Implant Adhesion Technology

Abstract

The implant (20) is advanceable within the catheter (22) into the tissue of a subject. The implant includes at least one porous wall (28, 34) having an exterior surface and is shaped to define an interior. The adhesive applicator (50) is disposed within the implant and has a nozzle (54) configured to controllably apply an adhesive (52) to the interior of the implant. The adhesive and porous wall are configured such that, when applied to the interior of the implant, a portion of the adhesive passes through the porous wall to reach the exterior surface of the implant, sufficient to adhere the implant to the tissue.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 62 / 951,995 to Chappel-Ram, entitled "IMPLANT-ADHERING TECHNIQUES," filed December 20, 2019, which is incorporated herein by reference.

[0002] Some applications of the present invention relate generally to medical implants, and more particularly to the percutaneous implantation of medical implants. [Background technology]

[0003] Dilation of the heart valve annulus, caused for example by ischemic heart disease, prevents the valve leaflets from fully coapting when the valve closes. Backflow of blood from the ventricle to the atrium leads to increased stroke volume and decreased cardiac output, ultimately weakening the ventricles secondary to atrial volume and pressure overload. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] U.S. Patent Application Publication No. 2018 / 0049875 [Patent Document 2] International Publication No. 2018 / 175619 [Patent Document 3] U.S. Patent Application Publication No. 2014 / 0348896 [Patent Document 4] U.S. Patent No. 9,949,828 Summary of the Invention [Means for solving the problem]

[0005] This summary is intended to illustrate some examples and is not intended to limit the scope of the invention in any way. For example, none of the features included in the examples of this summary are required by the claims unless the claims explicitly recite the feature. Also, features, components, steps, concepts, etc. described in the examples of this summary and elsewhere in this disclosure can be combined in various ways. Various features and steps described elsewhere in this disclosure may be included in the examples summarized here.

[0006] In some applications, adhesives are used to adhere the implant to tissue. An adhesive applicator can be used to apply adhesive to the interior of the porous wall of the implant such that some of the applied adhesive passes through the wall to the exterior surface of the implant, and some of the adhesive is sufficient to adhere the implant to the tissue.

[0007] In some applications, aspects include and / or relate to adhering an annuloplasty structure to a cardiac annulus of a subject. For example, a delivery tool may deploy a sleeve of the annuloplasty structure from a catheter such that a portion of the sleeve aligns with an adhesion site in tissue of the annulus. An adhesive applicator extends from the catheter into the sleeve, and adhesive is applied from a nozzle of the adhesive applicator to the interior of the wall such that the adhesive passes through a portion of the sleeve to reach the adhesion site. In some such applications, the delivery tool is used to hold a portion of the sleeve in place until the adhesive hardens into a hardened adhesive.

[0008] For some applications, the guide channel is configured to facilitate directional deployment of the implant, with at least a distal portion of the guide channel disposed within the implant and at least a portion of the adhesive applicator disposed within the guide channel.

[0009] In some applications, the adhesive curing device is configured to cure the adhesive into a hardened adhesive, for example, by applying energy to the adhesive.

[0010] In some applications, a first adhesive component may be applied from an adhesive applicator and a second adhesive component may be attached (eg, embedded) in the wall.

[0011] In some applications, a first adhesive component may be applied from a first nozzle of a first adhesive applicator and a second adhesive component may be applied from a second nozzle of a second adhesive applicator.

[0012] In some applications, the annuloplasty structure includes a contraction member extending along a sleeve of the annuloplasty structure, and the adjustment mechanism of the annuloplasty structure is configured to contract the sleeve by applying tension to the contraction member.

[0013] Thus, in accordance with the present application, there is provided a system and / or device for use with tissue of a subject, the system and / or device comprising a catheter transluminally advanceable towards the tissue, an implant, and an adhesive.

[0014] For some applications, the implant is advanceable within a catheter toward the tissue and is configured to include at least one porous wall having an exterior surface and defining an interior.

[0015] For some applications, the system and / or apparatus further includes an adhesive applicator, the adhesive applicator including a nozzle disposed therein and configured to controllably apply adhesive thereto.

[0016] In some applications, the adhesive and wall are configured such that when applied internally, a portion of the adhesive passes through the wall to reach the external surface, sufficient to adhere the implant to tissue.

[0017] In one application, the adhesive includes at least one of a lysine-derived urethane and a cyanoacrylate.

[0018] In one application, the wall comprises a polymer.

[0019] In one application, the at least one porous wall has an interior-facing interior surface, and the adhesive applicator is configured to press the nozzle against the interior surface.

[0020] In one application, the nozzle is configured to press against the interior surface.

[0021] In one application, the system / device comprises a guide channel, at least a distal portion of which is or can be disposed within the guide channel.

[0022] In one application, at least a portion of the adhesive applicator is or can be disposed within the guide channel.

[0023] In one application, the guide channel is integral with the adhesive applicator.

[0024] In one application, at least a portion of the adhesive applicator is axially slidable within the guide channel.

[0025] In one application, the wall comprises a fabric.

[0026] In one application, the wall comprises polyethylene terephthalate.

[0027] In one application, the adhesive includes a first adhesive component, the adhesive applicator is configured to controllably apply the first adhesive component, and the system / device includes a second adhesive component.

[0028] In one application, at least one adhesive component selected from the group consisting of the first adhesive component and the second adhesive component comprises thrombin, and the other adhesive component of the group comprises fibrinogen.

[0029] In one application, at least one adhesive component selected from the group consisting of the first adhesive component and the second adhesive component comprises albumin, and the other adhesive component of the group comprises glutaraldehyde.

[0030] In one application, at least one adhesive component selected from the group consisting of the first adhesive component and the second adhesive component comprises gelatin-resorcinol, and the other adhesive component of the group comprises formaldehyde-glutaraldehyde.

[0031] In one application, at least one adhesive component selected from the group consisting of the first adhesive component and the second adhesive component comprises gelatin-resorcinol, and the other adhesive component of the group comprises pentanedi-ethanedial.

[0032] In one application, the second adhesive component is attached to a wall.

[0033] In one application, the system / device includes a second adhesive applicator, the second adhesive applicator configured to controllably apply a second adhesive component.

[0034] In one use, the second adhesive applicator is disposed at least partially within the catheter and includes a second nozzle disposed therein and configured to controllably apply a second adhesive component therein.

[0035] In one use, at least a portion of the second adhesive applicator is axially slidable therein.

[0036] In one application, the system / apparatus includes an adhesive curing device configured to cure the adhesive by applying energy to the adhesive.

[0037] In one application, the adhesive comprises a polyethylene hydrogel.

[0038] In one application, the adhesive curing device is configured to apply heat to the adhesive.

[0039] In one application, the adhesive curing device is configured to apply ultraviolet light to the adhesive.

[0040] In one application, the adhesive comprises poly(glycerol sebacate acrylate).

[0041] In one application, the adhesive curing device is located internally.

[0042] In one application, at least a portion of the adhesive curing device is disposed within the adhesive applicator.

[0043] In one application, at least a portion of the adhesive curing device is axially slidable therein.

[0044] In one application, the implant comprises an annuloplasty structure, the annuloplasty structure comprises a sleeve, and the porous wall is a tubular sidewall defining an elongated lumen through the sleeve.

[0045] In one use, the adhesive applicator is configured to define a secondary lumen within the elongate lumen.

[0046] In one application, the system / device includes a constriction member having a first portion that extends along at least the constricted portion of the sleeve and a second portion that exits the sleeve at an exit point.

[0047] In one application, the system / device includes an actuatable adjustment mechanism coupled to the contraction member at an end portion of the contraction member and configured, when actuated, to adjust the length of the annuloplasty structure by applying tension to the contraction member.

[0048] In one application, the adjustment mechanism is flexibly connected to the sleeve by a connector.

[0049] According to one application, there is also provided a method of adhering an implant to tissue of a subject, the method comprising advancing, within a catheter, the implant and an adhesive applicator into the tissue (which may occur simultaneously or sequentially), the adhesive applicator containing an adhesive.

[0050] In one application, the implant includes at least one porous wall having an exterior surface and is shaped to define an interior.

[0051] In one use, while the nozzle of the adhesive applicator is positioned inside, the method can include using the adhesive applicator to adhere the exterior surface of the implant to tissue by applying adhesive to the interior through the nozzle, such that some of the applied adhesive passes through the wall to reach the exterior surface.

