Patent Publication Number: US-2011054521-A1

Title: Clip and closure systems and methods

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation-in-part of and claims priority to and the benefit of U.S. patent application Ser. No. 12/549,094, entitled “Clip And Closure System”, Ser. No. 12/549,104, entitled “Device For Delivering A Clip Within A Patient”, Ser. No. 12/549,107, entitled “Vascular Clip”, and Ser. No. 12/549,109, entitled “Method For Closing An Aperture In A Patient&#39;s Body”, each of which was filed Aug. 27, 2009, the entirety of each of which is incorporated herein by reference. 
    
    
     TECHNICAL FIELD 
     The invention generally relates to systems and methods for closing an aperture in a patient, such as an aperture in a vessel wall of a patient. 
     BACKGROUND 
     Catheterization and interventional procedures, such as angioplasty and stenting, generally are performed by inserting a hollow needle through a patient&#39;s skin and muscle tissue into the vascular system. A guide wire then is passed through the needle lumen into the patient&#39;s blood vessel. The needle is removed and an introducer sheath is advanced over the guide wire into the vessel. A catheter typically is passed through the lumen of the introducer sheath and advanced over the guide wire into position for a medical procedure. The introducer sheath therefore facilitates insertion of various devices into the vessel while minimizing trauma to the vessel wall and minimizing blood loss during a procedure. 
     Upon completion of the medical procedure, the catheter and introducer sheath are removed, leaving an aperture in the vessel. Commonly, external pressure is applied until clotting and wound sealing occurs. However, this procedure is time consuming and expensive, requiring as much as an hour of time from a physician or nurse, is uncomfortable for the patient, and requires that the patient be immobilized in the operating room, catheterization laboratory, or holding area. Furthermore, a risk of hematoma exists from bleeding prior to hemostasis. 
     Various apparatuses have been developed for sealing a vascular aperture by occluding, clipping, or suturing the aperture of the vessel. A problem with these prior art devices and techniques is that the introducer sheath must be removed prior to using the closure apparatus to close the aperture. By introducing a new device through the existing puncture site, there becomes an increased risk of contaminating the vessel with skin flora, thereby increasing the chance of infection. Further, the requirement of removing the introducer sheath and then providing the closure apparatus prolongs the intervention. 
     There is an unmet need for systems and methods that provide for vascular aperture closure that do not require introduction of additional apparatuses or the removal of the introducer sheath at the end of a surgical intervention to achieve closure of an aperture in a patient. 
     SUMMARY 
     The invention generally relates to universal closure systems, devices, clips, and methods that allow for closure of an aperture in a patient, for example, arterial wound closure after femoral artery catheterization. Systems and methods of the invention reduce time for hemostasis and time of patient immobility in the cardiology catheter room, angiography suite, or operating room, thereby reducing hospital stay, and a patient&#39;s personal discomfort. The delivery device and/or clip is compatible with standard medical devices, such as introducer sheaths and guiding catheters, is easy to use, and allows the operator to attach the delivery device and/clip on any sheath or guiding catheter being used prior to beginning or at the end of the procedure and close the aperture in the vessel upon removal of the sheath or guiding catheter from a patient. Features of the invention (bioabsorbable clip, compact delivery system, universal compatibility, low cost, easy use) address previous problems in the vascular closure field. 
     Systems of the invention for closing an aperture in a patient generally include a delivery device that is attachable to and removable from an exterior of an introducer sheath, and a clip releasably disposed within the delivery device. Systems of the invention may further include an introducer sheath. The introducer sheath may be the existing introducer sheath already implanted in a patient to perform a surgical intervention. The delivery device can be attached to the introducer sheath prior to beginning a surgical intervention. Alternatively, the delivery device can be attached to the introducer sheath after starting a surgical intervention, without removal of the sheath from the patient. The delivery device is generally clipped to the exterior of the sheath, although other attachment methods can be envisioned by one of skill in the art. 
     The delivery device is generally situated at a proximal portion of the sheath prior to and during a surgical intervention. Upon completion of the surgical intervention, the delivery device is advanced to a distal portion of the sheath for deployment of the clip. The clip can be deployed without removal of the sheath from the patient. 
     The clip can be any type of clip that is suitable to be deployed within the body of a patient and close an aperture in the patient. Exemplary clips include vascular clips and surgical clips. In a preferred embodiment, the clip is a vascular clip. 
     The clip can include a resilient body having a first ring portion, a second ring portion, and at least one mid-region joining the first and second portions, the body having a compressed delivery configuration and an expanded deployed configuration, and at least one tissue engaging member disposed about each of the first portion and the second portion of the body. The clip is expandable from a delivery configuration in which the clip is loaded within the delivery device to a deployed configuration in which opposite ends of the clip are directed inward towards each other. The clip can be bioresorbable or bioabsorbable. Tissue engaging members of the clip can further include barbs. 
     In the delivery configuration, the clip is configured to exert a positive pressure on walls of a delivery device, thereby maintaining the clip within the delivery device until deployed. In the deployed configuration, the clip is configured to engage tissue and close an aperture in a patient&#39;s body, such as an aperture in a vessel wall. In the deployed configuration, the body of the clip substantially defines a plane and tissue engaging members on the first and second portions are directed inward toward each other. In the deployed configuration, the tissue engaging members on the first and second portions of the body of the clip lie beneath the plane defined by the body. In the deployed configuration, the tissue engaging members of the first and second portions can interlock with each other. The first and second portions of the body of the clip can include a different number of tissue engaging members. 
     In certain embodiments, the body of the clip is a unitary body. In other embodiments, the mid-region of the clip is spring loaded. Each of the first ring portion and second ring portion can have any shape. Exemplary shapes include a circle, a polygon (regular or irregular), or a modified polygon. 
     The delivery device can further include a mechanical force regulator. The regulator generates an audible and tactile click during deployment of the clip. The delivery device can further include a pusher sleeve and a constraining sleeve. Each of the pusher sleeve and the constraining sleeve include a body and a handle. The handle of each of the pusher sleeve and the constraining sleeve can be flexible. In certain embodiments, at least a portion of the body of the pusher sleeve is configured to slidably fit within the body of the constraining sleeve. In other embodiments, the pusher sleeve is slidably disposed within the constraining sleeve and the pusher sleeve is flush against the constraining sleeve. 
     The delivery device can further include a stopper that extends around at least a portion of the device, in which the stopper is positioned at a distal end of the device to prevent the pusher sleeve from advancing into a vessel. The delivery device can further include a protective sheath disposed along an interior of the delivery device, in which the protective sheath is capable of being peeled away from the delivery device after the delivery device has been attached to the introducer sheath or other medical device. 
     The clip can be deployed by pushing the pusher sleeve, while holding stationary the constraining sleeve, to advance the clip from the delivery device. The delivery device can be configured such that a distal end of the device is tapered such that tissue engaging members of the clip simultaneously contact an exterior wall of a vessel upon deployment of the clip. The clip, in the delivery configuration, can be configured such that upon deployment of the clip from a delivery device, the tissue engaging members of the clip simultaneously contact an exterior wall of a vessel. In certain embodiments, the clip closes the aperture in the vessel by attaching to an exterior wall of the vessel. 
     In certain embodiments, the delivery device is shaped as a tubular channel having a lateral opening disposed along its length. In other embodiments, the delivery device has a C-shaped cross section. In certain embodiments, the clip has a semicircular shape when it is disposed within the delivery device. In other embodiments, the clip has a C-shape when it is disposed within the delivery device. In other embodiments, the body of the clip has a C-shaped cross section and tissue engaging members on the first and second portions are directed away from each other and toward the tissue to be engaged. These configurations allow the delivery device to be attached to and removed from the introducer sheath or any other medical device. 
     Another aspect of the invention provides a method for closing an aperture in a vessel in a patient&#39;s body, the method including advancing a first medical device through an aperture in a vessel, advancing a delivery device distally along an exterior surface of the medical device to contact an exterior of a vessel wall; and deploying a clip that engages tissues portions adjacent to the aperture in the vessel and closes the aperture in the vessel upon withdrawal of the first medical device from the aperture. 
     The method can further include, prior to advancing the first medical device through the aperture in the vessel, attaching the delivery device to an exterior surface of the first medical device. The method can further include, after advancing the first medical device through the aperture in the vessel, attaching the delivery device to an exterior surface of the first medical device. 
     The method can further include introducing at least a second medical device through the introducer sheath into the vessel. The second medical device can be any medical device needed to perform the desired surgical intervention. Exemplary second medical devices include an angioplasty balloon, an atherectomy device, an IVC filter, an angiography catheter, or a stent delivery device. The method can further include performing a surgical intervention within the patient&#39;s body using the second medical device introduced through the introducer sheath into the vessel. The method can further include delivering a tissue sealant into the aperture. 
