Implant techniques
A bioprinted implant using an energy-activated adhesive or barbed fabric secures within the heart to treat valve issues, enhancing heart function and preventing regurgitation.
Patent Information
- Application Number
- PCT/US2025/033728
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2025-03-07
- Filing Date
- 2025-06-16
- Publication Date
- 2026-01-02
AI Technical Summary
There is a need for effective devices and methods to treat valve issues such as leaflet flail, prolapse, and restricted leaflet motion in heart valves, particularly the mitral valve, which can lead to valve regurgitation and cardiovascular compromise.
A bioprinter is used to print an implant within the heart from a bioink that adheres to tissue, which can change the heart's dimension during the cardiac cycle and inhibit bloodflow, and is secured using an energy-activated adhesive or a fabric with barbs that penetrate the tissue, along with a scaffold to hold the implant in place.
The implant effectively addresses valve issues by adhering to heart tissue, maintaining its position and functionality, thereby improving heart function and preventing regurgitation.
Smart Images

Figure US2025033728_02012026_PF_FP_ABST
Abstract
Description
IMPLANT TECHNIQUES CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Patent Application No.63 / 663,831, filed June 25, 2024, and of U.S. Patent Application No. 63 / 768,687, filed March 7, 2025, the entire disclosures all of which are incorporated by reference for all purposes. TECHNICAL FIELD
[0002] Some applications of this disclosure relate in general to bioprinting an implant within an organ of a subject. More specifically, some applications relate to bioprinting an implant within a heart of the subject, e.g., to improve function of the heart. BACKGROUND
[0003] The native heart valves (e.g., the aortic, pulmonary, tricuspid, and mitral valves) serve critical functions in assuring the forward flow of an adequate supply of blood through the cardiovascular system. These heart valves can be rendered less effective by congenital malformations, inflammatory processes, infectious conditions, or disease. Such damage to the valves can result in serious cardiovascular compromise or death. Treatment for such disorders can be done with the surgical repair or replacement of the valve during open heart surgery or with transcatheter transvascular techniques for introducing and implanting prosthetic devices in a manner that is much less invasive than open heart surgery.
[0004] A healthy heart has a generally conical shape that tapers to a lower apex. The heart has four chambers: the left atrium, right atrium, left ventricle, and right ventricle. The left and right sides of the heart are separated by a wall generally referred to as the septum. The native mitral valve of the human heart connects the left atrium to the left ventricle. The mitral valve includes an annulus portion, which is an annular portion of the native valve tissue surrounding the mitral valve orifice, and a pair leaflets (as referred to as cusps) that extend downward from the annulus into the left ventricle. The mitral valve annulus can form a “D” shaped, oval, or otherwise out-of-round cross-sectional shape having major and minor axes. The anterior leaflet can be larger than the posterior leaflet, forming a generally “C” shaped boundary between the abutting free edges of the leaflets when they are closed together.
[0005] When operating properly, the anterior leaflet and the posterior leaflet function together as a one-way valve to allow blood to flow only from the left atrium to the left ventricle. The left atrium receives oxygenated blood from the pulmonary veins. When the muscles of the left atrium contract and the muscles of the left ventricle relax, the oxygenated blood that is collected in the left atrium flows into the left ventricle. When the muscles of the left atrium relax and the muscles of the left ventricle contract, the increased blood pressurein the left ventricle urges the two leaflets together, thereby closing the one-way mitral valve so that blood cannot flow back to the left atrium and is instead expelled out of the left ventricle through the aortic valve. To prevent the two leaflets from prolapsing or flailing under pressure and folding back through the mitral annulus toward the left atrium, a plurality of fibrous cords called chordae tendineae tether the leaflets to papillary muscles in the left ventricle.
[0006] Valve regurgitation occurs when the native valve fails to close properly and blood flows into the left atrium from the left ventricle during the systole phase of heart contraction. Valve regurgitation (especially mitral valve regurgitation) is the most common form of valvular heart disease. Mitral regurgitation has different causes, including leaflet prolapse or flail, restricted leaflet motion (e.g., due to leaflet rigidity / leaflet calcification), and / or dysfunctional papillary muscles stretching.
[0007] There is a continuing need for effective devices and methods for treating valve issues, including leaflet flail, prolapse, and restricted leaflet motion. SUMMARY
[0008] This summary is meant to provide some examples and is not intended to be limiting of the scope in any way. For example, any feature included in an example of this summary is not required by the claims, unless the claims explicitly recite the features. Also, the features, components, steps, concepts, etc. described in examples in this summary and elsewhere in this disclosure can be combined in a variety of ways. Various features and steps as described elsewhere in this disclosure may be included in the examples summarized here.
[0009] In some implementations, a system comprising a bioprinter is used to print an implant within the heart. In some such implementations, the bioprinter prints the implant from a bioink comprising a biomaterial that adheres to tissue of the heart. For example, the implant can change a dimension of the heart during the cardiac cycle. Alternatively or in addition, the implant can inhibit bloodflow through an orifice of the heart.
[0010] In some implementations, the implant is part of an implant assembly that comprises the printed biomaterial and an unprinted prosthesis. In some such implementations, the implant adheres to tissue of the heart and to the prosthesis in a manner that secures the prosthesis in place. Alternatively or in addition, the printed biomaterial is secured to the tissue via the prosthesis.
[0011] In some implementations, an energy-activated adhesive is pre-disposed on the implant (e.g., on an implant body and / or an anchor of the implant), and the system is used to deploy the implant such that the implant body, e.g., a contact-portion thereof, contacts tissue of the heart. In some such implementations, while the implant body remains incontact with the tissue, the system applies energy to the adhesive (e.g., via an energy- applicator, such as an implant-electrode, defined by the implant) thereby adhering the implant to the tissue by activating the adhesive.
[0012] In some implementations, the energy-applicator activates the adhesive by applying energy to the adhesive, responsively to detecting contact between the contact- portion and the tissue. In some such implementations, the energy-applicator is used to detect the contact between the contact-portion and the tissue, prior to activating the adhesive.
[0013] In some implementations, the adhesive and the energy-applicator are disposed at the same portion of the implant body. In some such implementations, the adhesive and the energy-applicator are disposed at the contact-portion. In some implementations, the adhesive and the energy applicator are disposed elsewhere on the implant body.
[0014] In some implementations, the implant-electrode is used to facilitate navigating the system (e.g., a delivery tool thereof) within the heart. In some such implementations, the implant-electrode is used to measure endogenic electrophysiological signals, which are used to determine the implant-electrode’s location while navigating the delivery tool within the heart.
[0015] In some implementations, the implant-electrode is activated to produce electrical signals that are detected and used to determine the implant-electrode’s location while navigating the delivery tool within the heart.
[0016] In some implementations, the adhesive may be chemically activated, instead of or in addition to being energy-activated. In some such implementations, the adhesive is a protein-based bioadhesive that is activated by applying a chemical activator, e.g., via the delivery tool. For example, the bioadhesive can comprise an oxidation-dependent adhesive, e.g., a mussel foot protein, and the activator comprises a biocompatible oxidizing agent that chemically activates the adhesive.
[0017] In some implementations, a fabric for use in an implant is prepared by weaving a weft yarn with warp yarns such that the weft yarn skips under certain portions of selected warp yarns. In some such implementations, the skipped portions of the selected warp yarns define warp floats, which are shaped (e.g., by cutting away part of the warp float) into barbs that protrude obliquely from the fabric’s face.
[0018] In some implementations, the warp floats are shape-set prior to cutting the warp floats into barbs. In some such implementations, the warp floats are shape-set while a pin is disposed between the warp floats and the fabric’s face, e.g., such that the warp float adopts the pin’s shape. For example, shape-setting the warp floats using the pin can result inidentically shaped barbs, e.g., that protrude from the fabric’s face in parallel or symmetrically.
[0019] In accordance with some implementations, the fabric is used in a cardiovascular implant. In some such implementations, the fabric is held against cardiovascular tissue such that the barbs penetrate the tissue, thereby retaining the implant at the tissue while adhesive adheres the fabric to the tissue. For example, the barbs can be angled so as to resist hemodynamic forces that, in absence of the barbs, might displace the implant from the tissue.
[0020] In some implementations, the barbs hold the implant in place at the tissue while the adhesive is used to adhere the implant to the tissue. In some such implementations, a scaffold temporarily holds the fabric against the tissue such that the barbs penetrate the tissue while the adhesive is used to adhere the fabric to the tissue, e.g., such that the implant remains adhered to the tissue after the scaffold is withdrawn from the subject. For example, the scaffold can be withdrawn before the adhesive adheres the fabric to the tissue. Alternatively, the adhesive can adhere the fabric to the tissue while the scaffold holds the fabric in place.
[0021] In some implementations, the scaffold is a leaflet-clip that holds the fabric against leaflets of a native valve of the heart, such that the barbs penetrate the leaflets while the adhesive adheres the fabric to the leaflets. In some such implementations, the fabric is bioabsorbable, such that the leaflets will remain adhered to each other after the fabric is absorbed by tissue of the leaflets.
[0022] In some implementations, the delivery tool comprises an adhesive applicator that is used to apply the adhesive to the implant / and or the tissue, while the barbs hold the implant in place at the tissue. Alternatively or in addition, the adhesive can be pre-disposed on the fabric, e.g., prior to implanting the implant.
[0023] In some implementations, the adhesive is energy-activated adhesive, and an energy-applicator is used to adhere the implant to the tissue by activating the adhesive. In some such implementations, the energy-applicator is advanced transluminally to the tissue via the delivery tool. Alternatively, the energy-applicator is an extracorporeal energy- applicator that activates the adhesive by transferring the energy to the adhesive from outside the subject’s body.
[0024] In some implementations, the implant comprises one or more implant- electrodes, e.g., that are embedded within the adhesive. In some such implementations, the energy-applicator causes current to flow from the implant-electrode and through the adhesive, thereby adhering the fabric to the tissue by activating the adhesive.
[0025] There is further provided, in accordance with some implementations, a system for use with a heart of a subject, the system including: a catheter, transluminally advanceable to the heart; a bioink including a biomaterial; and / or a bioprinter.
[0026] In some implementations, the bioprinter houses the bioink, and can include a nozzle that is transluminally advanceable via the catheter to the heart.
[0027] In some implementations, the system is configured to, while the nozzle extends from a distal portion of the catheter, extrude the bioink from the nozzle into the heart such that the biomaterial assumes a three-dimensional implant-shape.
[0028] In some implementations, at least one of the catheter, the nozzle and the bioink is sterile.
[0029] In some implementations, the system is configured to, while the nozzle extends from a distal portion of the catheter, extrude the bioink from the nozzle into the heart such that the biomaterial: assumes a three-dimensional implant-shape, and / or adheres to tissue of the heart.
[0030] In some implementations, the bioprinter is configured to, after extruding the bioink from the nozzle into the heart, fixate the biomaterial such that the biomaterial retains the implant-shape.
[0031] In some implementations, the bioprinter is configured to, after extruding the bioink from the nozzle into the heart, fixate the biomaterial such that the biomaterial: adheres to tissue of the heart, and / or retains the implant-shape.
[0032] In some implementations, the system further includes a fixator that is: transluminally advanceable via the catheter to the heart, and / or configured to fixate the biomaterial such that the biomaterial retains the implant-shape.
[0033] In some implementations, the fixator is configured to fixate the biomaterial such that the biomaterial: retains the implant-shape, and / or adheres to tissue of the heart.
[0034] There is further provided, in accordance with some implementations, a system for use in a heart of a subject, the system including: an implant, the implant including: an implant body, an energy-activated adhesive, pre-disposed on the implant, and / or an energy- applicator.
[0035] In some implementations, the system includes a delivery tool, configured to: transluminally deliver the implant to the heart, and position the adhesive in contact with tissue of the heart, and / or while the adhesive remains in contact with the tissue, activate the adhesive to adhere the implant body to the tissue by driving the energy-applicator to apply energy to the adhesive.
[0036] In some implementations, at least one of the implant, the delivery tool, and the adhesive is sterile.
[0037] In some implementations, the energy-applicator is configured to apply heat to the adhesive.
[0038] In some implementations, the energy-applicator is coupled to the implant body.
[0039] In some implementations, the energy-applicator is embedded within the adhesive.
[0040] In some implementations, the implant is configured to be seated at an annulus of a native valve of the heart such that the adhesive is placed in contact with the annulus.
[0041] In some implementations, the implant includes a tissue anchor defining the energy-applicator.
[0042] In some implementations, the tissue anchor includes a resistor heater defining the energy-applicator.
[0043] In some implementations, the tissue anchor includes an implant-electrode defining the energy-applicator.
[0044] In some implementations, the tissue anchor includes a tissue-engaging element defining the energy-applicator.
[0045] In some implementations, the adhesive is pre-disposed on the tissue-engaging element.
[0046] In some implementations, the energy-applicator includes an implant-electrode that is coupled to the implant and configured to apply electrical current to the adhesive.
[0047] In some implementations, the delivery tool includes a terminal that is reversibly electrically connected to the energy-applicator.
[0048] In some implementations, the implant: includes a pair of electrodes including: the implant-electrode, and / or a return electrode configured to remove current from the subject, and / or is configured such that application of voltage to the implant-electrode causes current to flow from the respective implant-electrode, through the adhesive, to the return electrode.
[0049] In some implementations: the implant includes multiple pairs of electrodes, each pair of electrodes including an implant-electrode and a return electrode; and / or the implant is configured such that application of voltage to a respective implant-electrode causes current to flow from the implant-electrode, through a respective portion of the adhesive, to a respective return electrode.
[0050] In some implementations, the delivery tool is configured to transmit energy to the implant, and / or the implant includes a terminal configured to receive the energy from the delivery tool, and direct the energy to the energy-applicator.
[0051] In some implementations, the delivery tool is configured to wirelessly transmit energy to the implant, and / or the implant includes a wireless terminal configured to receive the energy from the delivery tool, and direct the energy to the energy-applicator.
[0052] In some implementations, the adhesive includes: a first portion of adhesive, predisposed on a first part of the implant body, and / or a second portion of adhesive, predisposed on a second part of the implant body; and / or the delivery tool is configured to, while the first portion of adhesive remains in contact with the tissue, activate the first portion of adhesive to adhere the first part of the implant body to the tissue by driving the energy-applicator to apply the energy to the first portion of adhesive.
[0053] In some implementations, the delivery tool is configured to, while the first portion of adhesive remains in contact with the tissue, activate the first portion of adhesive to adhere the first part of the implant body to the tissue by driving the energy-applicator to apply the energy to the first portion of adhesive while the second portion of the implant body is not in contact with the tissue.
[0054] In some implementations, the delivery tool is configured to, while the first portion of adhesive remains in contact with the tissue, activate the first portion of adhesive to adhere the first part of the implant body to the tissue by driving the energy-applicator to apply the energy to the first portion of adhesive while the second portion of the implant body is disposed within the delivery tool.
[0055] In some implementations, the implant includes a tissue-engaging element.
[0056] In some implementations, the tissue-engaging element includes the energy- applicator.
[0057] In some implementations, the delivery tool is configured to mechanically attach the implant to the tissue via the tissue-engaging element.
[0058] In some implementations: the tissue-engaging element defines an adhesive- coated surface, and / or the delivery tool is configured to mechanically attach the implant to the tissue via the tissue-engaging element, prior to driving the energy-applicator to apply energy to the adhesive-coated surface.
[0059] In some implementations: the implant body defines an adhesive-coated surface, and / or the delivery tool is configured to mechanically attach the implant to the tissue via thetissue-engaging element, prior to driving the energy-applicator to apply energy to the adhesive-coated surface.
[0060] In some implementations: the tissue-engaging element includes a clip; and / or the delivery tool is configured to mechanically attach the implant to the tissue by closing the clip on the tissue, prior to driving the energy-applicator to apply energy to the adhesive.
[0061] In some implementations: the implant includes a tissue anchor defining the tissue-engaging element; and / or the delivery tool includes an anchor driver, configured to mechanically attach the implant body to the tissue by driving the tissue-engaging element into the tissue.
[0062] In some implementations: implant defines an adhesive-coated surface, and / or the delivery tool is configured to mechanically attach the adhesive-coated surface to the tissue by, via the anchor driver, driving the tissue-engaging element into the tissue, prior to driving the energy-applicator to apply energy to the adhesive-coated surface.
[0063] In some implementations: the implant body defines the adhesive-coated surface, and / or the delivery tool is configured to mechanically attach the adhesive-coated surface to the tissue by, via the anchor driver, driving the tissue-engaging element into the tissue, prior to driving the energy-applicator to apply energy to the adhesive-coated surface.
[0064] In some implementations: the tissue-engaging element of the tissue anchor defines the adhesive-coated surface, and / or the delivery tool is configured to mechanically attach the implant to the tissue via the anchor driver by driving the tissue-engaging element into the tissue, prior to driving the energy-applicator to apply energy to the adhesive-coated surface.
[0065] In some implementations, the adhesive-coated surface is a first adhesive-coated surface, and / or the implant further defines a second adhesive-coated surface.
[0066] In some implementations, the delivery tool is configured to concurrently activate the adhesive of the first adhesive-coated surface and the second adhesive-coated surface by driving the energy-applicator to apply energy concurrently to each adhesive-coated surface.
[0067] In some implementations, the delivery tool is configured to: activate the adhesive of the first adhesive-coated surface by driving the energy-applicator to apply energy to the first adhesive-coated surface, and / or subsequently activate the adhesive of the second adhesive-coated surface by driving the energy-applicator to apply energy to the second adhesive-coated surface.
[0068] In some implementations: the tissue anchor is a first tissue anchor; the implant further includes a second tissue anchor; and / or the delivery tool is configured to: activate theadhesive of the first adhesive-coated surface by driving the energy-applicator to apply energy, via the first tissue anchor, to the first adhesive-coated surface, and / or subsequently activate the adhesive of the second adhesive-coated surface by driving the energy-applicator to apply energy, via the second tissue anchor, to the second adhesive-coated surface.
[0069] In some implementations: a first part of the implant body defines the first adhesive-coated surface, and / or a second part of the implant body defines the second adhesive-coated surface.
[0070] In some implementations: the tissue-engaging element of the first tissue anchor defines the first adhesive-coated surface, and / or the tissue-engaging element of the second tissue anchor defines the second adhesive-coated surface.
[0071] In some implementations, the anchor driver is configured to: drive the tissue- engaging element of each tissue anchor into the tissue, and / or activate the adhesive of each adhesive-coated surface by driving the energy-applicator to apply energy, via the respective tissue-engaging element, to the respective adhesive-coated surface.
[0072] In some implementations, the delivery tool is configured to activate the adhesive of the first adhesive-coated surface by driving the energy-applicator to apply energy, via the first tissue anchor, to the first adhesive-coated surface while the second adhesive-coated surface is not in contact with the tissue.
[0073] In some implementations, the delivery tool is configured to activate the adhesive of the first adhesive-coated surface by driving the energy-applicator to apply energy, via the first tissue anchor, to the first adhesive-coated surface while the second adhesive-coated surface is disposed within the delivery tool.
[0074] In some implementations, the delivery tool is configured to activate the adhesive of the first adhesive-coated surface by driving the energy-applicator to apply energy, via the first tissue anchor, to the first adhesive-coated surface while the second tissue anchor is disposed within the delivery tool.
[0075] In some implementations, the energy-applicator includes an implant-electrode configured to apply current to the adhesive, the delivery tool includes a return electrode configured to remove current from the subject, and / or the delivery tool is configured to apply voltage to the implant-electrode, such that current flows from the implant-electrode, through the adhesive, to the return electrode, thereby activating the adhesive to adhere the implant body to the tissue.
[0076] In some implementations, the system has: adhesive-curing mode in which the delivery tool applies voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive, to the return electrode; and / or a navigation modein which the implant-electrode is configured to measure endogenic electrical signals within the heart.
[0077] In some implementations, the system is configured to, responsively to the measured endogenic electrical signals, calculate a location of the implant-electrode.
[0078] In some implementations: the implant includes a plurality of implant-electrodes, and / or the delivery tool is adjustable to selectively apply voltage to one of the implant- electrodes, such that current flows from the selected implant-electrode, through a selected portion of the adhesive, to the return electrode.
[0079] In some implementations, the system is transitionable between: a first state in which the delivery tool is configured to apply voltage to a first implant-electrode, such that current flows from the first implant-electrode, through a first portion of the adhesive, to the return electrode; and / or a second state in which the delivery tool is configured to apply voltage to a second implant-electrode, such that current flows from the second implant- electrode, through a second portion of the adhesive, to the return electrode.
[0080] In some implementations, the energy-applicator includes an implant-electrode; the system includes a return electrode, configured to be positioned on a skin surface of the subject; and / or the system has: adhesive-curing mode in which the delivery tool applies voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive, to the return electrode; and / or a bioimpedance-measuring mode in which the delivery tool applies voltage to the implant-electrode such that current flows from the implant-electrode, through tissue of the subject, to the return electrode.
[0081] In some implementations: the return electrode is a first return electrode, the system further includes a second return electrode, and / or the system is configured to: measure current that flows to each return electrode, and / or responsively to the measurements, calculate a location of the implant-electrode.
[0082] In some implementations, the system is configured to apply a higher voltage to the implant-electrode while the system is in the adhesive-curing mode than while the system is in the bioimpedance-measuring mode.
[0083] There is further provided, in accordance with some implementations, a system for use at a tissue of a heart of a subject, the system including: an implant, the implant including: an implant body, and / or an energy-activated adhesive, pre-disposed on the implant body.
[0084] In some implementations, the system includes a delivery tool, configured to: transluminally deliver the implant to the heart, and position the adhesive in contact with thetissue, and / or while the adhesive remains in contact with the tissue, activate the adhesive to adhere the implant body to the tissue by applying energy to the adhesive.
[0085] In some implementations, at least one of the implant, the delivery tool and the adhesive is sterile.
[0086] In some implementations, the delivery tool includes an energy-applicator configured to be removed from the subject after activating the adhesive.
[0087] In some implementations, the energy-applicator is configured to apply heat to the adhesive.
[0088] In some implementations, the energy-applicator is configured to apply electrical current to the adhesive.
[0089] In some implementations, the implant includes an energy-applicator that is fixedly coupled to the implant body.
[0090] In some implementations, the energy-applicator is embedded within the adhesive.
[0091] In some implementations, the energy-applicator includes an implant-electrode configured to activate the adhesive by applying electrical current to the adhesive.
[0092] In some implementations, the delivery tool includes a terminal that is reversibly electrically connected to the energy-applicator.
[0093] In some implementations, the implant further includes a tissue anchor defining an energy-applicator; and / or the delivery tool is configured to, while the adhesive remains in contact with the tissue, transmit energy to the energy-applicator, thereby activating the adhesive to adhere the implant body to the tissue by applying energy to the adhesive.
[0094] In some implementations, the tissue anchor includes a resistor heater defining the energy-applicator.
[0095] In some implementations, the tissue anchor includes an implant-electrode defining the energy-applicator.
[0096] In some implementations, the tissue anchor includes a tissue-engaging element defining the energy-applicator.
[0097] There is further provided, in accordance with some implementations, a method for implanting an implant in a heart of a subject, the method including: transluminally advancing a bioprinter nozzle to the heart, the bioprinter nozzle housing a bioink including a biomaterial.
[0098] In some implementations, the method includes, within the heart, printing the implant by extruding the bioink from the bioprinter nozzle such that the biomaterial defines the implant.
[0099] In some implementations, the method further includes sterilizing the implant, the nozzle and the bioink.
[0100] In some implementations, the method includes, subsequently to the step of printing, transluminally withdrawing the bioprinter nozzle from the subject.
[0101] In some implementations, printing the implant includes printing the implant within the heart by extruding the bioink from the bioprinter nozzle such that the biomaterial: assumes a three-dimensional implant-shape, and / or adheres to tissue at a site in the heart.
[0102] In some implementations, printing the implant includes printing the implant within the heart by extruding the bioink from the bioprinter nozzle at the site in the heart such that the implant inhibits bloodflow at the site.
[0103] In some implementations: the implant is a first implant, the three-dimensional implant-shape is a three-dimensional first-implant-shape, the site is a first site, and / or the method further includes printing a second implant within the heart by extruding the bioink from the bioprinter nozzle at a second site in the heart such that the biomaterial: assumes a three-dimensional second-implant-shape, and / or adheres to tissue at the second site.
[0104] In some implementations: printing the implant includes printing the implant within the heart by extruding the bioink from the bioprinter nozzle at the site such that a first portion of the biomaterial adheres to tissue at the site, and / or the method further includes securing a prosthesis within the heart by adhering a second portion of the biomaterial to the prosthesis.