[0052] In one use, the method includes using an adhesive applicator to contact the exterior surface with tissue before applying adhesive internally through a nozzle.

[0053] In one application, applying adhesive internally using an adhesive applicator through a nozzle such that a portion of the applied adhesive passes through the wall to the exterior surface includes applying adhesive internally using an adhesive applicator through a nozzle such that a majority of the applied adhesive passes through the wall to the exterior surface.

[0054] In one application, the method includes using an adhesive applicator to press the adhesive applicator against the interior surface of the implant while applying adhesive to the interior through a nozzle.

[0055] In one use, applying adhesive internally via a nozzle using an adhesive applicator includes aiming the nozzle of the adhesive applicator at the same height toward the interior surface of the implant.

[0056] In one application, the adhesive includes a first adhesive component, and applying the adhesive to the interior through a nozzle using an adhesive applicator includes applying the first adhesive component to the interior through a nozzle using the adhesive applicator such that the first adhesive component contacts the second adhesive component and together form a cured adhesive.

[0057] In one use, applying a first adhesive component internally through a nozzle using an adhesive applicator includes applying an adhesive component selected from thrombin, fibrinogen, albumin, glutaraldehyde, gelatin-resorcinol, formaldehyde-glutaraldehyde, and pentanediol-ethanediol.

[0058] In one use, the second adhesive component is attached to the wall, and applying the first adhesive component to the interior through a nozzle using an adhesive applicator, and applying the first adhesive component to the interior from the adhesive applicator such that the first adhesive component contacts the second adhesive component and together form a hardened adhesive, includes applying the first adhesive component to the interior through a nozzle using the adhesive applicator such that the first adhesive component contacts the second adhesive component attached to the wall and together form a hardened adhesive.

[0059] In one application, the method includes applying a second adhesive component to the interior using a second adhesive applicator through a second nozzle of the second adhesive applicator.

[0060] In one use, applying a first adhesive component internally through a nozzle using a first adhesive applicator includes applying at least one adhesive component selected from the group consisting of thrombin and fibrinogen, and applying a second adhesive component internally through a second nozzle using a second adhesive applicator includes applying another adhesive component from the group consisting of thrombin and fibrinogen.

[0061] In one use, applying a first adhesive component to the interior through a nozzle using a first adhesive applicator includes applying at least one adhesive component selected from the group consisting of albumin and glutaraldehyde, and applying a second adhesive component to the interior through a second nozzle using a second adhesive applicator includes applying another adhesive component from the group consisting of albumin and glutaraldehyde.

[0062] In one use, applying a first adhesive component internally through a nozzle using a first adhesive applicator includes applying at least one adhesive component selected from the group consisting of gelatin-resorcinol and formaldehyde-glutaraldehyde, and applying a second adhesive component internally through a second nozzle using a second adhesive applicator includes applying another adhesive component from the group consisting of gelatin-resorcinol and formaldehyde-glutaraldehyde.

[0063] In one use, applying a first adhesive component internally through a nozzle using a first adhesive applicator includes applying at least one adhesive component selected from the group consisting of gelatin-resorcinol and pentanedi-ethanedial, and applying a second adhesive component internally through a second nozzle using a second adhesive applicator includes applying another adhesive component from the group consisting of gelatin-resorcinol and pentanedi-ethanedial.

[0064] In one use, applying a first adhesive component to the interior through a nozzle using a first adhesive applicator and applying a second adhesive component to the interior through a second nozzle using a second adhesive applicator includes applying the first adhesive component and the second adhesive component such that the first adhesive component and the second adhesive component pass through the wall to form a cured adhesive on the exterior surface.

[0065] In one application, the method includes curing the adhesive by applying energy to the adhesive from an adhesive curing device.

[0066] In one use, applying an adhesive to the interior via a nozzle using an adhesive applicator includes applying a polyethylene hydrogel to the interior.

[0067] In one application, applying energy to the adhesive from an adhesive curing device includes applying heat to the adhesive from an adhesive curing device.

[0068] In one application, applying energy to the adhesive from an adhesive curing device includes applying ultraviolet radiation to the adhesive from an adhesive curing device.

[0069] In one use, applying an adhesive to the interior via a nozzle using an adhesive applicator includes applying poly(glycerol sebacate acrylate) to the interior.

[0070] In one application, the tissue includes tissue of a valve annulus of the subject's heart, the implant comprises an annuloplasty structure, and adhering an outer surface of the implant to the tissue includes adhering an outer surface of the annuloplasty structure to the tissue of the valve annulus.

[0071] In one use, the implant includes a sleeve defining a wall, and applying adhesive internally using an adhesive applicator through a nozzle such that a portion of the applied adhesive passes through the wall of the sleeve and reaches the external surface includes applying adhesive internally using an adhesive applicator through a nozzle such that a portion of the applied adhesive passes through the sleeve and reaches the external surface.

[0072] In one application, the adhesive applicator is a component of the delivery tool.

[0073] In one application, adhering the outer surface of the annuloplasty structure to tissue of the valve annulus includes deploying a sleeve from a catheter such that a portion of the sleeve aligns with the adhesion site on the tissue of the valve annulus, extending an adhesive applicator from the catheter into the sleeve, and applying adhesive from a nozzle of the adhesive applicator to an interior of the implant such that the adhesive passes through a portion of the sleeve to the adhesion site, thereby adhering a portion of the outer surface of the structure to the adhesion site on the tissue of the valve annulus. In one application, a delivery tool is used, or can be used, to hold a portion of the sleeve in place until the adhesive hardens into a hardened adhesive.

[0074] In one application, holding the portion in place using a delivery tool includes holding the portion in place using an adhesive applicator.

[0075] In one application, the method includes the steps of separating the structure from the delivery tool and transluminally retracting the delivery tool from the subject's heart.

[0076] In one application, the portion of the exterior surface is a first portion of the exterior surface, the adhesion site is a first adhesion site, and adhering the portion of the exterior surface of the wall to the adhesion site includes adhering the first portion of the exterior surface of the wall to the first adhesion site of tissue of the annulus, and the method includes, after adhering the first portion to the first adhesion site, adhering a second portion of the exterior surface of the wall to the second adhesion site of tissue of the annulus by applying adhesive from a nozzle of an adhesive applicator to the interior of the implant such that the adhesive passes through a second portion of the sleeve to reach the second adhesion site.

[0077] In one application, the first adhesion site is at the left fibrous trigon, and adhering the first portion of the external surface to the first adhesion site includes adhering the first portion of the external surface to the first adhesion site at the left fibrous trigon of the annulus.

[0078] In one application, the first adhesion site is in the right fibrous trigone, and adhering the first portion of the external surface to the first adhesion site includes adhering the first portion of the external surface to the first adhesion site in the right fibrous trigone of the annulus.

[0079] In one application, the annuloplasty structure comprises a constriction portion, the structure comprising a constriction member extending along at least the constriction portion of the sleeve, and the method includes the step of constricting the constriction portion by applying tension to the constriction member.

[0080] In one application, contracting the contraction portion by tensioning the contraction member includes adjusting an adjustment mechanism.

[0081] In one application, the adjustment mechanism includes a rotatable spool, the spool coupled to the contraction member, and wherein tensioning the contraction member to contract the contraction portion includes rotating the spool.

[0082] In one application, contracting the contraction portion by tensioning the contraction member includes adjusting a circumference of the sleeve.

[0083] In one application, adjusting the circumference of the sleeve includes decreasing the distance between bond locations.

[0084] In one application, adjusting the circumference of the sleeve includes decreasing the distance between the bond sites.

[0085] These methods can be performed on live animals or replicas such as cadavers, cadaver hearts, and simulated devices (eg, simulated body parts, hearts, tissues, etc.).

[0086] According to one application, there is further provided a system and / or device for use with tissue of a subject, the system and / or device comprising a catheter transluminally advanceable towards the tissue, an implant, an adhesive, and an adhesive applicator.

[0087] For some applications, the implant is advanceable within the catheter towards the tissue and is configured with at least one porous wall and defining an interior.

[0088] In some applications, the adhesive applicator has a nozzle disposed therein and is configured to controllably apply adhesive thereto.

[0089] In some applications, the adhesive and wall are configured such that the adhesive is applied internally through a nozzle while the wall is positioned against tissue, such that at least a portion of the applied adhesive passes through the wall and adheres the implant to the tissue.

