DETAILED DESCRIPTION

[0084] The invention is further illustrated by the following (preceding) pictorial embodiments, which in no way should be construed as further limiting. The present invention specifically contemplates other embodiments not illustrated but intended to be included in the appended claims. FIGS. 1-11 , 18 - 19 are directed to a basic stent frame; FIGS. 12-14 are directed to a single-leaflet valve; FIGS. 15-16 are directed to an occluder (or filter); FIGS. 17 and 32 are directed to a stent adaptor for a stent graft, FIG. 20-27 , 35 - 40 , 42 - 50 are directed to a multi-leaf valve; and FIG. 28-31 are directed to a constrained frame which can be used to form any of the other embodiments.

[0085] FIG. 1 depicts a top view of one embodiment of the medical device 10 of the present invention comprising a frame 11 of resilient material, preferably metal wire made of stainless steel or a superelastic alloy (e.g., nitinol). While round wire is depicted in each of the embodiments shown herein, other types, e.g., flat, square, triangular, D-shaped, delta-shaped, etc. may be used to form the frame. In the illustrative embodiment, the frame comprises a closed circumference 62 of a single piece 59 of material that is formed into a device 10 having a plurality of sides 13 interconnected by a series of bends 12 . The depicted embodiment includes four sides 13 of approximately equal length. Alternative embodiments include forming a frame into any polygonal shape, for example a pentagon, hexagon, octagon, etc. One alternative embodiment is shown in FIG. 19 that includes a four-sided frame 11 having the general shape of a kite with two adjacent longer sides 66 and two adjacent shorter sides 67 . In the embodiment of FIG. 1 , the bends 12 interconnecting the sides 13 comprise a coil 14 of approximately one and a quarter turns. The coil bend produces superior bending fatigue characteristics than that of a simple bend 40 , as shown in FIG. 9 , when the frame is formed from stainless steel and most other standard materials. The embodiment of FIG. 9 may be more appropriate, however, if the frame is formed from nitinol (NiTi) or other superelastic alloys, as forming certain type of bends, such as coil 14 , may actually decrease fatigue life of a device of superelastic materials. Therefore, the bend 12 should be of a structure that minimizes bending fatigue. Alternative bend 12 embodiments include an outward-projecting fillet 41 as shown in FIG. 10 , and an inward-projecting fillet 42 comprising a series of curves 63 , as shown in FIG. 11 . Fillets are well known in the stent art as a means to reduce stresses in bends. By having the fillet extend inward as depicted in FIG. 11 , there is less potential trauma to the vessel wall.

[0086] When using stainless steel wire, the size of the wire which should be selected depends on the size of device and the application. An occlusion device, for example, preferably uses 0.010″ wire for a 10 mm square frame, while 0.014″ and 0.016″ wire would be used for 20 mm and 30 mm frames, respectively. Wire that is too stiff can damage the vessel, not conform well to the vessel wall, and increase the profile of the device when loaded in the delivery system prior to deployment.

[0087] Returning to FIG. 1 , the single piece 59 of material comprising the frame 11 is formed into the closed circumference 62 by securing the first and second ends 60 , 61 with an attachment mechanism 15 such as a piece of metal cannula. The ends 60 , 61 of the single piece 59 are then inserted into the cannula 15 and secured with solder 25 , a weld, adhesive, or crimping to form the closed frame 11 . The ends 60 , 61 of the single piece 59 can be joined directly without addition of a cannula 15 , such as by soldering, welding, or other methods to join ends 61 and 62 . Besides joining the wire, the frame could be fabricated as a single piece of material 59 , by stamping or cutting the frame 11 from another sheet (e.g., with a laser), fabricating from a mold, or some similar method of producing a unitary frame.