     Another aspect of the invention provides a method for closing an aperture in a vessel in a patient&#39;s body including advancing a medical device through an aperture in a vessel, attaching a delivery device to an exterior surface of the medical device after the medical device has been advanced through the aperture in the vessel, advancing the delivery device distally along the exterior surface of the medical device to contact an exterior of a vessel wall, and deploying a clip from the delivery device that engages tissues portions adjacent to the aperture in the vessel and closes the aperture in the vessel upon withdrawal of the medical device from the aperture. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a drawing showing an embodiment of a clip and closure system according to an embodiment. 
         FIG. 2  is a drawing showing an embodiment in which the delivery device is attached to an introducer sheath prior to beginning a surgical intervention. 
         FIG. 3  is a drawing showing an embodiment in which the delivery device is attached to an introducer sheath after a physician starts a surgical intervention. 
         FIGS. 4 and 5  are side and top views, respectively, of a delivery device according to an embodiment. 
         FIG. 6  panel A is a drawing showing an embodiment of a delivery device having a straight distal end.  FIG. 6  panel B is a drawing showing an embodiment of a delivery device having an angled distal end. 
         FIG. 7  panel A is a drawing showing a clip loaded into a delivery device having a straight distal end.  FIG. 7  panel B is a drawing showing a clip loaded into a delivery device having an angled distal end. 
         FIG. 8  is a drawing showing a delivery device with a protective sheath spanning only a portion of the length of the interior of the delivery device. 
         FIG. 9  is a drawing showing a delivery device with a protective sheath spanning a full length of the interior of the delivery device. 
         FIG. 10  is a set of drawings showing an embodiment of a clip of the invention. Panel A shows the clip in a deployed configuration. Panels B and C show the clip in a delivery configuration. 
         FIG. 11  is a drawing showing exemplary shapes and exemplary sizes of tissue engaging members. 
         FIG. 12  is a drawing showing a magnified section of the clip of  FIG. 10 . This drawing shows interlocking of tissue engaging members on the left and right portions of the clip in the deployed configuration. 
         FIG. 13  is a drawing showing an embodiment of the clip in which the clip is compressed into a delivery configuration and loaded within a delivery device. 
         FIG. 14  is a set of drawings showing different views of an embodiment of a clip of the invention in a delivery configuration. Panel A is a ⅓ lateral view, panel B is a lateral view, and panel C is a front view. 
         FIG. 15  is a set of drawings showing a delivery device having grooved channels according to an embodiment. 
         FIG. 16  is a set of drawings showing of an embodiment of a clip from different views and in different configurations. Panel A is a lateral view of the clip in a delivery configuration. Panel B is a lateral view of the clip in a deployed configuration. Panel C is a front view of the clip in the deployed configuration. 
         FIG. 17  is a set of drawings showing an embodiment of a clip from different views and in different configurations. Panel A is a lateral view of the clip in a delivery configuration. Panel B is a front view of the clip in the delivery configuration. Panel C is a front view of the clip in a deployed configuration. 
         FIG. 18  is a magnified view of a tissue engaging member on a clip according to an embodiment. 
         FIG. 19  is a drawing showing a tab that holds together the handles of the pusher sleeve and the constraining sleeve of the delivery device to prevent premature and/or inadvertent deployment of the clip. 
         FIG. 20  panels A and B are a set of drawings showing a stopper positioned at a distal end of the constraining sleeve, preventing the pusher sleeve from advancing into the vessel. 
         FIG. 21  shows a delivery device including a mechanical force regulator. 
         FIG. 22  shows of a delivery device including a displacement limiter. 
         FIGS. 23-24  are side views of a system according to an embodiment in a first configuration and a second configuration, respectively. 
         FIG. 25  is an expanded view of a portion of the system of  FIG. 23 . 
         FIG. 26  is a perspective view of a portion of the system of  FIG. 25  with a portion of an outer member of a delivery device of the system removed. 
         FIG. 27  is a front view of a clip of the system of  FIG. 25 . 
         FIG. 28  is a front view of the clip of  FIG. 25  and a portion of the delivery device of the system of  FIG. 23 . 
         FIGS. 29-31  are cross-sectional front views of a portion of the system of  FIGS. 23-24  in a first configuration, a second configuration, and a third configuration, respectively, in a body of a patient. 
         FIGS. 32-44  are front views of clips and portions thereof according to embodiments. 
         FIG. 45  is a front view of a portion of a system for closing an aperture in a bodily tissue according to an embodiment. 
         FIG. 46  is a front view of nested clips according to an embodiment. 
         FIG. 47  is a front and partial cross-sectional view of a system for closure an aperture in a bodily tissue according to an embodiment. 
         FIG. 48  is a front view of a portion of a system for closure an aperture in a bodily tissue according to an embodiment. 
     
    
    
     A fuller understanding of the aspects, objects, features, and advantages of certain embodiments according to the invention will be obtained and understood from the following description when read together with the accompanying drawings, which primarily illustrate the principles of the invention and embodiments thereof. The drawings are for illustrative purposes only, and are not necessarily to scale. Any measurements provided in the drawings are exemplary and are not intended to limit the invention in any regard. The drawings and the disclosed embodiments of the invention are exemplary only and not limiting on the invention. 
     DETAILED DESCRIPTION 
     Systems and devices constructed in accordance with the present invention provide vascular introduction and wound closure in a single device, eliminating the time and manipulation required to insert a separate closure device at the completion of a procedure. 
     Referring to  FIG. 1 , a system  1  according to an embodiment, includes a delivery device  3  and a clip  4  disposed in the delivery device  3 . Generally, the delivery device  3  is configured to deliver the clip  4  to a bodily tissue and, upon delivery, the clip  4  is configured to close an opening in the bodily tissue. The system  1  can further include an introducer sheath  2 . While  FIG. 1  shows an introducer sheath  2 , the delivery device  3  can be clipped to any suitable medical device, such as a catheter. Introducer sheath  2  is constructed of a material typically used for vascular introducer sheaths, such as polyethylene or nylon, and includes central lumen  5  through which other devices may be introduced in the vasculature, for example, to perform a diagnostic or interventional procedure such as angiography, angioplasty or stenting. 
     Delivery device  3  is attachable to and removable from the introducer sheath  2 . The delivery device  3  can be attached to the introducer sheath  2  prior to beginning a surgical intervention, as shown in  FIG. 2 . In this embodiment, a physician assembles the preloaded clip device and delivery system  1  to the exterior of the introducer sheath  2 , over a distal end of the sheath prior to introduction to the patient. Once the system  1  is loaded onto the introducer sheath  2  and pulled towards a proximal end of the introducer sheath, the introducer sheath can be used as normal through the entire intervention, without regard to the closure clip system  1 . The clip  4  can be delivered to the vessel via the delivery device  3 , as the physician is completing the procedure. In this embodiment the physician pre-plans the use of the device  3 . 
     Alternatively, the delivery device  3  can be attached to the introducer sheath after a physician has started a surgical intervention.  FIG. 3  shows attachment of the delivery device  3  to the introducer sheath  2  after a physician has started a surgical intervention. In this embodiment, the physician can place the delivery device  3  onto the introducer sheath  2  after the interventional procedure has begun, without removal of the introducer sheath  2  from a patient&#39;s body. This system  1  can be clipped onto the sheath  2 , to then be delivered to the vessel via the delivery system, as the physician is completing the procedure. 
     As mentioned above, the delivery device  3  is pulled towards the proximal end of the introducer sheath  2  so that the introducer sheath can be used as normal through the entire intervention ( FIG. 1 , panel A). Upon completion of the surgical procedure, the delivery device  3  can be advanced along the exterior of the introducer sheath  2  until contact with a target tissue, such as vessel wall  6 , occurs for deployment of the clip  4  ( FIG. 1  panels B and C). As shown in  FIG. 1  panel C, the clip  4  is deployed prior to removal of the introducer sheath  2  from a patient&#39;s body. Upon deployment of the clip  4 , the clip attaches to an exterior of the wall  6  of a vessel  7 . Upon removal of the system  1  and the introducer sheath  2  the aperture in the vessel wall  6  is closed by the clip  4 , as described in more detail herein. 
     As shown in  FIGS. 4 and 5 , an embodiment of the delivery device  3  includes a constraining sleeve  8  and a pusher sleeve  9 . Each of the constraining sleeve  8  and the pusher sleeve  9  includes a body  10 ,  11 , respectively and a handle  12 ,  13 , respectively. The delivery device  3  is configured such that at least a portion of the body  11  of the pusher sleeve  9  is configured to slidably fit within the body  10  of the constraining sleeve  8 . In certain embodiments, the pusher sleeve  9  is flush against the constraining sleeve  8 . The handles  12 ,  13  of the constraining sleeve and the pusher sleeve can be flexible (as exemplified in  FIG. 4  by the handles in a first position  14  and the handles in a second position  15 , shown in dashed lines). As such, the handles  12 ,  13  permit a physician to manipulate placement of the delivery device so that the introducer sheath can be used unimpeded during the intervention, without regard to the delivery device  3 . 
