  301  moves proximally along the loading funnel/cannula assembly  395  such that the flexible wing of the implant  5  is folded by the funnel as the implant progresses toward the loading cannula  335 . Upon further pulling the device  301 , the implant  5  moves into the tube  336  of cannula  335 , which maintains the folded configuration of the implant  5  until the implant  5  is deployed along the guidewire as described in further detail herein with regard to other examples. 
     Upon further retraction of the device  301 , a positive stop engages between the loading cannula  335  and the shaft of the device  301 , such that the cannula  335  is pulled away from and breaks free of the loading funnel  396 . Upon further retraction of the device  301 , the device  301  is freed from the tray, with the loading funnel  396  retained in the tray. 
     Referring to  FIG. 61 , the positive stop that engages between the cannula  335  and the shaft of the device  300  is formed between a loading cannula retaining ring  360  and the cap  397  of the cannula  335 . 
     The device  300  includes an alignment mark  175  that extends longitudinally along the device  300  to provide a visual indication that the device  301  is properly rotated with respect to the tray  400  and the offset loading funnel  396  to ensure that the wing of the implant  5  is properly folded by the funnel  396 . Geometric engagement of the device  301  with the tray  400  also facilitates this alignment. The alignment of the offset funnel  396  is facilitated by the geometry of the tray  400 , the recess  405  of which is shaped to match the offset of the funnel  396  to thereby resist rotation of the funnel  396 . 
     The tray  400  also includes a cover  450  that prevents inadvertent actuation of the lock member  240 , thumb slider  250  or any other operable mechanism of the handle  300  while the device  301  is in the tray  400 . 
     The tray  400  may provide a specific and defined atmosphere for storage of the implant pre- and post-sterilization, which may further add to increasing the post-sterilization shelf-life stability of the polymer from which the exemplary implant  5  is formed. One such mechanism is the use of a controlled atmosphere, specifically one where excessive moisture is reduced by means of use of a vacuum or low moisture containing dried gases such as nitrogen, argon, etc. Furthermore, the use of packaging materials with a low moisture vapor transmission rate, for example orientated polypropylene (OPP), Polyethylene terephthalate (PET), Linear low-density polyethylene (LLDPE), polyethylene (PE), foil-based packaging materials (e.g. aluminium), or combinations thereof, in combination with a low moisture environment can further aid in enhancing the stability of the polymeric material post-sterilization. 
       FIG. 62  shows the components of the device  301  once removed from the tray  400 , with the implant  5  being folded and loaded into the loading cannula  335 . The device  301  further includes an insertion mark  380  that provides the operator with a visual indication of how deep to insert the device  301  into the procedural sheath  100 . 
       FIG. 63  shows a loading funnel  500  configured for loading of the closure implant  5 . The loading funnel  500  generally shares the features of the other loading funnels (e.g., loading funnel  95   c ) described herein, except to the extent indicated otherwise. 
     Referring to  FIG. 63 , the loading funnel  500  has four distinct zones  501 ,  502 ,  503 , and  504 , each having a specific function during the loading of the implant  5  into the loading cannula  530 . These four zones  501 ,  502 ,  503 , and  504  may ensure that the wing  60  is not damaged during the loading process. 
     The packaging zone protects the implant  5  from packaging (e.g., protective tray  400  illustrated in  FIG. 58 ) and user during shipping and prior to use of the product. As illustrated in  FIG. 64 , the implant  5  is positioned in this zone  501  during manufacture assembly and is therefore at this position at the beginning of the loading procedure. The wing  60  is in its open position and does not need to touch the internal surface of the funnel  500  to bias its form or position in the state illustrated in  FIG. 64 . Further, maintaining the wing in the protective packaging zone  501  in its relaxed, or unbiased, position ensures that the polymeric wing  60  does not take a memory set due to being stored in a folded or biased configuration. 
     Referring again to  FIG. 63 , the narrowed zone  502  ensures that the implant wing  60  folds downwardly under the implant foot core  20  rather than above the foot core  20 . If, during loading, the wing  60  folds upwardly above the foot core  20 , this may result in damage to the implant wing  60  as it is drawn into the loading cannula  530 . This damage may result in less than optimum sealing when the implant is placed in an artery or other tissue. It should be noted that the funnel becomes narrowed at the narrowed zone  502  when compared to the packaging zone  501 . 