[0088] A alternate method of forming the frame 11 of the present invention is depicted in FIGS. 76-79 , whereby rather than one continuous length of wire being used, the frame 11 comprises a two or more sub-portions 205 that include an attachment 15 such as a weld, solder, glue, crimping with the illustrative cannula 15 , or another means, or combination thereof, to form a closed circumference 62 . In the embodiment depicted in FIG. 76-77 , a first and a second C-shaped sub-portion 206 , 207 are overlaid such that first ends 210 of the C-shaped sub-portion 206 , 207 extend beyond the adjoining sub-portion to form a barb 16 for anchoring the device 10 within the vessel. As shown in FIG. 77 , the assembled frame 11 includes four barbs that either represent the ends 210 , 211 of the sub-portions 206 , 207 , or are formed by cutting away excess material 228 from the ends, depending on how the sides 13 of the C-shaped portions are sized.

[0089] FIGS. 78-79 depict an alternative embodiment using sub-portions 205 to assemble a closed frame, whereby there are four L-shaped sub-portions 214 , 220 , 221 , 222 with attachments at each of the four sides 13 that make up the closed circumference 62 . In the illustrative embodiments only two of the ends 217 are used to form barbs 17 , 18 ; however, additional barbs can be formed by lengthening any leg of the L-shaped sub-portion 214 , 220 , 221 , 222 such that it extends beyond the closed circumference 62 . Other configurations are possible in addition to those depicted, for example, having three sub-portions 205 or even more than four if making a frame having more than four sides.

[0090] The device 10 depicted in FIG. 1 is shown in its first configuration 35 whereby all four bends 20 , 21 , 22 , 23 and each of the sides 13 generally lie within a single flat plane. To resiliently reshape the device 10 into a second configuration 36 , shown in FIG. 2 , the frame 11 of FIG. 1 is folded twice, first along one diagonal axis 94 with opposite bends 20 and 21 being brought into closer proximity, followed by opposite bends 22 and 23 being folded together and brought into closer proximity in the opposite direction. The second configuration 36 , depicted in FIG. 2 , has two opposite bends 20 , 21 oriented at the first end 68 of the device 10 , while the other opposite bends 22 , 23 are oriented at the second end 69 of the device 10 and rotated approximately 90° with respect to bends 20 and 21 when viewed in cross-section. The medical device in the second configuration 36 can be used as a stent 44 to maintain an open lumen 34 in a vessel 33 , such as a vein, artery, or duct. The bending stresses introduced to the frame 11 by the first and second folds required to form the device 10 into the second configuration 36 , apply force radially outward against the vessel wall 70 to hold the device 10 in place and prevent vessel closure. Absent any significant plastic deformation occurring during folding and deployment, the device in the second configuration 36 , when not with the vessel or other constraining means, will at least partially return to the first configuration 25 , although some deformation can occur as depicted in FIG. 34 , depending on the material used. It is possible to plastically form the stent into this configuration which represents an intermediate condition between the first configuration (which it also can obtain) and the second configuration. It is also possible to plastically deform the device 10 into the second configuration 36 , such that it does not unfold when restraint is removed. This might be particularly desired if the device is made from nitinol or a superelastic alloy.

[0091] The standard method of deploying the medical device 10 in a vessel 33 , depicted in FIG. 6 , involves resiliently forming the frame 11 into a third configuration 37 to load into a delivery device 26 , such as a catheter. In the third configuration 37 the adjacent sides 13 are generally beside each other in close proximity extending generally along the same axis. To advance and deploy the device from the distal end 28 of the delivery catheter 26 , a pusher 27 is placed into the catheter lumen 29 . When the device 10 is fully deployed, it assumes the second configuration 36 within the vessel as depicted in FIG. 2 . The sides 13 of the frame, being made of resilient material, conform to the shape of the vessel wall 70 such that when viewed on end, the device 10 has a circular appearance when deployed in a round vessel. As a result, sides 13 are arcuate or slightly bowed out to better conform to the vessel wall.