[0105] In some implementations: the prosthesis is a prosthetic valve, the site is within a ventricle of the heart, and / or securing the prosthesis includes securing the prosthetic valve by adhering the first portion of the biomaterial to the site within the ventricle of the heart.
[0106] In some implementations, printing the implant includes printing the implant within the heart by extruding the bioink from the bioprinter nozzle such that the biomaterial defines a tether connecting the prosthesis to the site.
[0107] In some implementations: the site is a first site in the heart; and / or printing the implant includes printing the implant within the heart by extruding the bioink from the bioprinter nozzle in the heart such that the biomaterial adheres to tissue at: the first site of the heart, and / or a second site of the heart.
[0108] In some implementations, printing the implant includes printing the implant within the heart by extruding the bioink from the bioprinter nozzle in the heart such that the biomaterial defines a tether connecting the first site to the second site.
[0109] In some implementations, printing the implant includes printing the implant within the heart by extruding the bioink from the bioprinter nozzle in the heart such that tether restricts movement of the first site relative to the second site.
[0110] In some implementations, printing the implant includes printing the implant within the heart by extruding the bioink from the bioprinter nozzle in the heart such that, during a cardiac cycle of the heart, the tether limits a dimension of the heart.
[0111] In some implementations, the first site is at a leaflet of a valve of the heart, the second site is an anchor site located within a chamber of the heart, and / or printing the implant includes printing the implant within the heart by extruding the bioink from the bioprinter nozzle in the heart such that, during a cardiac cycle of the heart, the tether limits a distance between the leaflet and the anchor site.
[0112] In some implementations: the first site is at an annulus of a valve of the heart, the second site is located at the annulus, opposite the first site, and / or printing the implant includes printing the implant within the heart by extruding the bioink from the bioprinter nozzle in the heart such that, during a cardiac cycle of the heart, the tether limits a diameter of the annulus.
[0113] In some implementations: the first site is at a chamber of the heart, the second site is located at the chamber, opposite the first site, and / or printing the implant includes printing the implant within the heart by extruding the bioink from the bioprinter nozzle in the heart such that, during a cardiac cycle of the heart, the tether limits a width of the chamber.
[0114] In some implementations: the first site is located at a tip-portion of a first leaflet of a valve of the heart, the second site is located at a tip portion of a second leaflet of the valve, opposite the tip-portion of the first leaflet, and / or printing the implant includes printing the implant within the heart by extruding the bioink from the bioprinter nozzle in the heart such that, during a cardiac cycle of the heart, the tether limits a distance between the tip-portion of the first leaflet and the tip-portion of the second leaflet.
[0115] In some implementations, the method includes, subsequently to the step of printing, fixating the biomaterial such that the biomaterial retains the implant-shape.
[0116] In some implementations, fixating the biomaterial includes applying fixating the biomaterial by applying heat to the bioink such that the biomaterial retains the implant- shape.
[0117] In some implementations, fixating the biomaterial includes applying fixating the biomaterial by applying a chemical fixator to the bioink such that the biomaterial retains the implant-shape.
[0118] In some implementations, fixating the biomaterial includes applying fixating the biomaterial by applying ultrasound energy to the bioink such that the biomaterial retains the implant-shape.
[0119] In some implementations, fixating the biomaterial includes applying fixating the biomaterial by applying electrical current to the bioink such that the biomaterial retains the implant-shape.
[0120] In some implementations, fixating the biomaterial includes applying fixating the biomaterial by applying light to the bioink such that the biomaterial retains the implant- shape.
[0121] In some implementations, fixating the biomaterial includes applying fixating the biomaterial by applying radio waves to the bioink such that the biomaterial retains the implant-shape.
[0122] In some implementations, fixating the biomaterial includes, subsequently to the step of printing: transluminally advancing a fixator to the heart, and / or using the fixator, fixating the biomaterial such that the biomaterial retains the implant-shape.
[0123] In some implementations, the fixating the biomaterial includes fixating the biomaterial such that the biomaterial: retains the implant-shape, and / or adheres to tissue of the heart.
[0124] There is further provided, in accordance with some implementations, a method for implanting an implant in a simulated heart of a subject, the method including: transluminally advancing a bioprinter nozzle to the heart, the bioprinter nozzle housing a bioink including a biomaterial.
[0125] In some implementations, the method includes, within the heart, printing the implant by extruding the bioink from the bioprinter nozzle such that the biomaterial defines the implant.
[0126] There is further provided, in accordance with some implementations, a method for use with a heart of a subject, the method including, using a delivery tool, transluminally advancing an implant to the heart, the implant including: an implant body, an adhesive, pre- disposed on the implant, and / or an energy-applicator.
[0127] In some implementations, the method includes positioning the implant in the heart such that the adhesive contacts tissue of the heart; and / or activating the adhesive bydriving the energy-applicator to apply energy to the adhesive, thereby adhering the implant body to tissue of the heart.
[0128] In some implementations, the method further includes sterilizing the implant, the delivery tool and the adhesive.
[0129] In some implementations, the method further includes, subsequently to activating the adhesive, removing the delivery tool from the subject.
[0130] In some implementations, activating the adhesive includes activating the adhesive by driving the energy-applicator to apply heat to the adhesive, thereby adhering the implant body to the tissue.
[0131] In some implementations, activating the adhesive includes activating the adhesive by driving the energy-applicator to apply electrical current to the adhesive, thereby adhering the implant body to the tissue.
[0132] In some implementations: the energy-applicator includes an implant-electrode; and / or activating the adhesive includes activating the adhesive by applying voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive, to a return electrode, thereby adhering the implant body to the tissue.
[0133] In some implementations: the implant-electrode is a first implant-electrode; the energy-applicator further includes a second implant-electrode; and / or activating the adhesive includes activating the adhesive by applying voltage to: the first implant-electrode such that current flows from the first implant-electrode, through a first portion of the adhesive, to the return electrode, thereby adhering a first part of the implant body to the tissue, and / or the second implant-electrode such that current flows from the second implant-electrode, through a second portion of the adhesive, to the return electrode, thereby adhering a second part of the implant body to the tissue.
[0134] In some implementations, activating the adhesive includes activating the adhesive by concurrently applying voltage to: the first implant-electrode such that current flows from the first implant-electrode, through the first portion of the adhesive, to the return electrode, thereby adhering a first part of the implant body to the tissue, and / or the second implant-electrode such that current flows from the second implant-electrode, through the second portion of the adhesive, to the return electrode, thereby adhering a second part of the implant body to the tissue.
[0135] In some implementations, activating the adhesive includes activating the adhesive by: applying voltage to the first implant-electrode such that current flows from the first implant-electrode, through the first portion of the adhesive, to the return electrode, thereby adhering a first portion of the implant body to the tissue, and / or subsequently,applying voltage to the second implant-electrode such that current flows from the second implant-electrode, through the second portion of the adhesive, to the return electrode, thereby adhering a second portion of the implant body to the tissue.
[0136] In some implementations, the method further includes deploying the implant from the delivery tool in a stepwise manner, such that applying voltage to the first implant- electrode includes applying voltage to the first implant-electrode while the second portion of the implant body is not in contact with the tissue.
[0137] In some implementations, deploying the implant from the delivery tool in the stepwise manner includes deploying the implant such that applying voltage to the first implant-electrode includes applying voltage to the first implant-electrode while the second portion of the implant body is disposed within the delivery tool.
[0138] In some implementations, the implant body includes a tissue-engaging element, and / or the method further includes, prior to activating the adhesive, mechanically attaching the tissue-engaging element to the tissue.
[0139] In some implementations: the tissue-engaging element of the implant body includes a clip; and / or mechanically attaching the tissue-engaging element to the tissue includes closing the clip on the tissue, prior to activating the adhesive.
[0140] In some implementations: the implant includes a tissue anchor; and / or mechanically attaching the tissue-engaging element to the tissue includes driving the tissue anchor through the implant body and into tissue of the heart, prior to driving the energy- applicator to apply energy to the adhesive, thereby adhering the implant body to tissue of the heart.
[0141] In some implementations: the adhesive is pre-disposed on the tissue-engaging element of the implant body, and / or activating the adhesive includes, subsequently to mechanically attaching the tissue-engaging element to the tissue, activating the adhesive by driving the energy-applicator to apply energy to the adhesive, thereby adhering the tissue- engaging element of the implant body to tissue of the heart.
[0142] In some implementations: the implant further includes a tissue anchor; and / or mechanically attaching the tissue-engaging element to the tissue includes driving the tissue anchor through the tissue-engaging element and into the tissue.
[0143] In some implementations: the tissue anchor defines the energy- applicator; and / or the method further includes activating the adhesive by driving the energy-applicator to apply energy to the adhesive, thereby adhering the tissue-engaging element of the implant body to tissue of the heart.
[0144] In some implementations: the tissue anchor is a first tissue anchor; the implant further includes a second tissue anchor; and / or mechanically attaching the tissue-engaging element of the implant body to the tissue includes: driving the first tissue anchor through a first segment of the tissue-engaging element and into the tissue, and / or driving the second tissue anchor through a second segment of the tissue-engaging element and into the tissue.
[0145] In some implementations: the first tissue anchor includes a first energy- applicator; the second tissue anchor includes a second energy-applicator; and / or activating the adhesive includes activating the adhesive by: driving the first energy-applicator to apply energy to adhesive on the first segment of the tissue-engaging element, thereby adhering the first segment to tissue of the heart, and / or driving the second energy-applicator to apply energy to adhesive on the second segment of the tissue-engaging element, thereby adhering the second segment to tissue of the heart.
[0146] In some implementations, activating the adhesive includes activating the adhesive by concurrently: driving the first energy-applicator to apply energy to adhesive on the first segment of the tissue-engaging element, thereby adhering the first segment to tissue of the heart, and / or driving the second energy-applicator to apply energy to adhesive on the second segment of the tissue-engaging element, thereby adhering the second segment to tissue of the heart.
[0147] In some implementations, driving the first energy-applicator includes driving the first energy-applicator to apply energy to adhesive on the first segment of the tissue- engaging element, thereby adhering the first segment to tissue of the heart, prior to driving the second energy-applicator to apply energy to adhesive on the second segment of the tissue-engaging element.
[0148] In some implementations, driving the first energy-applicator includes driving the first energy-applicator to apply energy to adhesive on the first segment of the tissue- engaging element, thereby adhering the first segment to tissue of the heart, while the second segment of the tissue-engaging element is not in contact with the tissue.
[0149] In some implementations, driving the first energy-applicator includes driving the first energy-applicator to apply energy to adhesive on the first segment of the tissue- engaging element, thereby adhering the first segment to tissue of the heart, while the second segment of the tissue-engaging element is disposed within the delivery tool.
[0150] In some implementations, the implant includes a tissue anchor on which the adhesive is pre-disposed; and / or mechanically attaching the tissue-engaging element to the tissue includes driving the tissue anchor through the implant body and into tissue of the heart.
[0151] In some implementations: the tissue anchor includes the energy-applicator; and / or activating the adhesive includes, subsequently to driving the tissue anchor through the implant body and into tissue of the heart, activating the adhesive on the tissue anchor by driving the energy-applicator to apply energy to the adhesive, thereby adhering the tissue anchor to tissue of the heart.
[0152] In some implementations: the tissue anchor is a first tissue anchor including a first energy-applicator; the implant further includes a second tissue anchor including a second energy-applicator; mechanically attaching the tissue-engaging element to the tissue further includes driving the second tissue anchor through the implant body and into tissue of the heart; and / or activating the adhesive includes: activating the adhesive that is pre- disposed on the first tissue anchor by driving the energy-applicator to apply energy to the adhesive that is pre-disposed on the first tissue anchor, thereby adhering the first tissue anchor to tissue of the heart, and / or activating the adhesive that is pre-disposed on the second tissue anchor by driving the energy-applicator to apply energy to the adhesive that is pre-disposed on the second tissue anchor, thereby adhering the second tissue anchor to tissue of the heart.
[0153] In some implementations, the method further includes deploying the implant from the delivery tool in a stepwise manner, such that activating the adhesive includes activating the adhesive that is pre-disposed on the first tissue anchor while the second tissue anchor is not in contact with the tissue.
[0154] In some implementations, deploying the implant from the delivery tool in the stepwise manner includes deploying the implant such that activating the adhesive includes activating the adhesive that is pre-disposed on the first tissue anchor while the second tissue anchor is disposed within the delivery tool.
[0155] In some implementations, the method further includes measuring endogenic electrophysiological signals, and / or positioning the implant includes, responsively to the measured endogenic electrophysiological signals, positioning the implant in the heart such that the adhesive contacts tissue of the heart.
[0156] In some implementations: the implant includes a sensory electrode; and / or the step of measuring includes, using the sensory electrode, measuring endogenic electrophysiological signals.
[0157] In some implementations, the energy-applicator includes an implant-electrode; and / or the method further includes: positioning a bioimpedance measuring-electrode on a skin surface of the subject, and / or using the delivery tool: transluminally advancing the implant-electrode to the heart, and / or applying voltage to the implant-electrode such thatcurrent flows from the implant-electrode, through tissue of the subject, to the bioimpedance measuring-electrode.
[0158] In some implementations, the method further includes: while applying voltage to the implant-electrode, measuring current that flows to the bioimpedance measuring- electrode; and / or responsively to the measurements of current, calculating a position of the implant-electrode.
[0159] In some implementations, the method further includes, responsively to the calculated position of the implant-electrode, repositioning the implant.
[0160] In some implementations: the energy-applicator includes an implant-electrode; and / or responsively to the calculated position of the implant-electrode, activating the adhesive includes activating the adhesive by applying voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive, to a return electrode, thereby adhering the implant body to the tissue.
[0161] In some implementations, the method further includes, prior to activating the adhesive: ungrounding the bioimpedance measuring-electrode, and / or grounding the return electrode.
[0162] In some implementations: applying voltage to the implant-electrode such that current flows from the implant-electrode, through tissue of the subject, to the bioimpedance measuring-electrode includes applying a lower voltage to the implant-electrode, and / or applying voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive, to the return electrode, thereby adhering the implant body to the tissue includes applying a higher voltage to the implant-electrode.
[0163] There is further provided, in accordance with some implementations, a method for use with a simulated heart of a subject, the method including, using a delivery tool, transluminally advancing an implant to the heart, the implant including: an implant body, an adhesive, pre-disposed on the implant, and / or an energy-applicator.
[0164] In some implementations, the method includes positioning the implant in the heart such that the adhesive contacts tissue of the heart; and / or activating the adhesive by driving the energy-applicator to apply energy to the adhesive, thereby adhering the implant body to tissue of the heart.
[0165] There is further provided, in accordance with some implementations, a method for use at a heart of a subject, the method including: transluminally advancing a bioprinter nozzle into the heart.
[0166] In some implementations, the method includes, within the heart, using the bioprinter nozzle, adhering a bioink to tissue of the heart.
[0167] In some implementations, the method includes, within the heart, using the bioprinter nozzle, printing, from the bioink, an implant that is adhered to the tissue.
[0168] In some implementations, the method further includes sterilizing the implant, the nozzle and the bioink.
[0169] There is further provided, in accordance with some implementations, a method for use at a simulated heart of a subject, the method including: transluminally advancing a bioprinter nozzle into the heart.
[0170] In some implementations, the method includes, within the heart, using the bioprinter nozzle, adhering a bioink to tissue of the heart.
[0171] In some implementations, the method includes, within the heart, using the bioprinter nozzle, printing, from the bioink, an implant that is adhered to the tissue.
[0172] There is further provided, in accordance with some implementations, a system for use in a heart of a subject, the system including: an implant, the implant including: an implant body, an adhesive, pre-disposed on the implant body, and / or an activator.
[0173] In some implementations, the system includes a delivery tool, configured to: transluminally deliver the implant to the heart, and position the adhesive in contact with tissue of the heart.
[0174] In some implementations, the delivery tool is configured to, while the adhesive remains in contact with the tissue, activate the adhesive to adhere the implant body to the tissue by applying the activator to the adhesive.
[0175] In some implementations, at least one of the implant and the delivery tool is sterile.
[0176] In some implementations: the adhesive is a mussel foot protein-based bioadhesive, and / or the activator is configured to activate the bioadhesive by cross-linking amino acid residues of the mussel foot protein.
[0177] There is further provided, in accordance with some implementations, a method, including: weaving a fabric that defines a face by interlacing a weft yarn with a warp that includes multiple warp yarns.
[0178] In some implementations, weaving includes forming a warp float from a given one of the warp yarns by, on at least one pass of the weft yarn across the warp, skipping the given one of the warp yarns.
[0179] In some implementations, weaving includes shaping the warp float into a directional barb that protrudes obliquely from the face of the fabric by selectively cutting away a part of the warp float.
[0180] In some implementations, the method further includes sterilizing the weft yarn and the warp yarns.
[0181] In some implementations, weaving includes weaving a planar fabric.
[0182] In some implementations, weaving includes weaving a non-planar fabric.
[0183] In some implementations, weaving includes weaving a concave fabric.
[0184] In some implementations, weaving includes weaving a convex fabric.
[0185] In some implementations, the method further includes, prior to cutting away the part of the warp float, adhering a non-floating segment of the warp yarn to a back of the fabric.
[0186] In some implementations, adhering includes adhering the non-floating segment of the warp yarn to the back of the fabric by heating the back of the fabric.
[0187] In some implementations, adhering includes adhering the non-floating segment of the warp yarn to the back of the fabric by adhering a laminate to the back of the fabric.
[0188] In some implementations, shaping the warp float into the directional barb includes, prior to selectively cutting, shape-setting the warp float, and / or selectively cutting includes selectively cutting away the part of the warp float to form a shape-set directional barb that protrudes obliquely from the face of the fabric.
[0189] In some implementations, selectively cutting includes selectively cutting away the part of the warp float to form a shape-set hooked barb that protrudes obliquely from the face of the fabric.
[0190] In some implementations, shape-setting includes shape-setting the warp float by applying electromagnetic energy to the fabric.
[0191] In some implementations, shape-setting includes shape-setting the warp float by heating the fabric.
[0192] In some implementations, shape-setting includes shape-setting the warp float by heating the fabric to a temperature exceeding a melting point of the warp yarn.
[0193] In some implementations, shape-setting includes shape-setting the warp float by heating the fabric to a temperature not exceeding a melting point of the weft yarn.
[0194] In some implementations, shape-setting includes shape-setting the warp float by heating the fabric to 180–240 °C.
[0195] In some implementations, the method further includes, prior to selectively cutting away the part of the warp float, distancing the warp float from the face of the fabric by inserting a pin between the warp float and the face of the fabric.
[0196] In some implementations, inserting includes, while weaving the fabric, inserting the pin between the warp float and the face of the fabric.
[0197] In some implementations, inserting includes, after weaving the fabric, inserting the pin between the warp float and the face of the fabric.
[0198] In some implementations, selectively cutting includes, while the pin is disposed between the warp float and the face of the fabric, using a blade to cut the warp float.
[0199] In some implementations, selectively cutting includes using the blade to cut the warp float along the pin, such that the pin serves as a blade-guide.
[0200] In some implementations: the pin has a cross-section defining a base and an apex, and / or inserting the pin includes inserting the pin such that the base of the pin faces the face of the fabric, and the apex is positioned further away than the base from the face of the fabric.
[0201] In some implementations, selectively cutting includes cutting the warp yarn along the apex of the pin.
[0202] In some implementations, selectively cutting includes cutting the warp yarn along the base of the pin.
[0203] In some implementations, shaping the warp float into the directional barb includes, prior to selectively cutting, shape-setting the warp float while the pin is disposed between the warp float and the face of the fabric.
[0204] In some implementations, shape-setting includes shape-setting the warp float by heating the pin while the pin is disposed between the warp float and the face of the fabric.
[0205] In some implementations, shape-setting includes shape-setting the warp float by heating the fabric while the pin is disposed between the warp float and the face of the fabric.
[0206] In some implementations, shape-setting includes shape-setting the warp float by applying electromagnetic energy to the fabric while the pin is disposed between the warp float and the face of the fabric.
[0207] In some implementations, forming the warp float from the given one of the warp yarns includes forming a first warp float from a first warp yarn; shaping the warp float intothe directional barb includes shaping the first warp float into a first directional barb that protrudes obliquely from the face of the fabric by selectively cutting away a part of the first warp float; weaving further includes forming a second warp float from a second warp yarn by, on the at least one pass of the weft yarn across the warp, skipping the second warp yarn; and / or the method further includes shaping the second warp float into a second directional barb that protrudes obliquely from the face of the fabric by selectively cutting away a part of the second warp float.
[0208] In some implementations: weaving further includes forming a third warp float from a third warp yarn by, on the at least one pass of the weft yarn across the warp, skipping the third warp yarn; and / or the method does not include cutting away a part of the third warp float.
[0209] In some implementations, the method further includes folding the fabric into a bi-layer fabric such that: the first directional barb protrudes obliquely from a first layer of the fabric, and / or the second directional barb protrudes obliquely from a second layer of the fabric.
[0210] In some implementations, folding includes folding the fabric along a longitudinal axis of the fabric.
[0211] In some implementations, folding includes folding the fabric in parallel to the warp yarns.
[0212] In some implementations, folding includes folding the fabric such that the first directional barb and the second directional barb each protrude symmetrically from a respective layer of the fabric.
[0213] In some implementations, folding includes folding the fabric such that the first directional barb and the second directional barb protrude at equal angles from a respective layer of the fabric.
[0214] In some implementations, the method further includes distancing the first warp float and the second warp float from the face of the fabric by inserting a pin between the face of the fabric and the first and second warp floats.
[0215] In some implementations: weaving further includes forming a third warp float from a third warp yarn by, on the at least one pass of the weft yarn across the warp, skipping the third warp yarn; and / or the method does not include inserting the pin between the face of the fabric and the third warp float.
[0216] In some implementations, shaping includes shaping the first warp float and the second warp float into directional barbs that protrude obliquely from the face of the fabric byselectively cutting away respective parts of the first warp float and the second warp float by advancing a blade along the pin.
[0217] In some implementations, shaping includes shaping the first warp float and the second warp float into directional barbs that protrude in parallel from the face of the fabric by advancing the blade along the pin to cut away corresponding parts of the first warp float and the second warp float.
[0218] In some implementations, shaping includes shaping the first warp float and the second warp float into similarly shaped barbs that protrude from the face of the fabric by advancing the blade along the pin to cut away corresponding parts of the first warp float and the second warp float.
[0219] In some implementations, forming the warp float from the given one of the warp yarns includes forming a first warp float from the given one of the warp yarns by, on a first pass of the weft yarn across the warp, skipping the given one of the warp yarns; shaping includes shaping the first warp float into a first directional barb that protrudes obliquely from the face of the fabric by selectively cutting away a part of the first warp float; and / or the method further includes: forming a second warp float from the given one of the warp yarns by, on a second pass of the weft yarn across the warp, skipping the given one of the warp yarns, and / or shaping further including shaping the second warp float into a second directional barb that protrudes obliquely from the face of the fabric by selectively cutting away a part of the second warp float.
[0220] In some implementations: weaving further includes forming a third warp float from the given one of the warp yarns by, on a third pass of the weft yarn across the warp, skipping the given one of the warp yarns; and / or the method does not include cutting away a portion of third warp float.
[0221] In some implementations, the method further includes folding the fabric into a bi-layer fabric such that: the first directional barb protrudes obliquely from a first layer of the fabric, and / or the second directional barb protrudes obliquely from a second layer of the fabric.
[0222] In some implementations, folding includes folding the fabric perpendicularly to a longitudinal axis of the fabric.
[0223] In some implementations, folding includes folding the fabric perpendicularly to the warp yarns.
[0224] In some implementations, folding includes folding the fabric such that the first directional barb and the second directional barb each protrude symmetrically from a respective layer of the fabric.
[0225] In some implementations, folding includes folding the fabric such that the first directional barb and the second directional barb protrude at equal angles from a respective layer of the fabric.
[0226] In some implementations, the method further includes, prior to selectively cutting, distancing the first warp float and the second warp float from the face of the fabric by inserting: a first pin between the first warp float and the face of the fabric, and / or a second pin between the second warp float and the face of the fabric.
[0227] In some implementations, distancing the first warp float and the second warp float from the face of the fabric includes inserting the first pin and the second pin in parallel.
[0228] In some implementations, distancing the first warp float and the second warp float from the face of the fabric includes inserting the first pin and the second pin in parallel with the weft yarn.
[0229] In some implementations, shaping includes shaping the first warp float and the second warp float into directional barbs that protrude obliquely from the face of the fabric by advancing a blade along the first pin and the second pin to selectively cut away respective parts of the first warp float and the second warp float.
[0230] In some implementations, shaping includes shaping the first warp float and the second warp float into directional barbs that protrude in opposite directions from the face of the fabric by advancing a blade along the first pin and the second pin to selectively cut away respective parts of the first warp float and the second warp float.