[0090] The present invention will be more fully understood from the following detailed description of its application in conjunction with the drawings. [Brief explanation of the drawings]

[0091] [Figure 1]1 is a schematic diagram of a multi-component system including an implant and a delivery tool for delivering the implant to a subject's heart, according to several applications. [Figure 2A] 1A-1C are schematic diagrams illustrating an implant and a tool deployed at a heart annulus, according to some applications. [Figure 2B] 1A-1C are schematic diagrams illustrating an implant and a tool deployed at a heart annulus, according to some applications. [Figure 3A] 1A-1C are schematic diagrams showing adhesive being applied to the interior of an implant wall from an adhesive applicator, according to some applications. [Figure 3B] 1A-1C are schematic diagrams showing adhesive being applied to the interior of an implant wall from an adhesive applicator, according to some applications. [Figure 3C] 1A-1C are schematic diagrams showing adhesive being applied to the interior of an implant wall from an adhesive applicator, according to some applications. [Figure 3D] 1A-1C are schematic diagrams showing adhesive being applied to the interior of an implant wall from an adhesive applicator, according to some applications. [Figure 3E] 1A-1C are schematic diagrams showing adhesive being applied to the interior of an implant wall from an adhesive applicator, according to some applications. [Figure 3F] 1A-1C are schematic diagrams showing adhesive being applied to the interior of an implant wall from an adhesive applicator, according to some applications. [Figure 4A] 1A-1C are schematic diagrams illustrating adhesive being applied from an adhesive applicator and energy being applied to the adhesive from an adhesive curing device according to some applications. [Figure 4B] 1A-1C are schematic diagrams illustrating adhesive being applied from an adhesive applicator and energy being applied to the adhesive from an adhesive curing device according to some applications. [Figure 4C] 1A-1C are schematic diagrams illustrating adhesive being applied from an adhesive applicator and energy being applied to the adhesive from an adhesive curing device according to some applications. [Figure 4D] 1A-1C are schematic diagrams illustrating adhesive being applied from an adhesive applicator and energy being applied to the adhesive from an adhesive curing device according to some applications. [Figure 4E] 1A-1C are schematic diagrams illustrating adhesive being applied from an adhesive applicator and energy being applied to the adhesive from an adhesive curing device according to some applications. [Figure 5A] 1 is a schematic diagram illustrating a multi-component system including an implant and a delivery tool for delivering the implant to a subject's heart, according to several applications. [Figure 5B] 1 is a schematic diagram illustrating a multi-component system including an implant and a delivery tool for delivering the implant to a subject's heart, according to several applications. [Figure 5C] 1 is a schematic diagram illustrating a multi-component system including an implant and a delivery tool for delivering the implant to a subject's heart, according to several applications. [Figure 5D] 1 is a schematic diagram illustrating a multi-component system including an implant and a delivery tool for delivering the implant to a subject's heart, according to several applications. [Figure 5E] 1 is a schematic diagram illustrating a multi-component system including an implant and a delivery tool for delivering the implant to a subject's heart, according to several applications. [Figure 6A] 1 is a schematic diagram illustrating a multi-component system including an implant and a delivery tool for delivering the implant to a subject's heart, according to several applications. [Figure 6B] 1 is a schematic diagram illustrating a multi-component system including an implant and a delivery tool for delivering the implant to a subject's heart, according to several applications. [Figure 6C] 1 is a schematic diagram illustrating a multi-component system including an implant and a delivery tool for delivering the implant to a subject's heart, according to several applications. [Figure 6D]1 is a schematic diagram illustrating a multi-component system including an implant and a delivery tool for delivering the implant to a subject's heart, according to several applications. [Figure 6E] 1 is a schematic diagram illustrating a multi-component system including an implant and a delivery tool for delivering the implant to a subject's heart, according to several applications. DETAILED DESCRIPTION OF THE INVENTION

[0092] 1, which is a schematic diagram of a multi-component system 10 including an implant and a delivery tool 8 for delivering the implant to a subject's heart 90, according to several applications. Throughout this specification, the implant of system 10 will be described as embodied as an annuloplasty structure 20. However, it should be noted that for several applications, the systems, devices, and techniques described herein may be used, mutatis mutandis, to facilitate the implantation of other implants.

[0093] FIG. 1 shows a distal portion of system 10 including an annuloplasty structure 20 (e.g., an annuloplasty band) partially positioned within a guide channel of catheter 22 of tool 8. Sleeve 30 is typically a flexible sleeve including a braided fabric mesh, for example, including polyethylene terephthalate (such as Dacron™). Sleeve 30 is typically configured to be positioned only partially around heart valve annulus 88 (i.e., assuming a C-shape) and, once adhered to the annulus, to be contracted to adjust the circumference of the annulus (i.e., to circumferentially tighten the annulus). Alternatively, structure 20 is configured to be positioned entirely around the annulus 88.

[0094] Typically, as shown, structure 20 defines an interior, and sleeve 30 includes a tubular sidewall 28 having an exterior surface. In some applications, as shown, sleeve 30 defines an elongated lumen (e.g., the interior of structure 20 is shaped as an elongated lumen). In some applications, end wall 34 defines an end wall of annuloplasty structure 20.

[0095] Delivery tool 8 further includes an adhesive applicator 50 configured to controllably apply adhesive 52 to the interior of structure 20. In some applications, distal segment 32 of adhesive applicator 50 includes or defines a nozzle 54, which facilitates controlled application of adhesive 52 to the interior of structure 20. For example, adhesive applicator nozzle 54 may be positioned within (or advanceable into) the interior of structure 20. In some applications, adhesive applicator 50 is shaped to define a secondary lumen within the elongated lumen of sleeve 30.

[0096] In some applications, tool 8 includes guide channel 18 configured to facilitate directional deployment of structure 20, for example, as described in U.S. Patent Application Publication No. 2018 / 0049875 to Iflah et al., which is incorporated mutatis mutandis by reference herein. In such applications, at least a distal portion of guide channel 18 is disposed within structure 20. In some applications, sleeve 30 comprises a flexible material such that moving guide channel 18 causes sleeve 30 to move (e.g., advance) into position. In some such applications, a portion of adhesive applicator 50 is disposed within guide channel 18. In some such applications, at least a portion of adhesive applicator 50 is axially slidable within guide channel 18. In some such applications, longitudinal axis d12 of adhesive applicator 50 is generally parallel to longitudinal axis d14 of guide channel 18.

[0097] In some applications, as shown in FIG. 1, adhesive applicator 50 is integral with (eg, defined by) guide channel 18.

[0098] In some applications, the distal portion of channel 18 is loaded into sleeve 30 and structure 20 is loaded into catheter 22 immediately prior to implantation (eg, in the operating room or an adjacent room).

[0099] In some applications, the annuloplasty structure 20 includes a flexible, elongated contraction member 42 extending along at least a portion of the sleeve 30; thus, the portion of the sleeve along which the member 42 extends is defined as the contraction portion of the sleeve. Typically, a first portion of the contraction member 42 extends along the contraction portion of the sleeve 30, and a second portion of the contraction member exits the sleeve at an exit point. The contraction member 42 can include a wire, ribbon, rope, or band and typically includes a flexible and / or superelastic material, such as nitinol, polyester, stainless steel, or cobalt chrome. In some applications, the wire includes a radiopaque material. In some applications, the contraction member 42 includes a braided polyester suture (e.g., Ticron). In some applications, the contraction member 42 is coated with polytetrafluoroethylene (PTFE). In some applications, the contraction member 42 includes multiple wires intertwined to form a rope structure.

[0100] For some applications, the annuloplasty structure 20 further comprises an adjustment mechanism 40 to facilitate contraction and expansion of the annuloplasty structure 20. The adjustment mechanism 40 may be disposed within a housing 44 and may comprise a rotatable structure (e.g., a spool, as described herein below). The adjustment mechanism 40 is coupled to the contraction member 42 at an end portion of the contraction member. When actuated, the adjustment mechanism 40 adjusts the length of the structure 20 by applying tension to the contraction member 42. The adjustment mechanism 40 may be coupled (e.g., sutured or otherwise coupled) to the sleeve 30. For some applications, the adjustment mechanism 40 is coupled to an outer side of the sleeve 30.

[0101] In some applications in which the annuloplasty structure 20 includes an adjustment mechanism 40, the system 10 includes a flexible longitudinal guide member 46 (e.g., a wire) coupled to a portion of the adjustment mechanism (e.g., a portion of the rotatable structure). The guide member 46 extends proximally from the adjustment mechanism 40 through the catheter 22 (e.g., through a parallel side lumen of the catheter) and has a proximal end accessible from outside the subject's body.