[0092] A second embodiment of the present invention is depicted in FIG. 3 wherein one or more barbs 16 are included to anchor the device 10 following deployment. As understood, a barb can be a wire, hook, or any structure attached to the frame and so configured as to be able to anchor the device 10 within a lumen. The illustrative embodiment includes a first barb 16 with up to three other barbs 17 , 71 , 72 , indicated in dashed lines, representing alternative embodiments. As depicted in detail view A of FIG. 3 , the barb combination 38 that comprises barbs 17 and 18 , each barb is an extension of the single piece 59 of material of the frame 11 beyond the closed circumference 59 . The attachment cannula 15 secures and closes the single piece 59 of material into the frame 11 as previously described, while the first and second ends 60 , 61 thereof, extend from the cannula 15 , running generally parallel with the side 13 of the frame 11 from which they extend, each preferably terminating around or slightly beyond respective bends 20 , 23 . To facilitate anchoring, the distal end 19 of the barb 16 in the illustrative embodiment contains a bend or hook.

[0093] Optionally, the tip of the distal end 19 can be ground to a sharpened point for better tissue penetration. To add a third and fourth barb as shown, a double ended barb 39 comprising barbs 71 and 72 is attached to the opposite side 13 as defined by bends 21 and 22 . Unlike barb combination 38 , the double barb 39 , as shown in detail view B of FIG. 3 , comprises a piece of wire, usually the length of barb combination 38 , that is separate from the single piece 59 comprising the main frame 11 . It is secured to the frame by attachment mechanism 15 using the methods described for FIG. 1 . FIG. 4 depicts barb 17 (and 18 ) engaging the vessel wall 70 while the device 10 is in the second, deployed configuration 36 . While this embodiment describes up to a four barb system, more than four can be used.

[0094] FIG. 7 depicts a top view of a third embodiment of the present invention in the first configuration 35 that includes a plurality of frames 11 attached in series. In the illustrative embodiment, a first frame 30 and second frame 31 are attached by a barb 16 that is secured to each frame by their respective attachment mechanisms 15 . The barb 16 can be a double-ended barb 39 as shown in FIG. 3 (and detail view B) that is separate from the single pieces 59 comprising frames 30 and 31 , or the barb may represent a long extended end of the one of the single pieces 59 as shown in detail view A of FIG. 3 . Further frames, such as third frame 32 shown in dashed lines, can be added by merely extending the length of the barb 16 . FIG. 8 depicts a side view of the embodiment of FIG. 7 in the second configuration 36 as deployed in a vessel 33 .

[0095] FIGS. 12-18 depict embodiments of the present invention in which a covering 45 comprising a sheet of fabric, collagen (such as small intestinal submucosa), or other flexible material is attached to the frame 11 by means of sutures 50 , adhesive, heat sealing, “weaving” together, crosslinking, or other known means. FIG. 12 depicts a top view of a fourth embodiment of the present invention while in the first configuration 35 , in which the covering 45 is a partial covering 58 , triangular in shape, that extends over approximately half of the aperture 56 of the frame 11 . When formed into the second configuration 36 as shown in FIGS. 13-14 , the device 10 can act as an artificial valve 43 such as the type used to correct valvular incompetence. FIG. 13 depicts the valve 43 in the open configuration 48 . In this state, the partial covering 58 has been displaced toward the vessel wall 70 due to positive fluid pressure or flow in a first direction 46 , e.g., normal venous blood flow, thereby opening a passageway 65 through the frame 11 and the lumen 34 of the vessel 33 . As the muscles relax, producing flow in a second, opposite direction 47 , e.g., retrograde blood flow 47 , as shown in FIG. 14 , the partial covering 58 acts as a normal valve by catching the backward flowing blood and closing the lumen 34 of the vessel. In the case of the artificial valve 43 , the partial covering 58 is forced against the vessel wall to seal off the passageway 65 , unlike a normal venous valve which has two leaflets, which are forced together during retrograde flow. Both the artificial valve 43 of the illustrative embodiment and the normal venous valve, have a curved structure or cusp that facilitates the capture of the blood and subsequent closure. In addition to the triangular covering, other possible configurations of the partial covering 58 that result in the cupping or trapping of fluid in one direction can be used. Selecting the correct size of valve for the vessel ensures that the partial covering 58 properly seals against the vessel wall 70 . If the lumen 34 of the vessel is too large for the device 10 , there will be retrograde leakage around the partial covering 58 .