[0231] In some implementations, shaping includes shaping the first warp float and the second warp float into directional barbs that protrude symmetrically from the face of the fabric by advancing a blade along the first pin and the second pin to selectively cut away respective parts of the first warp float and the second warp float.
[0232] In some implementations, shaping includes shaping the first warp float and the second warp float into similarly shaped directional barbs that protrude from the face of the fabric by advancing a blade along the first pin and the second pin to selectively cut away respective parts of the first warp float and the second warp float.
[0233] There is further provided, in accordance with some implementations, a method, including weaving a fabric by interlacing a weft yarn with a warp that includes multiple warp yarns, the weaving including forming a warp float from a given one of the warp yarns by passing the weft yarn under the given one of the warp yarns on multiple consecutive passes of the weft yarn across the warp.
[0234] In some implementations, weaving includes shaping the warp float into a directional barb that protrudes obliquely from a plane of the fabric by cutting away a portion of the warp float.
[0235] In some implementations, the method further includes sterilizing the weft yarn and the warp yarns.
[0236] There is further provided, in accordance with some implementations, a method, including weaving a fabric that defines a face by interlacing a weft yarn with a warp that includes multiple warp yarns, by passing the weft yarn, in a first pass along a width of the warp, over a first warp yarn, under a second warp yarn, and over a third warp yarn.
[0237] In some implementations, weaving includes passing the weft yarn, in a second pass along the width of the warp: under the first warp yarn, the second warp yarn and the third warp yarn, such that the second warp yarn defines a warp float spanning a length of the face of the fabric.
[0238] In some implementations, weaving includes shaping the warp float into a directional barb that protrudes obliquely from the face of the fabric by selectively cutting away a part of the warp float.
[0239] In some implementations, the method further includes sterilizing the weft yarn and the warp yarns.
[0240] In some implementations, the method does not include cutting away a portion of the first warp yarn.
[0241] In some implementations, the method does not include cutting away a portion of the third warp yarn.
[0242] In some implementations, cutting includes selectively cutting away a portion of the second warp yarn, adjacent to the weft yarn.
[0243] In some implementations, cutting includes selectively cutting away a portion of the second warp yarn, along a length of the weft yarn.
[0244] There is further provided, in accordance with some implementations, a method for use at a tissue of a cardiovascular system of a subject, the method including, using a delivery tool: transluminally advancing an implant including a barbed fabric to the tissue, and holding the fabric against the tissue such that barbs of the fabric penetrate the tissue.
[0245] In some implementations, the method includes, while the barbs remain in the tissue, manipulating an adhesive to adhere the fabric to the tissue; and / or subsequently, removing the delivery tool from the subject.
[0246] In some implementations, the method further includes sterilizing the implant, the adhesive and the delivery tool.
[0247] In some implementations, leaflets of a native valve of the cardiovascular system define the tissue, the implant includes a prosthetic valve, and / or holding the fabric includes holding the fabric against the tissue such that barbs of the fabric penetrate the leaflets.
[0248] In some implementations, the delivery tool includes a scaffold; and / or holding includes, using the scaffold, pressing the fabric against the tissue such that the barbs penetrate the tissue.
[0249] In some implementations, holding includes sandwiching the tissue between the scaffold and the fabric such that the barbs penetrate the tissue.
[0250] In some implementations, manipulating includes manipulating the adhesive to adhere the fabric to the tissue while, using the scaffold, pressing the fabric against the tissue such that the barbs penetrate the tissue.
[0251] In some implementations, the method further includes, after pressing the fabric against the tissue such that the barbs penetrate the tissue, retracting the scaffold from the tissue; and / or subsequently manipulating the adhesive to adhere the fabric to the tissue while the barbs remain in the tissue.
[0252] In some implementations: the scaffold includes a shape-memory material having a compressed state and an expanded state; and / or the method further includes: delivering the scaffold to the tissue while the scaffold is in the compressed state, deploying the scaffold such that the scaffold assumes the expanded state, and / or holding includes holding the fabric against the tissue such that the barbs penetrate the tissue, while the scaffold is in the expanded state.
[0253] In some implementations, deploying includes deploying the scaffold such that the scaffold engages the tissue as the scaffold transitions from the compressed state to the expanded state.
[0254] In some implementations: the scaffold includes a leaflet-clip; holding includes, using the leaflet-clip, holding the fabric against leaflets of a native valve of the cardiovascular system such that the barbs penetrate the leaflets; and / or manipulating includes, while the barbs remain in the leaflets, manipulating the adhesive to adhere the fabric to the leaflets.
[0255] In some implementations: the leaflet-clip includes a shape-memory material having a compressed state and an expanded state; and / or the method includes deploying the leaflet-clip such that the leaflet-clip ensnares the leaflets, such that the barbs penetrate the leaflets, as the leaflet-clip transitions from the compressed state to the expanded state.
[0256] In some implementations: the native valve defines an upstream side and a downstream side, and / or holding the fabric includes holding the fabric against the leaflets on the upstream side of the native valve of the cardiovascular system such that the barbs penetrate an upstream of the leaflets.
[0257] In some implementations: the native valve defines an upstream side and a downstream side, and / or holding the fabric includes holding the fabric against the leaflets on the upstream side of the native valve of the cardiovascular system such that the barbs penetrate a downstream-facing surface of the leaflets.
[0258] In some implementations: in the absence of the implant, the leaflets of the native valve deflect in an upstream direction and in a downstream direction, and / or holding the fabric includes holding the fabric against the leaflets such that the barbs penetrate the tissue at an angle that inhibits deflection of the leaflets in the upstream direction.
[0259] In some implementations, holding the fabric includes, using the delivery tool, holding the fabric against leaflets of the native valve such that the barbs penetrate: a first leaflet on a first side of the fabric, and / or a second leaflet on a second side of the fabric.
[0260] In some implementations, the adhesive is a chemically-activated adhesive that is pre-disposed on the implant, and / or manipulating the adhesive includes activating the adhesive by applying a chemical agent to the adhesive to adhere the fabric to the tissue.
[0261] In some implementations: the adhesive is a protein-based bioadhesive, and / or manipulating the bioadhesive includes activating the bioadhesive by applying a chemical agent that facilitates cross-linking of amino acid residues of the protein to adhere the fabric to the tissue.
[0262] In some implementations, the adhesive is an energy-activated adhesive that is pre-disposed on the implant, and / or manipulating the adhesive includes activating the adhesive by applying energy to the adhesive to adhere the fabric to the tissue.
[0263] In some implementations, activating includes activating the adhesive by applying electromagnetic energy to the adhesive.
[0264] In some implementations, activating includes activating the adhesive by applying heat to the adhesive.
[0265] In some implementations, activating includes, using an extracorporeal energy- applicator, activating the adhesive by driving the extracorporeal energy-applicator to apply energy to the adhesive from outside of the subject.
[0266] In some implementations, activating includes activating the adhesive to adhere the fabric to the tissue by applying energy to the adhesive from within the subject.
[0267] In some implementations, the method further includes using the delivery tool, transluminally advancing an energy-applicator toward the tissue; and / or wherein activating includes, using the energy-applicator, activating the adhesive to adhere the fabric to the tissue by applying energy to the adhesive from within the cardiovascular system.
[0268] In some implementations, activating includes activating the adhesive by applying electrical current to the adhesive.
[0269] In some implementations: the implant includes an implant-electrode; and / or applying electrical current to the adhesive includes applying voltage to the implant-electrode such that current flows from the implant-electrode and through the adhesive, thereby activating the adhesive.
[0270] In some implementations: the delivery tool includes a return electrode; and / or applying electrical current to the adhesive includes applying voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive and to the return electrode, thereby activating the adhesive.
[0271] In some implementations: the implant-electrode is a first implant-electrode; the implant further includes a second implant-electrode; and / or applying electrical current to the adhesive includes applying voltage to: the first implant-electrode such that current flows from the first implant-electrode and through a first portion of the adhesive, thereby activating the first portion of the adhesive, and / or the second implant-electrode such that current flows from the second implant-electrode and through a second portion of the adhesive, thereby activating the second portion of the adhesive.
[0272] In some implementations, the delivery tool includes an adhesive applicator, and / or manipulating the adhesive includes, using the adhesive applicator, applying the adhesive to the fabric while the barbs remain in the tissue to adhere the fabric to the tissue.
[0273] In some implementations, the method further includes, subsequently to the step of applying the adhesive, activating the adhesive by applying a chemical agent to the adhesive to adhere the fabric to the tissue.
[0274] In some implementations: the adhesive is a protein-based bioadhesive, and / or applying the chemical agent to the bioadhesive facilitates cross-linking of amino acid residues of the protein to adhere the fabric to the tissue.
[0275] In some implementations, manipulating the adhesive includes, using an energy- applicator, activating the adhesive by applying energy to the adhesive while the barbs remain in the tissue to adhere the fabric to the tissue.
[0276] In some implementations, applying energy includes applying electromagnetic energy to the adhesive while the barbs remain in the tissue to adhere the fabric to the tissue.
[0277] In some implementations: the energy-applicator is an extracorporeal energy- applicator; and / or activating includes, using the extracorporeal energy-applicator, activating the adhesive by applying energy to the adhesive from outside of the subject while the barbs remain in the tissue to adhere the fabric to the tissue.
[0278] In some implementations, the method further includes, using the delivery tool, transluminally advancing the energy-applicator toward the tissue; and / or wherein activating includes, using the energy-applicator, activating the adhesive by driving the energy- applicator to apply energy to the adhesive from within the cardiovascular system.
[0279] In some implementations, activating includes activating the adhesive by applying electrical current to the adhesive while the barbs remain in the tissue.
[0280] In some implementations: the implant includes an implant-electrode; and / or applying electrical current to the adhesive includes applying voltage to the implant-electrode such that current flows from the implant-electrode and through the adhesive, thereby activating the adhesive.
[0281] In some implementations: the delivery tool includes a return electrode; and / or applying electrical current to the adhesive includes applying voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive and to the return electrode, thereby activating the adhesive.
[0282] In some implementations: the implant-electrode is a first implant-electrode; the implant further includes a second implant-electrode; and / or applying electrical current to the adhesive includes applying voltage to: the first implant-electrode such that current flows from the first implant-electrode and through a first portion of the adhesive, thereby activating the first portion of the adhesive, and / or the second implant-electrode such that current flows from the second implant-electrode and through a second portion of the adhesive, thereby activating the second portion of the adhesive.
[0283] There is further provided, in accordance with some implementations, a method for use at a tissue of a simulated cardiovascular system of a subject, the method including, using a delivery tool: transluminally advancing an implant including a barbed fabric to the tissue, and holding the fabric against the tissue such that barbs of the fabric penetrate the tissue.
[0284] In some implementations, the method includes, while the barbs remain in the tissue, manipulating an adhesive to adhere the fabric to the tissue; and / or subsequently, removing the delivery tool from the subject.
[0285] There is further provided, in accordance with some implementations, a system for use at a tissue of a cardiovascular system of a subject, the system including: a fabric defining barbs that protrude from a face of the fabric and / or an adhesive.
[0286] In some implementations, the system includes a transluminally advanceable delivery tool including a scaffold.
[0287] In some implementations, the scaffold is configured to temporarily restrain the face of the fabric against the tissue such that the barbs penetrate the tissue.
[0288] In some implementations, the delivery tool is configured to adhere the fabric to the tissue by manipulating the adhesive, and / or transluminally withdraw the scaffold from the subject.
[0289] In some implementations, at least one of the fabric, the adhesive and the delivery tool is sterile.
[0290] In some implementations, the adhesive is pre-disposed on the fabric.
[0291] In some implementations, the delivery tool further includes an adhesive applicator.
[0292] In some implementations, the fabric is bioabsorbable.
[0293] In some implementations, the scaffold is configured to temporarily restrain the face of the fabric against the tissue by sandwiching the tissue between the scaffold and the fabric, such that the barbs penetrate the tissue.
[0294] In some implementations, the delivery tool is configured to adhere the fabric to the tissue by manipulating the adhesive while the scaffold restrains the face of the fabric against the tissue such that the barbs penetrate the tissue.
[0295] In some implementations, the delivery tool is configured to: adhere the fabric to the tissue by manipulating the adhesive while the scaffold restrains the face of the fabric against the tissue such that the barbs penetrate the tissue, and / or subsequently, transluminally withdraw the scaffold from the subject, leaving the fabric adhered to the tissue.
[0296] In some implementations, the delivery tool further includes an adhesive applicator, configured to apply the adhesive to the fabric while the scaffold restrains the face of the fabric against the tissue such that the barbs penetrate the tissue.
[0297] In some implementations, the fabric and the scaffold are configured such that penetration of the tissue by the barbs, while the scaffold restrains the face of the fabricagainst the tissue, is such that upon release of the tissue by the scaffold, the barbs retain the fabric in contact with the tissue.
[0298] In some implementations, leaflets of a native valve of the cardiovascular system defines the tissue, and / or the scaffold includes a leaflet-clip, configured to temporarily restrain the face of the fabric against the leaflets such that the barbs penetrate the leaflets.
[0299] In some implementations, the fabric and the scaffold are configured such that penetration of the leaflets by the barbs, while the scaffold restrains the face of the fabric against the leaflets, is such that upon release of the leaflets by the scaffold, the barbs retain the fabric in contact with the leaflets during a cardiac cycle of the cardiovascular system.
[0300] In some implementations, the adhesive is a chemically-activated adhesive, the system further includes an activator, and / or the delivery tool includes a nozzle, configured to chemically activate the adhesive by applying the activator to the adhesive.
[0301] In some implementations: the adhesive is a mussel foot protein-based bioadhesive, and / or the activator is configured to activate the bioadhesive by cross-linking amino acid residues of the mussel foot protein.
[0302] In some implementations, the adhesive is an energy-activated adhesive, and / or the system further includes an energy-applicator, configured to adhere the fabric to the tissue by applying energy to the adhesive.
[0303] In some implementations, the energy-applicator is an extracorporeal energy- applicator, configured to activate the adhesive by applying energy to the adhesive from outside of the subject.
[0304] In some implementations, the delivery tool includes the energy-applicator, which is configured to adhere the fabric to the tissue by applying energy to the adhesive from within the cardiovascular system.
[0305] In some implementations, the energy-applicator is configured to adhere the fabric to the tissue by applying electromagnetic energy to the adhesive from within the cardiovascular system.
[0306] In some implementations, the energy-applicator is configured to adhere the fabric to the tissue by applying heat to the adhesive from within the cardiovascular system.
[0307] In some implementations, the energy-applicator is configured to adhere the fabric to the tissue by applying electrical current to the adhesive from within the cardiovascular system.
[0308] In some implementations: the system includes an implant that includes the fabric and an implant-electrode; and / or the energy-applicator is configured to apply electricalcurrent to the adhesive by applying voltage to the implant-electrode such that current flows from the implant-electrode and through the adhesive, thereby activating the adhesive.
[0309] In some implementations, the implant-electrode is disposed on the face of the fabric.
[0310] In some implementations, the implant-electrode is embedded within the adhesive on the face of the fabric.
[0311] In some implementations: the delivery tool includes a return electrode; and / or the energy-applicator is configured to apply electrical current to the adhesive by applying voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive and to the return electrode, thereby activating the adhesive.
[0312] In some implementations: the implant-electrode is a first implant-electrode; the implant further includes a second implant-electrode; and / or the energy-applicator is configured to apply electrical current to the adhesive by applying voltage to: the first implant-electrode such that current flows from the first implant-electrode and through a first portion of the adhesive, thereby activating the first portion of the adhesive, and / or the second implant-electrode such that current flows from the second implant-electrode and through a second portion of the adhesive, thereby activating the second portion of the adhesive.
[0313] In some implementations, the scaffold includes a shape-memory material having a compressed state and an expanded state, and / or the delivery tool is configured to: deliver the scaffold to the tissue while the scaffold is in the compressed state, and / or deploy the scaffold at the tissue such that the scaffold engages the tissue as the scaffold transitions from the compressed state to the expanded state.
[0314] In some implementations, the delivery tool is configured to deploy the scaffold at the tissue such that the scaffold restrains the face of the fabric against the tissue such that the barbs penetrate the tissue, as the scaffold transitions from the compressed state to the expanded state.
[0315] In some implementations: leaflets of a native valve of the cardiovascular system defines the tissue, the scaffold includes a leaflet-clip, and / or the delivery tool is configured to deploy the leaflet-clip at the leaflets such that, during a cardiac cycle of the cardiovascular system, the leaflet-clip restrains the face of the fabric against the leaflets such that the barbs penetrate the leaflets as the leaflet-clip transitions from the compressed state to the expanded state.
[0316] In some implementations: the delivery tool includes a catheter, configured to house the scaffold while the scaffold is in the compressed state, and / or the delivery tool isconfigured to retract the scaffold into catheter such that the scaffold transitions from the expanded state to the compressed state, prior to transluminally withdraw the scaffold from the subject.
[0317] In some implementations, the fabric is a woven fabric including: a weft yarn, and / or multiple warp yarns, including: first warp yarns extending from a first end of the fabric to a second end of the fabric, and / or second warp yarns, each of the second warp yarns being cut in a manner that defines at last one of the barbs.
[0318] In some implementations, each of the second warp yarns includes steel.
[0319] In some implementations, each of the second warp yarns includes nitinol.
[0320] In some implementations, each of the second warp yarns includes nylon.
[0321] In some implementations, each of the second warp yarns is a monofilament yarn.
[0322] In some implementations, each of the first warp yarns is a polyfilament yarn.
[0323] In some implementations, the weft yarn is a polyfilament yarn.
[0324] In some implementations, each of the second warp yarns includes a polyester resin.
[0325] In some implementations, the first warp yarns have a different composition from the second warp yarns.
[0326] In some implementations, the weft yarn has a different composition from the first warp yarns and the second warp yarns.
[0327] In some implementations, the weft yarn has the same composition as the first warp yarns.
[0328] In some implementations, the fabric includes a laminate disposed on a back of the fabric.
[0329] In some implementations, the laminate includes a high weight polyethylene.
[0330] In some implementations, the laminate includes a thermoplastic polyurethane.
[0331] In some implementations, the laminate has the same composition as at least one of the barbs.
[0332] There is further provided, in accordance with some implementations, a system for use at a heart of a subject, the system including: an implant including, on an exterior of the implant, a fabric defining barbs; and / or a delivery tool, configured to secure the implant to tissue of the heart by pressing the fabric against the tissue such that the barbs penetrate the tissue.
[0333] In some implementations, the implant includes a prosthetic heart valve.
[0334] There is further provided, in accordance with some implementations, a system for use in a heart of a subject, the system including: an implant, the implant including: an implant body and an energy-activated adhesive disposed at the implant body.
[0335] In some implementations, the implant includes an implant-electrode that is disposed at the adhesive.
[0336] In some implementations, the system includes a delivery tool, configured to transluminally position a contact-portion of the implant at a tissue of the heart while electrically connected to the implant-electrode.
[0337] In some implementations, the delivery tool is configured to, using the implant- electrode, detect contact between the contact-portion and the tissue.
[0338] In some implementations, the delivery tool is configured to activate the adhesive to adhere the implant body to the tissue by driving the implant-electrode to apply energy to the adhesive.
[0339] In some implementations, at least one of the implant and the delivery tool is sterile.
[0340] In some implementations, the implant-electrode is disposed at the contact- portion.
[0341] In some implementations, the adhesive is disposed at the contact-portion.
[0342] In some implementations, the delivery tool is configured to, responsively to detecting contact between the contact-portion and the tissue, move the implant-electrode toward the tissue.
[0343] In some implementations, the implant-electrode is embedded within the adhesive.
[0344] In some implementations, the delivery tool is configured to automatically drive the implant-electrode to apply energy to the adhesive, responsively to detecting contact between the contact-portion and the tissue.
[0345] In some implementations, the delivery tool is configured to provide a notification, responsively to detecting contact between the contact-portion and the tissue.
[0346] In some implementations: the contact-portion is a first contact-portion of the implant; the implant-electrode is a first implant-electrode disposed at the first contact- portion; the implant further includes a second implant-electrode disposed at a second contact-portion of the implant; and / or the delivery tool is configured to: adhere the firstcontact-portion to the tissue by driving the first implant-electrode to apply energy to adhesive at the first contact-portion, and / or adhere the second contact-portion to the tissue by driving the second implant-electrode to apply energy to adhesive at the second contact- portion.
[0347] In some implementations: the implant-electrode is a first implant-electrode; the implant further includes a second implant-electrode; and / or the delivery tool is configured to activate the adhesive by driving the first implant-electrode such that energy flows from the first implant-electrode, through the adhesive, to the second implant-electrode.
[0348] In some implementations: the implant-electrode includes: an activation-electrode configured to apply energy to the adhesive, and / or a sensing-electrode that is configured to receive a signal indicative of contact between the contact-portion and the tissue; and / or the delivery tool is configured to: drive the sensing-electrode to receive the signal indicative of contact between the contact-portion and the tissue, and / or activate the adhesive to adhere the implant body to the tissue by driving the activation-electrode to apply energy to the adhesive.
[0349] In some implementations: the implant-electrode is a first implant-electrode, at a first portion of the adhesive; the implant further includes a second implant-electrode, at a second portion of the adhesive; and / or the delivery tool is adjustable to selectively drive one of the implant-electrodes, to apply energy to a selected portion of the adhesive.
[0350] In some implementations: the contact-portion is a first contact-portion, at which the first implant-electrode is disposed, and / or the implant defines a second contact-portion, at which the second implant-electrode is disposed.
[0351] In some implementations: the system further includes a return electrode configured to remove energy from the subject; and / or the delivery tool is configured to adhere the implant body to the tissue by driving the implant-electrode such that energy flows from the implant-electrode, through the adhesive to the return electrode, thereby activating the adhesive.
[0352] In some implementations, the delivery tool includes the return electrode.
[0353] In some implementations, the implant includes the return electrode.
[0354] In some implementations: the delivery tool is configured to, using the implant- electrode, detect contact between the contact-portion and the tissue by driving the implant- electrode to apply energy through the tissue and to the return electrode.
[0355] In some implementations: the return electrode is a first return electrode; the system further includes a second return electrode; and / or the delivery tool is configured to,using the implant-electrode, detect contact between the contact-portion and the tissue by driving the implant-electrode to apply energy through the tissue and to the second return electrode.
[0356] In some implementations, the delivery tool includes the first return electrode.
[0357] In some implementations, the implant includes the first return electrode.
[0358] In some implementations, the second return electrode is configured to contact a skin surface of the subject while the contact-portion is positioned at the tissue of the heart.
[0359] In some implementations, the system has: a bioimpedance-measuring mode in which the delivery tool drives the implant-electrode such that energy flows from the implant- electrode, through the tissue and to the return electrode; and / or an adhesive-curing mode in which the delivery tool drives the implant-electrode such that energy flows from the implant- electrode, through the adhesive to the return electrode.
[0360] In some implementations, the deliver tool is configured to drive the implant- electrode to apply greater amount of energy to the adhesive while the system is in the adhesive-curing mode than while the system is in the bioimpedance-measuring mode.
[0361] In some implementations, the delivery tool is operable to transition between: a navigation mode in which the implant-electrode receives endogenic electrical signals within the heart; and / or an adhesive-curing mode in which the delivery tool drives the implant- electrode such that energy flows from the implant-electrode, through the adhesive to the return electrode.
[0362] In some implementations, the system is configured to, responsively to the received endogenic electrical signals, calculate a location of the implant-electrode.
[0363] In some implementations, the system further includes an external power supply, and / or wherein the implant includes a terminal that is configured to receive the energy from the power supply, and to direct the energy to the implant-electrode.
[0364] In some implementations, the delivery tool is configured to transluminally transmit energy from the power supply, via a wired connection with the terminal, to the implant.
[0365] In some implementations, the power supply is configured to transmit energy via a wireless connection with the terminal, to the implant.
[0366] In some implementations: the contact-portion defines a tissue-engaging element, and / or the delivery tool is configured to mechanically attach the implant to the tissue via the tissue-engaging element, prior to driving the implant-electrode to apply energy to the adhesive.
[0367] In some implementations: the tissue-engaging element includes a clip; and / or the delivery tool is configured to mechanically attach the implant to the tissue by closing the clip on the tissue, prior to driving the implant-electrode to apply energy to the adhesive.
[0368] There is further provided, in accordance with some implementations, a method for use with a heart of a subject, the method including, using a delivery tool, transluminally advancing an implant to the heart, the implant including: an implant body defining a contact-portion, and an energy-activated adhesive, disposed at the implant body.
[0369] In some implementations, the implant includes an implant-electrode, electrically connected to the delivery tool.
[0370] In some implementations, the method includes positioning the contact-portion at a tissue of the heart, and while the contact-portion remains positioned at the tissue, driving the implant-electrode to detect contact between the contact-portion and the tissue.