[0102] Reference is now made to Figures 2A-2B, which are schematic diagrams illustrating structure 20 and tool 8 deployed in annulus 88 of heart 90, according to some applications.

[0103] The annuloplasty structure 20 is advanced into the left atrium 80 using the catheter 22 (FIG. 2A). In some applications, as shown, this is performed by advancing the catheter 22 with the annuloplasty structure 20 disposed therein. Alternatively, the catheter 22 may be advanced first, and the annuloplasty structure 20 (or another implant) may be advanced thereafter through the catheter. In some applications, as shown, the annuloplasty structure 20 may be advanced with a distal portion of the channel 18 and / or adhesive applicator 50 (e.g., nozzle 54) disposed within the annuloplasty structure. Alternatively, the channel 18 and / or adhesive applicator 50 (e.g., nozzle 54) may be introduced into the annuloplasty structure 20 (or another implant) after its advancement. While a transfemoral, transseptal approach to the mitral valve is shown in FIG. 2A, the scope of this specification includes alternative approaches to the mitral valve, approaches to other locations (e.g., valves) in the heart, and approaches to other locations within the body.

[0104] In some applications in which the annuloplasty structure 20 includes an adjustment mechanism 40, the adjustment mechanism is positioned distal (i.e., forward) of the structure during advancement. For example, the adjustment mechanism 40 may be positioned on axis d12 (e.g., collinear with the sleeve 30). In some such applications, the mechanism 40 is coupled to the sleeve 30 in a manner that allows the mechanism 40 to move (e.g., translate) from being aligned with axis d12 to being aligned with the sleeve 30 ( FIG. 2B ). In some applications, it is advantageous to (1) advance the structure into the mitral valve while the mechanism 40 is positioned on the longitudinal axis of the sleeve 30 (e.g., collinear with the sleeve) to maintain a small cross-sectional diameter of the structure for transluminal delivery, and (2) subsequently move the mechanism 40 away from the longitudinal axis, for example, to allow the end wall 34 of the sleeve to be positioned against the annulus and / or to allow adhesive to be applied through the end wall of the sleeve.

[0105] In some applications, one or more connectors 66 (e.g., sutures) facilitate translation of adjustment mechanism 40 by flexibly and / or articulatingly coupling the mechanism to sleeve 30. In some such applications, connectors 66 are tensioned or relaxed to reposition mechanism 40 relative to sleeve 30. In some applications, guide member 46 is tensioned or relaxed to reposition mechanism 40.

[0106] Reference is now made to Figures 3A-3E, which are schematic diagrams illustrating a structure 20 adhered to tissue by applying adhesive 52 from an adhesive applicator 50 to the interior of the structure 20, according to several applications.

[0107] In FIG. 3A , guide channel 18 is shown abutting end wall 34 of sleeve 30 such that manipulation of the guide channel directs the end wall toward first adhesive site 68a. Sleeve 30 typically comprises a flexible material, such as a fabric (e.g., polyethylene terephthalate), such that use of guide channel 18 allows the sleeve to be advanced into position. That is, guide channel 18 is typically more rigid than sleeve 30 such that manipulation of the guide channel effectively manipulates the sleeve. As described hereinabove, guide channel 18 may be a separate element within which adhesive applicator 50 is disposed, or adhesive applicator 50 may be integral with or function as guide channel 18.

[0108] 3A-3E, during implantation of the annuloplasty structure 20, an adhesive applicator 50 is positioned within the annuloplasty structure and used to controllably apply adhesive 52 to the interior of the annuloplasty structure. At least a portion of the wall 28 is porous, and the wall and adhesive are configured such that, when applied internally, a portion of the adhesive can pass through the wall to the exterior surface of the wall, where it can adhere the implant to tissue.

[0109] 3A, the first location of tissue to which structure 20 is adhered is near the left fibrous trigone 82 of the valve annulus 88. Alternatively, the first location is near the right fibrous trigone (not shown) of the mitral valve. Further alternatively, end wall 34 is not located near any of the trigone, but instead is located elsewhere near the mitral valve, such as near the anterior commissure or posterior commissure (not shown).

[0110] In some applications, as shown, structure 20 is adhered to tissue by adhering a plurality of individual portions 70 of the structure to a corresponding plurality of individual adhesion sites 68 of the tissue, e.g., by applying a corresponding plurality of individual portions of adhesive 52 to the corresponding plurality of portions of the structure (this may be true regardless of whether structure 20 has individually defined features that define portions 70; i.e., portions 70 may be defined as individual portions of structure 20 by the application of individual portions of adhesive 52). Alternatively, adhesive 52 may be applied to the entire interior of structure 20.

[0111] In some applications, as shown, the first portion of the structure 20 that is adhered to the tissue (e.g., at the first adhesion site 68a) is the distal end wall 34 of the sleeve 30. That is, in some applications, the distal end wall 34 defines the first portion 70a of the structure that is adhered to the tissue.

[0112] As described hereinabove, as shown in FIG. 3B , adhesive 52 is applied from nozzle 54 of adhesive applicator 50 to the interior of structure 20 (e.g., the interior of wall 28) such that at least a portion of the adhesive passes through the wall and reaches the exterior surface of wall 28 at portion 70 a. Typically, the exterior surface of wall 28 is contacted with tissue (e.g., adhesion site 68 a of valve annulus 88) before applying adhesive 52 to the interior. Alternatively, adhesive may be applied to the interior before contacting the wall with tissue. In this manner, the exterior surface of structure 20 is adhered to valve annulus 88.

[0113] In some such applications, the nozzle 54 of the adhesive applicator 50 is pressed against the interior of the wall 28 while adhesive is being applied from the adhesive applicator. In some applications, the nozzle 54 is flush with the wall 28 while adhesive 52 is being applied to the first portion 70a.

[0114] At least a portion (e.g., a majority) of the adhesive 52 applied to the interior of the structure 20 via the nozzle 54 passes through the wall 28 to reach the exterior surface of the structure. In some such applications, the adhesive is directed through the wall 28 toward the bond site 68. The inventors hypothesize that aligning the nozzle 54 flush with the interior surface of the wall 28 and / or pressing the adhesive applicator 50 against the interior surface while applying the adhesive 52 will facilitate directing the adhesive through the wall to the bond site 68 and / or bonding the portion 70 to the bond site, e.g., by reducing adhesive leakage laterally from the nozzle.

[0115] Typically, adhesive 52 within adhesive applicator 50 is in a fluid state. As shown in the inset of FIG. 3B , porous wall 28 is configured to allow adhesive 52 to pass through the wall. Typically, the portion of adhesive 52 that passes through wall 28 is sufficient to adhere structure 20 (e.g., portion 70 thereof) to tissue (e.g., adhesion site 68 thereof). Passage of sufficient adhesive 52 through wall 28 is typically facilitated by at least one of the following factors: (i) the porosity of wall 28, (ii) the fluidity of adhesive 52, and (iii) interactions between the wall and the adhesive (e.g., interfacial phenomena).

[0116] The inventors hypothesize that in some applications, adhering structure 20 to tissue by applying adhesive 52 to the interior of the structure may facilitate proper placement of the structure relative to the tissue compared to applying adhesive directly to the tissue prior to placement of the structure. For example, applying adhesive 52 after placement of structure 20 may (1) provide the operator with additional time to manipulate guide catheter 22 and / or guide channel 18, and (2) allow for repositioning of the structure if the initial position was deemed suboptimal prior to application of adhesive 52.

[0117] Typically, after passage through the wall 28, the adhesive 52 cures while it remains in contact with both the wall 28 and the tissue. As known in the art, curing is a process that involves hardening and / or strengthening of an adhesive. In some applications, the delivery tool 8 (e.g., the adhesive applicator 50 and / or the guide channel 18) is used to hold the portion 70 in place until the adhesive 52 cures into a hardened adhesive 52'. As shown in FIG. 3C, the hardened adhesive 52' bonds the first portion 70a of the sleeve 30 to the first adhesion site 68a of the annulus 88.

[0118] In some applications, the rate at which adhesive 52 cures may depend on the application of energy (e.g., in the form of heat or light). In other applications, adhesive 52 may cure independently of the applied energy. In some applications, adhesive 52 includes a cyanoacrylate. In some applications, adhesive 52 includes a lysine-derived urethane. In some applications, adhesive 52 includes a polyethylene hydrogel. In some applications, adhesive 52 includes poly(glycerol sebacate acrylate). This list is not intended to be exhaustive, and the scope of this specification includes the use of other suitable adhesives.