[0096] FIG. 15 depicts a top view of a fifth embodiment of the present invention in the first configuration 35 , whereby there is a full covering 57 that generally covers the entire aperture 56 of the frame 11 . When the device 10 is formed into the second configuration 36 , as depicted in FIG. 16 , it becomes useful as an occlusion device 51 to occlude a duct or vessel, close a shunt, repair a defect, or other application where complete or substantially complete prevention of flow is desired. As an intravascular device, studies in swine have shown occlusion to occur almost immediately when deployed in an artery or the aorta with autopsy specimens showing that thrombus and fibrin which had filled the space around the device. The design of the present invention permits it to be used successfully in large vessels such as the aorta. Generally, the occlusion device should have side 13 lengths that are at least around 50% or larger than the vessel diameter in which they are to be implanted.

[0097] FIGS. 17-18 depict two embodiments of the present invention in which the device 10 functions as a stent graft 75 to repair a damaged or diseased vessel, such as due to formation of an aneurysm. FIG. 17 shows a stent graft 75 having a tubular graft prosthesis 54 that is held in place by a pair of frames 11 that function as stent adaptors 52 , 53 . Each stent adaptor 52 , 53 has a covering attached to each of the frame sides 13 which includes a central opening 55 through which the graft prosthesis 54 is placed and held in place by friction or attachment to prevent migration. One method of preventing migration is placement of a stent adaptor 52 , 53 according to the present invention at each end and suturing the graft prosthesis 54 to the covering of the stent adaptors 52 , 53 . The stent adaptors 52 , 53 provide a means to seal blood flow while centering the graft prosthesis in the vessel. A long double-ended barb 39 connects to each stent adaptor 52 , 53 and assists to further anchor the stent graft 75 . In the embodiment depicted in FIG. 18 , the covering 45 comprises a outer sleeve 64 that is held in place by first and second 30 , 31 frames that function as stents 44 to hold and seal the sleeve 64 against a vessel wall and maintain an open passageway 65 . In the illustrative embodiment, the stents 44 are secured to the graft sleeve 64 by sutures 50 that are optionally anchored to the coils 14 of the bends 12 . If the embodiment of FIG. 18 is used in smaller vessels, a single frame 11 can be used at each end of the stent graft 75 . Another stent graft 75 embodiment is depicted in FIG. 32 for repairing a vessel defect 97 , such as an aneurysm in a bifurcated vessel. The stent adaptor 52 of the present invention is placed in the common vessel 96 such as the abdominal aorta. Two tubular grafts 54 are secured within an aperture 55 in the covering 45 of the frame 11 by one or more internal stent adapters 102 , or another type of self-expanding stent, that bias the opening of the grafts 54 against the surrounding covering 45 to provide an adequate seal. Each leg 98 , 99 of the stent graft prosthesis 75 transverses the vessel defect 97 and feeds into their respective vessel branches 100 , 101 such the right and left common iliac arteries. As with the embodiment of FIG. 17 , a second stent adapter 53 can be used to anchor the other end of the tubular graft 54 in each vessel branch 100 , 101 .