     The body  10  of the constraining sleeve  8  and the body  11  of the pusher sleeve  9  are each formed as a tubular channel having a lateral opening disposed along its length. This can appear as a C-shaped cross-section of the delivery device  3 . Because of the shape of the delivery device  3 , the delivery device  3  can be attached to the introducer sheath  2 , for example, to an exterior surface of the sheath, prior to starting or after beginning a surgical intervention. Additionally, the shape allows for the delivery device  3  to be attached to or removed from any medical device, i.e., a universal delivery device that is suitable to mate with any standard medical device. 
     In use, the clip  4  is deployed by applying a forward or distal pressure to the pusher sleeve  9  while holding the constraining sleeve  8  in place. As the pusher sleeve  9  is moved distally, the clip  4  that is stored in the body  10  of the constraining sleeve  8  is moved distally until the clip  4  is deployed from the delivery device  3 . In some embodiments, as illustrated in  FIG. 15 , the constraining sleeve  8  defines one or more grooved channels  21  configured to received at least a portion of tissue engaging members  20  of clip  4 . The grooved channels  21  ensure that clip  4  will be deployed from the delivery device  3  having a specific orientation with respect to a vessel wall in a patient&#39;s body. The body of the constraining sleeve can include any number of grooved channels. In certain embodiments, the number of grooved channels is equal to the number of tissue engaging members on the clip. In other embodiments, the number of grooved channels is less than the number of tissue engaging members on the clip. In other embodiments, the number of grooved channels is greater than the number of tissue engaging members on the clip. As well as ensuring the specific alignment of the clip  4  in the constraining sleeve  8 , the grooved channels  21 , in addition to the tapered shape of barbs  24  of the tissue engaging members  20  ( FIG. 12 ), also provide the tissue engaging members and/or the barbs additional engagement thickness or strength beyond the aperture in the vessel wall  6  that the introducer sheath goes through. 
     Numerous features of the delivery device prevent the clip from being deployed into an interior of the vessel. The delivery device can include a stopper that extends around at least a portion of the device, in which the stopper is positioned at a distal end of the constraining sleeve of the delivery device to prevent the pusher sleeve from advancing into the vessel.  FIGS. 20A  and B show exemplary stoppers  26  positioned at a distal end of the constraining sleeve  8 , preventing the pusher sleeve  9  from advancing into the vessel  6 . 
     The delivery device  3  can also include a mechanical force regulator  22 , as shown in  FIG. 21 . The mechanical force regulator  22  is designed such that the pusher sleeve  9  will not advance, and thus the clip will not move inside the constraining sleeve  8 , until a prescribed force is overcome. The mechanical force regulator  22  generates an audible and/or tactile click during deployment of the clip  4 , and thus is configured to alert the physician that deployment of the clip  4  has occurred. As such, the mechanical force regulator  22  also ensures that the clip  4  attaches to the vessel wall  6  and is not pushed through the vessel wall  6  and into an interior space in the vessel. 
     The delivery device can also include a displacement limiter  27  built into the delivery device  3 .  FIG. 22  shows a drawing of a delivery device  3  including a displacement limiter  27 . The movement of the pusher sleeve  9  inside the constraining sleeve  8  is limited to a prescribed distance by the displacement limiter  27 , thus a user cannot push the clip  4  or pusher sleeve  9  beyond a position in which the clip  4  obtains full attachment to the vessel wall  6 . 
     In certain embodiments, a distal end of the delivery device  3  is angled ( FIG. 6  panel B compared to panel A), similar to the angle at which a surgeon may approach the vessel with the introducer sheath during such a procedure. The angled distal end of the delivery device  3  biases the loaded clip such that tissue engaging members on a first side of the clip protrude further from tissue engaging members on a second side of the clip, ensuring that upon deployment of the clip, the tissue engaging members on the first and second sides of the clip simultaneously contact an exterior of the vessel wall, as is shown in  FIG. 7  panel B compared to  FIG. 7  panel A. Deployment in such a manner ensures that the clip does not engage the vessel wall at an angle. 
     As shown in  FIGS. 8 and 9 , in some embodiments, the delivery device  3  includes a protective sheath  23 . The protective sheath  23  is disposed along or over at least a portion of an interior of the delivery device  3 . In this manner, the protective sheath  23  minimizes human contact with the components that will enter a patient&#39;s body, i.e., the delivery device and the introducer sheath. In  FIG. 8 , the protective sheath  23  spans only a portion of the length of the interior of the delivery device  3 . In  FIG. 9 , the protective sheath  23  spans a full length of the interior of the delivery device  3 . 
     The protective sheath is capable of being peeled away from the delivery device after the delivery device has been attached to the medical device. In some embodiments, the protective sheath includes a perforated seam, thus after attachment of the delivery device to the introducer sheath, the excess material is removed along the perforation prior to advancement of the delivery device into the body. 
     Referring to  FIG. 10 , the clip  4  includes a resilient body  16  including a first portion  17 , a second portion  18 , and at least one mid-region  19  joining the first and second portions. The body  16  is flexible to permit the first portion  17  and second portion  18  to move between a first configuration (e.g., as shown in  FIG. 10  panel A), a second configuration (e.g., as shown in  FIG. 10  panel B), and/or a third configuration (e.g., as shown in  FIG. 10  panel C). Because the body  16  is resilient, the body  16  returns to the first, or original, configuration in the absence of any deforming or deflective pressure (e.g., such as the pressure present as the clip  4  is expanded for retention on the delivery device  3 ). In other words, the body  16  exhibits shape memory. In some embodiments, the body  16  is a unitary body, as shown in  FIG. 10 . In other embodiments, the mid-region  19  is spring loaded. 
     Although  FIG. 10  shows clip  4  having a single mid region  19 , in other embodiments the clip  4  can have a different number of mid regions. For example, as shown in  FIG. 17 , the clip  4  can have two mid-regions  19  joining the first and second portions  17 ,  18  respectively. 
     The first and second portions  17 ,  18 , respectively can be any suitable shape. In the embodiment illustrated in  FIG. 10 , for example, the first and second portions  17 ,  18 , respectively, are substantially ring-shaped in their first configuration. In other embodiments, the first and second portions can be circular, oval, square, rectangular, a polygon (regular or irregular) or a modified polygon. A modified polygon refers to shapes that include a linear portion and a non-linear portion. In certain embodiments, the first and second portions have the same shape. In other embodiments, the first and second portions have different shapes. 
     The clip  4  includes at least one tissue engaging member  20  disposed on or extended from each of the first portion  17  and the second portion  18  of the body  16 . The tissue engaging members  20  are configured to engage a bodily tissue to help retain the respective first or second portion  17 ,  18 , with respect to a portion of the bodily tissue. In other words, the tissue engaging members help to anchor the clip  4  in the bodily tissue. The bodily tissue can include, for example, subcutaneous tissue, a neural tissue (i.e., in the peripheral or central nervous system,), a muscle (e.g., skeletal, cardiac, or smooth muscle, including a blood vessel), an organ (e.g., the brain, heart, bladder, urethra, or kidney), or other tissue of the body. 
     As illustrated in  FIG. 12 , the clip  4  includes two tissue engaging members  20  on the first portion  17  of the body  16  and three tissue engaging members  20  on the second portion  18  of the body. In other embodiments, however, each of the first and second portions  17 ,  18 , respectively, can include the same number of tissue engaging members. Additionally, in other embodiments, the first and second portions of the clip can include any suitable number of tissue engaging members, for example, at least 1, at least 2, at least 3, at least 4, at least 5, at least 10, at least 20, at least 50, etc. The number of tissue engaging members can be determined by one of skill in art based on the surgical intervention to be performed and the size of the instrumentation to be inserted into a patient&#39;s body. 
     The tissue engaging members  20  can be of any suitable shape, size and/or length. The shape, size and/or length of tissue engaging members  20  can be determined by one of skill in art based on the surgical intervention to be performed and the size of the instrumentation to be inserted into a patient&#39;s body.  FIGS. 11 and 18  provide exemplary shapes, sizes and lengths of tissue engaging members  20 . In certain embodiments, the tissue engaging members on the first portion of the body of the clip are the same shape, size, and length as the tissue engaging members on the second portion of the body of the clip. In other embodiments, the tissue engaging members on the first portion of the body of the clip are a different shape, size, and/or length as the tissue engaging members on the second portion of the body of the clip. Clips with tissue engaging members according to still other embodiments are described in detail below. 