[0371] In some implementations, the method includes positioning the contact-portion at a tissue of the heart, and while the contact-portion remains positioned at the tissue, activating the adhesive to adhere the implant body to the tissue by driving the implant- electrode to apply energy to the adhesive.
[0372] In some implementations, the method further includes sterilizing the implant and the delivery tool.
[0373] In some implementations, the method further includes, responsively to detecting contact between the contact-portion and the tissue, mechanically attaching the implant to the tissue.
[0374] In some implementations, positioning the contact-portion at the tissue includes positioning the implant-electrode at the tissue.
[0375] In some implementations, the method further includes, responsively to detecting contact between the contact-portion and the tissue, repositioning the implant.
[0376] In some implementations, the method further includes providing a notification, responsively to detecting contact between the contact-portion and the tissue.
[0377] In some implementations: the implant-electrode is a first implant-electrode; the implant further includes a second implant-electrode; and / or activating the adhesive includes driving the first implant-electrode such that energy flows from the first implant-electrode, through the adhesive, to the second implant-electrode.
[0378] In some implementations, driving the implant-electrode includes, responsively to detecting contact between the contact-portion and the tissue, driving the implant-electrode to apply energy to the adhesive.
[0379] In some implementations, driving the implant-electrode includes automatically driving the implant-electrode to apply energy to the adhesive, responsively to detecting contact between the contact-portion and the tissue.
[0380] In some implementations, the method further includes operating the delivery tool to, via the implant-electrode, detect endogenic electrical signals within the heart.
[0381] In some implementations, the method further includes, responsively to the detected endogenic electrical signals, calculating a location of the implant-electrode.
[0382] In some implementations: activating the adhesive to adhere the implant body to the tissue by driving the implant-electrode includes: driving a first implant-electrode to apply energy to a first portion of the adhesive, and / or driving a second implant-electrode to apply energy to a second portion of the adhesive.
[0383] In some implementations: driving the first implant-electrode includes driving the first implant-electrode to apply energy to the first portion of the adhesive at a first contact- portion of the implant, and / or driving the second implant-electrode includes driving the second implant-electrode to apply energy to the second portion of the adhesive at a second contact-portion of the implant.
[0384] In some implementations, the method further includes, responsively to detecting contact between the contact-portion and the tissue, moving the implant-electrode toward the tissue.
[0385] In some implementations, moving the implant-electrode toward the tissue includes mechanically attaching the implant to the tissue.
[0386] In some implementations, moving the implant-electrode toward the tissue includes sandwiching the tissue between the contact-portion and the implant-electrode.
[0387] In some implementations, driving the implant-electrode includes applying electrical energy to the implant-electrode.
[0388] In some implementations: driving the implant-electrode to detect contact between the contact-portion and the tissue includes applying a lower voltage to the implant- electrode; and / or driving the implant-electrode to apply energy to the adhesive includes applying a higher voltage to the implant-electrode.
[0389] In some implementations: the implant-electrode includes an activation-electrode and a sensing-electrode; driving the implant-electrode to detect contact between the contact- portion and the tissue includes applying the lower voltage to the sensing-electrode; and / or driving the implant-electrode to apply energy to the adhesive includes applying the higher voltage to the activation-electrode.
[0390] In some implementations: driving the implant-electrode to detect contact between the contact-portion and the tissue includes driving the implant-electrode to apply energy through the tissue to a first return electrode; and / or driving the implant-electrode to apply energy to the adhesive includes driving the implant-electrode to apply energy through the adhesive to a second return electrode.
[0391] In some implementations, the method further includes, prior to activating the adhesive: ungrounding the first return electrode, and / or grounding the second return electrode.
[0392] In some implementations, the method further includes placing the first return electrode in contact with a skin surface of the subject.
[0393] In some implementations, the method further includes placing the first return electrode within the subject.
[0394] In some implementations: the method further includes, using the delivery tool, transmitting energy from an external power supply to a terminal of the implant; and / or via the terminal, directing the energy to the implant-electrode.
[0395] In some implementations: transmitting includes transluminally transmitting energy from the external power supply, via a wired connection, to the terminal; and / or the method further includes, subsequently to activating the adhesive: severing the wired connection, and / or withdrawing the delivery tool from the subject.
[0396] In some implementations, transmitting includes wirelessly transmitting energy from the external power supply to the terminal.
[0397] There is further provided, in accordance with some implementations, a method for use with a simulated heart of a subject, the method including, using a delivery tool, transluminally advancing an implant to the heart, the implant including: an implant body defining a contact-portion, and an energy-activated adhesive, disposed at the implant body.
[0398] In some implementations, the implant includes an implant-electrode, electrically connected to the delivery tool.
[0399] In some implementations, the method includes positioning the contact-portion at a tissue of the heart, and while the contact-portion remains positioned at the tissue, driving the implant-electrode to detect contact between the contact-portion and the tissue.
[0400] In some implementations, the method includes positioning the contact-portion at a tissue of the heart, and while the contact-portion remains positioned at the tissue, activating the adhesive to adhere the implant body to the tissue by driving the implant- electrode to apply energy to the adhesive.
[0401] Any of the techniques, methods, operations, steps, etc. described or suggested herein can be performed on a living animal (e.g., human, other mammal, etc.) or on a non- living simulation such as a cadaver, a cadaver heart, an anthropomorphic ghost, and / or a simulator device (which may include computerized and / or physical representations of body parts, tissue, etc.).
[0402] The present disclosure will be more fully understood from the following detailed description of applications thereof, taken together with the drawings, in which: BRIEF DESCRIPTION OF THE DRAWINGS
[0403] Fig.1 is a schematic illustration showing a system for use with a heart of a subject, in accordance with some applications;
[0404] Figs.2A–C, 3A–C and 4A–C are schematic illustrations showing use of the system to improve function of the heart, in accordance with some applications;
[0405] Figs.5A–B, 6A–B, 7A–B, 8A–B, 9A–B and 10 are schematic illustrations showing applications of bioprinted implants, in accordance with some applications;
[0406] Figs.11, 12A–B, 13A–D, 14, 15A–C, 16A–D, 17–20, 21A–D, 22 and 23A-F are schematic illustrations showing systems for delivering implants comprising energy- applicators, in accordance with some applications;
[0407] Fig.24 schematically illustrates a system for guiding a catheter within the heart, in accordance with some applications;
[0408] Figs.25A–G, 26A–B, 27A–B, 28A–B and 29A–E are schematic illustrations showing steps of preparing fabrics for use in an implant, in accordance with some applications;
[0409] Figs.30–33 are schematic illustrations showing use of fabric at a native valve of the cardiovascular system, in accordance with some applications; and
[0410] Figs.34, 35A–H and 36A–D are schematic illustrations showing use of a system comprising a delivery tool for implanting an implant to tissue of the cardiovascular system, in accordance with some applications. DETAILED DESCRIPTION
[0411] The present disclosure includes different variants of some elements. Variants of a given element typically have the same structure and / or function as each other except for any differences described. For any given element for which different variants are disclosed, the identical name is used for each variant, in order to denote that they are, in fact, variants of the same given element. Unless stated otherwise, applications of the devices, systems, andtechniques described herein may include any arrangement in which one variant of an element is substituted with another identically-named variant of that element. Furthermore, throughout the figures, suffixes are used to denote different variants of the same element. Unless stated otherwise, such variants may be substituted with each other, mutatis mutandis. That is, unless stated otherwise, any element having a given reference numeral may be substituted with any other element (e.g., any other variant of the element) having the same reference numeral, independent of any suffix.
[0412] In order to avoid undue clutter from having too many reference numbers and lead lines on a particular drawing, some elements are introduced via one or more drawings and not explicitly identified in every other drawing that contains that element.
[0413] The described systems, apparatuses, devices, methods, etc. should not be construed as limiting in any way. Instead, the present disclosure is directed toward all novel and nonobvious features and aspects of the various disclosed implementations and applications, alone and in various combinations and sub-combinations with one another. The disclosed systems, apparatuses, devices, methods, etc. are not limited to any specific aspect, feature, or combination thereof, nor do the disclosed systems, apparatuses, devices, methods, etc. require that any one or more specific advantages be present or problems be solved.
[0414] Reference is made to Fig.1, which is a schematic illustration showing a system 100 for use with a heart 4 of a subject, in accordance with some applications. In some implementations, and as described hereinbelow, system 100 comprises a bioprinter 110 that is used to print an implant (e.g., a component of an implant assembly) within heart 4.
[0415] In some implementations, and as shown, bioprinter 110 is used to minimally- invasively print implant 150 within heart 4. In some such implementations, and as shown, at least a portion of bioprinter 110 (e.g., a console 111 comprising a display 112 and / or a processor 114) is located outside of the subject, and a portion of the bioprinter (e.g., a nozzle 116 thereof) is transluminally advanced to heart 4. For example, and as shown, nozzle 116 is advanced through a catheter 120 (e.g., through an extracorporeally manipulated proximal portion 122 of the catheter), such that the nozzle extends from a distal portion 124 of the catheter, within heart 4.
[0416] In some implementations, and as shown in the inset of Fig.1, nozzle 116 extends distally from the catheter’s distal opening 125, toward a target site 50 within heart 4. As shown, the catheter’s distal portion 124 is advanced (e.g., transeptally) to left atrium 6, and nozzle 116 extends distally from the catheter, between leaflets 12, 14 of mitral valve 10, such that the nozzle’s distal opening 118 is positioned within the left ventricle 8. In some suchimplementations, nozzle 116 can be manipulated within heart 4 in three dimensions (e.g., the nozzle can have three or more degrees of freedom), via console 111.
[0417] Reference is made to Figs.2A–C, 3A–C and 4A–C, which are schematic illustrations showing use of system 100 to improve function of heart 4, in accordance with some applications. In some implementations, and as described hereinbelow, while nozzle 116 extends from the catheter’s distal portion 124, a bioink 140 (e.g., a hydrogel-based bioink comprising a biomaterial 142 such as collagen, gelatin and / or living cells) is extruded from the nozzle (e.g., from the nozzle’s distal opening 118) into the heart at the target site 50, such that the biomaterial assumes a three-dimensional implant-shape.
[0418] In some implementations, biomaterial 142 spontaneously undergoes fixation (e.g., the biomaterial polymerizes by units of the biomaterial spontaneously cross-linking) after bioink 140 has been released from nozzle 116, such that the biomaterial retains the implant-shape. In some such implementations, bioink 140 comprises a chemical inhibitor that inhibits cross-linking of units of biomaterial 142 while the bioink is contained within nozzle 116, facilitating flow of the bioink within the nozzle. For example, contact of bioink 140 with tissue (e.g., with blood) may cause the inhibitor to dissolve and / or may inactivate at least a portion of the inhibitor, thereby allowing the biomaterial to retain the implant-shape after being extruded from nozzle 116.
[0419] In some implementations, biomaterial 142 is actively fixated by application of energy (e.g., thermal and / or light energy) to bioink 140, e.g., via an energy-applying sublumen (not shown) of nozzle 116. Alternatively or in addition, biomaterial 142 may be actively fixated by application of a chemical fixator - e.g., from a fixator-applying sublumen (not shown) of nozzle 116. For example, a biomaterial 142 containing fibrinogen may be extruded from the nozzle’s distal opening 118, and a fixative comprising thrombin and / or calcium may be released from the nozzle’s fixator-applying sublumen, thereby causing the fibrinogen to coagulate into fibrin.
[0420] In some implementations, bioink 140 is extruded from nozzle 116 and / or fixated while the bioink is disposed within a removable isolation chamber (not shown). In some such implementations, at least partially isolating bioink 140 from bloodflow within the heart increases the efficiency at which biomaterial 142 is fixated, thereby reducing the amount of chemical fixator or fixating energy required in order to fixate the biomaterial.
[0421] In accordance with some implementations, Fig.2A shows nozzle 116 extending from the catheter’s distal portion 124 such that the nozzle’s distal opening 118 is adjacent to a tissue site 50a at wall 9 of ventricle 8. Typically for such implementations, and as shown, bioink 140 is extruded from the nozzle’s distal opening 118 at tissue site 50a. In some suchimplementations, bioink 140 (e.g., biomaterial 142 thereof) adheres to tissue at site 50a. For example, biomaterial 142 may spontaneously adhere to the tissue after being extruded from nozzle 116, as a result of the biomaterial’s properties. Alternatively or in addition, biomaterial 142 may adhere to the tissue by application of energy and / or a chemical fixator, e.g., as described hereinabove regarding fixation of the biomaterial.
[0422] In accordance with some implementations, Fig.2B shows a portion of the extruded biomaterial 142 having undergone fixation such that the biomaterial begins to assume a three-dimensional shape defining an implant 150a. In some such implementations, and as shown, by adhering to tissue of the ventricle’s wall 9, the fixated biomaterial serves as the implant’s anchor 154a. Anchor 154a is shown in fluid communication with bioink 140 that is less fixated than the anchor. That is, biomaterial 142 of bioink 140 may either be entirely non-fixated or may be relatively less fixated than the biomaterial comprising anchor 154a.
[0423] In accordance with some implementations, Fig.2C shows additional bioink 140 having been extruded from nozzle 116, such that biomaterial 142 defines implant 150a, e.g., in the implant’s entirety. As shown, a portion of biomaterial 142 defines a second anchor 154b that is adhered to a second site 50b of tissue of the heart, e.g., to chordae 16 and / or a leaflet 12, 14 of the heart. In some such implementations, and as shown, first and second anchors 154a, 154b are connected by a span of biomaterial 142 that defines a tether 158. For example, tether 158 may restrict deflection of one or both leaflets 12, 14, e.g., in an upstream direction. In this way, implant 150a may supplement and / or repair native chordae of the heart, thereby limiting a distance between leaflet 12, 14 and anchor 154a as the heart cycles between systole and diastole.
[0424] In some implementations, and as shown in Fig.2C, nozzle 116 is withdrawn proximally into catheter 120 after printing implant 150a. In some such implementations, catheter 120 is steered to advance nozzle 116 to additional target sites within the subject, (e.g., within heart 4) at which the nozzle may again be advanced distally from the catheter for printing another implant. Catheter 120 and nozzle 116 may then be transluminally withdrawn from the subject.
[0425] It is to be noted that, although nozzle 116 and its movement are shown simplistically, in some implementations nozzle 116 may be (or may be a component of) a print head that iteratively moves (e.g., sweeps) in multiple passes in order to build up the resulting structure. For example, during each pass the nozzle may deposit a small (e.g., microscopic) amount of bioink 140 in order to build up the resulting macroscopic structure.
[0426] Figs.3A–C show use of a modified nozzle 116a to implant a hybrid implant 150b in the heart. Nozzle 116a and implant 150b are in many ways identical to nozzle 116 and implant 150a described hereinabove, and the description below will therefore focus on specific features of nozzle 116a and implant 150b.
[0427] In some implementations, and as shown, implant 150b comprises a nonprinted prosthesis 130 (e.g., a clip 132, as shown) in addition to biomaterial 142. In some such implementations, nonprinted prosthesis 130 is mounted on a distal portion 117b of nozzle 116b while the nozzle is advanced to target site 50. For example, and as shown, nonprinted prosthesis 130 may be shaped and / or positioned on the nozzle’s distal portion 117 such that bioink 140 can be extruded from the nozzle’s distal opening 118 through and / or around the nonprinted prosthesis 130 (Figs.3A–B). In some such implementations, extruding bioink 140 through and / or around nonprinted prosthesis 130 aids in adhering biomaterial 142 to the nonprinted prosthesis.
[0428] In some implementations, nonprinted prosthesis 130 is fastened to tissue of heart 4. In some such implementations, and as shown in Fig.3C, clip 132 is fastened to the heart, e.g., to a tip-portion 13 of posterior leaflet 12. For example, and as shown, biomaterial 142 defines a tether 158 that tethers anchor 154 to the leaflet’s tip-portion 13 via clip 132. In this way, implant 150b and clip 132 together comprise an implant assembly 160b, e.g., a replacement chordae implant assembly. Implant assembly 160b may supplement and / or repair native chordae of the heart, thereby limiting a distance between leaflet 12 and anchor 154 as the heart cycles between systole and diastole.
[0429] In accordance with some implementations, Figs.4A–C show use of nozzle 116 to print implants 150c, 150d for securing a prosthesis to the heart. In some such implementations, and as shown, implants 150c, 150d are used to secure a prosthetic valve 134 at native valve 10. Implants 150c, 150d are in many ways similar to implants 150a, 150b described hereinabove, and the description below will therefore focus on specific features of implants 150c, 150d.
[0430] In some implementations, and as shown in Fig.4A, Prosthetic valve 134 is implanted to native valve 10 before implants 150c, 150d are fully printed. In some such implementations, prosthetic valve 134 is implanted by a separate delivery tool (not shown), or catheter 120 may be modified to facilitate delivery of the prosthetic valve, mutatis mutandis. For example, and as shown, nozzle 116 can be advanced through a lumen defined by prosthetic valve 134, which affords the nozzle access to the target site 50 at which anchor 154 is printed (Fig.4A).
[0431] In some implementations, and as shown in Fig.4B, nozzle 116 is steerable e.g., the nozzle is actively steered by the user, via the catheter’s proximal portion 122 and / or the bioprinter’s console 111 (Fig.1). In some such implementations, and as shown, steering nozzle 116 facilitates application of bioink 140 to prosthetic valve 134, such that implant 150c defines a tether 158c between anchor 154c and the prosthetic valve.
[0432] In some implementations, implant 150c may be found to sufficiently secure prosthetic valve 134 at native valve 10. In some implementations, as shown in Fig.4C, nozzle 116 is further used to print a second implant 150d that is similar to implant 150c. In some such implementations, and as shown, implants 150c, 150d are printed opposite each other, such that tethers 158c, 158d connect prosthetic valve 134 to respective anchors 154c, 154d, thereby securing the prosthetic valve in place at native valve 10. In this way, prosthetic valve 134 and tethers 158c, 158d comprise together an implant assembly 160c that functions in place of the native mitral valve 10.
[0433] Reference is made to Figs.5A–B, 6A–B, 7A–B, 8A–B, 9A–B and 10, which are schematic illustrations showing applications of bioprinted implants 150e, 150f, 150g, 150h, 150i, 150j, 150k, 150l, in accordance with some applications.
[0434] In some implementations, and as shown in Figs.5A–B and 6A–B, implants 150e, 150f, 150g are used to change a dimension of heart 4, e.g., during at least part of the cardiac cycle. In some such implementations, a dimension of heart 4 (e.g., a width of a ventricle 8 or of an annulus 11) changes reciprocatingly during the cardiac cycle, and implants 150e, 150f, 150g limit change of the dimension. For example, and as shown, each implant 150e, 150f, 150g can comprise a pair of anchors 154, each of which is printed at a respective tissue site 50a, 50b. In this way, each anchor 154 adheres to tissue at one of the sites, and a tether 158 connects between the anchors, thereby restricting movement of tissue sites 50a, 50b during the cardiac cycle.
[0435] In accordance with some implementations, Figs.5B and 6B show each implant’s tether 158 under tension, such that the tether limits a distance between tissue sites 50a, 50b. In some such implementations, tether 158 is reciprocatingly tensioned and relaxed as the heart changes shape during the cardiac cycle. For example, tether 158 can have a constant length, such that tether 158 is tensioned during part of the cardiac cycle. Alternatively, tether 158 (e.g., biomaterial 142 thereof) can have elasticity that allows the tether to lengthen to a certain degree in response to tension, which may keep the tether under tension during a greater part of the cardiac cycle.
[0436] In some implementations, and as shown in Figs.5A–B, tissue sites 50a and 50b are located on wall 9 of left ventricle 8, e.g., on opposite sides of the ventricular wall’s innersurface. Fig.5A shows left ventricle 8 of the heart that is undesirably wide during ventricular diastole, and Fig.5B shows implant 150e having reduced the heart’s ventricular width during ventricular diastole.
[0437] In some implementations, and as shown in Figs.6A–B, more than one implant may be bioprinted in heart 4. In some such implementations, and as shown, implants 150f, 150g span pairs of tissue sites 50a, 50b and 50c, 50d that are located on annulus 11 of mitral valve 10. Fig.6A shows leakage zones 30 between the mitral valve’s leaflets 12, 14, which enable retrograde bloodflow therethrough during ventricular systole. Fig.6B shows tensioned implants 150f, 150g, which reduce a width of annulus 11 during ventricular systole, thereby drawing leaflets 12, 14 into coaptation and reducing or eliminating retrograde bloodflow.
[0438] Reference is again made to Figs.7A–B, which are schematic illustrations showing an application of bioprinted implant 150h, in accordance with some applications. Fig.7A shows a leakage zone 30 that allows retrograde bloodflow between leaflets 12, 14 of mitral valve 10 during ventricular systole, e.g., due to dilation of the mitral valve’s annulus 11. Fig. 7B shows implant 150h having adhered to respective tip-portions 13, 15 of leaflets 12, 14, thereby drawing the leaflets into coaptation and reducing or eliminating retrograde bloodflow.
[0439] Reference is again made to Figs.8A–B, 9A–B and 10, which are schematic illustrations showing applications of bioprinted implants 150i, 150j, 150k, 150l, in accordance with some applications. In some implementations, and described hereinbelow, bioink 140 is extruded to define implants 150i, 150j, 150k, 150l that serve as plugs 156 that inhibit bloodflow therethrough.
[0440] Fig.8A is a cross-sectional view of heart 4 in which leakage zone 30 at the mitral valve’s commissures 34 allow retrograde bloodflow during ventricular systole. In accordance with some implementations, Fig.8B shows implants 150i, 150j having been extruded at respective commissures 34, such that biomaterial 142 defines commissural plugs 156 that reduce or eliminate retrograde bloodflow therethrough.
[0441] In accordance with some implementations, Fig.9A shows nozzle 116 having been advanced via catheter 120, to left atrial appendage 40. Fig.9B shows bioink 140 having been extruded into left atrial appendage 40 such that biomaterial 142 defines a plug 156 that reduces or eliminates bloodflow into left atrial appendage 40.
[0442] Fig.10 shows bioink 140 having been extruded into an orifice in atrial septum 3, such that biomaterial 142 defines implant 150l, which serves as a plug 156 that reduces or eliminates bloodflow through the atrial septum. In some implementations, implant 150l maybe extruded following procedures (e.g., implantation of implants 150a, 150b, 150c, 150d, 150e, 150f, 150g, 150h, 150i, 150j, 150k described hereinabove) that may require puncturing atrial septum 3 in order to access the left side of the heart. Alternatively, implant 150 can be implanted to treat an organically insufficient atrial septum 3, such as a patent foramen ovale.
[0443] Reference is made to Figs.11, 12A–B, 13A–D, 14, 15A–C, 16A–D, 17–20, 21A–D, 22 and 23A-F, which are schematic illustrations showing systems 200, 200a, 200b, 200c, 200d, 200e, 200f, 200g, 200h, each system comprising an implant 250, 250a, 250b, 250c, 250d, 250e, 250f, 250g, 250h and a delivery tool 210, 210a, 210b, 210c, 210d, 210e, 210f, 210g, 210h, in accordance with some applications.
[0444] In some implementations, and described hereinbelow, an energy-activated adhesive 280 (e.g., an adhesive that can be activated by applying heat, electrical current and / or electromagnetic energy, such as ultraviolet light) is predisposed on the implant, e.g., on an implant body 254, 254a, 254b, 254c, 254d, 254e, 254f, 254g, 254h, and / or an anchor 260, 260c of the implant. In some such implementations, implant 250, 250a, 250b, 250c, 250d, 250e, 250f, 250g, 250h is supplied such that adhesive 280 defines an adhesive-coated surface of implant body 254, 254a, 254b, 254c, 254d, 254e, 254f, 254g, 254h and / or anchor 260, 260c. Alternatively or in addition, the user may apply adhesive 280 to the implant.
[0445] In some implementations, adhesive 280 has therapeutic properties, such as antibacterial, anti-inflammatory and / or antioxidant properties. In some such implementations, the adhesive’s therapeutic properties are augmented by applying energy to the adhesive.
[0446] In some implementations, delivery tool 210, 210a, 210b, 210c, 210d, 210e, 210f, 210g, 210h is used to deploy the implant such that adhesive 280 contacts tissue of the heart, and while the adhesive remains in contact with the tissue, to apply energy to the adhesive, thereby adhering the implant to the tissue by activating the adhesive. In some such implementations, the implant comprises an energy-applicator 252a, 252c, 252d, 252e, 252f, 252g, 252h that activates the adhesive by applying energy thereto. Alternatively or in addition, the delivery tool can comprise an energy-applicator 222b (Figs.15A–B) that activates the adhesive by applying energy thereto.