[0098] FIGS. 20-27 and 35 - 41 depict embodiments of present inventions in which the device 10 comprises an implantable valve having multiple leaflets 25 that act together to regulate and augment the flow of fluid through a duct or vessel 33 , or within the heart to treat patients with damaged or diseased heart valves. The covering 45 of each of these embodiments includes one or a series of partial coverings 58 that form the leaflets 25 of the valve. As with the other embodiments, the covering 45 may comprise a biomaterial or a synthetic material. While DACRON, expanded polytetrafluoroethylene (ePTFE), or other synthetic biocompatible materials can be used to fabricate the covering 45 , a naturally occurring biomaterial, such as collagen, is highly desirable, particularly a specially derived collagen material known as an extracellular matrix (ECM), such as small intestinal submucosa (SIS). Besides SIS, examples of ECM's include pericardium, stomach submucosa, liver basement membrane, urinary bladder submucosa, tissue mucosa, and dura mater. SIS is particularly useful, and can be made in the fashion described in Badylak et al., U.S. Pat. No. 4,902,508; Intestinal Collagen Layer described in U.S. Pat. No. 5,733,337 to Carr and in 17 Nature Biotechnology 1083 (Nov. 1999); Cook et al., WIPO Publication WO 98/22158, dated 28 May 1998, which is the published application of PCT/US97/14855. Irrespective of the origin of the valve material (synthetic versus naturally occurring), the valve material can be made thicker by making multilaminate constructs, for example SIS constructs as described in U.S. Pat. Nos. 5,968,096; 5,955,110; 5,885,619; and 5,711,969. Animal data show that the SIS used in venous valves of the present invention can be replaced by native tissue in as little as a month's time. In addition to xenogenic biomaterials, such as SIS, autologous tissue can be harvested as well, for use in forming the leaflets of the valve. Additionally Elastin or Elastin Like Polypetides (ELPs) and the like offer potential as a material to fabricate the covering or frame to form a device with exceptional biocompatibility. Another alternative would be to used allographs such as harvested native valve tissue. Such tissue is commercially available in a cryopreserved state.

[0099] To more completely discuss and understand the multi-leaflet valve 43 embodiments of FIGS. 20 - 27 , 35 - 41 , it is useful to now add certain supplemental terminology which in some instances, could be applied to the embodiments depicted in the earlier figures. In the illustrative multi-leaflet embodiments, the valve 43 is divided into a plurality of legs 113 , each of which further comprises a leaflet 25 . To anchor, support, and provide the proper orientation of the leaflets 25 , a separate or integral frame 11 is included, such as the wire frame 11 depicted in FIG. 1 . Ideally, the wire used to construct the frame is made of a resilient material such as 302 , 304 stainless steel; however, a wide variety of other metals, polymers, or other materials are possible. It is possible for the frame to be made of the same material as the leaflets 25 . One other example of a suitable frame material would be a superelastic alloy such as nitinol (NiTi). Resiliency of the frame 11 , which provides radial expandability to the valve 43 when in the second configuration 36 for deployment, is not necessarily an essential property of the frame. For example, optional barbs 16 can provide the means to anchor the valve 43 after delivery, even if the valve 43 lacks sufficient expansile force to anchor itself against the vessel wall. Additionally, the frame can comprise a ductile material with the device 10 being designed to be balloon expandable within the vessel.