     The front face of the narrowed zone  502  includes a pair of sloped surfaces  512  angled to match the angle of the foot core  20  (i.e., the angle formed between the length of the foot core and the longitudinal axis of the loading funnel  500 ). This ensures that any curvature of the wing  60  does not cause the wing  60  to fold upwardly. As the implant is withdrawn into this narrowed section of the funnel, the wing is forced downwards relative to the foot core  20  by the walls of the funnel. 
     The overlap zone  503  allows one side of the implant wing  60  to pass over or under the other side. This stops the edges of the wing from butting into each other, an action which can result in damage to the wing. This may be achieved via an overlap guide comprised of, for example, a channel  510 . As the implant is withdrawn into the overlap zone  503 , one side of the now folded down wing  60  runs down into the channel  510 , lowering that side of the wing which allows the other side of the wing to pass over it, thus eliminating the possibility of implant wing  600  edge-butting. The overlapping of the opposite sides of the wing  60  while the wing  60  is passing over the channel  510  is illustrated, for example, in  FIG. 66 . 
     Referring to  FIG. 79 , an alternative to having a channel  510  to allow the wings to overlap is a raised rib  515  that runs proud along the length of the overlap zone  503 . The intent of the rib  515  is to lift one side of the implant wing  60 , thereby allowing the other side to pass under it, thus eliminating the possibility of implant wing edge-butting. 
     Referring to  FIG. 80 , the proximal end of the loading cannula zone  504  houses the loading cannula  530 . The inner diameter of the funnel  500  just distal of the cannula  530  is smaller than that of the loading cannula  530  so that the implant wing cannot catch on the tip of the cannula as it is proximally drawn inside the cannula  530 . Further, the loading cannula  530  is orientated to the loading funnel  500  such that the angle of the cut edge of the loading cannula  530  is sloped towards the center of the loading cannula  530  to provide smooth entry of the folded wing  60 . 
     Referring to sequential illustration of  FIGS. 64 to 69  and the sequential illustration of  FIGS. 70 to 78 , the funnel  500  may be used at the start of a procedure to load the implant  5  into the loading cannula  530 . The funnel  500  is housed in the tray  400  and held stationary as the device is withdrawn from the tray. As the implant is withdrawn through the funnel  500 , the wing  60  is folded down under the foot core  20  and the edges are overlapped allowing the implant  5  to be pulled into the loading cannula  530  in the folded, or wrapped, configuration. 
     Referring to the sequential illustration of  FIGS. 64 to 69 ,  FIG. 64  shows the implant wing  60  in an open position in the packaging zone  501 .  FIG. 65  shows the implant wing  60  being progressively folded down as it passes proximally through the narrowed zone  502 .  FIGS. 66 and 67  show the implant wing  60  in an overlapped state (i.e., rolled or folded over onto itself) as it passes proximally through the in the overlap zone  503 .  FIG. 68  shows the implant in its folded state in the loading cannula. As illustrated, the folded implant  5  is prepared for direct insertion into an artery and is optimally orientated for insertion and closure and needs no other manipulation. It should be understood, however, that in some implementations secondary manipulations (e.g., further folding) may be utilized after the implant  5  is in the position shown in  FIG. 68  and, e.g., prior to insertion in the artery. 
     In the position shown in  FIG. 68 , the implant  5  is orientated within the loading cannula  530  to allow insertion of the guidewire  50  discussed in further detail above. In this regard, the loading cannula  530  is open at its proximal end to allow insertion of the guidewire  50 , which may be placed, for example, before the wing  60  is folded as it is retracted through the funnel  500  and into loading cannula  530 . 
     In the illustrated implementation, the implant  5  may be delivered in reverse direction of loading such that the loading and delivery system is not a “through” system. It should be understood, however, that other implementations may incorporate through systems whereby the implant is delivered to the implantation site in the same direction as the loading direction relative to the loading cannula  530 . 
     As illustrated, the funnel  500  may advantageously include distinct zoned areas within funnel to eliminate incorrect reverse folding of the implant wing  60  and provide distinct features, for example, (a) ensuring that the implant wing  60  folds correctly down under the implant foot core  20 , (b) ensuring that during the implant loading and folding process, the implant wing lateral edges do not crash or butt into each other; rather, that there is a biased lifting and/or lowering of one lateral side of the wing  60  relative to the other, (c) narrowing the funnel orifice to ensure continuous folding of implant  5  during the loading cycle, (d) providing a final inner diameter of funnel being of a smaller dimension as compared to that of the loading cannula  530  and orientation of the loading cannula  530  relative to the funnel  500  is such that the implant wing  60  does not catch on the tip of the cannula  530  as it is withdrawn proximally into the interior of the cannula  530 , and (e) provide a pull-through system with “front-to-back” withdrawal with the proximal or back exit delivering the folded implant into the cannula  530 . It should be understood that other features may be provided and/or that one or more of these listed features may be omitted in some alternative implementations. 