[0119] Following adhesion of first portion 70a to first adhesive site 68a, a portion of structure 20 (e.g., sleeve 30) is typically advanced, mutatis mutandis, from guide channel 18 (FIG. 3C), for example, as described in U.S. Patent Application Publication No. 2018 / 0049875 to Iflah et al. After the portion of sleeve 30 is released in this manner, a second portion 70b of structure 20 is positioned at second adhesive site 68b (FIGS. 3C-3D), for example, by repositioning channel 18, adhesive applicator 50, and / or catheter 22.

[0120] As shown in FIG. 3D, while second portion 70b is aligned with second adhesive site 68b, adhesive 52 is again applied from adhesive applicator 50 to second adhesive site 68b through porous wall 28 of second portion 70b. As shown in FIG. 3E, adhesive 52 is then cured such that cured adhesive 52′ bonds second portion 70b to second adhesive site 68b. Typically, adhesive application and curing is repeated for a plurality of respective portions 70 and adhesive sites 68. This repetition bonds successive portions 70 to successive adhesive sites 68, as shown in FIG. 3F.

[0121] The portions 70 may be spaced longitudinally at regular intervals along the sleeve 30, or may be spaced as deemed appropriate by the operating physician.

[0122] For some applications, sleeve 30 includes a plurality of radiopaque markers 72 disposed at respective longitudinal locations along the sleeve. In some applications, markers 72 comprise radiopaque ink. Markers 72 can provide an indication in an x-ray image (e.g., a fluoroscopic image) of how far the sleeve has deployed at any point during the implantation procedure, for example, to enable setting a desired distance between bonded portions 70 along the sleeve.

[0123] In some applications, the longitudinal distance between adjacent / consecutive bonded portions 70 is approximately equal to the longitudinal distance between adjacent / consecutive markers 72. For example, as shown, a portion of adhesive 52 may be applied to approximately each of the markers 72. Alternatively, or additionally, a portion of adhesive 52 may be applied between adjacent / consecutive markers.

[0124] Typically, after the structure 20 is adhered to the annulus 88, the sleeve 30 (e.g., the constriction portion thereof) is constricted, for example, using the adjustment mechanism 40. For example, an adjustment tool may be advanced along (e.g., over) the guide member 46 to the adjustment mechanism 40 and used to actuate the adjustment mechanism. In some such applications, the adjustment mechanism 40 is configured to adjust the circumference of the annuloplasty structure 20 by tensioning the constriction member 42, as described, for example, in U.S. Patent Application Publication No. 2018 / 0049875 to Iflah et al., mutatis mutandis.

[0125] Adhesion of portions 70 to adhesion sites 68 can adjust (e.g., reduce) the circumference of annuloplasty structure 20, thereby adjusting (e.g., reducing) the circumference of annulus 88. For example, this can reduce (i) inter-portion distance d92 between adhered portions 70 of structure 20, and (ii) inter-adhesion site distance d94 between adhesion sites 68 of the annulus.

[0126] The inventors hypothesize that in some applications, bonding the annuloplasty structure 20 only at individual portions of the annuloplasty structure (e.g., rather than applying adhesive to the entire annuloplasty structure) may facilitate contraction of the annuloplasty structure and annulus, for example, because the unglued portions of the annuloplasty structure offer less resistance to contraction compared to the adhered portions of the annuloplasty structure.

[0127] Once the desired level of adjustment of the structure 20 is detected, for example, by monitoring the degree of valvular regurgitation using echocardiography (such as Doppler echocardiography) and / or fluoroscopy, the adjustment tool and guide member 46 are removed from the heart. Typically, the annuloplasty structure 20 is separated from the delivery tool 8, and the delivery tool is transluminally retracted from the subject's heart 90.

[0128] 4A-4E, which are schematic illustrations of a multi-component system 110 including an implant (e.g., annuloplasty structure 20) and a delivery tool 108 for delivering the implant to a subject's heart 90, according to some applications. Except where noted, system 110 and tool 108 are typically identical to system 10 and tool 8, mutatis mutandis. Similarly, the techniques illustrated in FIGS. 4A-4E are typically identical to system 10 and tool 8, mutatis mutandis, except where noted. Tool 108 also includes an adhesive curing device 24 in addition to the components of tool 8.

[0129] The adhesive curing device 24 is configured to cure the adhesive 52 into a hardened adhesive 52′ by applying energy 25 to the adhesive. Typically, as shown, the adhesive curing device 24 is disposed within the structure 20 (e.g., within the sleeve 30). In some applications, the adhesive curing device 24 is disposed within the guide channel 18. In some applications, the adhesive curing device 24 is a component of the adhesive applicator 50. More typically, at least a portion of the adhesive curing device 24 is axially slidable within the structure 20. In some applications, the adhesive curing device 24 is operable independently of the adhesive applicator 50. As shown in FIG. 4B , the adhesive applicator 50 applies the adhesive 52, which passes through the wall 28 to the exterior surface of the implant (e.g., through the first portion 70a to the first adhesion site 68a), for example, as described mutatis mutandis hereinabove with reference to the system 10. The adhesive curing device 24 applies energy 25 to the applied adhesive 52, curing the adhesive into a hardened adhesive 52'.

[0130] The adhesive curing device 24 may be configured to apply various forms of energy for curing adhesives known in the art, including, but not limited to, electromagnetic radiation (e.g., ultraviolet or infrared light), heat, and / or acoustic energy (e.g., ultrasound). In some applications, the adhesive curing device 24 transmits energy provided by an external energy source. For example, the adhesive curing device 24 may include a channel (e.g., an optical fiber) configured to transmit energy. In some applications, the adhesive 52 comprises a polyethylene hydrogel. In some applications, the adhesive 52 comprises poly(glycerol sebacate acrylate). This list is not intended to be exhaustive, and the scope of this specification includes the use of other adhesives.

[0131] 4C-4E, tool 108 may be used to adhere a plurality of individual portions 70 of structure 20 to a corresponding plurality of adhesion sites 68, for example, as described with reference to Figures 3C-3E, mutatis mutandis. Subsequent contraction of annuloplasty structure 20, detachment of the structure from delivery tool 108, and transluminal retraction of the tool is as described mutatis mutandis hereinabove.

[0132] Reference is now made to Figures 5A-5E and 6A-6E, which are schematic illustrations of respective multi-component systems 210 and 310, each system including an implant (e.g., annuloplasty structure 20) and a respective delivery tool 208 and 308 for delivering the implant to a subject's heart 90, for several applications.

[0133] In systems 210 and 310, a first adhesive component 52a and a second adhesive component 52b are used to adhere the implant to the tissue of the valve annulus 88. Typically, the adhesive components 52a and 52b are combined (e.g., contacted and / or mixed) with one another at the implant to be adhered. In some applications, the combined adhesive components 52a and 52b can be considered the adhesive 52. Typically, after they are combined, the first adhesive component 52a and the second adhesive component 52b cure to form a hardened adhesive 52'. In some applications, the formation of the hardened adhesive 52' by the first adhesive component 52a and the second adhesive component 52b can avoid the use of the adhesive curing device 24.

[0134] Alternatively, the tool 208 may include an adhesive curing device 24, which is used in a complementary manner with the first adhesive component 52a and the second adhesive component 52b to produce a cured adhesive 52' (not shown). That is, as described hereinabove with respect to FIG. 4A, curing the first adhesive component 52a and the second adhesive component 52b into a cured adhesive 52' may include the application of energy (e.g., electromagnetic radiation, heat, and / or acoustic energy). In some applications, one of the adhesive components 52a and 52b includes thrombin, and the other includes fibrinogen. In some applications, one of the adhesive components 52a and 52b includes albumin, and the other includes glutaraldehyde. In some applications, one of the adhesive components 52a and 52b includes gelatin-resorcinol, and the other includes an aliphatic dialdehyde (e.g., pentanediol and / or ethanediol). In some applications, one of adhesive components 52a and 52b comprises gelatin-resorcinol and the other comprises formaldehyde. This list is not intended to be exhaustive, and the scope of this specification includes the use of other adhesives.

[0135] Reference is made to Figures 5A-5E, which are schematic diagrams illustrating the use of tool 208 to deliver an implant to a subject's heart 90, according to several applications.