[0100] Typically, when used as a valve to correct venous insufficiency in the lower extremities, the valve 43 in situ comprises a plurality of bends 12 of the frame, that provide the majority of the outward radial force that helps anchor the device to vessel wall 70 , as depicted in FIGS. 22-27 . When deployed, the frame assumes the undulating or serpentine configuration characteristic of the invention with a first series of bends 115 of the first or proximal end alternating with a second series of bends 116 of the second or distal end, with the second or distal bends 116 being located at the bottom of the valve distal to the heart and the first or proximal bends 115 being located at the top of the valve proximal to the heart. It should be understood that the valve can assume other orientations, depending on the particular clinical use, and thus, any directional labels used herein (‘distal’, ‘top’, etc.) are merely for reference purposes. The leaflet 25 , which generally covers the valve leg 113 and therefore, assumes the same roughly triangular ‘U’ or ‘V’ shape of that portion of the frame 11 perimeter, includes an resilient arcuate outer edge 112 that conforms to and/or seals with the contours of the vessel wall 70 , and an inner edge 111 that traverses the vessel lumen 34 . The central portion or body 156 of the leaflet 25 extends inward from the vessel wall 70 and outer edge 112 in an oblique direction toward the first end 68 of the valve 43 where it terminates at the inner edge 111 thereof. The valve leaflets that come in contact with the vessel wall carry the supporting frame along the outer edge to better conform to and directly seal with the vessel wall. The leaflets 25 assume a curvilinear shape when in the deployed configuration 36 . The portion of the body 156 proximate the inner edge 111 is sufficiently flexible such that is can move in and out of contact with the inner edge 111 the opposite or other leaflets 25 ; however, the remainder of the body 156 , particular that near the outer edge 112 or second end 69 of the device 10 , can be made less flexible or even rigid in some instances, essentially functioning more for support, similar to the function of the frame 11 , rather than to cooperate with other leaflet(s) 25 . FIGS. 20-27 depict the present invention as an implantable, intraluminal, vascular adapted for use as a implantable multi-leaflet valve 43 including a stent 44 or frame 11 with at least a partial covering 58 . The covering comprises a first and a second valve leaflets 78 , 79 that at least partially seal the aperture 56 within the frame 11 while the valve 43 is in the deployed configuration 36 and forms the opening 117 or valve orifice which regulates the flow of fluid 46 , 47 through the valve. FIG. 20 shows the device 10 in the first, generally planar configuration 35 where the frame 11 is generally rectangular or in particular square in shape. The partial covering 58 forming the leaflets 78 , 79 generally extends across the entire frame 11 with the aperture 56 comprising a slit 108 that extends across the first axis 94 of the frame 11 , the first axis being defined as traversing diagonally opposite bends ( 22 and 23 in this example) that are in line with the valve orifice 117 that forms the valve 43 . The covering 45 is therefore divided into at least first and second portions (making it a partial covering 58 ) which define the first and second valve leaflets 78 , 79 . To form the leaflets 78 , 79 , a complete covering 45 can be slit open along the axis after it is affixed to the frame, or at least first and second adjacent triangular portions (partial coverings 58 ) can be separately attached, eliminating the need for mechanically forming a slit 108 . In the embodiment of FIG. 20 , the slit 108 is made in the covering 45 such that the slit terminates a few millimeters from each of the corner bends 22 , 23 , creating a pair of corner gaps 155 , thereby eliminating two of the most likely sources of leakage around the valve 43 . In the illustrative embodiments, the outer edge 112 of the partial covering 58 that comprises the leaflet 25 is stretched over the frame 11 comprising the valve leg 113 and sutured or otherwise attached as disclosed herein. The leaflet 25 is secured in place such that the material is fairly taut, such that when the valve 43 is situated in the vessel 33 and its diameter constrained to slightly less than the valve width 146 , the leaflet 25 assumes a relatively loose configuration that gives it the ability to flex and invert its shape, depending on the direction of fluid flow. The inner edge 111 of the leaflet 25 is generally free and unattached to the frame and generally extends between the bends 22 and 23 (the bends 115 of the first end) of the valve leg 113 . The inner edge 111 may be reinforced by some means, such as additional material or thin wire, that still would allow it to be sufficiently pliable to be able to seal against another leaflet 25 when retrograde flow 47 forces the leaflets 78 , 79 together. The leaflet 25 is sized and shaped such that the inner edge 111 of one leaflet 78 can meet or overlap with the inner edge 111 of the opposing leaflet 79 (or leaflets, e.g., 119 , 120 ), except when degree of normal, positive flow 46 is sufficient to force the leaflets 25 open to permit fluid passage therethrough.

[0101] The embodiments of FIGS. 21-27 are configured into an elongated diamond shape 153 in the planar configuration 35 with the distance between the two bends 22 , 23 aligned with the valve orifice 117 and first axis 94 being less than the distance between bends 20 and 21 along the second, perpendicular axis 95 . This diamond configuration 153 can be accomplished by forming the frame 11 into that particular shape, or constraining a square frame into a diamond shape 153 , which will be discussed later. By configuring the valve 43 into the diamond shape 153 , the valve legs 127 , 128 become more elongated in shape, which can help add stability when positioning the device 10 during deployment, provides more surface area to receive retrograde flow, and more closely mimics a natural venous valve. In the deployed configuration 36 of the embodiment of FIG. 21 , which is shown in FIGS. 22-25 , the valve leaflets 78 , 79 are forced apart by the normal pulsatile blood flow 46 ( FIGS. 22,24 ). The respective valve leaflets 78 , 79 naturally move back into closer proximity following the pulse of blood. Retrograde blood flow 47 forces the valve leaflets 78 , 79 against one another, as depicted in FIGS. 23 and 25 thereby closing off the lumen 34 of the vessel 33 and the valve orifice 117 .