     As shown in  FIG. 12 , the tissue engaging member  20  includes at least one barb  24  extended from a body portion of the tissue engaging member  20 . The barb  24  is configured to facilitate insertion of the tissue engaging member  20  into the bodily tissue. For example, the barb  24  has a sharp end configured to facilitate penetration into the bodily tissue. The barb  24  is configured to facilitate retention of the tissue engaging member  20  with respect to the bodily tissue. For example, the barb  24  includes at least one shoulder around which the bodily tissue can collapse when the barb is inserted into bodily tissue. As such, the barb  24  can prevent a backward (or proximal) movement of the tissue engaging member  20  with respect to the bodily tissue. 
     At least a portion of the barb  24  can be rigid or flexible. In use, a rigid barb  24  substantially maintains its shape as it is inserted into bodily tissue. Once inserted in the bodily tissue, the tissue collapses around the rigid barb  24  such that regression (or proximal movement) of the barb is substantially prevented. 
     The clip  4  is biocompatible. In certain embodiments, the clip, or portions thereof, may be fabricated from a bioresorbable, biodegradable, or bioabsorbable material. In other words, the clip, or portions thereof, can be fabricated of a material capable of being degraded, disassembled, or digested by action of a biological environment, including the action of living organisms and most notably at physiological pH, temperature, and electrical stimulation. For example, at least a portion of the clip  4  can be constructed of a bioerodible polymer. As discussed above, the body  16  of the clip  4  is constructed of resilient materials. Exemplary resilient materials include a variety of polymers, or co-polymers thereof, or metals, or alloys thereof. Suitable materials include, but are not limited to, PLLA, PEO/PBTP, PET, PLGA, Fe, Mg, and Nitinol. The clip  4  can be fabricated using any suitable method of fabrication, including, but not limited to, molding/casting, machining, laser cutting, stereolithography, laser powder forming, fused deposition modeling, selective laser sintering, etc. 
     Because the body  16  of the clip  4  is made from a resilient material, the clip can have numerous configurations. In certain embodiments, the body  16  of the clip  4  has a compressed delivery configuration and an expanded deployed configuration.  FIG. 10  panel A shows clip  4  in a deployed configuration, and  FIG. 10  panels B and C show the clip  4  in delivery configurations. In the deployed configuration, the tissue engaging members  20  of the first and second portions  17 ,  18  interlock with each other, as shown in  FIG. 12 , thereby being configured to close an aperture in the patient&#39;s body. 
     In greater detail,  FIGS. 13 ,  14 , and  16  panel A show the clip  4  in a delivery configuration, i.e., the compressed configuration in which the clip is loaded into the delivery device. In the delivery configuration, the first and second portions  17 ,  18  are compressed such that edges of the first and second portions are directed toward a proximal end of the delivery device  3 , and tissue engaging members  20  are directed away from each other and toward a distal end of the delivery device. Referring to  FIG. 13 , in the delivery configuration, the clip  4  exerts positive pressure on the body  10  of the constraining sleeve  8  of the delivery device  3 , thereby maintaining the clip  4  within the delivery device  3  until deployed by the delivery device  3 . When in its delivery configuration, the clip  4  is contained or otherwise received within the delivery device  3 . In this manner, the delivery device  3  prevents the tissue engaging members  20  of the clip  4  from snagging on tissue during advancement of the delivery device  3  to the aperture in the patient&#39;s body. 
     Resiliency of the clip also allows the clip to be attached to different sized medical devices, such as different sized introducer sheaths. For example, introducer sheaths and/or catheters are commonly sized using the French measurement scale. The French measurement scale measures the outer diameter of cylindrical medical instruments. Due to the resiliency of the clip, the clip of the invention can be attached to a medical device of any size as measured by the French measurement system. 
     In some embodiments, as shown in  FIG. 14  panels B and C the clip  4  has a C-shaped cross section when in its delivery configuration. It is the C-shaped cross section of the clip  4  in the delivery configuration that allows for loading of the clip  4  onto any medical device, i.e., a universal clip. Further, the C-shaped cross-section of clip  4  allows for the clip to be loaded onto a medical device after a surgical intervention has begun, without removal of the medical device from the patient&#39;s body. 
       FIG. 16  panels B and C show clip  4  in deployed configurations, i.e., expanded configurations in which the clip is engaged with bodily tissue to close the aperture in the patient&#39;s body. In the deployed configuration, the body  16  of the clip  4  substantially defines a plane and tissue engaging members  20  on the first and second portions  17 ,  18  are directed inward toward each other. In the deployed configuration, the tissue engaging members  20  on the first and second portions  17 ,  18  lie beneath the plane defined by the body  16 . Because the tissue engaging members  20  lie beneath the plane defined by the body  16  of clip  4 , the clip  4  can engage an exterior vessel wall and tissue engaging members  20  will penetrate tissue surrounding the aperture in the vessel and close the aperture when the clip  4  is in a deployed configuration (e.g., as shown in  FIG. 1 ). 
     Referring back to  FIG. 1 , methods of closing an aperture in a bodily tissue are described with respect to system  1 . In  FIG. 1  panel A, the introducer sheath  2  has been advanced through skin, fat, and muscle tissue into the vessel  7  through an aperture in the vessel wall  6 , which is formed in accordance with well-known techniques. With the delivery device  3  situated at a proximal end of the introducer sheath  2 , an interventional procedure is then performed by introducing one or more interventional devices, e.g. angioplasty balloons, stent delivery systems, atherectomy devices, etc., through the introducer sheath  2  in accordance with well-known techniques. 
     Upon completion of the procedure, a medical device, e.g., system  1 , may be used to close the aperture in vessel wall  6  of vessel  7 . The delivery device  3  is oriented on the introducer sheath  2 , such that the handles  12  and  13  of delivery device  3  are in a plane that the introducer sheath  2  generates with the patient&#39;s vessel  7 . The clip  4  is oriented in the delivery system  3  such that the tissue engaging members  20  are on the medial and lateral sides of the vessel  7 . The delivery device  3  is advanced over an exterior of the introducer sheath  2  through the cut-down in the skin, muscle, etc. until a distal tip of the delivery device  3  contacts the vessel  7  ( FIG. 1  panel B). In some embodiments, the method includes detecting the position of the distal tip of the delivery device within the body of the patient. For example, in some embodiments, the physician will detect the position of the distal tip of the delivery device by detecting the point at which the delivery device  3  contacts the vessel  7 . Such detection can occur, for example, by feeling a change in resistance to advancement of the delivery device because the vessel is significantly stiffer than the soft tissue between the skin and the vessel. The vessel properties vary with age of the patient, but the stiffness of the vessel in which the physician is working can be determined while beginning the procedure and initiating access. 
     The delivery device  3  is configured such that the handles  12  and  13  are held in a position that prevents premature and/or inadvertent delivery of the clip  4 , as shown in  FIG. 19 . The handles may be held together naturally by a user. Alternatively, a break-away tab can be used to hold the handles together. The tab is removed once the user is prepared to deploy the clip. For example,  FIG. 19  shows an embodiment in which handles  12 ,  13  of delivery device  3  are held together by a tab  25 , locking the handles  12 ,  13  in a relative position such that deployment cannot occur until the tab  25  is removed from handles  12 ,  13 . 
     In preparation for clip deployment, the tab  25  between the handles  12  and  13 , which maintains the relative position between the pusher sleeve  9  and the constraining sleeve  8 , is removed while maintaining the location of the delivery device  3  at the vessel wall  6 . The handle  12  of the constraining sleeve  8  is then held in one hand, along with the introducer sheath  2 , while the handle  13  of the pusher sleeve  9  is held in the other hand. Again, while maintaining the position at the initial contact with the vessel wall  6  with the constraining sleeve  8  and introducer sheath  2 , the pusher sleeve  9  is then advanced distally to deploy the clip  4 . 
     The advancing of the pusher sleeve  9  requires a specified applied force before any movement occurs, at which time the pusher sleeve  9  will move forward into the fully deployed position. During this movement at least one of an audible or a tactile click will occur to signify to the physician that deployment of the clip  4  has occurred. The click can be generated, for example, by the mechanical force-regulator  22 , which also ensures that the deployment is both sufficient to attach to the vessel  7  and will ensure that the clip does not penetrate through the vessel wall  6  and enter the interior space of the vessel  7 . 