[0447] In some implementations, and as shown in Fig.11, driver 230 comprises a proximal handle 231 that is connected by a shaft 235 to the driver’s distal portion 234. In some implementations, and as shown, shaft 235 extends distally to a drive head 236 that reversibly interfaces with the anchor’s anchor head 262 to mechanically drive (e.g., to screw) a tissue-engaging element 264 of the anchor into the tissue.
[0448] In some implementations, a distal portion 204 of system 200 is used to transluminally deliver driver 230 via catheter 120 to the heart, and Fig.12A shows tissue- engaging element 264 of anchor 260 having been driven into the tissue, such that anchor head 262 is seated against the tissue. In some such implementations, implant 250 is driven to anchor an implant body (not shown) to the tissue.
[0449] In some implementations, system 200 transmits energy (e.g., conducts electrical energy from an external power supply) via shaft 235 to drive head 236. In some such implementations, while the drive head interfaces with anchor head 262, energy is transmitted from drive head 236 to energy-applicator 252a defined by anchor 260 (e.g., by anchor head 262 and / or tissue-engaging element 264 thereof). In this way, the interface between drive head 236 and anchor 260 can define a terminal at which driver 230 is reversibly electrically connected to energy-applicator 252a. Alternatively or in addition, energy is transmitted wirelessly (e.g., by RF or magnetic induction) to the implant’s energy- applicator 252a, which transforms the transmitted energy into current and / or heat, which in turn activates the adhesive. In some such implementations, implant 250 comprises a wireless terminal (e.g., an antenna, not shown) that receives energy 270 from delivery tool 210, and directs the energy to energy-applicator 252a.
[0450] In some implementations, the transmission of energy from driver 230 to energy- applicator 252a can be controlled extracorporeally, e.g., by operating an actuator 233 of handle 231. In some such implementations, drive head 236 can transmit energy to anchor head 262 independently of mechanically driving tissue-engaging element 264 into tissue. For example, actuating a second actuator (not shown) of handle 231 can cause drive head 236 to rotate, thereby screwing tissue-engaging element 264 into the tissue. In this way, driver 230 can selectively transmit electricity to energy-applicator 252a before, during or after driving tissue-engaging element 264 into the tissue. Alternatively, actuating a single actuator 233 can transmit energy from driver 230 to energy-applicator 252a while driving tissue-engaging element 264 into the tissue.
[0451] In some implementations, and as shown, adhesive-coated tissue-engaging element 264 serves as energy-applicator 252a, which is driven to apply activation energy to adhesive 280. In some such implementations, adhesive 280 is predisposed upon tissue- engaging element 264, such that transmitting energy to the tissue-engaging element (Fig. 12B) activates the adhesive into activated adhesive 280′ that adheres the tissue-engaging element to the tissue. For example, energy-applicator 252a can be embedded within a layer of adhesive 280, which may serve to (i) insulate the tissue from direct exposure to the energy-applicator, and / or (ii) increase the surface area at which the adhesive adheres to the tissue.
[0452] In some implementations, energy-applicator 252a applies electromagnetic radiation, e.g., the energy-applicator can define a UV-emitting LED and / or a heater resistor that increases in temperature in response to receiving electrical energy from driver 230. In some such implementations, the anchor’s head 262 is also heated, which aids in activating adhesive 280′, thereby adhering tissue-engaging element 264 to the tissue.
[0453] In some implementations, energy-applicator 252a comprises an implant- electrode, and adhesive 280 can be electrically and / or magnetically sensitive, such that driving current through the adhesive, and / or exposing the adhesive to magnetic fields, activates the adhesive.
[0454] In some implementations, and as shown, delivery tool 210 (e.g., the driver’s distal portion 234) comprises a grounded return electrode 242. In this way, transmitting energy to the energy-applicator 252a drives current from the energy-applicator, through adhesive 280 and to return electrode 242 (Fig.12B), thereby adhering tissue-engaging element 264 to the tissue.
[0455] In accordance with some implementations, the inset of Fig.12A schematically shows adhesive 280 disposed on an adhesive-coated surface of the anchor’s tissue-engaging element 264. In accordance with some such implementations, prior to activation, adhesive 280 is contained within microspheres 282. For example, microspheres 282 can limit interaction between adhesive 280 and the tissue, e.g., by sequestering an active ingredient of the adhesive within the microspheres.
[0456] In accordance with some implementations, Fig.12B schematically shows energy- applicator 252a (e.g., defined by anchor’s tissue-engaging element 264) being driven to activate the adhesive into activated adhesive 280′. In some such implementations, and as shown, application of energy 270 (e.g., electrical current and / or a magnetic field) has disrupted microspheres 282, from which adhesive 280′ has been released, thereby increasing the interaction between the adhesive and the tissue such that the adhesive adheres the implant (e.g., the anchor’s tissue-engaging element 264) to the tissue. Alternatively or in addition to releasing adhesive 280 from within microspheres 282, adhesive 280 may be activated by absorbing energy 270. For example, energy 270 can facilitate the adhesive’s curing and / or bonding between the adhesive and the tissue.
[0457] Reference is made again to Figs.13A–D, which are schematic illustrations showing use of system 200a to anchor and adhere implant 250a to native valve 10 of heart 4, in accordance with some applications. In some implementations, and as described hereinbelow, implant 250a comprises several anchors 260, each of which defines an energy- applicator 252a that is driven to activate the adhesive into activated adhesive 280′.
[0458] In accordance with some implementations, Fig.13A shows distal portion 204a of system 200a having been transluminally advanced to the heart’s left atrium 6, where the implant’s implant body 254a is shown being deployed from catheter 120 (e.g., from a distal opening 125 at the catheter’s distal portion 124) to annulus 11 of mitral valve 10. In some such implementations, implant body 254a comprises a sleeve, e.g., a contractable sleeve such as described in the following references, each of which is incorporated herein by reference in its entirety: US 8,715,342 to Zipory; and US 8,926,697 to Gross.
[0459] In accordance with some implementations, the upper inset of Fig.13A shows implant body 254a abutting a tissue site 50 at annulus 11. As shown in the lower inset, driver 230 is used to drive the anchor’s tissue-engaging element 264 into site 50, thereby mechanically attaching implant body 254a to the tissue. In some such implementations, and as shown in greater detail in Fig.12A, adhesive 280 is disposed on the anchor’s tissue- engaging element 264 (e.g., on an adhesive-coated surface thereof). For example, adhesive 280 can be inactive while tissue-engaging element 264 is driven into the tissue.
[0460] In accordance with some implementations, the upper inset of Fig.13B shows energy 270 being applied from energy-applicator 252 to activate adhesive 280′, as described hereinabove with reference to Fig.12B. In some implementations, and as shown in the lower inset of Fig.13B, a second adhesive-coated anchor 260 is extended through implant body 254a and driven into tissue at a second tissue site 50a. Thus, in some such implementations, the second anchor’s adhesive-coated surface is not yet in contact with the tissue (e.g., the second anchor is still disposed within delivery tool 210a) while the first anchor’s energy- applicator 252 activates adhesive 280.
[0461] Fig.13C shows driver 230 driving the second anchor’s energy-applicator 252a (upper inset) to activate adhesive 280′ on the second anchor’s adhesive-coated surface, such that the second anchor remains adhered to the tissue after the driver is retracted (lower inset). In some implementations, and as shown in Fig.13D, several adhesive-coated anchors 260 are driven to mechanically attach a portion of implant body 254 to annulus 11, after which, each anchor’s energy-applicator 252a is driven to activate adhesive 280′ disposed on that anchor’s tissue-engaging element 264.
[0462] Reference is made again to Figs.14, 15A–E and 16A–D, which are schematic illustrations showing an implant 250b and use of systems 200b, 200c to adhere the implant at annulus 11 of the native valve, in accordance with some applications.
[0463] In some implementations, and as shown in Fig.14, implant 250b is generally similar to implant 250a, except that implant body 254b has adhesive 280 predisposed thereupon, e.g., upon the implant body’s entire exterior surface. In some suchimplementations, implant body 254b is dimensioned to be seated at annulus 11 such that adhesive 280 is placed in contact with the annulus.
[0464] In some implementations, and shown in Figs.15A–C, segments 281b of implant body 254b are progressively extended from catheter 120, such that each segment of the implant body can be adhered to annulus 11 in a stepwise manner. In some such implementations, the deployment of implant 250d to annulus 11 is monitored, e.g., by visualizing radiopaque markers 256 using fluoroscopy.
[0465] In accordance with some implementations, the upper inset of Fig.15A shows an adhesive-coated segment 281b of implant body 254b abutting tissue site 50 of annulus 11. In some such implementations, and as shown in the lower inset, energy-applicator 222b is then advanced via catheter 120 to contact segment 281b, and driving the energy-applicator activates adhesive 280′ at the segment, thereby adhering the segment to tissue site 50.
[0466] In some implementations, and as shown in the upper inset of Fig.15B, the catheter’s distal portion 124 is repositioned in order to place a second segment 281b of implant body 254b in contact with a second site 50a at annulus 11. In some such implementations, and as shown in the lower inset of Fig.15B, energy-applicator 222b is again advanced to contact activate adhesive 280′ at the second segment. Typically for such implementations, and as shown, the second adhesive-coated segment 281b is not yet in contact with the tissue (e.g., the second segment 281b is still disposed within delivery tool 210b) while energy-applicator 222b activates adhesive 280 of the first segment 281b.
[0467] In some implementations, and as shown in Fig.15C, several segments 281b of implant body 254b are sequentially adhered to respective tissue sites of annulus 11 by driving energy-applicator 222b to activate adhesive 280′ disposed on each segment.
[0468] Figs.16A–D show system 200c being used to anchor and adhere implant 250c to the native valve’s annulus 11. In some implementations, and as shown, implant 250c comprises implant body 254b shown in Fig.14, in addition to anchors 260c. In some such implementations, anchors 260c are similar to anchors 260 described hereinabove, except that tissue-engaging element 264 of anchors 260c are not necessarily coated with adhesive. Anchors 260c comprise an energy-applicator 252c that is used to apply energy to adhesive 280 that is predisposed on implant body 254b. For example, and as shown, tissue-engaging element 264 can define energy-applicator 252c. Alternatively or in addition, the anchor’s anchor head 262 can define the energy-applicator, mutatis mutandis.
[0469] In accordance with some implementations, Fig.16A shows distal portion 204c of system 200c having been transluminally advanced to the heart’s left atrium 6, where theimplant’s implant body 254b is shown being deployed from catheter 120, to annulus 11 of mitral valve 10.
[0470] In accordance with some implementations, the upper inset of Fig.16A shows implant body 254b (e.g., a first segment 281c thereof) abutting tissue site 50 at annulus 11, and driver 230 has been advanced within the implant body such that anchor 260c is deployed out from the catheter, within the implant body. As shown in the lower inset, driver 230 is used to drive the anchor’s tissue-engaging element 264 into site 50, thereby mechanically attaching implant body 254b to the tissue. In some such implementations, the adhesive disposed at segment 281c is inactive while the tissue-engaging element 264 is driven into the tissue.
[0471] The upper inset of Fig.16B shows energy 270 being applied via energy-applicator 252c to activate adhesive 280′ at segment 281c, thereby adhering the segment to tissue site 50, as described hereinabove with reference to Fig.12B. In some implementations, and as shown in the lower inset of Fig.16B, the catheter’s distal portion 124 is then repositioned to place a second segment 281c of implant body 254b in contact with annulus 11. As shown in the lower inset of Fig.16B, a second anchor 260c then is driven through the second segment and into tissue at a second tissue site 50a, e.g., while the second segment’s adhesive is inactive.
[0472] Fig.16C shows energy applied from the second anchor’s energy-applicator 252c (upper inset) activating adhesive 280′ at the second segment 281c, thereby adhering the second segment to the tissue site (lower inset). In some implementations, and as shown in Fig.16D, several anchors 260c are sequentially driven to mechanically attach a segment 281c of implant body 254b to annulus 11, after which the respective anchor’s energy-applicator 252c is driven to activate adhesive 280′ on that segment, thereby anchoring and adhering implant 250c to annulus 11.
[0473] Reference is made again to Figs.17–20 and 22, which are schematic illustrations showing systems 200d, 200e, 200f, 200g, 200h for deploying respective implants 250d, 250e, 250f, 250g, 250h, in accordance with some applications.
[0474] In some implementations, system 200d, 200e, 200f, 200g, 200h is electrically connected to energy-applicator 252d, 252e, 252f, 252g, 252h at implant body 254d, 254e, 254f, 254g, 254h, e.g., via a wired connector 273d, 273e, 273g, 273h or an antenna, such as antenna 271 of implant 250f shown in Fig.19. In some such implementations, delivery tool 210d, 210e, 210f, 210g, 210h is connected to several energy-applicators 252d, 252e, 252f, 252g, 252h at respective segments 281d, 281e, 281f, 281g, 281h of implant body 254d, 254e, 254g, 254h, e.g., at an adhesive-coated surface of the implant body. For example, eachenergy-applicator 252d, 252e, 252f, 252g, 252h can be fixedly coupled to implant body 254d, 254e, 254f, 254g, 254h, e.g., embedded within adhesive 280 on an adhesive-coated segment 281d, 281e, 281f, 281g, 281h of the implant body.
[0475] In some implementations, system 200d, 200e, 200f, 200g, 200h transmits energy (e.g., conducts electrical energy from an external power supply) to energy-applicator 252d, 252e, 252f, 252g, 252h via a terminal that is reversibly electrically connected to delivery tool 210d, 210e, 210f, 210g, 210h. Alternatively or in addition, energy is transmitted wirelessly (e.g., by RF or magnetic induction) to the implant’s energy-applicator 252d, 252e, 252f, 252g, 252h, which transforms the transmitted energy into current and / or heat, which in turn activates the adhesive. In some such implementations, implant 250d, 250e, 250f, 200g, 250h comprises a wireless terminal (e.g., an antenna, not shown) that receives energy 270 from delivery tool 210d, 210e, 210f, 210g, 210h, and directs the energy to energy- applicator 252d, 252e, 252f, 252g, 252h.
[0476] In some implementations, and as shown in Fig.17 regarding connector 273e, the connector comprises several wires 274 that connect each energy-applicator 252d, 252e, 252f, 252g, 252h to the delivery tool separately, e.g., allowing the user to select which portion of adhesive 280 to activate by transmitting energy to a chosen energy-applicator.
[0477] In some implementations, energy-applicator 252d, 252e, 252f, 252g, 252h comprises an implant-electrode, such that transmitting energy from the delivery tool to the implant-electrode activates adhesive 280 by passing current through the adhesive. Alternatively or in addition, energy-applicator 252d, 252e, 252f, 252g, 252h can comprise a resistor heater that activates the adhesive by heating the adhesive.
[0478] In some implementations in which energy-applicator 252d, 252e, 252f, 252g, 252h comprises an implant-electrode, the system’s distal portion 204d, 204e, 204f, 204g, 204h comprises a return electrode 212. In this way, the current is directed from the activated implant-electrode 252d, 252e, 252f, 252g, 252h, through a portion of adhesive 280 and to return electrode 212. In some such implementations, a single return electrode 212 is used in conjunction with each implant-electrode. Alternatively, implant 250d, 250e, 250f, 250g, 250h can comprise a return electrode (not shown), sufficiently spaced from the implant- electrode 252d, 252e, 252f, 252g, 252h to direct current from the implant-electrode, through adhesive 280 and to the return electrode.
[0479] In accordance with some implementations, Fig.17 shows implant 250d having been deployed from a delivery tool 210d at the system’s distal portion 204d, e.g., from the catheter’s distal opening 125. In some implementations, and similarly to implant body 254b described hereinabove, implant body 254d defines a sleeve, having adhesive disposed alongthe sleeve’s exterior surface, that is dimensioned to be seated at annulus 11 of the native valve. In some such implementations, energy-applicator 252d is ring-shaped, e.g., spanning the sleeve’s circumference. In this way, even if the sleeve is twisted or otherwise manipulated during implantation, the adhesive-coated surface of the sleeve will contact annulus 11, and energy-applicator 252d will be positioned to activate adhesive 280 positioned in contact with the annulus.
[0480] In some implementations, system 200d is used to transmit energy separately to each energy-applicator 252d while the segment 281d at which that energy-applicator is disposed is extended from catheter 120 and positioned at annulus 11. In some such implementations, and similarly to as described hereinabove with reference to implant 250b, discrete portions of adhesive 280 can be progressively activated as segments 281d of implant body 254d are sequentially extended from catheter 120, thereby adhering the implant body to annulus 11 in a stepwise manner.
[0481] In some implementations, implantation of implant 250d can be further facilitated by driving tissue anchors (e.g., anchors 260 or 260c described hereinabove) through implant body 254b and into tissue of annulus 11, mutatis mutandis.
[0482] In accordance with some implementations, Figs.18–19 show systems 200e, 200f having deployed respective implants 250e, 250f. As shown, implant body 254e, 254f of implant 250e, 250f defines a prosthetic valve, such as (but not limited to) those described in US 10,639,143 to Oba et al., which is incorporated herein by reference.
[0483] In some such implementations, the prosthetic valve has an annular portion 257 from which a tissue-engaging element 264e, e.g., legs 258 extend radially. In this way, when implant 250e, 250f is implanted at the native mitral valve 10, legs 258 contact ventricular tissue and annular portion 257 contacts the native valve’s annulus 11.
[0484] In accordance with some such implementations, Figs.18–19 show energy- applicators 252e, 252f (e.g., implant-electrodes), as well as portions of adhesive 280, disposed at segments 281e of annular portion 257. In this way, transmitting energy from system 200e, 200f (e.g., via delivery tool 210e) to energy-applicators 252e, 252f, while annular portion 257 is disposed at the native valve, activates adhesive 280, thereby adhering the prosthetic valve’s annular portion to tissue of the native valve. For example, and as shown in Figs.18–19, implant 250e, 250f can be implanted such that leaflets 12, 14 are sandwiched between legs 258 and annular portion 257, e.g., such that activating adhesive 280 will adhere the annular portion to the native leaflets. Alternatively or in addition, energy-applicators 252e, 252f and adhesive 280 can be located elsewhere on the prosthetic valve (e.g., on legs 258), in order to adhere the prosthetic valve to additional tissue locations.
[0485] In accordance with some implementations, Fig.18 shows delivery tool 210e electrically connected via a connector 273e to energy-applicators 252e. In some such implementations, and similarly to as described hereinabove with reference to implant 250d, connector 273e comprises several wires 274 that connect each energy-applicator 252e to delivery tool 210e separately, e.g., allowing the user to select which portion of adhesive to activate by transmitting energy to a chosen energy-applicator. Alternatively, connector 273e may be a simplified connector that connects all of the energy-applicators (e.g., via a single wire 274) in a manner that concurrently activates each portion of adhesive 280 by transmitting energy to each energy-applicator 252e at once.
[0486] In accordance with some implementations, Fig.19 shows delivery tool 210f wirelessly connected to energy-applicators 252f. In some such implementations, and as shown, delivery tool 210f transmits energy that is received by the prosthetic valve’s antenna 271, e.g., by RF or magnetic induction. Alternatively or in addition, each energy-applicator 252f can include an antenna of its own (not shown), e.g., to receive energy directly from delivery tool 210f, mutatis mutandis.
[0487] In some implementations in which implant 250f receives energy from delivery tool 210f via antenna 271, a wire 274f connects antenna 271 to each energy-applicator 252f. Similarly to as described hereinabove with reference to implant 250e, energy-applicators 252f can be connected separately to antenna 271, facilitating activation of a selected portion of adhesive 280 by transmitting energy to a respective energy-applicator. Alternatively, antenna 271 may be connected to all of the energy-applicators (e.g., via a single wire) in a manner that concurrently activates each portion of adhesive 280 by transmitting energy to each energy-applicator 252f at once.
[0488] Alternatively or in addition to applying energy to adhesive 280, an activator (not shown) may also be applied (e.g., via delivery tool 210f) to chemically activate the adhesive.
[0489] Reference is made again to Figs.20 and 22, which are schematic illustrations showing implants 250g, 250h, in accordance with some applications. In some implementations, implants 250g, 250h can be similar to each other, at least in their general purpose, e.g., for implantation at a native valve by mechanical attachment and / or by adhesion. Certain components of implants 250g, 250h correspond to each other, and therefore make use of the same reference numerals.
[0490] In some implementations, and as shown, implant body 254g, 254h of implant 250g, 250h defines a tissue-engaging element 264g, 264h, e.g., that is used to mechanically attach the implant to tissue of the heart. In some implementations, and as shown, tissue- engaging elements 264g, 264h define contact-portions 286g, 286h that are used to contacttissue of the heart, e.g., prior to mechanically attaching and / or adhering the implant to the heart.
[0491] In some implementations, implant body 254g, 254h defines a collar 284g, 284 that is articulatable with respect to contact-portions 286g, 286h, e.g., shoulders 285g, 285h of the implant body, as shown. In some such implementations, and as shown, tissue- engaging elements 264g, 264h each define a leaflet-clip that comprise the contact-portions 286g, 286h. For example, tissue-engaging elements 264g, 264h may be similar to prosthetic devices disclosed in US 11,051,940 to Metchik et al., which is incorporated herein by reference..
[0492] In some implementations, the location on implant body 254g, 254h at which adhesive 280 and energy-applicators 252g, 252h are disposed may be different between implants 250g, 250h. For example, adhesive 280 and energy-applicators 252g are shown disposed at contact-portion 286g (e.g., at shoulder 285g) of implant body 254g, whereas the adhesive and energy-applicators 252h of implant 250h are shown disposed at the implant body's collar 284h.
[0493] In accordance with some implementations, Figs.20 and 22 show implant 250g, 250h having been deployed from delivery tool 210g, 210h, at which stage tissue-engaging element 264g, 264h has assumed an open configuration in which contact-portions 286g, 286h are exposed.
[0494] In accordance with some implementations, Figs.21A–B and Figs.23A-F show use of systems 200g, 200h to deploy implants 250g, 250h at a native valve. In accordance with some implementations, Figs.21A and 23A show implant 250g, 250h having been transluminally advanced, via delivery tool 210g, 210h, to the heart such that implant body 254g, 254h is at least partially disposed within ventricle 8, and contact-portions 286g, 286h abut a downstream side of native leaflets 12, 14.
[0495] In some implementations, and as shown in Fig.21B, tissue-engaging element 264g is then closed, mechanically attaching implant 250g to leaflets 12, 14 by sandwiching the leaflets’ tips between contact-portions 286g (e.g., shoulders 285g) and collar 284g.
[0496] In some implementations, and as shown in Fig.23B, tissue-engaging element 264h assumes (e.g., prior to mechanically attaching implant 250h to leaflets 12, 14) a contact-detecting conformation in which the tissue-engaging element holds the leaflets against contact-portions 286h, e.g., by sandwiching the leaflets between collar 284h and contact-portions 286h, as shown. In some implementations, and as shown in Fig.23C, delivery tool 210h then drives energy-applicator 252h to detect contact between contact- portions 286h and the leaflets.
[0497] In some implementations in which energy-applicator 252h is an implant- electrode, delivery tool 210h detects contact between contact-portions 286h and leaflets 12, 14 while operating in a contact-detecting (e.g., a bioimpedance-measuring) mode in which the delivery tool drives implant-electrode such that current flows from energy-applicator 252h through leaflets 12, 14 and to a sensing electrode (not shown).
[0498] In some implementations, the sensing-electrode is disposed on implant body 254h (e.g., on shoulders 285h), such that current flows from energy-applicator 252h through leaflets 12, 14 to the sensing electrode while the leaflets are sandwiched between (i) the energy-applicator on collar 284h, and (ii) the sensing-electrode on shoulders 285h.
[0499] In some implementations, energy-applicator 252h comprises both an activation- electrode and the sensing-electrode, such that current flows from the activation-electrode, through leaflets 12, 14 to the sensing-electrode while the leaflets are sandwiched between collar 284h and shoulders 285h
[0500] In some implementations, a return electrode (e.g., return electrode 212 and / or to an unshown return electrode disposed on implant 250h, or on the subject's skin) serves as the sensing-electrode.
[0501] In some implementations, and as shown in Fig.23C, less energy 270' (e.g., a lower voltage) is applied to energy-applicator 252h while operating in the contact-detecting mode than would be required to activate adhesive 280. In this way, delivery tool 210h can detect the amount of energy received (e.g., via the return electrode) in order to determine the degree of contact between contact-portions 286h and leaflets 12, 14. In case that the contact between contact-portions 286h and leaflets 12, 14 is determined to be suboptimal, tissue- engaging element 264h can be reopened (Fig.23A) and repositioned.