[0102] FIGS. 21A-21B depict embodiments of the valve 43 in which each leaflet 78 , 79 includes a flap 77 of overhanging material along the slit edge 111 to provide advantageous sealing dynamics when the valve 43 is in the deployed configuration 36 as depicted in FIGS. 22-25 . The flaps 77 are typically formed by suturing two separate pieces of covering 45 material to the frame such that the inner edge 111 is extendable over the slit 108 and inner edge 111 of the adjacent leaflet 25 . By overlapping with an adjacent flap 77 or leaflet 25 , the flap 77 can provide additional means to help seal the valve orifice 117 . Two embodiments of leaflets 25 with flaps 77 are shown. In FIG. 21A , the inner edge 111 is basically straight and extends over the first axis 94 of the frame 11 . The flaps 77 can be cut to create a corner gap 155 that covers and seals the corner region around the bend 22 , 23 . In the embodiment of FIG. 21B , the flap 77 is cut such that there is a notch 157 in the leaflet where the leaflet meets the corner bends 22 , 23 . While these flaps 77 may provide benefit in certain embodiments, the optional flaps 77 shown in FIG. 21 are not necessary to provide a good seal against backflow 47 if the valve 43 and leaflets 25 are properly sized and configured.

[0103] FIGS. 26-26A depict one method of affixing a covering 45 comprising a biomaterial, such as SIS, to the frame 11 which has been constrained using a temporary constraining mechanism 121 , such as a suture, to achieve the desired frame configuration. As shown in FIG. 26 , the covering 45 is cut larger than the frame 11 such that there is an overhang 80 of material therearound, e.g, 5-10 mm. The frame 11 is centered over the covering 45 and the overhang 80 is then folded over from one long side 142 , with the other long side 143 subsequently being folded over the first. As shown in FIG. 26A , the covering 45 is sutured to the frame along one side 142 , typically using forceps 158 and needle, thereby enclosing the frame 11 and the coiled eyelet 14 with the overhang 80 along side 142 . The covering 45 is sutured to the frame with resorbable or non-resorbable sutures 50 or some other suitable method of attaching two layers of biomaterials can be used. In the case of SIS, a single ply sheet, usually about 0.1 mm thick, is used in the hydrated condition. In the illustrative embodiments, 7-0 Prolene suture is used, forming a knot at one bend (e.g., bend 20 ), then continuing to the next bend (e.g., 22) with a running suture 50 , penetrating the layers of SIS around the frame at about 1-2 mm intervals with loops formed to hold the suture 50 in place. When the next coil turn 14 is reached, several knots are formed therethrough, and the running suture 50 continues to the next coil turn 14 . If barbs are present, such as shown in the embodiment of FIG. 21 , the suture 50 is kept inside of the barbs 16 located about each coil turn 14 . In the illustrative example, the covering 45 is affixed to the frame 11 such that one side of the overhang 80 is not sutured over the other side in order to maintain the free edge of the overhang 80 , although the alternative condition would be an acceptable embodiment. Alternative attachment methods include, but are not limited to, use of a biological adhesive, a cross-linking agent, heat welding, crimping, and pressure welding. For synthetic coverings, other similar methods of joining or attaching materials are available which are known in the medical arts. The covering 45 , whether made from a biomaterial or synthetic material, can be altered in ways that improve its function, for example, by applying a coating of pharmacologically active materials such as heparin or cytokines, providing a thin external cellular layer, e.g., endothelial cells, or adding a hydrophilic material or other treatment to change the surface properties.