[0136] Except where noted, system 210 and tool 208 are typically identical to system 10 and tool 8, mutatis mutandis. Similarly, the techniques illustrated in Figures 5A-5E are typically identical to system 10 and tool 8, mutatis mutandis, except where noted. Tool 208 is essentially similar to tool 8, except that rather than applying adhesive 52, tool 208 applies first adhesive component 52a from adhesive applicator 50. Second adhesive component 52b is typically already present outside of tool 208.

[0137] Typically, as shown in Figure 5A, second adhesive component 52b is attached to wall 28. For example, second adhesive component 52b may be coated on and / or embedded within wall 28.

[0138] First adhesive component 52a is typically applied to the interior of structure 20 from adhesive applicator 50 while sleeve 30 is already positioned within the subject's body, e.g., at a desired anatomical location (FIG. 5B). As described herein, the porosity of wall 28 facilitates passage of first adhesive component 52a through the wall to the exterior surface of the implant. Typically, adhesive applicator 50 is used to apply first adhesive component 52a to the interior via nozzle 54 such that the first adhesive component contacts the second adhesive component attached to wall 28 and together form a hardened adhesive 52′. In this manner, first adhesive component 52a and second adhesive component 52b form a hardened adhesive 52′ on the exterior surface of sleeve 30, adhering structure 20 to the tissue of valve annulus 88.

[0139] 5C-5E, tool 208 may be used, mutatis mutandis, to bond a plurality of individual portions 70 of structure 20 to a corresponding plurality of individual bond sites 68, for example, as described with reference to FIGS. 3C-3E. In some applications, adhesive component 52b is disposed only at predetermined portions 70 of structure 20. In some applications, as shown, adhesive component 52b is disposed more generally along structure 20 (e.g., along the entire structure 20) such that bonded portions 70 are defined by application of adhesive component 52a, e.g., such that portions of adhesive component 52b disposed between portions 70 are left unused.

[0140] Subsequent contraction of the annuloplasty structure 20, detachment of the structure from the delivery tool 208, and transluminal retraction of the tool is as described hereinabove mutatis mutandis.

[0141] Reference is again made to Figures 6A-6E, which are schematic diagrams illustrating the use of tool 308 to deliver an implant to a subject's heart 90, according to several applications.

[0142] Except where noted, system 310 and tool 308 are typically identical to system 10 and tool 8, mutatis mutandis. Similarly, the techniques illustrated in FIGS. 6A-6E are typically identical to system 10 and tool 8, mutatis mutandis, except where noted. Tool 308 is essentially similar to tool 8, except that rather than including adhesive applicator 50, tool 308 includes first adhesive applicator 50a and second adhesive applicator 50b. First adhesive applicator 50a is configured to controllably apply a first adhesive component 52a to the interior of the implant, and second adhesive applicator 50b is configured to controllably apply a second adhesive component 52b to the interior of the implant. In some applications, adhesive applicators 50a and 50b contain their respective adhesive components, for example, prior to advancement of tool 308 into a subject.

[0143] Typically, the first adhesive applicator 50a and the second adhesive applicator 50b are each at least partially disposed within the catheter 22. More typically, controlled application of the adhesive is facilitated by each adhesive applicator having a respective nozzle. As shown in FIGS. 6A-6B , the first adhesive applicator 50a is used to apply a first adhesive component 52a via a first nozzle 54a, and the second adhesive applicator 50b is used to apply a second adhesive component 52b via a second nozzle 54b. In some applications, a portion of the first adhesive applicator 50a (e.g., the first nozzle 54a) and a portion of the second adhesive applicator 50b (e.g., the second nozzle 54b) are axially slidable within the structure 20.

[0144] Typically, first adhesive component 52a and second adhesive component 52b pass through wall 28 and harden to form hardened adhesive 52' on the exterior surface of the structure. As described hereinabove with respect to adhesive 52, each adhesive component 52a and 52b typically remains fluid if kept separate from the other adhesive component. In some applications, contact between the adhesive components is typically sufficient to result in hardened adhesive 52'. In other applications (not shown), tool 308 includes adhesive curing device 24, and application of energy by the adhesive curing device accelerates the hardening of each adhesive component into hardened adhesive 52'.

[0145] 6C-6E, tool 308 may be used to adhere a plurality of individual portions 70 of structure 20 to a corresponding plurality of individual adhesion sites 68, for example, as described with reference to Figures 3C-3E, mutatis mutandis. Alternatively, adhesive components 52a and 52b may be applied to the entire interior of structure 20. Subsequent contraction of annuloplasty structure 20, detachment of the structure from delivery tool 308, and transluminal retraction of the tool is as described mutatis mutandis herein above.

[0146] Curable compositions suitable for use as adhesives in connection with the implants described herein can include a crosslinking prepolymer and an initiator. Exemplary curable compositions that can be used in connection with the implantable medical devices disclosed herein are described in PCT Application WO 2018 / 175619, published September 27, 2018, and U.S. Patent Application Publication No. 2014 / 0348896, published November 27, 2014, the entire contents of which are incorporated herein by reference. In preferred embodiments, the prepolymer has one or more of the following properties: (1) the prepolymer has sufficient viscosity to withstand hemodynamic forces and resist washing away from the application site; (2) the prepolymer does not react or crosslink in the presence of bodily fluids, particularly blood; (3) the prepolymer is hydrophobic; (4) the prepolymer is capable of adhering to wet tissue; (5) the prepolymer is biocompatible; and (6) the prepolymer is biodegradable.

[0147] In one application, the prepolymer is activated by introducing one or more functional groups (i.e., incorporated into the prepolymer backbone) that can react to form crosslinks between polymer chains. In one embodiment, the functional groups can be selected from the group consisting of substituted vinyl groups, unsubstituted vinyl groups, substituted acrylate groups, unsubstituted acrylate groups, vinyl esters, vinyl carbamates, vinyl ketones, vinyl amides, vinyl carbonates, vinyl ether groups, or allyl forms of vinyl groups. In one embodiment, the polymer chains are polyesters formed from a substituted or unsubstituted polyol, such as a triol, and a substituted or unsubstituted diacid. The triol can be glycerol. The functional groups can also form crosslinks with tissue. The activity can be 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, or 1.5. The activity can be provided in a range between and including any two of the above values.

[0148] The activity can be selected based on whether the curable composition is a sealant or an adhesive. Generally, the activity of a sealant is expected to be lower than the activity of an adhesive.

[0149] In one application, the curable composition includes or consists of a sealant, and the prepolymer has an activity of about 0.5 or less, about 0.4 or less, about 0.3 or less, about 0.2 or less, about 0.1 or less, about 0.09 or less, about 0.08 or less, about 0.07 or less, about 0.06 or less, about 0.05 or less, about 0.04 or less, about 0.03 or less, about 0.02 or less, about 0.01 or less, about 0.009 or less, about 0.008 or less, about 0.007 or less, about 0.006 or less, about 0.005 or less, about 0.004 or less, about 0.003 or less, about 0.002 or less, or about 0.001 or less.

[0150] In one application, the curable composition comprises or consists of an adhesive and a prepolymer with an activity of about 0.5 or greater, 0.6 or greater, 0.7 or greater, 0.8 or greater, 0.9 or greater, 0.1 or greater, 0.2 or greater, 0.3 or greater, 0.4 or greater, 0.5 or greater, 0.6 or greater, 0.7 or greater, 0.8 or greater, 0.9 or greater, 1.0 or greater, 1.1 or greater, 1.2 or greater, 1.3 or greater, 1.4 or greater, or 1.5 or greater.

[0151] The viscosity of the prepolymer of the curable composition depends in part on the molecular weight of the prepolymer, with higher molecular weight prepolymers resulting in more viscous compositions. In one application, the prepolymer also has an tensile strength of about 1,000 daltons or more, about 2,000 daltons or more, about 3,000 daltons or more, about 4,000 daltons or more, about 5,000 daltons or more, about 6,000 daltons or more, about 7,000 daltons or more, about 8,000 daltons or more, about 9,000 daltons or more, about 10,000 daltons or more, about 11,000 daltons or more, about 12,000 daltons or more, about 13,000 daltons or more, 14,000 daltons or more, about 15,000 daltons or more, about 16,000 daltons or more, about 17,000 daltons or more, about 18,000 daltons or more, about 19,000 daltons or more, about 20,000 daltons or more, about 21,000 daltons or more, about 22,000 daltons or more, about 23 The polypeptide may have a molecular weight of about 2,000 daltons or more, about 24,000 daltons or more, about 25,000 daltons or more, about 26,000 daltons or more, about 27,000 daltons or more, about 28,000 daltons or more, about 29,000 daltons or more, about 30,000 daltons or more, about 35,000 daltons or more, about 40,000 daltons or more, about 45,000 daltons or more, about 50,000 daltons or more, about 55,000 daltons or more, about 60,000 daltons or more, about 65,000 daltons or more, about 70,000 daltons or more, about 75,000 daltons or more, about 80,000 daltons or more, about 85,000 daltons or more, about 90,000 daltons or more, about 95,000 daltons or more, or about 100,000 daltons or more. The molecular weight of the prepolymer can be provided within a range between and including any two of the above values, for example, the molecular weight range can be from about 3,000 daltons to about 10,000 daltons.