     Deployment of the clip  4  from delivery device  3  results in tissue engaging members  20  of clip  4  penetrating into the vessel wall  6  on the medial and lateral sides of the aperture. Barbs on the tissue engaging members  20  assist the tissue engaging members in engaging the vessel wall  6 . In certain embodiments, the tissue engaging members  20  are biased beyond a centerline of the clip  4 , i.e., the tissue engaging members are biased outward, so that penetration of the tissue engaging members  20  into the vessel wall  6  begins away from the wall  6  surrounding the aperture in the vessel  7 . The length of the tissue engaging members  20  are such that they are approximately the thickness of the vessel wall  6 , so in some embodiments the tissue engaging members  20  will slightly protrude into the interior of the vessel. A base of each tissue engaging member  20  is large enough to limit movement so that the clip does not penetrate through the vessel wall  6 . 
     At this stage of deployment, the clip  4  is still in the delivery configuration. As the introducer sheath  2  is withdrawn from the vessel  7 , the clip  4  expands to its deployed configuration in which the body  16  of the clip  4  is flat and in a plane. In some embodiments, the tissue engaging members  20  lie in the same plane as the body  16  of the clip  4  when the tissue engaging members engage the exterior vessel wall  6 , as shown in  FIG. 1  panel C. In other embodiments, the tissue engaging members  20  can lie below the plane when they are engaged with the exterior vessel wall  6 , as shown in  FIG. 16  panel B. The transition of the clip  4  from the delivery configuration to the deployed configuration pulls vessel wall tissue on each side of the aperture together to close the aperture in the vessel  7 . The clip  4  in the deployed configuration has the tissue engaging members  20  directed toward each other and interlocking with each other. 
     A system  100  according to another embodiment is illustrated in  FIGS. 23-28 . The system  100  includes a delivery device  110  and a clip  140 . The system  100  is configured to deliver the clip  140  to a bodily tissue for closure of an opening in the tissue. For example, the delivery device  110  can deliver the clip  140  to bodily tissue proximate to an aperture in the wall of a blood vessel, and the clip  140  can close the aperture following a medical procedure, such as an interventional procedure described above. 
     The delivery device  110  is configured to be disposed about at least a portion of a medical device  102  (e.g. a sheath or catheter). The delivery device  110  defines a channel  111  configured to receive a portion of the medical device  102 . The delivery device  110  can be movably disposable about the medical device  102 . 
     The delivery device  110  includes an inner member  120 , an outer member  130 , and a pusher  126  disposed between the outer member and the inner member. The inner member  120  is configured to be disposed about at least a portion of the medical device  102 . For example, the inner member  120  can define a channel  121  slidably disposable about the medical device  102 . The inner member  120  is configured to be received within a channel  131  defined by the outer member  130 . 
     The inner member  120  includes a distal end portion  122  configured to engage a bodily tissue. The distal end portion  122  is configured to facilitate delivery of the clip  140  to the bodily tissue. In one embodiment, as shown in  FIG. 25 , at least a portion of the distal end portion  122  is angled. As such, the distal end portion  122  of the inner member  120  is configured to guide at least a portion of the clip  140  in a direction away from the medical device during delivery of the clip. Specifically, the distal end portion  122  directs tissue engaging members  144 ,  146  of the clip  140  away from the medical device during delivery. In this manner, the tissue engaging members  144 ,  146  can engage bodily tissue further from the aperture caused by the medical device, thus providing increased tension in the clip to facilitate closure of the aperture, as described in more detail below. Although the distal end portion  122  of the inner member  120  is illustrated and described herein as being angled, in other embodiments, the distal end portion can have a different configuration for guiding the direction of advancement of portions of the clip. For example, the distal end portion can be curved. In another example, the distal end portion can define at least one recess, groove, or notch for directing the advancement of the clip  140 . 
     The pusher  126  is similar in many respects to the pusher sleeve  9  described above. The pusher  126  is configured to move the clip  140  from a loaded configuration in which the clip  140  is disposed between the inner member  120  and the outer member  130  of the delivery device  110  to a deployed configuration in which at least a portion of the clip  140  is disposed exterior to the outer member  130  of the delivery device. At least a portion of the pusher  126  is disposed between the inner member  120  and the outer member  130 . In one embodiment, the pusher  126  defines a channel configured to receive at least a portion of the inner member  120  and the medical device  102 . During insertion of the delivery device  110  into the body of the patient and prior to deployment of the clip  140 , a distal end  128  of the pusher  126  is positioned proximally to the clip, which is also received between the inner member  120  and the outer member  130 . 
     The outer member  130  can be similar in many respects to the constraining sleeve  8  described above. The outer member  130  is configured to be disposed about at least a portion of at least one of the inner member  120 , the pusher  126 , and/or the medical device  102 . In one embodiment, for example, the outer member  130  defines a channel  131  configured to receive at least a portion of the inner member  120 , the pusher  126 , and/or the medical device  102 . Said another way, the outer member  130  is disposable about at least a portion of the inner member  120 , the pusher  126  and/or the medical device  102 . In some embodiments, the outer member  130  is movably (e.g., slidably) disposable about the inner member  120 , the pusher  126  and/or the medical device  102 . The outer member  130  is configured to be disposed about the clip  140  prior to delivery of the clip. For example, the clip  140  can be received in the channel  131  defined by the outer member  130 . 
     The outer member  130  includes a distal end portion  132  configured to facilitate deployment of the clip  140 . For example, as illustrated in  FIG. 26 , at least a portion of the distal end portion of the outer member can be perforated. The perforation in the distal end portion  132  is configured to tear or otherwise break apart during deployment of the clip. In use, as the pusher  126  advances the clip  140  towards its deployed configuration, at least the tissue engaging members  144 ,  146  of the clip are guided in an outward direction by the angled distal end portion of the inner member  120  such that the tissue engaging members push outward against the perforated portion of the distal end portion of the outer member. The perforations are configured to break in the presence of the pressure caused by the tissue engaging members  144 ,  146  pushing outwards. 
     Although the distal end portion  132  is illustrated and described herein as including perforations to permit deployment of the clip, in other embodiments, the distal end portion can be configured differently to permit clip deployment. For example, in some embodiments, the distal end portion is configured permit deflection or displacement of the distal end portion during deployment of the clip. For example, the distal end portion can be flexile or elastic, can have a thinner cross-sectional wall diameter than other portions of the outer member, or a combination of the foregoing, to permit deflection or displacement of the distal end portion during deployment of the clip. 
     The clip  140  is configured to substantially close an aperture in a tissue of a patient. The clip  140  can be similar in many respects to clip  4 , described above. The clip  140  is configured to be disposed on the delivery device  110  between the inner member  120  and the outer member  130 . The clip  140  includes a body portion  142  and a first tissue engaging member  144  and a second tissue engaging member  146  disposed on the body portion. The clip  140  has a first, or neutral, configuration (e.g., as shown in  FIG. 27 ), and a second, or loaded, configuration (e.g., as shown in  FIG. 28 ). The clip  140  is biased towards its first, or neutral, configuration. As such, when the clip  140  is in its second, or loaded, configuration, at least the body portion  142  of the clip exerts a pressure to return towards its first configuration. Said another way, at least a portion of the clip  140  has shape memory characteristics, and thus the clip  140  is biased towards its original shape. In some embodiments, the body portion  142 , at least one tissue engaging member  144 ,  146 , or a combination thereof has shape memory. 
     As shown in  FIG. 25 , the body portion  142  of the clip  140  defines a channel  141 . At least the body portion  142  is configured to be disposed about a portion of the delivery device  110 . For example, the body portion  142  defining the channel  141  can be disposed about a portion of the inner member  120  of the delivery device  110 . Said another way, the channel  141  defined by the body portion  142  of the clip  140  is configured to receive a portion of the delivery device  110 . The clip  140  is in its second configuration when it is disposed about the delivery device  110 , as shown in  FIG. 28 . 
     The body portion  142  defining the channel  141  is configured to deform to increase a cross-sectional diameter of the channel to accommodate the portion of the delivery device  110 . Said another way, the body portion  142  defines a channel having a first cross-sectional diameter when the clip is in its first, or neutral configuration, and defines a channel having a second cross-sectional diameter greater than the first cross-sectional diameter when the clip is in its second, or loaded, configuration. For example, in its loaded configuration, the channel defined by the body portion can have a cross-sectional diameter up to twice the cross-sectional diameter of the channel defined by the body portion when the clip is in its neutral configuration. In another example, in its loaded configuration, the channel defined by the body portion can have a cross-sectional diameter greater than twice the cross-sectional diameter of the channel defined by the body portion when the clip is in its neutral configuration. Because the clip  140  is biased towards its first configuration, the clip  140  exerts a pressure on the delivery device  110  which helps to retain the clip on the delivery device. The clip  140  may also be retained on the delivery device  110  by the outer member  130  being disposed about the clip. 