[0104] Once the covering 45 has been sutured into place or otherwise attached to the frame, the overhang 80 is folded back away from the frame, as shown on the second side 143 of the frame of FIG. 26A , and part of the excess overhang 80 is trimmed away with a scalpel 159 or other cutting instrument to leave a 2-4 mm skirt around the frame 11 . The overhang 80 or skirt provides a free edge of SIS (or material with similar remodeling properties) to help encourage more rapid cell in growth from the vessel wall, such that the SIS replaces native tissue as quickly as possible. An unattached edge of the overhang 80 can also form a corner flap 81 or pocket as depicted in FIG. 27 . This corner flap 81 can serve to catch retrograde blood flow 47 to provide a better seal between the device 10 and the vessel wall 70 as well as providing an improved substrate for ingrowth of native intimal tissue from the vessel 33 , if made of SIS or another material with remodeling properties.

[0105] Referring now to FIGS. 28-31 , the frame 11 used to form the valve 43 embodiments, e.g., FIGS. 20-27 , that are placed in the legs or other deep veins as replacement for incompetent venous valves, is sized according to the size of the target vessel. For example, a typical venous valve might be made of 0.0075″ 304 stainless steel mandril wire with an attachment mechanism 15 comprising 23 to 24 gauge thin-wall stainless steel cannula or other tubing. Larger wire (e.g., 0.01″) and attachment cannula 15 are typically used for valves 43 of the larger diameter (greater than 15 mm). Selection of the attachment cannula 15 depends on competing factors. For example, use of larger gauge attachment cannula 15 results in a slightly increased device 10 profile, yet it includes additional room for flux when the attachment mechanism 15 is soldered over the continuous wire 59 comprising the frame 11 . FIG. 30 best depicts an uncovered frame 11 used to form a venous valve 43 , wherein the length of the sides 13 typically range from about 15 to 25 mm. For larger frames, heavier gauge wire is typically used. For example, 25 mm frames might use 0.01″ wire, with larger diameter embodiments such as stent occluders used for femoral bypass or stent adaptors, such as shown in FIGS. 17 and 32 , requiring an even heavier gauge. The appropriate gauge or thickness of the frame wire also depends on the type of alloy or material used. As previously disclosed, the frame is typically formed in a generally flat configuration and then manipulated into its characteristic serpentine configuration and loaded into a delivery system. Therefore, the frame usually will tend to reassume the first or generally flat configuration if the restraint of the delivery system or vessel is removed. Deformation of the frame 11 can occur after it has been manipulated into the second configuration, however, such that it no longer will lie completely flat, as depicted in FIG. 34 . This angle of deformation 129 , which varies depending on the frame thickness and material used, generally does not compromise the function of the device 10 , which can be reconfigured into the serpentine configuration (of the second, deployed configurations) without loss of function.

[0106] The frame 11 of the present invention can be made either by forming a series of bends in a length of straight wire and attaching the wire to itself, as previously discussed, to form a closed configuration, or the frame 11 can be formed in the deployment (second) configuration 35 as depicted in FIGS. 41-41A by cutting it out of a flat sheet 152 of material, e.g., stainless steel or nitinol. Further finishing procedures can then be performed after it has been cut or formed, such as polishing, eliminating sharp edges, adding surface treatments or coatings, etc. In addition to metal, the frame 11 can comprise one or more polymers, composite materials, or other non-metallic materials such as collagen with the frame either being cut from a thin sheet of the material, or molded into the deployment configuration 36 as depicted in FIG. 43 . Unlike the majority of the depicted embodiments, the frame 11 of FIG. 43 does not naturally assume a flattened configuration 35 when the device 10 is unconstrained by the vessel or delivery system.

[0107] The illustrative embodiments of FIGS. 41-41A and 43 include integral barbs 124 that extend from the frame 11 , which being formed as a closed frame, does not have free ends 60 , 61 that can be used to serve as barbs 16 as depicted in FIG. 3 and other embodiments. FIGS. 41-41A depict a series of integral barbs 124 comprising V-shaped cuts 139