[0502] In some implementations, delivery tool 210h receives, e.g., via the sensing- electrode, a signal indicating contact between contact-portion 286h and leaflets 12, 14. In case that the contact is determined to be sufficient, delivery tool 210h can be transitioned to an adhesive-curing mode in which energy flows from energy-applicator 252h, through the adhesive to the return electrode. In some such implementations, transitioning delivery tool 210h from the contact-sensing mode to the adhesive-curing mode changes the direction in which the energy flows, e.g., by ungrounding a first return electrode and grounding a second return electrode.
[0503] In some implementations, delivery tool 210 transitions automatically from the contact-detecting mode to the adhesive-curing mode, when the contact between contact- portion 286h and the leaflets is determined to be sufficient.
[0504] In some implementations, delivery tool 210 provides a notification to notify the user that the contact between contact-portion 286h and the leaflets is sufficient.
[0505] In some implementations, and as shown in Fig.23D, tissue-engaging element 264h is then closed, mechanically attaching implant 250h to leaflets 12, 14 by sandwiching the leaflets’ tips between contact-portions 286h (e.g., shoulders 285h) and collar 284h.
[0506] In some implementations, and as shown in Figs.21C and 23E, energy 270 is then transmitted via connectors 273g, 273h to drive energy-applicators 252g, 252h, thereby activating adhesive 280 and adhering leaflets 12, 14 to implant body 254g, 254h, e.g., to tissue-engaging element 264g, 264h.
[0507] In some implementations, energy-applicators 252g, 252h comprise implant- electrodes, and electrical energy is transmitted to the implant-electrodes such that current flows from the implant-electrodes, through adhesive 280 to return electrode 212 of delivery tool 210g, 210h. In some such implementations, energy applicator 252g, 252h comprises more than one implant-electrode, e.g., which can be selectively driven in order to activate a selected portion of adhesive 280.
[0508] In some implementations, connector 273g is extracorporeally operated (e.g., at the delivery tool’s proximal portion) to mechanically and electrically detach delivery tool 210g, 210h from implant 250g, 250h. Figs.21D and 23F show delivery tool 210g, 210h being withdrawn, leaving implant body 254g, 254h both mechanically fastened and adhered to leaflets 12, 14.
[0509] Reference is made to Fig.24, which is a schematic illustration showing use of a system 300 for guiding a delivery tool 310 within heart 4, in accordance with some applications. In some implementations, and as shown, delivery tool 310 comprises catheter 120 that is used to transluminally advance an implant 350 to the heart.
[0510] In some implementations, implant 350 comprises an implant-electrode 340 (e.g., any of the implant-electrodes described hereinabove) that is used to measure endogenic electrophysiological signals. In some such implementations, the endogenic electrophysiological signals are used to calculate the implant-electrode’s location within the heart. For example, information relating to the endogenic signals (e.g., bioimpedance of certain cardiovascular structures) reaches the system’s processor 114, which uses the information to calculate the implant-electrode’s location, which can then be visualized on the system’s display 112.
[0511] Alternatively or in addition to implant-electrode 340, delivery tool 310 can comprise a catheter-electrode (not shown) that, similarly to implant-electrode 340, is used to detect endogenic electrophysiological signals. In some such implementations, informationrelating to the signals detected by the catheter-electrode reach processor 114, which uses the information to calculate the catheter-electrode’s location, which can then be visualized on the system’s display 112. For example, the catheter-electrode can be positioned at a site of catheter 120 proximally or distally of implant 350, and processor 114 can calculate the location of the site relative to the cardiac anatomy, e.g., to determine if the catheter’s site has passed from the right atrium to the left atrium.
[0512] In some such implementations, implant-electrode 340 further serves to activate adhesive 280, as described hereinabove with reference to energy-applicators 252a, 252c, 252d, 252e, 252f, 252g, 252h. In some such implementations, when implant 350 is determined to have reached a desired location within the heart, implant-electrode 340 is transitioned from a navigation mode to adhesive-curing mode in which delivery tool 310 applies voltage to the implant-electrode such that current flows through adhesive 280, thereby adhering implant 350 to tissue of the heart by activating the adhesive. For example, delivery tool 310 can comprise one or more return electrodes, e.g., a return electrode (not shown) disposed on catheter 120 and / or a plurality of return electrodes 342 that are disposed on the subject’s skin, as shown.
[0513] In some implementations, implant-electrode 340 is activated in order to produce exogenic electrical signals that are used to aid the user in navigating delivery tool 310 to a desired location within the heart. In some such implementations, system 300 comprises one or more return electrodes, e.g., disposed on catheter 120 and / or a plurality of return electrodes 342 that are disposed on the subject’s skin, as shown. In this way, implant- electrode 340 is activated within heart 4, which causes current to flow from the implant- electrode, through tissue of the heart and to the return electrodes 342.
[0514] In some implementations, implant-electrode 340 is one of several implant- electrodes, and delivery tool 310 is adjustable to selectively apply voltage to one of the implant-electrodes, such that current flows from the selected implant-electrode, through a selected portion of adhesive 280, to the return electrode. Similarly to as described hereinabove with reference to implant 250d, discrete portions of adhesive 280 can be progressively activated, thereby adhering implant 350 to annulus 11 in a stepwise manner.
[0515] In some implementations, information reflecting the current is transmitted to the system’s processor 114, which uses the information to calculate a location of implant- electrode 340 within the heart. In some such implementations, processor 114 uses the information to determine bioimpedance between implant-electrode 340 and respective return electrodes 342 in order to determine the implant-electrode’s location, e.g., which is visualized on the system’s display 112.
[0516] In some implementations, system 300 is transitioned from a navigation mode (e.g., a bioimpedance-measuring mode) in which delivery tool 310 transmits power at a lower voltage to implant-electrode 340, to adhesive-curing mode in which the delivery tool transmits power to the implant-electrode at a higher voltage for activating adhesive 280, as described hereinabove.
[0517] In some such implementations, delivery tool 310 comprises a secondary return electrode (not shown) that is inactivated while system 300 is in the navigation mode. For example, the secondary return electrode can be activated when system 300 is in the adhesive-curing mode, such that the adhesive-activating current is removed from the subject’s body after passing through less of the subject’s tissue, reducing exposure to the higher current used to activate the adhesive. Thus, a lower level of current can be directed from implant-electrode 340 to return electrodes 342 on the subject’s skin while navigating within the heart, and a higher level of current can be directed from the implant-electrode, through adhesive 280 and to the secondary return electrode.
[0518] Reference is made to Figs.25A–G, which are schematic illustrations showing steps of a method for preparing a fabric 440a for use in an implant, in accordance with some applications.
[0519] In accordance with some implementations, Fig.25A shows fabric 440a that has been woven by interlacing a weft yarn 448 with a warp 442 comprising multiple warp yarns 444, 446 that extend longitudinally along a length of fabric 440a. In some such implementations, and as shown, weft yarn 448 passes back and forth across the warp, such that the weft yarn passes alternatingly over and under warp yarns 444, 446. In this way, weft yarn 448 alternatingly defines a portion of the fabric’s face 480a where the weft yarn passes over the warp, or a portion of the fabric’s back 482a where the weft yarn passes under the warp.
[0520] In some implementations, and as shown in the inset of Fig.25A, weft yarn 448 is interlaced with warp yarns 444, 446 such that the weft yarn skips under certain portions of selected warp yarns 446 as the weft yarn passes across warp 442. The portions of the selected warp yarns 446 where weft yarn 448 has skipped its sequential pass over the selected warp yarn define warp floats 447, which therefore may be allowed to ‘float’ above the fabric’s face 480a.
[0521] In some implementations, the selected warp yarns 446 differ in composition from the nonselected warp yarns 444 and / or from weft yarn 448. Selected warp yarns 446 may comprise a metal (e.g., steel or nitinol) or a polymer (e.g., a nylon or a polyester). In somesuch implementations, selected warp yarns 446 are monofilament yarns. In some such implementations, weft yarn 448 are polyfilament yarns.
[0522] In some implementations, and as shown in the inset of Fig.25A, each warp float 447 is formed by passing a skipping portion 448′ of weft yarn 448 under selected warp yarn 446 such that the weft yarn 448 deviates from alternatingly passing over and under warp yarns 444, 446, e.g., such that the weft yarn’s skipping portion passes under three consecutive warp yarns. In some such implementations, and as shown, the resultant warp float 447 is juxtaposed between two passes of weft yarn 448 that pass alternatingly over and under warp yarns 444, 446. For example, and as shown, the preceding pass of weft yarn 448 passes over a first warp yarn 444, under a second, selected warp yarn 446 and over a third warp yarn. In the weft yarn’s next pass across warp 442, the weft yarn’s skipping portion 448′ passes consecutively under the first warp yarn 444, the selected warp yarn 446 and the third warp yarn. In some such implementations, and as shown, the subsequent pass of weft yarn 448 passes over the first warp yarn 444, under the selected warp yarn 446 and over a third warp yarn. Alternatively, weft yarn 448 can pass under selected warp yarn 446 during two or more consecutive passes across warp 442.
[0523] In accordance with some implementations, the inset of Fig.25A is a cutaway side- view of fabric 440a which shows weft yarn 448 passing alternatively over and under warp yarn 444, e.g., such that the warp yarn’s path of travel between successive passes of the weft yarn resembles a periodic waveform. For example, and as shown, warp float 447 resembles a deviation from the periodic waveform (e.g., resembling an increased amplitude, a decreased frequency, and / or a phase shift), e.g., such that the warp float is distanced from the fabric’s face 480.
[0524] In accordance with some implementations, Fig.25B shows a pin 450a having been inserted between warp floats 447 and the fabric’s face 480a. Although Fig.25B shows insertion of pin 450a into warp float 447 after fabric 440a is woven, the pin may be pre- disposed (e.g., oriented along the warp’s width) before the weft yarn 448 is interlaced with the weft, mutatis mutandis. Alternatively or in addition, the pin can comprise a second weft yarn (e.g., a monofilament weft yarn) that is inserted between the warp floats and the fabric’s face, e.g., during the weaving process.
[0525] In some implementations, and as shown in Fig.25B, pin 450a is dimensioned to fit (e.g., to snugly fit) between warp floats 447 and the fabric’s face 480a. In some such implementations, inserting pin 450a into warp floats 447 distances each warp float from the fabric’s face 480a. For example, and as shown in the inset of Fig.25B, pin 450a is inserted such that the pin’s base 454 faces the weft yarn 448 and / or the fabric’s face 480a. In somesuch implementations, and as shown, pin 450a also defines an apex 452 that is positioned opposite the pin’s base 454, such that the apex faces (e.g., contacts) warp float 447.
[0526] Although Fig.25B shows one pin 450a that is inserted through two warp floats 447, please note that this is one representative pin, and use of multiple pins, which can be inserted into some or all of multiple warp floats (e.g., at different portions along the fabric’s length), is contemplated.
[0527] In accordance with some implementations, Fig.25C shows use of an energy- applicator 460 to shape-set warp floats 447. In some such implementations, and as shown, warp floats 447 are shape-set while pin 450a is disposed between the warp floats and the fabric’s face 480a, e.g., such that the warp float conforms to the pin’s shape and adopts the pin’s shape.
[0528] In some implementations, and as shown, energy-applicator 460 shape-sets warp floats 447 by applying energy 462 (e.g., heat and / or electromagnetic energy) to the fabric, e.g., to the warp floats. Alternatively or in addition, energy may be applied to pin 450a, e.g., by heating the pin such that the pin in turn shape-sets the warp floats by heating them.
[0529] In some implementations, warp floats 477 are shape-set by heating the fabric to a temperature (e.g., between 180–240 °C) approaching the selected warp yarns’ melting point. For example, the warp floats can be shape-set by heating the fabric to a temperature above the warp yarns’ glass transition temperature, yet below the warp yarns’ melting point. In some implementations, the selected warp yarns 446 defining warp floats 447 have a lower melting temperature and / or glass transition temperature than the other, non-selected warp yarns 444 and / or the weft yarn 448, such that the warp floats 447 can be shape-set without shape-setting the weft yarn and / or the non-selected warp yarns 444.
[0530] In accordance with some implementations, Fig.25D schematically shows use of blades 470 to trim away warp portions of warp floats 447. Alternatively or in addition, thermal and / or laser energy (not shown) can be applied to cut the warp floats. Although Fig. 25D shows manual use of blades 470 to trim the warp floats after fabric 440a is woven, the trimming may be mechanized, e.g., to cut the warp floats during the weaving process, mutatis mutandis.
[0531] In some implementations, and as shown, warp floats 447 are each cut twice, in order to trim away a portion of the warp float. In some such implementations, pin 450a defines grooves (not shown) that each serve as blade guide along which the blades are advanced, thereby cutting away respective portions of each warp float 447. For example, the grooves can be located along the pin’s apex and / or along the pin’s base, e.g., adjacent to a preceding pass of weft yarn 448, such that the warp float is trimmed along a length of theweft yarn. In some implementations, blades 470 may be used to selectively trim certain warp floats 447, while leaving other warp floats uncut.
[0532] In accordance with some implementations, Fig.25E shows warp floats 447 having been trimmed such that a remaining portion of each warp float defines a barb 449a. Fig.25F shows a representative barb 449a protruding obliquely from face 480a of fabric 440a after removal of pin 450a. In some implementations, and as shown in Fig.25G, multiple barbs 449a protrude from the fabric’s face 480a in the same direction (e.g., in parallel). Thus, cutting away corresponding parts of warp floats 447 can result in similarly (e.g., identically) shaped barbs 449a.
[0533] In some implementations, the remaining portions of the selected warp yarns 446 are adhered to the fabric’s back 482a, e.g., by applying energy such as heat to the back of the fabric. In some such implementations, the remaining selected warp yarns are adhered to the fabric’s back 482a during a lamination process, e.g., by adhering a laminate to the back of the fabric. In some such implementations, the laminate may comprise the same material as one of the yarns, e.g., the selected warp yarns 446. For example, the laminate may comprise a high weight polyethylene and / or a polyurethane thermoplastic.
[0534] In some implementations, and as shown in Fig.25G, fabric 440a is a generally planar fabric. However, the method described hereinabove can be adapted to non-planar (e.g., concave or convex fabrics), mutatis mutandis. For example, laminating the fabric using a non-planar laminate and / or shape-setting fabric 440a while non-planar pins are disposed within warp floats 447 may shape-set the fabric into a desired non-planar shape.
[0535] Reference is made to Figs.26A–B, 27A–B and 28A–B, which are schematic illustrations of fabrics 440b, 440c, 440d, in accordance with some applications. Figs.26A, 27A and 28A show each fabric with differently shaped pins 450b, 450c, 450c disposed within respective warp floats 447b, 447c, 447d, e.g., after each warp float has been shape-set as described hereinabove with reference to Fig.25C. Figs.26B, 27B and 27B show each fabric 440b, 440c, 440d after that fabric’s warp float 447b, 447c, 447d has been trimmed and pin 450b, 450c, 450c has been removed, such that barbs 449b, 449c, 449d protrude from the fabric’s face 480b, 480c, 480d. In Figs.26B, 27B and 27B, each barb 449b, 449c, 449d retains the shape that the respective warp float 447b, 447c, 447d assumed while shape-set in contact with the respective pin 450b, 450c, 450c. In some such implementations, and as shown, barbs 449b, 449c, 449d are hook-shaped, yet use of differently shaped pins, in order to shape-set warp floats into non-hooked barbs, is contemplated.
[0536] Reference is made to Figs.29A–E, which are schematic illustrations showing steps of a method for preparing a fabric 440e for use in an implant, in accordance with someapplications. Fabric 440e, and the method of preparing the fabric for use in an implant is generally similar to the method described hereinabove of preparing fabric 440a. As such, the description hereinbelow will focus upon aspects that are specifically for preparing fabric 440f. For example, and as described hereinbelow, warp floats 447 can be trimmed to yield barbs 449e that protrude away from the fabric’s face 480e and towards each other.
[0537] In accordance with some implementations, Fig.29A shows fabric 440e after warp floats 447 have been shape-set, with pins 450a disposed within the warp floats, similarly to as shown in Fig.25C. In some such implementations, and as shown, a plurality of pins 450a are each disposed within a plurality of warp floats 447. In some such implementations, and as shown, pins 450a are disposed in parallel with each other, e.g., in parallel with weft yarn 448.
[0538] In some implementations, differently shaped pins, e.g., pins 450b, 450c, 450d described hereinabove, are used to shape-set the fabric’s warp floats. Differently shaped pins may be selected for different portions of the fabric, and the user may choose to insert pins into certain warp floats, but not into other warp floats. In this way, not every warp float is necessarily shape-set or trimmed to yield a barb, thereby allowing the user to customize the fabric’s pattern of barbs.
[0539] Fig.29B shows use of blades 470 to trim the fabric’s warp floats 447, similarly to as described hereinabove with reference to Fig.25D. However, in contrast to as shown in Fig. 25D, Fig.29B shows blades 470 being used to trim non-corresponding (e.g., facing) portions of the warp floats 477. Fig.29C shows the warp floats’ facing portions having been cut away, and removal of pins 450a (Fig.29D) exposes two pairs of shape-set barbs 449e that point towards each other, as shown in cross-section in Fig.29E.
[0540] Figs.29A–E are meant to illustrate that different portions of warp floats 447 can be trimmed away, in order to customize the shape of the resultant barbs. This strategy can be implemented independently of, or in conjunction with, inserting differently shaped pins into the warp floats, thereby increasing the number of differently shaped barbs that can be attained from the base fabric common to fabrics 440a, 440e. In addition, altering the parameters according to which the fabric is woven (e.g., altering a frequency and / or location of the warp floats) can further add to the user’s options for varying the barbs’ shape and number.
[0541] Reference is made to Figs.30–33, which are schematic illustrations showing use of fabric 440e at a native valve 10, in accordance with some applications.
[0542] Fig.30 schematically shows fabric 440e being folded to form a bi-layer fabric implant 540e for implantation in the heart. In accordance with some implementations, theupper frame of Fig.30 shows fabric 440e aligned along a plane, such that barbs 449e protrude away from the fabric’s face 480e and towards each other, e.g., from opposite sides of a center-line a490. The lower frame of Fig.30 show fabric 440e having been folded along center-line a490 such that portions of the fabric’s back 482e on either side of the center-line face each other, and barbs 449e disposed on opposite sides of the center-line point away from each other. In some such implementations, and as shown, barbs 449e protrude symmetrically (e.g., at equal angles relative to face 480e) from each layer of fabric 440e.
[0543] Folding fabric 440e perpendicularly to the fabric’s longitudinal axis and / or warp yarns 444 is only one exemplary manner in which fabric 440a can be folded, and folding the fabric along its length (e.g., along the fabric’s longitudinal axis and / or parallel to warp yarns 444), or obliquely to the fabric’s length, as well as folding the fabric more than once, is contemplated.
[0544] In accordance with some implementations, Fig.31 shows implant 540e having been implanted at a mitral valve 10 of the heart. The left frame of Fig.31 shows a perspective view of valve 10 from upstream, showing implant 540e having been implanted at a medial portion of mitral valve 10, where the implant adjoins respective upstream faces of the valve’s leaflets 12, 14. In this way, implant 540e is used to implement sutureless edge-to-edge mitral valve repair. Drawing tips of leaflets 12, 14 into coaptation in this way can mitigate mitral regurgitation during ventricular systole, while providing for sufficient antegrade blood flow during ventricular diastole, through the resultant double orifice.
[0545] In some implementations, and as shown in the right frame of Fig.31, implant 540e has been implanted on the upstream side of leaflets 12, 14 such that barbs 449e penetrate an upstream-facing surface of the leaflets. In some such implementations, and as shown, the barbs penetrate the tissue at an angle that inhibits deflection of the leaflets in the upstream direction.
[0546] In accordance with some implementations, Fig.32 shows fabric 440e being folded into a bi-layer fabric implant 640e, in an opposite direction from that shown above in Fig.30. Similarly to as shown in Fig.30, the upper frame of Fig.32 shows fabric 440e aligned along a plane, such that barbs 449e protrude away from the fabric’s face 480e and towards each other. The lower frame of Fig.32 shows fabric 440e having been folded such that portions of the fabric’s face 480e on either side of center-line a490 face each other, and barbs 449a disposed on opposite sides of the center-line point towards each other. In some such implementations, and as shown, barbs 449e protrude symmetrically (e.g., at equal angles relative to face 480e) from each layer of fabric 440e.
[0547] In accordance with some implementations, and corresponding to as shown above in Fig.31, Fig.33 shows implant 640e having been implanted at a downstream side of mitral valve 10, e.g., such that barbs 449e penetrate an upstream-facing surface of leaflets 12, 14. Similarly to implant 540e, implant 640e bridges between the valve’s leaflets 12, 14 to implement sutureless edge-to-edge mitral valve repair.
[0548] Reference is made to Figs.34, 35A–H and 36A–D, which are schematic illustrations showing use of a system 600 comprising a delivery tool 620 for implanting implant 540e (e.g., adhering the implant using adhesive 280) to tissue of the cardiovascular system of a subject, in accordance with some applications.
[0549] In accordance with some implementations, Fig.34 shows a distal portion 624 of a transluminally advanceable delivery tool 620. Delivery tool 620 comprises a scaffold 640 that is used, as described hereinbelow with reference to Figs.35A–H and 36A–D, to hold an implant (e.g., implant 540e) against the tissue while adhesive 280 is used to adhere the implant to the tissue. In some such implementations, and as described hereinbelow, the implant comprises fabric 440e, and scaffold 640 is used to restrain the fabric’s face 480e against the tissue such that barbs 449a penetrate the tissue. Typically for such implementations, adhesive 280 is manipulated (e.g., applied and / or activated) while the barbs remain in the tissue, in order to adhere the fabric to the tissue. In this way, implant 540e remains adhered to the tissue after scaffold 640 is withdrawn from the subject.
[0550] In accordance with some implementations, Fig.35A shows the delivery tool’s catheter 660 having entered left atrium 6 to advance scaffold 640 toward tissue (e.g., a native mitral valve 10) of the cardiovascular system. In some such implementations and as shown, delivery tool 620 holds scaffold 640 (e.g., within sleeves 650) in a compressed state during delivery to mitral valve 10. For example, scaffold 640 can comprise a shape-memory material that expands the scaffold into an expanded state as the scaffold is exposed from delivery tool 620.
[0551] In some implementations, and as shown in Fig.35A, scaffold 640 comprises a leaflet-clip 642, a distal portion 644 of which is initially exposed from sleeves 650. Fig.35B shows implant 540e partially deployed within left ventricle 8 as leaflet-clip 642 is further exposed from sleeves 650, such that the leaflet-clip’s distal portion 644 begins to transition into the expanded state. In some such implementations, the fabric’s barbs 449a begin to penetrate leaflets 12, 14 as leaflet-clip 642 expands. For example, expansion of leaflet-clip 642 can push fabric 440e against leaflets 12, 14, such that barbs 449a penetrate the leaflets.
[0552] In some implementations, and as shown in Fig.35C, leaflet-clip 642 captures the leaflets as the leaflet-clip expands, restraining the fabric’s face 480e against the leaflets (e.g.,sandwiching the leaflets between the leaflet-clip and the fabric), such that barbs 449a penetrate the tissue. In some such implementations, and as shown, the leaflet-clip’s distal portion 644 provides support to ventricular tissue of the native valve 10, e.g., pressing the tissue toward the fabric’s face 480e. For example, and as shown in Fig.34’s perspective view of delivery tool 620, the leaflet-clip’s distal portion 644 can taper towards the delivery tool’s central axis a620, such that the leaflet-clip’s distal portion is offset medially from the leaflet- clip’s stem 646 (Fig.34). In this way, fabric 440e and leaflets 12, 14 are pushed together such that barbs 449a readily penetrate the leaflets.
[0553] In some implementations, and as shown in Fig.35D, scaffold 640 is retracted before adhesive 280 adheres the implant’s fabric 440e to the tissue. In some such implementations, and as shown, leaflet-clip 642 is withdrawn back into sleeves 650, e.g., using a force sufficient to compress the leaflet-clip back into the compressed state.
[0554] In some implementations (e.g., implementations in which adhesive 280 is not pre-disposed on the implant), and as shown in Fig.35E, leaflet-clip 642 is retracted from leaflets 12, 14 before adhesive 280 is applied to fabric 440e. In some such implementations, barbs 449a hold the fabric to the tissue at this stage, e.g., independently of scaffold 640. For example, the fabric’s barbs 449a can be strong enough to hold the fabric’s face 480e against the tissue as the heart cycles between systole and diastole, at least until adhesive 280 adheres the fabric to the tissue.
[0555] In some implementations, and as shown in Fig.35F, delivery tool 620 comprises an adhesive applicator 630 (e.g., defining a nozzle 632), through which adhesive 280 is applied to fabric 440e and leaflets 12, 14. In some such implementations, adhesive 280 is self-activating, e.g., the adhesive hardens into activated adhesive 280′ spontaneously, such as during a period of minutes or hours.