[0152] In one application, the curable composition or adhesive includes or consists of a sealant, and the prepolymer can have any one of the molecular weights described above. For example, the prepolymer can have a molecular weight of about 11,000 daltons or greater.

[0153] In one application, the curable composition comprises or consists of an adhesive, and the prepolymer can have any of the molecular weights described above. For example, the prepolymer can have a molecular weight of from about 1,000 daltons to about 10,000 daltons.

[0154] The desired viscosity of the prepolymer can be adjusted based in part on the molecular weight of the prepolymer. In one application, the desired viscosity can be selected to provide a prepolymer that stays in place at the application site without being washed away by bodily fluids.The viscosity of the prepolymer may be about 0.5 Pa·s or more, 1 Pa·s or more, 2 Pa·s or more, 3 Pa·s or more, 4 Pa·s or more, 5 Pa·s or more, 6 Pa·s or more, 7 Pa·s or more, 8 Pa·s or more, 9 Pa·s or more, 10 Pa·s or more, 11 Pa·s or more, 12 Pa·s or more, 13 Pa·s or more, 14 Pa·s or more, 15 Pa·s or more, 16 Pa·s or more, 17 Pa·s or more, 18 Pa·s or more, 19 Pa·s or more, 20 Pa·s or more, 21 Pa·s or more, 22 Pa·s or more, 23 Pa·s or more, 24 Pa·s or more, 25 Pa s or more, 26 Pa s or more, 27 Pa s or more, 28 Pa s or more, 29 Pa s or more, 30 Pa s or more, 31 Pa s or more, 32 Pa s or more, 33 Pa s or more, 34 Pa s or more, 35 Pa s or more, 36 Pa s or more, 37 Pa s or more, 3 8 Pa s or more, 39 Pa s or more, 40 Pa s or more, 41 Pa s or more, 42 Pa s or more, 43 Pa s or more, 44 Pa s or more, 45 Pa s or more, 46 Pa s or more, 47 Pa s or more, 48 Pa s or more, 49 Pa s or more, 50 Pa s or more, 51 Pa s or more, 52 Pa s or more, 53 Pa s or more, 54 Pa s or more, 55 Pa s or more, 56 Pa s or more, 57 Pa s or more, 58 Pa s or more, 59 Pa s or more, 60 Pa s or more, 61 Pa s or more, 62 Pa s or more, 63 Pa s or more Above, 64 Pa s or more, 65 Pa s or more, 66 Pa s or more, 67 Pa s or more, 68 Pa s or more, 69 Pa s or more, 70 Pa s or more, 71 Pa s or more, 72 Pa s or more, 73 Pa s or more, 74 Pa s or more, 75 Pa s or more, 76 Pa s or greater, 77 Pa·s or greater, 78 Pa·s or greater, 79 Pa·s or greater, 80 Pa·s or greater, 81 Pa·s or greater, 82 Pa·s or greater, 83 Pa·s or greater, 84 Pa·s or greater, 85 Pa·s or greater, 86 Pa·s or greater, 87 Pa·s or greater, 88 Pa·s or greater, 89 Pa·s or greater, 90 Pa·s or greater, 91 Pa·s or greater, 92 Pa·s or greater, 93 Pa·s or greater, 94 Pa·s or greater, 95 Pa·s or greater, 96 Pa·s or greater, 97 Pa·s or greater, 98 Pa·s or greater, 99 Pa·s or greater, or 100 Pa·s or greater. The viscosity can be provided within a range between and including any two of the above values.For example, the viscosity range can be from about 0.5 Pa·s to about 50 Pa·s.

[0155] The prepolymer is optionally formed by the reaction of a polyol with a polyacid. The polyol can be one or a combination of compounds containing two or more hydroxyl groups, including diols, alkanediols, triols, glycerol, trimethylolpropane, triethanolamine, tetraols, erythritol, pentaerythritol, sorbital, unsaturated diols, tetradeca-2,12-diene-1,1,14-diol, macromonomer diols, polyethylene oxide, or N-methyldiethanolamine. The polyacid can be a diacid or higher acid, such as glutaric acid, adipic acid, pimelic acid, suberic acid, and azelaic acid. Exemplary long-chain acids include diacids having 5 or more, 10 or more, 15 or more, 20 or more, or 25 or more carbon atoms.

[0156] In one application, the prepolymer is a poly(glycerol sebacate) (PGS) prepolymer prepared by polycondensing equimolar amounts of glycerol and sebacic acid.

[0157] The curable composition can include an initiator. In one application, the initiator is a photoinitiator. In one application, the photoinitiator is 2-dimethoxy-2-phenyl-acetophenone, 2-hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone (IRGACURE® 2959), 1-hydroxycyclohexyl-1-phenyl ketone (IRGACURE® 184), 2-hydroxy-2-methyl-1-phenyl-1-propanone (DAROCUR® 1173), 2-benzyl-2-(dimethylamino)-1-[4-morpholinyl)phenyl]-1-butanone (Irgacure® 1173). 369), methyl benzoyl formate (DAROCUR® MBF), oxy-phenyl-acetic acid-2-[2-oxo-2-phenyl-acetoxy-ethoxy]-ethyl ester (IRGACURE® 754), 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone (IRGACURE® 907), diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide (DAROCUR® TPO), phosphine oxide, phenylbis(2,4,6-trimethylbenzoyl) (IRGACURE® 819), and combinations thereof. In one application, the preferred photoinitiator is IRGACURE® 2959.

[0158] The prepolymer can be crosslinked by photopolymerization through exposure to electromagnetic radiation, such as visible or UV light. The irradiation time can be varied to achieve the desired amount of crosslinking. In one application, the irradiation time is about 1 second, 5 seconds, 10 seconds, 15 seconds, 20 seconds, 30 seconds, 45 seconds, 1 minute, 90 seconds, or 2 minutes or more. The irradiation time can be provided within a range between any two values ​​inclusive. The light intensity can be varied as needed to achieve sufficient crosslinking. In one application, the intensity is about 0.45 W / cm. 2 is less than.

[0159] The crosslink density of the cured polymer can be adjusted by varying the degree of activation of the prepolymer, e.g., acrylate, or by varying the curing conditions, such as the cure time and the intensity of the energy applied to cure the prepolymer. It is believed that greater adhesion is obtained with a higher level of crosslinking.

[0160] The resulting crosslinked polymer, when comprising a sealant, can have a crosslink density of about 10% or less, about 9% or less, about 8% or less, about 7% or less, about 6% or less, about 5% or less, about 4% or less, about 3% or less, about 2% or less, about 1% or less, about 0.5% or less, about 0.1% or less, about 0.05% or less, about 0.01% or less, about 0.005% or less, or about 0.001% or less. The resulting crosslinked polymer can have a crosslink density ranging between and including any two of the above values.

[0161] When the resulting crosslinked polymer comprises an adhesive, it can have a crosslink density of about 1% or more, about 2% or more, about 3% or more, about 4% or more, about 5% or more, about 6% or more, about 7% or more, about 8% or more, about 9% or more, about 10% or more, about 15% or more, about 20% or more, about 25% or more, about 30% or more, about 35% or more, about 40% or more, about 45% or more, about 50% or more, about 55% or more, about 60% or more, about 65% or more, about 70% or more, about 75% or more, or about 80% or more. The resulting crosslinked polymer can have a crosslink density ranging between and including any two of the above values. The higher the crosslink density, the greater the polymer cohesive strength and adhesive strength.