     Potential advantages of the loading funnel  500  may include, for example, (a) distinct and predetermined withdraw, loading, and folding zones, (b) correction of any possible incorrect positioning of the implant wing  60  during the initial loading process, (c) ensuring that the implant wing  60  folds correctly and downwardly under the foot core  20 , (d) ensuring that the wing edges do not butt together or crash, via the biased lifting or lowering one side of the wing, and (e) loading of the implant  5  in a biased folded orientation into a loading cannula  530  for transfer into an introducer sheath to allow implantation. It should be understood that other potential advantages may be provided and/or that one or more of these listed advantages may not be provided by some alternative implementations. 
       FIGS. 81 to 90  show alternative funnel configurations. 
     Referring to  FIG. 81 , a loading funnel  500   a  provides a slot  515   a  (formed, for example, by removing material on the underside of the funnel) to enable the implant wings  60  not to meet together against a solid surface and be trapped by the implant foot. Instead, with this configuration, as the implant  5  is withdrawn into the funnel  500   a , the wing  60  can partially protrude into or through the slot  515   a  with a bias for one side portion of the wing  60  so that one side portion will always be lower than the other, thereby ensuring the wing side portions are biased to overlap each time. The flexible funnel tab  516   a  seen in  FIG. 81  is configured to gently guide the overlapped implant wing sides back inside the funnel and also enable the foot to be deflected back up without it hitting a stop point. 
       FIG. 82  shows a funnel  500   b  similar to that of  FIG. 81  except that the funnel  500   b  includes a inboard scoop  517   b  which is all in the line of draw of the core plus a modification to the lower cavity is used rather than an open surface. 
       FIG. 83  shows a funnel  500   c  that differs in that the lower funnel shape is changed in the critical area where the implant wing sides touch and the implant foot has the potential to trap them. This shape is elliptical making it deeper in height than it is in width. This allows more space for the wing side portions to furl, meet and then pop over each other before the foot comes into contact with them. This is all in the line of draw of the core plus a modification to the lower cavity. 
       FIG. 84  shows a funnel  500   d  that uses a non-symmetrical inner funnel surface to fold the wing side portions more rapidly and get them to overlap before the foot  20  comes into proximity. This is achieved by designing convex walls  518   d  (e.g., dimpled) on the. These convex aspects can be offset from the center line of the funnel path so as to bias one wing side portion from the other in order to get repeatable folding. Alternatively, concave versions or a mix or concave plus convex portions could be provided with the intention to bias the wing folding. 
       FIG. 85  shows a funnel  500   e  that is similar to that of  FIG. 82 , but uses a trajectory inboard scoop  519   e  which tapers away completely as it progresses proximally. This may be, for example, all in the line of draw of the core. 
       FIG. 86  shows a funnel  500   f  that has a dimple  521   f  to lift one side of the implant edge relative to the other, at a position just before the edges currently touch thereby allowing planned folding of the wing side portions relative to each other. 
       FIG. 87  shows a funnel  500   g  that is similar to that of  FIG. 86 , but includes a dimple  521   g  that is extended to create an elongated ramp surface. 
       FIG. 88  shows a funnel  500   h  that is similar to that of  FIG. 87  but the ramp surface  522   h  has been extended out to provide a smooth surface over the full length of travel. 
       FIG. 89  shows a funnel  500   i  that includes an exaggerated tear-drop shape to the inner lumen of the loading funnel to ensure bias in the overlapping and folding of the implant  5  as it is withdrawn up through the loading funnel  500   i.    
       FIG. 90  shows a funnel  500   j  that includes a further exaggerated tear-drop profile as compared to that of the funnel  500   i  of  FIG. 89 , whereby an additional provision to allow the overlapping aspect of the implant wing side portion can be guided underneath the opposite wing side portion to further ensure bias in the overlapping and folding of the implant  5  as it is withdrawn up through the loading funnel  500   j.    
     Although some example embodiments have been described herein in the context of vascular closure applications, it should be understood that the various mechanisms and concepts described herein are not limited to vascular applications and are applicable to any suitable applications that require closure of an aperture in a tissue. 
     Although the present invention has been described with reference to particular examples and exemplary embodiments, it should be understood that the foregoing description is in no manner limiting. Moreover, the features described herein may be used in any combination.