[0556] In some implementations, adhesive 280 is energy-activated. For example, adhesive can be activated by applying heat, electrical current and / or electromagnetic energy, such as ultraviolet light. In some such implementations, system 600 comprises a transluminally advanceable energy-applicator 634, shown in Fig.35G transmitting energy 636 that transforms the adhesive into activated adhesive 280′. Alternatively or in addition, an extracorporeal energy-applicator (not shown) is used to apply energy to adhesive 280 from outside of the subject.
[0557] In some implementations, the adhesive is chemically activated. In some such implementations, the adhesive is a protein-based bioadhesive that is activated by applying a chemical activator (e.g., via the delivery tool’s nozzle 632, or via an unshown second nozzle). For example, the bioadhesive comprises an oxidation-dependent adhesive, e.g., a mussel footprotein comprising 3,4-dihydroxy-L-phenylalanine (dopa). In some such implementations, the activator comprises a biocompatible oxidizing agent that chemically activates the adhesive, e.g., by cross-linking amino acid residues of the mussel foot protein.
[0558] In some implementations, implant 540e comprises an implant-electrode (not shown), e.g., as described hereinabove with reference to Figs.17–20, 21A–D. For example, the implant-electrode can be disposed on the fabric’s face 480e, e.g., embedded within adhesive 280 on the fabric’s face. In some such implementations, the energy-applicator applies voltage to the implant-electrode such that current flows from the implant-electrode and through adhesive 280, thereby activating the adhesive. For example, delivery tool 620 can include a return electrode (not shown, e.g., as described hereinabove with reference to Figs.17–20, 21A–D) that removes the current from the subject as the adhesive is activated.
[0559] In some implementations, implant 540e comprises a plurality of implant- electrodes, and the energy-applicator can be used to selectively apply current to each implant-electrodes, in order to selectively activate discrete portions of adhesive 280 on the fabric’s face 480e, e.g., as described hereinabove, with reference to Figs.17–20.
[0560] Fig.35H shows delivery tool 620 being withdrawn from the subject’s cardiovascular system via catheter 660, leaving behind implant 540e adhered to leaflets 12, 14. In some implementations, fabric 440e is bioabsorbable (e.g., materials comprising the fabric can be absorbed over time by the tissue) such as during a period of weeks or months, leaving behind the activated adhesive 280′ adhering leaflets 12, 14 together.
[0561] In accordance with some implementations, Figs.36A–D show a variation of the method described hereinabove with reference to Figs.35A–H. For example, in contrast to the sequence shown in Figs.35D–F, which show scaffold 640 being retracted before adhering implant 540e to the tissue, Figs.36A–D show scaffold 640 being retracted after using adhesive 280 to adhere the implant to the tissue.
[0562] In accordance with some implementations, Fig.36A shows adhesive 280 disposed on the implant’s fabric 440e while leaflet-clip 642 holds the fabric against leaflets 12, 14. In some such implementations, adhesive 280 is pre-disposed on fabric 440e, e.g., as described hereinabove with reference to Fig.20. Alternatively or in addition, adhesive applicator 630 is used to apply adhesive 280 to fabric 440e while leaflet-clip 642 holds the fabric against leaflets 12, 14, as shown hereinabove in Fig.35F.
[0563] In accordance with some implementations, Fig.36B shows energy-applicator 634 applying energy to activate adhesive 280′, e.g., as described hereinabove with reference to Fig.35G. In some implementations, and as shown in Fig.36C, leaflet-clip 642 is then retracted (e.g., recompressed) into delivery tool 620. A variety of factors may facilitateretracting leaflet-clip 642, e.g., through or around activated adhesive 280′. For example, leaflet-clip 642 can be retracted before adhesive 280 is fully activated, e.g., the leaflet-clip can be retracted while the energy-applicator is activating the adhesive. Alternatively or in addition, leaflet-clip 642 can comprise a material to which adhesive 280 adheres weakly, and / or the adhesive may be embedded on the fabric’s face 480e that contacts the leaflets, but not on the fabric’s back 482e that contacts the leaflet-clip.
[0564] Fig.36D shows delivery tool 620 being withdrawn from the subject’s cardiovascular system via catheter 660, leaving behind implant 540e adhered to leaflets 12, 14.
[0565] The various systems, devices, apparatuses, etc. in this disclosure can be sterilized (e.g., with heat, radiation, ethylene oxide, hydrogen peroxide, etc.) to ensure they are safe for use with patients, and the methods herein can comprise such sterilization of the associated system, device, apparatus, etc. Furthermore, the scope of the present disclosure includes, for some applications, sterilizing one or more of any of the various systems, devices, apparatuses, etc. in this disclosure.
[0566] Various implementations of systems, devices, methods, etc. are disclosed herein, and any combination of their features, components, and options can be made unless specifically excluded. For example, various descriptions of implants 150a, 150b, 150c, 150d, 150e, 150f, 150g, 150h, 150i, 150j, 150k, 150l, 250, 250a, 250b, 250c, 250d, 250e, 250f, 250g, 350 can be delivered and implanted by any appropriate method, even if a specific combination is not explicitly described. Although use of barbed fabric 440e is described hereinabove for use in implants 540e, 640e, fabrics defining barbs (e.g., fabrics 440a, 440b, 440c, 440d, 440e) can be used in a range of cardiac implants, such as implants 250b, 250c, 250c, 250d, 250e, 250f, 250g, mutatis mutandis. Likewise, the different constructions and features of system 100 can be mixed and matched, even if not explicitly disclosed. In short, individual components of the disclosed systems can be combined unless mutually exclusive or physically impossible.
[0567] Although the operations of some of the disclosed methods are described in a particular, sequential order for convenient presentation, it should be understood that this manner of description encompasses rearrangement, unless a particular ordering is required by specific language set forth herein. For example, operations described sequentially can in some cases be rearranged or performed concurrently. Moreover, for the sake of simplicity, the attached figures may not show the various ways in which the disclosed systems, apparatuses, devices, methods, etc. can be used in conjunction with other systems, apparatuses, devices, methods, etc.
[0568] Any of the various systems, assemblies, devices, components, apparatuses, etc. in this disclosure can be sterilized (e.g., with heat, radiation, ethylene oxide, hydrogen peroxide, etc.) to ensure they are safe for use with patients, and the methods herein can comprise (or additional methods comprise or consist of) sterilization of the associated system, device, component, apparatus, etc. (e.g., with heat, radiation, ethylene oxide, hydrogen peroxide, etc.). Furthermore, the scope of the present disclosure includes, in some implementations, sterilizing one or more of any of the various systems, devices, apparatuses, etc. in this disclosure.
[0569] The techniques, methods, operations, steps, etc. described or suggested herein or in the references incorporated herein can be performed on a living subject (e.g., human, other animal, etc.) or on a simulation, such as a cadaver, cadaver heart, simulator, imaginary person, etc. When performed on a simulation, the body parts, e.g., heart, tissue, valve, etc., can be assumed to be simulated or can optionally be referred to as “simulated” (e.g., simulated heart, simulated tissue, simulated valve, etc.) and can optionally comprise computerized and / or physical representations of body parts, tissue, etc. The term “simulation” covers use on a cadaver, computer simulator, imaginary person (e.g., if they are just demonstrating in the air on an imaginary heart), etc.
[0570] Example Implementations (some non-limiting examples of the concepts herein are recited below):
[0571] Example 1. A system for use with a heart of a subject, the system comprising: a catheter, transluminally advanceable to the heart; a bioink comprising a biomaterial; and / or a bioprinter: housing the bioink, comprising a nozzle that is transluminally advanceable via the catheter to the heart, wherein the system is configured to, while the nozzle extends from a distal portion of the catheter, extrude the bioink from the nozzle into the heart such that the biomaterial assumes a three-dimensional implant-shape.
[0572] Example 2. The system according to example 1, wherein at least one of the catheter, the nozzle and the bioink is sterile.
[0573] Example 3. The system according to any one of examples 1–2, wherein the system is configured to, while the nozzle extends from a distal portion of the catheter, extrude the bioink from the nozzle into the heart such that the biomaterial: assumes a three- dimensional implant-shape, and / or adheres to tissue of the heart.
[0574] Example 4. The system according to any one of examples 1–3, wherein the bioprinter is configured to, after extruding the bioink from the nozzle into the heart, fixate the biomaterial such that the biomaterial retains the implant-shape.
[0575] Example 5. The system according to example 4, wherein the bioprinter is configured to, after extruding the bioink from the nozzle into the heart, fixate the biomaterial such that the biomaterial: adheres to tissue of the heart, and / or retains the implant-shape.
[0576] Example 6. The system according to any one of examples 1–5, wherein the system further comprises a fixator that is: transluminally advanceable via the catheter to the heart, and / or configured to fixate the biomaterial such that the biomaterial retains the implant-shape.
[0577] Example 7. The system according to example 6, wherein the fixator is configured to fixate the biomaterial such that the biomaterial: retains the implant-shape, and / or adheres to tissue of the heart.
[0578] Example 8. A system for use in a heart of a subject, the system comprising: an implant, the implant comprising: an implant body, an energy-activated adhesive, pre- disposed on the implant, and / or an energy-applicator; and / or a delivery tool, configured to: transluminally deliver the implant to the heart, and position the adhesive in contact with tissue of the heart, and / or while the adhesive remains in contact with the tissue, activate the adhesive to adhere the implant body to the tissue by driving the energy-applicator to apply energy to the adhesive.
[0579] Example 9. The system according to example 8, wherein at least one of the implant, the delivery tool, and the adhesive is sterile.
[0580] Example 10. The system according to any one of examples 8–9, wherein the energy-applicator is configured to apply heat to the adhesive.
[0581] Example 11. The system according to any one of examples 8–10, wherein the energy-applicator is coupled to the implant body.
[0582] Example 12. The system according to any one of examples 8–11, wherein the energy-applicator is embedded within the adhesive.
[0583] Example 13. The system according to any one of examples 8–12, wherein the implant is configured to be seated at an annulus of a native valve of the heart such that the adhesive is placed in contact with the annulus.
[0584] Example 14. The system according to any one of examples 8–13, wherein the implant comprises a tissue anchor defining the energy-applicator.
[0585] Example 15. The system according to example 14, wherein the tissue anchor comprises a resistor heater defining the energy-applicator.
[0586] Example 16. The system according to example 14, wherein the tissue anchor comprises an implant-electrode defining the energy-applicator.
[0587] Example 17. The system according to any one of examples 14–16, wherein the tissue anchor comprises a tissue-engaging element defining the energy-applicator.
[0588] Example 18. The system according to example 17, wherein the adhesive is pre- disposed on the tissue-engaging element.
[0589] Example 19. The system according to any one of examples 8–18, wherein the energy-applicator comprises an implant-electrode that is coupled to the implant and configured to apply electrical current to the adhesive.
[0590] Example 20. The system according to example 19, wherein the delivery tool comprises a terminal that is reversibly electrically connected to the energy-applicator.
[0591] Example 21. The system according to example 19, wherein the implant: comprises a pair of electrodes comprising: the implant-electrode, and / or a return electrode configured to remove current from the subject, and / or is configured such that application of voltage to the implant-electrode causes current to flow from the respective implant- electrode, through the adhesive, to the return electrode.
[0592] Example 22. The system according to example 21, wherein: the implant comprises multiple pairs of electrodes, each pair of electrodes comprising an implant- electrode and a return electrode; and / or the implant is configured such that application of voltage to a respective implant-electrode causes current to flow from the implant-electrode, through a respective portion of the adhesive, to a respective return electrode.
[0593] Example 23. The system according to any one of examples 8–22, wherein: the delivery tool is configured to transmit energy to the implant, and / or the implant comprises a terminal configured to receive the energy from the delivery tool, and direct the energy to the energy-applicator.
[0594] Example 24. The system according to example 23, wherein: the delivery tool is configured to wirelessly transmit energy to the implant, and / or the implant comprises a wireless terminal configured to receive the energy from the delivery tool, and direct the energy to the energy-applicator.
[0595] Example 25. The system according to any one of examples 8–24, wherein: the adhesive comprises: a first portion of adhesive, predisposed on a first part of the implant body, and / or a second portion of adhesive, predisposed on a second part of the implant body; and / or the delivery tool is configured to, while the first portion of adhesive remains in contact with the tissue, activate the first portion of adhesive to adhere the first part of the implant body to the tissue by driving the energy-applicator to apply the energy to the first portion of adhesive.
[0596] Example 26. The system according to example 25, wherein the delivery tool is configured to, while the first portion of adhesive remains in contact with the tissue, activate the first portion of adhesive to adhere the first part of the implant body to the tissue by driving the energy-applicator to apply the energy to the first portion of adhesive while the second portion of the implant body is not in contact with the tissue.
[0597] Example 27. The system according to example 25, wherein the delivery tool is configured to, while the first portion of adhesive remains in contact with the tissue, activate the first portion of adhesive to adhere the first part of the implant body to the tissue by driving the energy-applicator to apply the energy to the first portion of adhesive while the second portion of the implant body is disposed within the delivery tool.
[0598] Example 28. The system according to any one of examples 8–27, wherein the implant comprises a tissue-engaging element.
[0599] Example 29. The system according to example 28, wherein the tissue-engaging element comprises the energy-applicator.
[0600] Example 30. The system according to example 28, wherein the delivery tool is configured to mechanically attach the implant to the tissue via the tissue-engaging element.
[0601] Example 31. The system according to example 30, wherein: the tissue-engaging element defines an adhesive-coated surface, and / or the delivery tool is configured to mechanically attach the implant to the tissue via the tissue-engaging element, prior to driving the energy-applicator to apply energy to the adhesive-coated surface.
[0602] Example 32. The system according to example 30, wherein: the implant body defines an adhesive-coated surface, and / or the delivery tool is configured to mechanically attach the implant to the tissue via the tissue-engaging element, prior to driving the energy- applicator to apply energy to the adhesive-coated surface.
[0603] Example 33. The system according to example 30, wherein: the tissue-engaging element comprises a clip; and / or the delivery tool is configured to mechanically attach the implant to the tissue by closing the clip on the tissue, prior to driving the energy-applicator to apply energy to the adhesive.
[0604] Example 34. The system according to example 30, wherein: the implant comprises a tissue anchor defining the tissue-engaging element; and / or the delivery tool comprises an anchor driver, configured to mechanically attach the implant body to the tissue by driving the tissue-engaging element into the tissue.
[0605] Example 35. The system according to example 34, wherein: implant defines an adhesive-coated surface, and / or the delivery tool is configured to mechanically attach theadhesive-coated surface to the tissue by, via the anchor driver, driving the tissue-engaging element into the tissue, prior to driving the energy-applicator to apply energy to the adhesive-coated surface.
[0606] Example 36. The system according to example 35, wherein: the implant body defines the adhesive-coated surface, and / or the delivery tool is configured to mechanically attach the adhesive-coated surface to the tissue by, via the anchor driver, driving the tissue- engaging element into the tissue, prior to driving the energy-applicator to apply energy to the adhesive-coated surface.
[0607] Example 37. The system according to example 35, wherein: the tissue-engaging element of the tissue anchor defines the adhesive-coated surface, and / or the delivery tool is configured to mechanically attach the implant to the tissue via the anchor driver by driving the tissue-engaging element into the tissue, prior to driving the energy-applicator to apply energy to the adhesive-coated surface.
[0608] Example 38. The system according to any one of examples 35–37, wherein: the adhesive-coated surface is a first adhesive-coated surface, and / or the implant further defines a second adhesive-coated surface.
[0609] Example 39. The system according to example 38, wherein the delivery tool is configured to concurrently activate the adhesive of the first adhesive-coated surface and the second adhesive-coated surface by driving the energy-applicator to apply energy concurrently to each adhesive-coated surface.
[0610] Example 40. The system according to example 38, wherein the delivery tool is configured to: activate the adhesive of the first adhesive-coated surface by driving the energy-applicator to apply energy to the first adhesive-coated surface, and / or subsequently activate the adhesive of the second adhesive-coated surface by driving the energy-applicator to apply energy to the second adhesive-coated surface.
[0611] Example 41. The system according to example 40, wherein: the tissue anchor is a first tissue anchor; the implant further comprises a second tissue anchor; and / or the delivery tool is configured to: activate the adhesive of the first adhesive-coated surface by driving the energy-applicator to apply energy, via the first tissue anchor, to the first adhesive-coated surface, and / or subsequently activate the adhesive of the second adhesive- coated surface by driving the energy-applicator to apply energy, via the second tissue anchor, to the second adhesive-coated surface.
[0612] Example 42. The system according to example 41, wherein: a first part of the implant body defines the first adhesive-coated surface, and / or a second part of the implant body defines the second adhesive-coated surface.
[0613] Example 43. The system according to example 41, wherein: the tissue-engaging element of the first tissue anchor defines the first adhesive-coated surface, and / or the tissue- engaging element of the second tissue anchor defines the second adhesive-coated surface.
[0614] Example 44. The system according to example 43, wherein the anchor driver is configured to: drive the tissue-engaging element of each tissue anchor into the tissue, and / or activate the adhesive of each adhesive-coated surface by driving the energy-applicator to apply energy, via the respective tissue-engaging element, to the respective adhesive-coated surface.
[0615] Example 45. The system according to example 41, wherein the delivery tool is configured to activate the adhesive of the first adhesive-coated surface by driving the energy- applicator to apply energy, via the first tissue anchor, to the first adhesive-coated surface while the second adhesive-coated surface is not in contact with the tissue.
[0616] Example 46. The system according to example 41, wherein the delivery tool is configured to activate the adhesive of the first adhesive-coated surface by driving the energy- applicator to apply energy, via the first tissue anchor, to the first adhesive-coated surface while the second adhesive-coated surface is disposed within the delivery tool.
[0617] Example 47. The system according to example 41, wherein the delivery tool is configured to activate the adhesive of the first adhesive-coated surface by driving the energy- applicator to apply energy, via the first tissue anchor, to the first adhesive-coated surface while the second tissue anchor is disposed within the delivery tool.
[0618] Example 48. The system according to any one of examples 8–47, wherein: the energy-applicator comprises an implant-electrode configured to apply current to the adhesive, the delivery tool comprises a return electrode configured to remove current from the subject, and / or the delivery tool is configured to apply voltage to the implant-electrode, such that current flows from the implant-electrode, through the adhesive, to the return electrode, thereby activating the adhesive to adhere the implant body to the tissue.
[0619] Example 49. The system according to example 48, wherein the system has: adhesive-curing mode in which the delivery tool applies voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive, to the return electrode; and / or a navigation mode in which the implant-electrode is configured to measure endogenic electrical signals within the heart.
[0620] Example 50. The system according to example 49, wherein the system is configured to, responsively to the measured endogenic electrical signals, calculate a location of the implant-electrode.
[0621] Example 51. The system according to example 48, wherein: the implant comprises a plurality of implant-electrodes, and / or the delivery tool is adjustable to selectively apply voltage to one of the implant-electrodes, such that current flows from the selected implant-electrode, through a selected portion of the adhesive, to the return electrode.
[0622] Example 52. The system according to example 51, wherein the system is transitionable between: a first state in which the delivery tool is configured to apply voltage to a first implant-electrode, such that current flows from the first implant-electrode, through a first portion of the adhesive, to the return electrode; and / or a second state in which the delivery tool is configured to apply voltage to a second implant-electrode, such that current flows from the second implant-electrode, through a second portion of the adhesive, to the return electrode.
[0623] Example 53. The system according to any one of examples 8–52, wherein: the energy-applicator comprises an implant-electrode; the system comprises a return electrode, configured to be positioned on a skin surface of the subject; and / or the system has: adhesive- curing mode in which the delivery tool applies voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive, to the return electrode; and / or a bioimpedance-measuring mode in which the delivery tool applies voltage to the implant-electrode such that current flows from the implant-electrode, through tissue of the subject, to the return electrode.
[0624] Example 54. The system according to example 53, wherein: the return electrode is a first return electrode, the system further comprises a second return electrode, and / or the system is configured to: measure current that flows to each return electrode, and / or responsively to the measurements, calculate a location of the implant-electrode.
[0625] Example 55. The system according to example 53, wherein the system is configured to apply a higher voltage to the implant-electrode while the system is in the adhesive-curing mode than while the system is in the bioimpedance-measuring mode.
[0626] Example 56. A system for use at a tissue of a heart of a subject, the system comprising: an implant, the implant comprising: an implant body, and / or an energy- activated adhesive, pre-disposed on the implant body; and / or a delivery tool, configured to: transluminally deliver the implant to the heart, and position the adhesive in contact with the tissue, and / or while the adhesive remains in contact with the tissue, activate the adhesive to adhere the implant body to the tissue by applying energy to the adhesive.
[0627] Example 57. The system according to example 56, wherein at least one of the implant, the delivery tool and the adhesive is sterile.
[0628] Example 58. The system according to any one of examples 56–57, wherein the delivery tool comprises an energy-applicator configured to be removed from the subject after activating the adhesive.
[0629] Example 59. The system according to example 58, wherein the energy- applicator is configured to apply heat to the adhesive.
[0630] Example 60. The system according to example 58, wherein the energy- applicator is configured to apply electrical current to the adhesive.
[0631] Example 61. The system according to any one of examples 56–60, wherein the implant comprises an energy-applicator that is fixedly coupled to the implant body.
[0632] Example 62. The system according to example 61, wherein the energy- applicator is embedded within the adhesive.
[0633] Example 63. The system according to example 61, wherein the energy- applicator comprises an implant-electrode configured to activate the adhesive by applying electrical current to the adhesive.
[0634] Example 64. The system according to example 61, wherein the delivery tool comprises a terminal that is reversibly electrically connected to the energy-applicator.
[0635] Example 65. The system according to any one of examples 56–64, wherein: the implant further comprises a tissue anchor defining an energy-applicator; and / or the delivery tool is configured to, while the adhesive remains in contact with the tissue, transmit energy to the energy-applicator, thereby activating the adhesive to adhere the implant body to the tissue by applying energy to the adhesive.
[0636] Example 66. The system according to example 65, wherein the tissue anchor comprises a resistor heater defining the energy-applicator.
[0637] Example 67. The system according to example 65, wherein the tissue anchor comprises an implant-electrode defining the energy-applicator.
[0638] Example 68. The system according to example 65, wherein the tissue anchor comprises a tissue-engaging element defining the energy-applicator.
[0639] Example 69. A method for implanting an implant in a real or simulated heart of a real or simulated subject, the method comprising: transluminally advancing a bioprinter nozzle to the heart, the bioprinter nozzle housing a bioink comprising a biomaterial; and / or within the heart, printing the implant by extruding the bioink from the bioprinter nozzle such that the biomaterial defines the implant.
[0640] Example 70. The method according to example 69, further comprising sterilizing the implant, the nozzle and the bioink.
[0641] Example 71. The method according to any one of examples 69–70, further comprising, subsequently to the step of printing, transluminally withdrawing the bioprinter nozzle from the subject.
[0642] Example 72. The method according to any one of examples 69–71, wherein printing the implant comprises printing the implant within the heart by extruding the bioink from the bioprinter nozzle such that the biomaterial: assumes a three-dimensional implant- shape, and / or adheres to tissue at a site in the heart.
[0643] Example 73. The method according to example 72, wherein printing the implant comprises printing the implant within the heart by extruding the bioink from the bioprinter nozzle at the site in the heart such that the implant inhibits bloodflow at the site.
[0644] Example 74. The method according to example 72, wherein: the implant is a first implant, the three-dimensional implant-shape is a three-dimensional first-implant- shape, the site is a first site, and / or the method further comprises printing a second implant within the heart by extruding the bioink from the bioprinter nozzle at a second site in the heart such that the biomaterial: assumes a three-dimensional second-implant-shape, and / or adheres to tissue at the second site.
[0645] Example 75. The method according to example 72, wherein: printing the implant comprises printing the implant within the heart by extruding the bioink from the bioprinter nozzle at the site such that a first portion of the biomaterial adheres to tissue at the site, and / or the method further comprises securing a prosthesis within the heart by adhering a second portion of the biomaterial to the prosthesis.
[0646] Example 76. The method according to example 75, wherein: the prosthesis is a prosthetic valve, the site is within a ventricle of the heart, and / or securing the prosthesis comprises securing the prosthetic valve by adhering the first portion of the biomaterial to the site within the ventricle of the heart.
[0647] Example 77. The method according to example 76, wherein printing the implant comprises printing the implant within the heart by extruding the bioink from the bioprinter nozzle such that the biomaterial defines a tether connecting the prosthesis to the site.
[0648] Example 78. The method according to example 72, wherein: the site is a first site in the heart; and / or printing the implant comprises printing the implant within the heart by extruding the bioink from the bioprinter nozzle in the heart such that the biomaterial adheres to tissue at: the first site of the heart, and / or a second site of the heart.