[0162] The resulting cross-linked polymer can be configured to adhere to wet tissue. In one embodiment, where the cross-linked polymer is an adhesive, the cross-linked polymer preferably has sufficient adhesive strength to secure the implantable medical device to an anatomical feature or tissue without the need for additional fixation mechanisms, such as sutures or staples. Depending on the forces that may act on the cross-linked polymer at the application site, such as hemodynamic forces, the adhesive strength may be greater than or equal to about 0.1 N / cm. 2 More than about 0.2N / cm 2Above, approximately 0.3 N / cm 2 Above, approximately 0.4 N / cm 2 Above, approximately 0.5 N / cm 2 Above, approximately 0.6 N / cm 2 Above, approximately 0.7 N / cm 2 Above, approximately 0.8 N / cm 2 Above, approximately 0.9 N / cm 2 Above, approximately 1.0 N / cm 2 Above, approximately 1.1 N / cm 2 Above, approximately 1.2 N / cm 2 Above, approximately 1.3 N / cm 2 Above, approximately 1.4 N / cm 2 Above, 1.5 N / cm 2 Above, approximately 1.6 N / cm 2 Above, approximately 1.7 N / cm 2 Above, approximately 1.8 N / cm 2 Above, approximately 1.9 N / cm 2 Above, approximately 2.0 N / cm 2 Above, approximately 2.1 N / cm 2 Above, approximately 2.2 N / cm 2 Above, approximately 2.3 N / cm 2 Above, approximately 2.4 N / cm 2 Above, approximately 2.5 N / cm 2 Above, approximately 2.6 N / cm 2 Above, approximately 2.7 N / cm 2 Above, approximately 2.8 N / cm 2 Above, approximately 2.9 N / cm 2 Above, approximately 3.0 N / cm 2 Above, approximately 3.5 N / cm 2 Above, approximately 4.0 N / cm 2 Above, approximately 4.5 N / cm 2 Above, approximately 5.0 N / cm 2 Above, approximately 5.5 N / cm 2 Above, approximately 6.0 N / cm 2 Above, approximately 6.5 N / cm 2 Above, approximately 7.0 N / cm 2 Above, approximately 7.5 N / cm 2 Above, approximately 8.0 N / cm 2 Above, approximately 8.5 N / cm 2 Above, approximately 9.0 N / cm 2 Above, approximately 9.5 N / cm 2 Above, about 10.0N / cm2 The adhesive strength can be provided within a range between and including any two of the above values.

[0163] When the cross-linked polymer comprises a sealant, the cross-linked polymer can have sufficient adhesive strength to allow the cross-linked polymer to remain at the application site. In some applications, the implantable medical device can adhere to an anatomical feature without the need for sutures or additional means to secure the device. The sealant can have adhesive strength to secure the implantable medical device to an anatomical feature. In some applications, the sealant only needs to have sufficient strength to resist detachment from the application site due to hemodynamic forces that may act on the application site. In some applications, sutures or additional means to secure the device may optionally be used with the sealant. In one application, the adhesive strength of the sealant is about 0.1 N / cm 2 Below, approximately 0.09N / cm 2 Below, approximately 0.08N / cm 2 Below, approximately 0.07N / cm 2 Below, approximately 0.06N / cm 2 Below, approximately 0.05N / cm 2 Below, approximately 0.04N / cm 2 Below, about 0.03N / cm 2 Below, approximately 0.02N / cm 2 Below, approximately 0.01N / cm 2 Below, approximately 0.009N / cm 2 Below, approximately 0.008N / cm 2 Below, approximately 0.007N / cm 2 Below, approximately 0.006N / cm 2 Below, approximately 0.005N / cm 2 Below, approximately 0.004N / cm 2 Below, approximately 0.003N / cm 2 Below, approximately 0.002N / cm 2 Less than or equal to 0.001N / cm 2 The wet adhesion can be provided within a range between and including any two of the above values.

[0164] Although the embodiments described herein primarily relate to annuloplasty bands adhered to the tissue of the annulus of a native heart valve, the methods, systems, and devices disclosed herein below relate, mutatis mutandis, to adhering the exterior surface of a range of implants to various tissues of a subject.

[0165] The systems, devices, and techniques described herein can be used in combination with those described in U.S. Patent Application Publication No. 2018 / 0049875 to Iflah et al. and / or U.S. Patent No. 9,949,828 to Sheps et al., both of which are incorporated herein by reference.

[0166] It will be understood by those skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof that are not within the prior art and that would occur to one of ordinary skill in the art upon reading the above description. Furthermore, the techniques, methods, acts, steps, etc. described or suggested herein can be performed on live animals or on non-living replicas, such as cadavers, cadaver hearts, replica devices (e.g., replicating body parts, tissues, etc.). [Explanation of symbols]

[0167] 8 Delivery Tools 10 Systems 18 Guide Channel 20 Annuloplasty structure 22 Catheter 24 Adhesive curing device 25 Energy 28 porous wall 30 sleeves 32 distal segment 34 Distal end wall 40 Adjustment mechanism 42 Contraction member 44 Housing 46 Guide member 50 adhesive applicator 50a adhesive applicator 50b adhesive applicator 52 Adhesive 52' Hardening Adhesive 52a First adhesive component 52b Second adhesive component 54 nozzles 54a nozzle 54b nozzle 66 Connector 68 Adhesion site 68a First adhesion site 68b Secondary adhesion site 70 portions 70a First Part 70b Second part 72 Radiopaque Marker 80 Left atrium 82 Left fibrous triangle 88 Valvular annulus 90 Heart 108 Delivery Tools 110 System 208 Delivery Tools 210 System 308 Delivery Tools 310 System d92 distance between parts d94 Distance between adhesive sites d12 Longitudinal axis d14 Longitudinal axis

Claims

1. 1. A device for use with tissue of a subject, the device comprising: a catheter transluminally advanceable towards the tissue; an implant having a first end and a second end, the implant being advanceable within the catheter towards the tissue, the implant defining a lumen from the first end to the second end, the implant including a porous wall surrounding the lumen and having an exterior surface; Adhesive and an adhesive applicator having a nozzle positioned proximate to the porous wall and configured to controllably apply the adhesive to the porous wall; Equipped with The adhesive and the porous wall are configured such that a portion of the adhesive passes through the porous wall and reaches the exterior surface, the portion of the adhesive being sufficient to adhere the implant to the tissue.

2. 10. The device of claim 1, wherein the adhesive comprises a lysine-derived urethane, a cyanoacrylate, a poly(glycerol sebacate acrylate), or a polyethylene hydrogel.

3. The device of claim 1 , wherein the porous wall comprises a polymer, a fabric, or a combination thereof.

4. The device of claim 3 , wherein the porous wall comprises polyethylene terephthalate.

5. The device of claim 1 , wherein the porous wall includes an interior surface, and the adhesive applicator is configured to press the nozzle against the interior surface.

6. The device further comprises a guide channel, at least a distal portion of the guide channel being disposed adjacent to the porous wall; The device of claim 1 , wherein at least a portion of the adhesive applicator is disposed within the guide channel.

7. The device of claim 6 , wherein the guide channel is integral with the adhesive applicator.

8. The device of claim 6 , wherein at least the portion of the adhesive applicator is axially slidable within the guide channel.

9. the adhesive comprises a first adhesive component; the adhesive applicator is configured to controllably apply the first adhesive component; The device of claim 8 , wherein the device further comprises a second adhesive component.

10. 10. The apparatus of claim 9, further comprising a second adhesive applicator, the second adhesive applicator configured to controllably apply the second adhesive component.

11. the second adhesive applicator is disposed at least partially within the catheter; a second nozzle disposed adjacent to the porous wall; The apparatus of claim 10 configured to controllably apply the second adhesive component to the porous wall.

12. The apparatus of claim 1 , further comprising an adhesive curing device configured to cure the adhesive by applying energy to the adhesive.

13. The apparatus of claim 12 , wherein at least a portion of the adhesive curing device is disposed within the adhesive applicator.

14. 10. The device of claim 1, wherein the implant comprises an annuloplasty structure, the annuloplasty structure comprising a sleeve, and the porous wall is a tubular sidewall defining the elongated lumen through the sleeve.

15. The device of claim 14 , wherein the adhesive applicator is shaped to define a secondary lumen within the elongate lumen.

16. The implant comprises a contraction member, the contraction member comprising: a first portion extending along at least a constricted portion of the implant; The device of claim 1 , having a second portion that exits the implant at an exit point.

17. 17. The device of claim 16, further comprising an actuatable adjustment mechanism coupled to the contraction member at an end portion thereof and configured, when actuated, to adjust the length of the implant by applying tension to the contraction member.

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