     The tissue engaging members  144 ,  146  of the clip  140  are configured to engage a bodily tissue proximate to the medical device  102  to help retain the clip proximate to an aperture in the bodily tissue caused by the medical device  102 . More specifically, the first and second tissue engaging members  144 ,  146  are configured to anchor the clip  140  into the bodily tissue such that the tissue engaging members remain in the bodily tissue after deployment from the delivery device  110  as the clip  140  moves towards its first configuration. The tissue engaging members  144 ,  146  can be similar in many respects to tissue engaging members  17 ,  18 , discussed in detail above. 
     The first and second tissue engaging members  144 ,  146  extend from opposing ends of the body portion  142 . In the embodiment illustrated in  FIG. 27 , the first and second tissue engaging members  144 ,  146  substantially extend along an axis different than a longitudinal axis defined by the body portion  142  of the clip  140 . As such, the tissue engaging members  144 ,  146  can engage the bodily tissue while the body portion  142  of the clip  140  remains above, or proximal to, the bodily tissue. 
     Each tissue engaging member  144 ,  146  can be of any suitable length for engaging the bodily tissue. In some embodiments, for example, the tissue engaging member  144  has a length less than a cross-sectional diameter of the medical device  102 . In another example, the tissue engaging member  144  has a length substantially equivalent to a cross-sectional diameter of the medical device  102 . In still another example, the tissue engaging member  144  has a length greater than a cross-sectional diameter of the medical device  102 . In some embodiments, the combined length of the tissue engaging members  144 ,  146  is less than the cross-sectional diameter of the medical device  102 . In other embodiments, the combined length of the tissue engaging members  144 ,  146  is substantially the same as or is greater than a cross-sectional diameter of the medical device  102 . 
     The tissue engaging members  144 ,  146  each include a barb  150 ,  152 , respectively. The barbs  150 ,  152  are configured to facilitate insertion of the tissue engaging members  144 ,  146  into the bodily tissue. For example, the barbs  150 ,  152  each include a sharpened point  154 ,  156 . The barbs  150 ,  152  are also configured to facilitate retention of the tissue engaging members  144 ,  146  in the bodily tissue. For example, the barbs  150 ,  152  each include a shoulder  155 ,  157 , respectively. After insertion of the barbs  150 ,  152  into the bodily tissue, the bodily tissue collapses about the shoulder  155 ,  157  of each barb  144 ,  146 . In this manner, the shoulders  155 ,  157  prevent regression, or proximal movement, of the tissue engaging members  144 ,  146  from the bodily tissue. Although the barbs  150 ,  152 , are illustrated and described herein as including a sharpened point  154 ,  156  and a shoulder  155 ,  157 , respectively, in other embodiments, the barbs  150 ,  152  can be of any suitable configuration, including those described above with respect to barb  24 . 
     The system  100  can be used in a surgical procedure to close an aperture in a bodily tissue. For example, the system  100  can be used in a surgical procedure to close an aperture in a wall of a blood vessel, as described herein with reference to  FIGS. 23-31 . In such a procedure, the medical device  102  (e.g., a catheter or sheath) is inserted into the bodily tissue. Prior to removal of the medical device  102  from the patient&#39;s body, the system  100  is coupled to the medical device  102 , as shown in  FIG. 24 . The system  100  is advanced in a distal direction until the system is in a desired positioned with respect to the vessel wall. For example, referring to  FIG. 29 , the system  100  can be advanced into the patient&#39;s body until the distal end  112  of the delivery device  110  is adjacent the vessel wall. 
     To deploy the clip  140 , the pusher  126  of the delivery device  110  is moved distally in the direction of arrow A 1  with respect to the inner and outer members  120 ,  130 . As the pusher  126  is moved distally, the distal end  128  of the pusher engages the clip  140  that is loaded within the delivery device. Additional distal movement of the pusher  126  moves the clip  140  distally in the direction of arrow A 1  until the tissue engaging members  144 ,  146  engage the distal end portion  122  of the inner member  120 . Still further distal movement of the pusher  126  against the clip  140  causes the tissue engaging members  144 ,  146  to move outwardly along the distal end portion  122  of the inner member  120  in the direction of arrows A 2  and A 3 , respectively. In some embodiments, the pusher  126  can move the clip  140  at least until the clip is no longer received in the space between the inner member  120  and the outer member  130 . Referring to  FIG. 30 , the tissue engaging members  144 ,  146  are moved in the direction of arrows A 2  and A 3 , respectively, to engage and break through the perforations on the distal end portion  132  of the outer member  130 . 
     As the clip  140  is deployed from the delivery device  110 , the tissue engaging members  144 ,  146  engage the vessel wall. For example, the tissue engaging members  144 ,  146  can engage a superficial layer of the vessel wall. The barbs  150 ,  152  on the tissue engaging members  144 ,  146  facilitate insertion and retention of the tissue engaging members in the vessel wall, as described in detail above. 
     Once the clip  140  has been deployed from the delivery device  110 , the delivery device and the medical device  102  are withdrawn from the body of the patient in the direction of arrow A 4 , as shown in  FIG. 31 . The delivery device  110  and the medical device  102  can be withdrawn concurrently or consecutively, at the discretion of the physician. Because the tissue engaging members  144 ,  146  are anchored in the vessel wall, the clip  140  remains in the body of the patient after withdrawal of the delivery device  110  and the medical device  102 . 
     In absence of the delivery device  110  and the medical device  102 , the clip  140  moves from its second, or loaded, configuration, to its first, or neutral, configuration, as described above. In doing so, the tissue engaging members  144 ,  146  are moved towards each other, thus moving the engaged portions of the vessel wall around the aperture towards each other and substantially closing the aperture, as shown in  FIG. 31 . In some embodiments, a distance between the tissue engaging members  114 ,  146  and/or between the barbs  150 ,  152  is less than a cross-sectional diameter of the medical device  102 . In other embodiments, a distance between the tissue engaging members  114 ,  146  and/or between the barbs  150 ,  152  is approximately equal to a cross-sectional diameter of the medical device  102 . In still other embodiments, a distance between the tissue engaging members  114 ,  146  and/or between the barbs  150 ,  152  is greater than a cross-sectional diameter of the medical device  102 . 
     Although closure of the aperture in the blood vessel is described above by engaging the vessel wall with the tissue engaging members  144 ,  146  and returning the clip  140  to its first configuration, in other embodiments, the aperture in the blood vessel is closed by engaging soft tissue proximate to the vessel wall with the tissue engaging members  144 ,  146  and returning the clip  140  to its first configuration. Because the soft tissue is pulled together by the clip in its first configuration, portions of the vessel wall about the aperture are also pulled together, thus closing the aperture. 
     While various embodiments have been described above, it should be understood that they have been presented by way of example only, and not limitation. Where methods described above indicate certain events occurring in certain order, the ordering of certain events may be modified. Additionally, certain of the events may be performed concurrently in a parallel process, when possible, as well as performed sequentially as described above. Furthermore, although methods are described above as including certain events, any events disclosed with respect to one method of the invention may be performed in a different method according to the invention. Thus, the breadth and scope of the invention should not be limited by any of the above-described embodiments. While the invention has been particularly shown and described with reference to specific embodiments thereof, it will be understood that various changes in form and details may be made. 
     For example, although the clips (e.g., clip  4 , clip  140 ) have been illustrated and described herein as including tissue engaging members (e.g., tissue engaging members  17 ,  18 ,  144 ,  146 ) of a certain shape and/or orientation, in other embodiments, a clip can include tissue engaging members having a different shape and/or orientation. 
     For example, although the clip  140  includes tissue engaging members  144 ,  146  extending from the body portion  142  to form an approximately 90 degree angle, in other embodiments, a clip can include a tissue engaging member that extends from a body portion at a different angle. In some embodiments, a clip  160  includes a tissue engaging member  164  that is extended from a body  162  of the clip at an angle less than 90 degrees, as shown in  FIG. 32 . For example, a tissue engaging member can form an angle of approximately 45 degrees with a body of a clip when the clip is in an original or neutral configuration. In other embodiments, a clip can include a tissue engaging member that is extended from a body of the clip at an angle greater than 90 degrees. 
     In another example, although the clip  140  has been illustrated and described herein as including substantially straight tissue engaging members  144 ,  146 , in other embodiments, the tissue engaging members can have a different shape. For example, as shown in  FIG. 33 , a clip  161  includes at least one curved tissue engaging member  165 . In use, the curve of the tissue engaging member  165  can facilitate engagement of the tissue engaging member  165  with adjacent bodily tissue by affecting the angle at which an end  167  of the tissue engaging member approaches the bodily tissue. 
     In some embodiments, a clip can be configured to increase a resistance to a deforming stress, such as that encountered during deployment of the clip or during movement of the clip towards its original configuration following deployment into the bodily tissue. For example, as shown in  FIG. 34 , a clip  170  includes a body  172  and a tissue engaging member  174  extended from a curved portion  176  of the body. The curved portion  176  of the body  172  is configured to increase the clip&#39;s  170  resistance to a deforming stress, thus reducing the likelihood that the tissue engaging member  174  and/or body  172  will break or tear in the presence of the deforming stress. The curved portion  176  of the body  172  can also enhance a bias of the clip  170  to a first configuration (e.g., as described below with respect to clip  250 ). 
     Although the clip  140  has been illustrated and described herein as having a first configuration in which the end of the body portion  142  adjacent to the first tissue engaging member  144  is spaced apart from the opposing end of the body portion adjacent the second tissue engaging member  146 , in other embodiments, a clip can have a first configuration in which the body portion and/or the tissue engaging members are differently spaced or positioned. For example, in some embodiments, a clip  180  is biased towards a first, or neutral, configuration in which opposing ends of a body  182  at least partially overlap, as shown in  FIG. 35 . As such, first and second tissue engaging members  184 ,  186 , respectively, may also at least partially overlap when the clip  180  is in its first configuration. In another example, as shown in  FIG. 36 , a clip  190  has a first, or neutral, configuration in which opposing ends of a body  182  include at least partially overlapping curved portions  195 ,  197  from which tissue engaging members  194 ,  196 , respectively, extend. The curved portion  195 ,  197  of the body  192  can be configured to increase the clip&#39;s  190  resistance to a deforming stress, as described above with respect to clip  170 . 
     Although the clip  4  has been illustrated and described as including a rigid barb  24 , in some embodiments, the tissue engaging member includes a flexible barb. For example, as shown in  FIGS. 37-38 , a tissue engaging member  175  includes a barb  178  including at least one flexible fixation tine  179 . The flexible fixation tine  179  is configured to move from a first (or non-deployed) position to a second (or deployed) position. Generally, the flexible fixation tine  179  in its non-deployed position ( FIG. 37 ) is closer to a body portion  177  of the tissue engaging member  175  than the flexible fixation tine in its deployed position ( FIG. 38 ). In some embodiments, the non-deployed fixation tine  179  is substantially parallel to the body portion  177  of the tissue engaging member  175 . In its deployed position, the flexible fixation tine  179  extends outwardly from at least a portion of the tissue engaging member  175 , e.g., outwardly from the barb  178  to engage the bodily tissue. The flexible fixation tine  179  can be configured to extend outwardly from the barb  178  at any suitable angle, such as an angle up to 90 degrees from the body portion of the barb. In other embodiments, the flexible fixation tine  179  can extend from the barb  178  at an angle greater than 90 degrees. In use, the flexible fixation tine  179  is in its first position during insertion into the bodily tissue. Once forward advancement of the barb  178  ceases, the flexible fixation tine  179  is moved to its second position, thereby engaging bodily tissue between the fixation tine  179  and the body portion  177  of the tissue engaging member  175 . The flexible fixation tine  179  can be biased towards one of its first position or its second position. 
     In the embodiment illustrated in  FIGS. 37-38 , the barb  178  includes two fixation tines  179 . In other embodiments, however, a barb can include any suitable number of fixation tines, such as one, three, four, or more fixation tines. In one embodiment including a plurality of fixation tines, such as illustrated in  FIG. 39 , a fixation tine  235  can extend from a barb  234  at an angle different than an angle at which another fixation tine  237  extends from the barb. For example, in one embodiment, a first fixation tine can be configured to extend from the barb at a 15 degree angle and a second fixation tine can be configured to extend from the barb at a 30 degree angle. In some embodiments, as illustrated in  FIG. 39 , the tissue engaging member can include a combination of rigid and flexible barbs and/or a barb with a combination of at least one rigid tine  236  and at least one flexible fixation tine  238 . In still another embodiment, a tissue engaging member includes a barb having no fixation tine, as illustrated in  FIG. 11 . In still other embodiments, a tissue engaging member can have no barbs. For example, the tissue engaging member itself can be otherwise configured to retain a clip in the bodily tissue, such as having a textured surface for engaging the bodily tissue. 
     Although the clip  140  has been illustrated and described above as including two tissue engagement members  144 ,  146  disposed on opposing ends of the body  142  of the clip, in some embodiments, a clip includes more than two tissue engagement members. For example, a clip can include two, three, four, or more tissue engaging members disposed at various locations along a body of the clip. In another example, in some embodiments, a clip is configured with a plurality of tissue engagement members wherein at least one of the plurality is configured to engage a first bodily tissue and at least a second of the plurality is configured to engage a second bodily tissue different than the first bodily tissue. 
     For example, as shown in  FIG. 40 , a clip  240  includes a body  242  and four tissue engagement members  244 ,  245 ,  246 ,  247 . The tissue engagement members  244 ,  246  are disposed on opposing ends of the body  242  and are each configured to engage a first bodily tissue. The tissue engagement members  245 ,  247  are disposed on opposing ends of the body  242  and are each configured to engage a second bodily tissue different than the first bodily tissue. In the clip  240  shown in  FIG. 40 , the tissue engagement members  245 ,  247  for engaging the second bodily tissue are longer than the tissue engagement members  244 ,  246  for engaging the first bodily tissue. In a surgical procedure to close an aperture in a wall of a blood vessel, for example, the shorter tissue engagement members  244 ,  246  can be configured to engage the vessel wall and the longer tissue engagement members  245 ,  247  can be configured to engage soft tissue further from a delivery device and proximal to the vessel wall. In this manner, when the clip is deployed in the patient&#39;s body, the shorter tissue engagement members  244 ,  246  close the aperture in the vessel wall and the longer tissue engagement members  245 ,  247  close an aperture in the proximal soft tissue. Each tissue engagement member  244 ,  245 ,  246 ,  247  can have characteristics different than another tissue engagement member  244 ,  245 ,  246 ,  247 . For example, the tissue engagement member  245  can be flexible and the tissue engagement member  244  can be rigid. In another example, the tissue engagement member  246  can include a barb with tines of a first length and the tissue engagement member  247  can include a barb with tines of a second length greater than the first length. 
     Although the clips (e.g., clip  4 , clip  140 ) have been illustrated and described herein as being resilient, in some embodiments, a clip is further configured to enhance a bias of the clip towards a first configuration. For example, as illustrated in  FIG. 41 , a clip  250  can include a curved portion  256  defined by a body  252  of the clip. The curved portion  256  of the body  252  permits the clip  250  to maintain a narrow profile when the clip is in a first, or neutral, configuration while having a longer body  252 , and thus a larger section having resilience. As such, the curved portion  256  helps to increase the bias (or collapsing) force of the clip. As used herein, bias (or collapsing) force refers to the energy or pressure with which an object resiliently returns to an original configuration. When the clip  250  is moved from a second, or loaded, configuration to its first, or neutral, configuration, the bias force is greater in the clip  250  with the curved portion  252  than in a clip (e.g., clip  140 ) without the curved portion. In other embodiments, as illustrated in  FIG. 42 , a clip  260  can include a curved portion  266  similar in many respects to clip  250 , that includes a tissue engaging member  265  extended from the curved portion. In still other embodiments, a clip  270 ,  280  can include a body  272 ,  282  with various curved portions to increase the bias (or collapsing) force of the clip, as illustrated in  FIGS. 43 and 44 , respectively. In some embodiments, the curved portion  256  can be configured to increase a resistance to a deforming stress, such as that encountered during deployment of the clip or during movement of the clip towards its original configuration following deployment into the bodily tissue, as described above with respect to the curved portion  176  of the clip  170 . 
     Although the delivery devices (e.g. delivery device  3 , delivery device  110 ), or portions thereof (e.g., constraining sleeve  8 , pusher sleeve  9 , inner member  120 , outer member  130 ), have been illustrated and described herein as defining a channel (e.g., channel  111 , channel  121 , channel  131 ) formed by a lateral opening disposed along its length, in other embodiments, a delivery device, or portion thereof, can define a lumen configured to be disposed about a medical device (e.g., a sheath or catheter) or other portion of the delivery device. 
     Although the systems (e.g., system  1 , system  100 ) have been illustrated and described herein as including a single clip for deployment, in other embodiments, a system can include or otherwise be configured to deploy a plurality of clips. 
     In one example, referring to  FIG. 45 , a system  300  includes an elongate member  320 , a pusher (not shown), a first closure device  330 , and a second closure device  340 . The system  300  is configured for substantially simultaneous deployment of the closure devices  330 ,  340 . 
     The elongate member  320  is removably couplable to a medical device (not shown), such as a catheter or sheath. The elongate member  320  can be similar in many respects to inner member  120  described above with respect system  100 . The elongate member  320  is positionable within the body of a patient about the medical device such that a distal end  322  of the elongate member is adjacent or proximate to at least one bodily tissue defining an aperture. 
     The first closure device  330  and the second closure device  340  are each configured to substantially close the aperture in the at least one bodily tissue. The closure devices  330 ,  340  can be similar in many respects to the clip  140  described above with respect to system  100 . Each closure device  330 ,  340  is configured to be disposed about the elongate member  320  such that fixation portions  331 ,  333 ,  341 ,  343  of the closure devices  330 ,  340  are at least partially received in a respective channel  332 ,  334 ,  342 ,  344  (or groove) defined by the distal end  322  of the elongate member. The channels  332 ,  334 ,  342 ,  344  are configured to guide the direction of advancement of the fixation portions  331 ,  333 ,  341 ,  343  as the closure devices  330 ,  340  are moved distally by the pusher during deployment of the closure devices from the system  300 . For example, the channels  332 ,  334  can guide the fixation portions  331 ,  333  of the first closure device  330  to the bodily tissue at a first distance from the elongate member  320  and the channels  342 ,  344  can guide the fixation portions  341 ,  343  of the second closure device  340  to the bodily tissue at a second distance from the elongate member  320 . In another example, the channels  332 ,  334  can guide the fixation portions  331 ,  333  of the first closure device  330  to a first bodily tissue, and the channels  342 ,  344  can guide the fixation portions  341 ,  343  of the second closure device  340  to a second bodily tissue different than the first bodily tissue. 
     As shown in  FIG. 45 , the elongate member  320  defines four channels  332 ,  334 ,  342 ,  344  to correspond to each of the four fixation portions  331 ,  333 ,  341 ,  343 . In other embodiments, however, the elongate member can include a different number of channels, e.g., one, two, three, five or more, which may correspond to a different number of fixation portions, e.g., one, two, three, five or more, and/or a different number of closure devices, e.g., one, three, four or more. In still other embodiments, the elongate member is differently configured to guide the direction of advancement of a fixation portion. For example, the elongate member can include a series of notches between which the fixation portion is disposed. 
     Although the system  300  is illustrated and described as including closure devices  330 ,  340 , in other embodiments, any suitable clip or closure device can be included. For example, in some embodiments, the system  300  includes nested closure devices  350 ,  360 , as illustrated in  FIG. 46 . 
     In another example, referring to  FIG. 47 , a system  400  is configured for substantially simultaneous deployment of a plurality of closure devices at multiple depths within a body of a patient. The system  400  includes a delivery device  410  including an inner member  420 , a pusher  450 , and an outer member  430 . The inner member  420  is configured to be at least partially disposed about a medical device (not shown), such as a catheter or sheath. The inner member  420  includes a plurality of ramps disposed at spaced locations on the inner member. The ramps  421 ,  423 ,  425  are configured to guide advancement of a plurality of clips (not shown), such as clips described herein (e.g., clip  4 , clip  140 , closure devices  330 ,  340 ), during deployment of the clips into the patient&#39;s body. The ramps  421 ,  423 ,  425  have an inclined surface to direct at least a portion of each clip of the plurality away from the inner member to an area outside of the outer member  430 . 
     The outer member  430  is disposable about at least a portion of the pusher  450  and at least a portion of the inner member  420 . The outer member  430  defines a plurality of slots. Each slot  431 ,  433 ,  435  of the plurality of slots corresponds to a respective ramp  421 ,  423 ,  425  of the inner member  420 . Each slot  431 ,  433 ,  435  is configured to permit a clip to pass through the slot from an area between the inner member  420  and the outer member  430  to an area outside of the outer member. 
     The pusher  450  is configured to be at least partially disposed about the inner member  420  between the inner member and the outer member  430 . The pusher  450  includes a plurality of pushing arms. Each pushing arm  451 ,  453 ,  455  of the plurality of pushing arms corresponds to its respective ramp  421 ,  423 ,  425  of the inner member and is configured to engage a clip of the plurality of clips. 
     In use, the pusher  450  is moved in a distal direction towards the patient&#39;s body. As the pusher  450  is moved distally, each pushing arm  451 ,  453 ,  455  is correspondingly moved distally to engage its respective clip. As each clip is moved distally by the pushing arms  451 ,  453 ,  455 , the respective ramp  421 ,  423 ,  425  guides the advancement of the clips away from the medical device and the inner member  420 . The clips exit the delivery device  410  through the slots  431 ,  433 ,  435  of the outer member  430 . Each clip engages a bodily tissue proximate to the site of deployment of the clip from the delivery device  410 . After deployment of the clips, the delivery device  410  and the medical device are removed from the patient&#39;s body. Each clip moved to an original configuration in absence of the delivery device  410  and the medical device. By returning to its original configuration, each clip pulls together tissue engaged by the clip to close a respective aperture or portion thereof in the bodily tissue. In this manner, the system  400  is configured to facilitate closure of an aperture (e.g., caused by the medical device) at multiple levels in the patient&#39;s body. For example, the system  400  can be used to close an aperture that extends from the skin to a blood vessel caused by the medical device by engaging and pulling together tissue in a wall of the blood vessel, in subcutaneous tissue between the blood vessel and skin, and in the skin. 
     Although the system  400  has been illustrated and described as being configured for simultaneous deployment of three clips, in other embodiments, the system can be configured for deployment of any suitable number of clips. For example, in other embodiments, a system can be configured to deploy two, four, five, or more clips simultaneously, with the system having a desired number of inner member ramps, pusher arms, and slots in the outer member. 
     Furthermore, although the system  400  has been illustrated and described as being configured for simultaneous deployment of a plurality of clips, in other embodiments, a system can be configured for selective deployment of a plurality of clips at multiple levels within the patient&#39;s body. For example, in one embodiment, the system can include a plurality of pushers each independently operable for selective deployment of a clip of the plurality of clips. 
     A portion of a system  500  for closure of an aperture in a bodily tissue according to an embodiment is illustrated in  FIG. 48 . The system  500  includes a delivery device  510  and a closure system  535 . The delivery device  510  can be similar in many respects to any delivery device described herein (e.g., delivery device  3 , delivery device  110 , etc.). The delivery device  510  is configured to deliver the closure system  535  to a body of a patient. 
     The closure system  535  is configured to close an aperture in a bodily tissue of the patient. The closure system  535  includes a clip  540  and a biocompatible material  550 . The clip  540  can be similar in many respects to any clip described herein (e.g., clip  4 , clip  140 , etc.). The clip  540  is configured to be deployed into the patient&#39;s body to engage and pull portions of the bodily tissue towards each other for closure of an aperture in the bodily tissue. The biocompatible material  550  is configured to facilitate closure of the aperture in the bodily tissue. For example, the biocompatible material can be configured to provide a seal about at least a portion of the clip. In another example, the biocompatible material  550  can expand in volume upon contact with bodily fluid to occlude small (e.g., microscopic) openings in the bodily tissue proximate to the deployed clip  540 . 
     The biocompatible material  550  is configured to be delivered into the patient&#39;s body. In the embodiment illustrated in  FIG. 48 , the biocompatible material  550  is disposed about a portion of the delivery device  510  and the clip  540  is disposed about a portion of the biocompatible material. In other embodiments, at least a portion of the biocompatible material is coupled to or disposed about at least a portion of the clip. For example, the biocompatible material can be disposed in the delivery device about a tissue engaging member or fixation tine of the clip. In another example, the biocompatible material can be disposed in the delivery device about or proximal to a body portion of the clip. In still another example, the biocompatible material can be disposed in the delivery device distal to the clip. 
     The biocompatible material  550  can be loaded to the delivery device  510  independently of the clip. The biocompatible material  550  can be loaded to the delivery device in any suitable form, including, but not limited to, a thin film, a scaffold, a tube, a mesh, or a web. 
     In some embodiments, the biocompatible material  550  is spongy. The biocompatible material can include any suitable polymer, co-polymer, olygomer, polyether, other suitable material, or combinations thereof. For example, in some embodiments, the biocompatible material includes polyethylene glycol (PEG). In some embodiments, the biocompatible material  550  includes a drug, a powder, or another substance formulated or configured to facilitate closure of the aperture. 
     Although various embodiments have been described as having particular features and/or combinations of components, other embodiments are possible having a combination of any features and/or components from any of the embodiments discussed above. 
     INCORPORATION BY REFERENCE 
     References and citations to other documents, such as patents, patent applications, patent publications, journals, books, papers, web contents, have been made throughout this disclosure. All such documents are hereby incorporated herein by reference in their entirety for all purposes. 
     Equivalents 
     Various modifications of the invention and many further embodiments thereof, in addition to those shown and described herein, will become apparent to those skilled in the art from the full contents of this document, including the references to the scientific and patent literature cited herein.