[0649] Example 79. The method according to example 78, wherein printing the implant comprises printing the implant within the heart by extruding the bioink from the bioprinter nozzle in the heart such that the biomaterial defines a tether connecting the first site to the second site.
[0650] Example 80. The method according to example 79, wherein printing the implant comprises printing the implant within the heart by extruding the bioink from the bioprinter nozzle in the heart such that tether restricts movement of the first site relative to the second site.
[0651] Example 81. The method according to example 80, wherein printing the implant comprises printing the implant within the heart by extruding the bioink from the bioprinter nozzle in the heart such that, during a cardiac cycle of the heart, the tether limits a dimension of the heart.
[0652] Example 82. The method according to example 81, wherein the first site is at a leaflet of a valve of the heart, the second site is an anchor site located within a chamber of the heart, and / or printing the implant comprises printing the implant within the heart by extruding the bioink from the bioprinter nozzle in the heart such that, during a cardiac cycle of the heart, the tether limits a distance between the leaflet and the anchor site.
[0653] Example 83. The method according to example 80, wherein: the first site is at an annulus of a valve of the heart, the second site is located at the annulus, opposite the first site, and / or printing the implant comprises printing the implant within the heart by extruding the bioink from the bioprinter nozzle in the heart such that, during a cardiac cycle of the heart, the tether limits a diameter of the annulus.
[0654] Example 84. The method according to example 79, wherein: the first site is at a chamber of the heart, the second site is located at the chamber, opposite the first site, and / or printing the implant comprises printing the implant within the heart by extruding the bioink from the bioprinter nozzle in the heart such that, during a cardiac cycle of the heart, the tether limits a width of the chamber.
[0655] Example 85. The method according to example 79, wherein: the first site is located at a tip-portion of a first leaflet of a valve of the heart, the second site is located at a tip portion of a second leaflet of the valve, opposite the tip-portion of the first leaflet, and / or printing the implant comprises printing the implant within the heart by extruding the bioink from the bioprinter nozzle in the heart such that, during a cardiac cycle of the heart, the tether limits a distance between the tip-portion of the first leaflet and the tip-portion of the second leaflet.
[0656] Example 86. The method according to any one of examples 72–85, further comprising, subsequently to the step of printing, fixating the biomaterial such that the biomaterial retains the implant-shape.
[0657] Example 87. The method according to example 86, wherein fixating the biomaterial comprises applying fixating the biomaterial by applying heat to the bioink such that the biomaterial retains the implant-shape.
[0658] Example 88. The method according to example 86, wherein fixating the biomaterial comprises applying fixating the biomaterial by applying a chemical fixator to the bioink such that the biomaterial retains the implant-shape.
[0659] Example 89. The method according to example 86, wherein fixating the biomaterial comprises applying fixating the biomaterial by applying ultrasound energy to the bioink such that the biomaterial retains the implant-shape.
[0660] Example 90. The method according to example 86, wherein fixating the biomaterial comprises applying fixating the biomaterial by applying electrical current to the bioink such that the biomaterial retains the implant-shape.
[0661] Example 91. The method according to example 86, wherein fixating the biomaterial comprises applying fixating the biomaterial by applying light to the bioink such that the biomaterial retains the implant-shape.
[0662] Example 92. The method according to example 86, wherein fixating the biomaterial comprises applying fixating the biomaterial by applying radio waves to the bioink such that the biomaterial retains the implant-shape.
[0663] Example 93. The method according to any one of examples 72–92, wherein fixating the biomaterial comprises, subsequently to the step of printing: transluminally advancing a fixator to the heart, and / or using the fixator, fixating the biomaterial such that the biomaterial retains the implant-shape.
[0664] Example 94. The method according to example 93, wherein the fixating the biomaterial comprises fixating the biomaterial such that the biomaterial: retains the implant-shape, and / or adheres to tissue of the heart.
[0665] Example 95. A method for implanting an implant in a simulated heart of a subject, the method comprising: transluminally advancing a bioprinter nozzle to the heart, the bioprinter nozzle housing a bioink comprising a biomaterial; and / or within the heart, printing the implant by extruding the bioink from the bioprinter nozzle such that the biomaterial defines the implant.
[0666] Example 96. A method for use with a real or simulated heart of a real or simulated subject, the method comprising, using a delivery tool, transluminally: advancing an implant to the heart, the implant including: an implant body, an adhesive, pre-disposed on the implant, and / or an energy-applicator; positioning the implant in the heart such that the adhesive contacts real or simulated tissue of the heart; and / or activating the adhesive by driving the energy-applicator to apply energy to the adhesive, thereby adhering the implant body to tissue of the heart.
[0667] Example 97. The method according to example 96, further comprising sterilizing the implant, the delivery tool and the adhesive.
[0668] Example 98. The method according to any one of examples 96–97, further comprising, subsequently to activating the adhesive, removing the delivery tool from the subject.
[0669] Example 99. The method according to any one of examples 96–98, wherein activating the adhesive comprises activating the adhesive by driving the energy-applicator to apply heat to the adhesive, thereby adhering the implant body to the tissue.
[0670] Example 100. The method according to any one of examples 96–99, wherein activating the adhesive comprises activating the adhesive by driving the energy-applicator to apply electrical current to the adhesive, thereby adhering the implant body to the tissue.
[0671] Example 101. The method according to example 100, wherein: the energy- applicator includes an implant-electrode; and / or activating the adhesive comprises activating the adhesive by applying voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive, to a return electrode, thereby adhering the implant body to the tissue.
[0672] Example 102. The method according to example 101, wherein: the implant- electrode is a first implant-electrode; the energy-applicator further includes a second implant-electrode; and / or activating the adhesive comprises activating the adhesive by applying voltage to: the first implant-electrode such that current flows from the first implant-electrode, through a first portion of the adhesive, to the return electrode, thereby adhering a first part of the implant body to the tissue, and / or the second implant-electrode such that current flows from the second implant-electrode, through a second portion of the adhesive, to the return electrode, thereby adhering a second part of the implant body to the tissue.
[0673] Example 103. The method according to example 102, wherein activating the adhesive comprises activating the adhesive by concurrently applying voltage to: the first implant-electrode such that current flows from the first implant-electrode, through the firstportion of the adhesive, to the return electrode, thereby adhering a first part of the implant body to the tissue, and / or the second implant-electrode such that current flows from the second implant-electrode, through the second portion of the adhesive, to the return electrode, thereby adhering a second part of the implant body to the tissue.
[0674] Example 104. The method according to example 102, wherein activating the adhesive comprises activating the adhesive by: applying voltage to the first implant-electrode such that current flows from the first implant-electrode, through the first portion of the adhesive, to the return electrode, thereby adhering a first portion of the implant body to the tissue, and / or subsequently, applying voltage to the second implant-electrode such that current flows from the second implant-electrode, through the second portion of the adhesive, to the return electrode, thereby adhering a second portion of the implant body to the tissue.
[0675] Example 105. The method according to example 104, further comprising deploying the implant from the delivery tool in a stepwise manner, such that applying voltage to the first implant-electrode comprises applying voltage to the first implant- electrode while the second portion of the implant body is not in contact with the tissue.
[0676] Example 106. The method according to example 105, wherein deploying the implant from the delivery tool in the stepwise manner comprises deploying the implant such that applying voltage to the first implant-electrode comprises applying voltage to the first implant-electrode while the second portion of the implant body is disposed within the delivery tool.
[0677] Example 107. The method according to any one of examples 96–106, wherein: the implant body includes a tissue-engaging element, and / or the method further comprises, prior to activating the adhesive, mechanically attaching the tissue-engaging element to the tissue.
[0678] Example 108. The method according to example 107, wherein: the tissue- engaging element of the implant body includes a clip; and / or mechanically attaching the tissue-engaging element to the tissue comprises closing the clip on the tissue, prior to activating the adhesive.
[0679] Example 109. The method according to example 107, wherein: the implant includes a tissue anchor; and / or mechanically attaching the tissue-engaging element to the tissue comprises driving the tissue anchor through the implant body and into tissue of the heart, prior to driving the energy-applicator to apply energy to the adhesive, thereby adhering the implant body to tissue of the heart.
[0680] Example 110. The method according to example 107, wherein: the adhesive is pre-disposed on the tissue-engaging element of the implant body, and / or activating theadhesive comprises, subsequently to mechanically attaching the tissue-engaging element to the tissue, activating the adhesive by driving the energy-applicator to apply energy to the adhesive, thereby adhering the tissue-engaging element of the implant body to tissue of the heart.
[0681] Example 111. The method according to example 110, wherein: the implant further includes a tissue anchor; and / or mechanically attaching the tissue-engaging element to the tissue comprises driving the tissue anchor through the tissue-engaging element and into the tissue.
[0682] Example 112. The method according to example 111, wherein: the tissue anchor defines the energy- applicator; and / or the method further comprises activating the adhesive by driving the energy-applicator to apply energy to the adhesive, thereby adhering the tissue- engaging element of the implant body to tissue of the heart.
[0683] Example 113. The method according to example 111, wherein: the tissue anchor is a first tissue anchor; the implant further includes a second tissue anchor; and / or mechanically attaching the tissue-engaging element of the implant body to the tissue comprises: driving the first tissue anchor through a first segment of the tissue-engaging element and into the tissue, and / or driving the second tissue anchor through a second segment of the tissue-engaging element and into the tissue.
[0684] Example 114. The method according to example 113, wherein: the first tissue anchor includes a first energy-applicator; the second tissue anchor includes a second energy- applicator; and / or activating the adhesive comprises activating the adhesive by: driving the first energy-applicator to apply energy to adhesive on the first segment of the tissue- engaging element, thereby adhering the first segment to tissue of the heart, and / or driving the second energy-applicator to apply energy to adhesive on the second segment of the tissue-engaging element, thereby adhering the second segment to tissue of the heart.
[0685] Example 115. The method according to example 114, wherein activating the adhesive comprises activating the adhesive by concurrently: driving the first energy- applicator to apply energy to adhesive on the first segment of the tissue-engaging element, thereby adhering the first segment to tissue of the heart, and / or driving the second energy- applicator to apply energy to adhesive on the second segment of the tissue-engaging element, thereby adhering the second segment to tissue of the heart.
[0686] Example 116. The method according to example 114, wherein driving the first energy-applicator comprises driving the first energy-applicator to apply energy to adhesive on the first segment of the tissue-engaging element, thereby adhering the first segment totissue of the heart, prior to driving the second energy-applicator to apply energy to adhesive on the second segment of the tissue-engaging element.
[0687] Example 117. The method according to example 116, wherein driving the first energy-applicator comprises driving the first energy-applicator to apply energy to adhesive on the first segment of the tissue-engaging element, thereby adhering the first segment to tissue of the heart, while the second segment of the tissue-engaging element is not in contact with the tissue.
[0688] Example 118. The method according to example 117, wherein driving the first energy-applicator comprises driving the first energy-applicator to apply energy to adhesive on the first segment of the tissue-engaging element, thereby adhering the first segment to tissue of the heart, while the second segment of the tissue-engaging element is disposed within the delivery tool.
[0689] Example 119. The method according to any one of examples 107–108, wherein: the implant includes a tissue anchor on which the adhesive is pre-disposed; and / or mechanically attaching the tissue-engaging element to the tissue comprises driving the tissue anchor through the implant body and into tissue of the heart.
[0690] Example 120. The method according to example 119, wherein: the tissue anchor includes the energy-applicator; and / or activating the adhesive comprises, subsequently to driving the tissue anchor through the implant body and into tissue of the heart, activating the adhesive on the tissue anchor by driving the energy-applicator to apply energy to the adhesive, thereby adhering the tissue anchor to tissue of the heart.
[0691] Example 121. The method according to example 120, wherein: the tissue anchor is a first tissue anchor including a first energy-applicator; the implant further includes a second tissue anchor including a second energy-applicator; mechanically attaching the tissue-engaging element to the tissue further comprises driving the second tissue anchor through the implant body and into tissue of the heart; and / or activating the adhesive comprises: activating the adhesive that is pre-disposed on the first tissue anchor by driving the energy-applicator to apply energy to the adhesive that is pre-disposed on the first tissue anchor, thereby adhering the first tissue anchor to tissue of the heart, and / or activating the adhesive that is pre-disposed on the second tissue anchor by driving the energy-applicator to apply energy to the adhesive that is pre-disposed on the second tissue anchor, thereby adhering the second tissue anchor to tissue of the heart.
[0692] Example 122. The method according to example 121, further comprising deploying the implant from the delivery tool in a stepwise manner, such that activating theadhesive comprises activating the adhesive that is pre-disposed on the first tissue anchor while the second tissue anchor is not in contact with the tissue.
[0693] Example 123. The method according to example 122, wherein deploying the implant from the delivery tool in the stepwise manner comprises deploying the implant such that activating the adhesive comprises activating the adhesive that is pre-disposed on the first tissue anchor while the second tissue anchor is disposed within the delivery tool.
[0694] Example 124. The method according to any one of examples 96–123, wherein: the method further comprises measuring endogenic electrophysiological signals, and / or positioning the implant comprises, responsively to the measured endogenic electrophysiological signals, positioning the implant in the heart such that the adhesive contacts tissue of the heart.
[0695] Example 125. The method according to example 124, wherein: the implant includes a sensory electrode; and / or the step of measuring comprises, using the sensory electrode, measuring endogenic electrophysiological signals.
[0696] Example 126. The method according to any one of examples 96–99, wherein: the energy-applicator includes an implant-electrode; and / or the method further comprises: positioning a bioimpedance measuring-electrode on a skin surface of the subject, and / or using the delivery tool: transluminally advancing the implant-electrode to the heart, and / or applying voltage to the implant-electrode such that current flows from the implant-electrode, through tissue of the subject, to the bioimpedance measuring-electrode.
[0697] Example 127. The method according to example 126, further comprising: while applying voltage to the implant-electrode, measuring current that flows to the bioimpedance measuring-electrode; and / or responsively to the measurements of current, calculating a position of the implant-electrode.
[0698] Example 128. The method according to example 127, further comprising, responsively to the calculated position of the implant-electrode, repositioning the implant.
[0699] Example 129. The method according to example 127, wherein: the energy- applicator includes an implant-electrode; and / or responsively to the calculated position of the implant-electrode, activating the adhesive comprises activating the adhesive by applying voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive, to a return electrode, thereby adhering the implant body to the tissue.
[0700] Example 130. The method according to example 129, further comprising, prior to activating the adhesive: ungrounding the bioimpedance measuring-electrode, and / or grounding the return electrode.
[0701] Example 131. The method according to example 129, wherein: applying voltage to the implant-electrode such that current flows from the implant-electrode, through tissue of the subject, to the bioimpedance measuring-electrode comprises applying a lower voltage to the implant-electrode, and / or applying voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive, to the return electrode, thereby adhering the implant body to the tissue comprises applying a higher voltage to the implant- electrode.
[0702] Example 132. A method for use with a simulated heart of a subject, the method comprising, using a delivery tool, transluminally: advancing an implant to the heart, the implant including: an implant body, an adhesive, pre-disposed on the implant, and / or an energy-applicator; positioning the implant in the heart such that the adhesive contacts tissue of the heart; and / or activating the adhesive by driving the energy-applicator to apply energy to the adhesive, thereby adhering the implant body to tissue of the heart.
[0703] Example 133. A method for use at a real or simulated heart of a real or simulated subject, the method comprising: transluminally advancing a bioprinter nozzle into the heart; and / or within the heart, using the bioprinter nozzle: adhering a bioink to real or simulated tissue of the heart, and / or printing, from the bioink, an implant that is adhered to the tissue.
[0704] Example 134. The method according to example 133, further comprising sterilizing the implant, the nozzle and the bioink.
[0705] Example 135. A method for use at a simulated heart of a subject, the method comprising: transluminally advancing a bioprinter nozzle into the heart; and / or within the heart, using the bioprinter nozzle: adhering a bioink to tissue of the heart, and / or printing, from the bioink, an implant that is adhered to the tissue.
[0706] Example 136. A system for use in a heart of a subject, the system comprising: an implant, the implant comprising: an implant body, an adhesive, pre-disposed on the implant body, and / or a activator; and / or a delivery tool, configured to: transluminally deliver the implant to the heart, and position the adhesive in contact with tissue of the heart, and / or while the adhesive remains in contact with the tissue, activate the adhesive to adhere the implant body to the tissue by applying the activator to the adhesive.
[0707] Example 137. The system according to example 136, wherein at least one of the implant and the delivery tool is sterile.
[0708] Example 138. The system according to example 136, wherein: the adhesive is a mussel foot protein-based bioadhesive, and / or the activator is configured to activate the bioadhesive by cross-linking amino acid residues of the mussel foot protein.
[0709] Example 139. A method, comprising: weaving a fabric that defines a face by interlacing a weft yarn with a warp that includes multiple warp yarns, the weaving comprising forming a warp float from a given one of the warp yarns by, on at least one pass of the weft yarn across the warp, skipping the given one of the warp yarns; and / or shaping the warp float into a directional barb that protrudes obliquely from the face of the fabric by selectively cutting away a part of the warp float.
[0710] Example 140. The method according to example 139, further comprising sterilizing the weft yarn and the warp yarns.
[0711] Example 141. The method according to any one of examples 139–140, wherein weaving comprises weaving a planar fabric.
[0712] Example 142. The method according to any one of examples 139–140, wherein weaving comprises weaving a non-planar fabric.
[0713] Example 143. The method according to example 142, wherein weaving comprises weaving a concave fabric.
[0714] Example 144. The method according to example 142, wherein weaving comprises weaving a convex fabric.
[0715] Example 145. The method according to any one of examples 139–144, further comprising, prior to cutting away the part of the warp float, adhering a non-floating segment of the warp yarn to a back of the fabric.
[0716] Example 146. The method according to example 145, wherein adhering comprises adhering the non-floating segment of the warp yarn to the back of the fabric by heating the back of the fabric.
[0717] Example 147. The method according to example 145, wherein adhering comprises adhering the non-floating segment of the warp yarn to the back of the fabric by adhering a laminate to the back of the fabric.
[0718] Example 148. The method according to any one of examples 139–147, wherein: shaping the warp float into the directional barb comprises, prior to selectively cutting, shape- setting the warp float, and / or selectively cutting comprises selectively cutting away the part of the warp float to form a shape-set directional barb that protrudes obliquely from the face of the fabric.
[0719] Example 149. The method according to example 148, wherein selectively cutting comprises selectively cutting away the part of the warp float to form a shape-set hooked barb that protrudes obliquely from the face of the fabric.
[0720] Example 150. The method according to example 148, wherein shape-setting comprises shape-setting the warp float by applying electromagnetic energy to the fabric.
[0721] Example 151. The method according to example 148, wherein shape-setting comprises shape-setting the warp float by heating the fabric.
[0722] Example 152. The method according to example 151, wherein shape-setting comprises shape-setting the warp float by heating the fabric to a temperature exceeding a melting point of the warp yarn.
[0723] Example 153. The method according to example 152, wherein shape-setting comprises shape-setting the warp float by heating the fabric to a temperature not exceeding a melting point of the weft yarn.
[0724] Example 154. The method according to example 153, wherein shape-setting comprises shape-setting the warp float by heating the fabric to 180–240 °C.
[0725] Example 155. The method according to any one of examples 139–154, further comprising, prior to selectively cutting away the part of the warp float, distancing the warp float from the face of the fabric by inserting a pin between the warp float and the face of the fabric.
[0726] Example 156. The method according to example 155, wherein inserting comprises, while weaving the fabric, inserting the pin between the warp float and the face of the fabric.
[0727] Example 157. The method according to example 155, wherein inserting comprises, after weaving the fabric, inserting the pin between the warp float and the face of the fabric.
[0728] Example 158. The method according to example 155, wherein selectively cutting comprises, while the pin is disposed between the warp float and the face of the fabric, using a blade to cut the warp float.
[0729] Example 159. The method according to example 158, wherein selectively cutting comprises using the blade to cut the warp float along the pin, such that the pin serves as a blade-guide.
[0730] Example 160. The method according to example 159, wherein: the pin has a cross-section defining a base and an apex, and / or inserting the pin comprises inserting the pin such that the base of the pin faces the face of the fabric, and the apex is positioned further away than the base from the face of the fabric.
[0731] Example 161. The method according to example 160, wherein selectively cutting comprises cutting the warp yarn along the apex of the pin.
[0732] Example 162. The method according to example 160, wherein selectively cutting comprises cutting the warp yarn along the base of the pin.
[0733] Example 163. The method according to example 155, wherein shaping the warp float into the directional barb comprises, prior to selectively cutting, shape-setting the warp float while the pin is disposed between the warp float and the face of the fabric.
[0734] Example 164. The method according to example 163, wherein shape-setting comprises shape-setting the warp float by heating the pin while the pin is disposed between the warp float and the face of the fabric.
[0735] Example 165. The method according to example 163, wherein shape-setting comprises shape-setting the warp float by heating the fabric while the pin is disposed between the warp float and the face of the fabric.
[0736] Example 166. The method according to example 163, wherein shape-setting comprises shape-setting the warp float by applying electromagnetic energy to the fabric while the pin is disposed between the warp float and the face of the fabric.
[0737] Example 167. The method according to any one of examples 139–166, wherein: forming the warp float from the given one of the warp yarns comprises forming a first warp float from a first warp yarn; shaping the warp float into the directional barb comprises shaping the first warp float into a first directional barb that protrudes obliquely from the face of the fabric by selectively cutting away a part of the first warp float; weaving further comprises forming a second warp float from a second warp yarn by, on the at least one pass of the weft yarn across the warp, skipping the second warp yarn; and / or the method further comprises shaping the second warp float into a second directional barb that protrudes obliquely from the face of the fabric by selectively cutting away a part of the second warp float.
[0738] Example 168. The method according to example 167, wherein: weaving further comprises forming a third warp float from a third warp yarn by, on the at least one pass of the weft yarn across the warp, skipping the third warp yarn; and / or the method does not include cutting away a part of the third warp float.
[0739] Example 169. The method according to example 167, further comprising folding the fabric into a bi-layer fabric such that: the first directional barb protrudes obliquely from a first layer of the fabric, and / or the second directional barb protrudes obliquely from a second layer of the fabric.
[0740] Example 170. The method according to example 169, wherein folding comprises folding the fabric along a longitudinal axis of the fabric.
[0741] Example 171. The method according to example 169, wherein folding comprises folding the fabric in parallel to the warp yarns.
[0742] Example 172. The method according to example 169, wherein folding comprises folding the fabric such that the first directional barb and the second directional barb each protrude symmetrically from a respective layer of the fabric.
[0743] Example 173. The method according to example 169, wherein folding comprises folding the fabric such that the first directional barb and the second directional barb protrude at equal angles from a respective layer of the fabric.
[0744] Example 174. The method according to example 167, further comprising distancing the first warp float and the second warp float from the face of the fabric by inserting a pin between the face of the fabric and the first and second warp floats.
[0745] Example 175. The method according to example 174, wherein: weaving further comprises forming a third warp float from a third warp yarn by, on the at least one pass of the weft yarn across the warp, skipping the third warp yarn; and / or the method does not include inserting the pin between the face of the fabric and the third warp float.
[0746] Example 176. The method according to example 174, wherein shaping comprises shaping the first warp float and the second warp float into directional barbs that protrude obliquely from the face of the fabric by selectively cutting away respective parts of the first warp float and the second warp float by advancing a blade along the pin.
[0747] Example 177. The method according to example 176, wherein shaping comprises shaping the first warp float and the second warp float into directional barbs that protrude in parallel from the face of the fabric by advancing the blade along the pin to cut away corresponding parts of the first warp float and the second warp float.
[0748] Example 178. The method according to example 176, wherein shaping comprises shaping the first warp float and the second warp float into similarly shaped barbs that protrude from the face of the fabric by advancing the blade along the pin to cut away corresponding parts of the first warp float and the second warp float.
[0749] Example 179. The method according to any one of examples 139–178, wherein: forming the warp float from the given one of the warp yarns comprises forming a first warp float from the given one of the warp yarns by, on a first pass of the weft yarn across the warp, skipping the given one of the warp yarns; shaping comprises shaping the first warp float into a first directional barb that protrudes obliquely from the face of the fabric by selectively cutting away a part of the first warp float; and / or the method further comprises: forming a second warp float from the given one of the warp yarns by, on a second pass of the weft yarn across the warp, skipping the given one of the warp yarns, and / or shaping furthercomprising shaping the second warp float into a second directional barb that protrudes obliquely from the face of the fabric by selectively cutting away a part of the second warp float.
[0750] Example 180. The method according to example 179, wherein: weaving further comprises forming a third warp float from the given one of the warp yarns by, on a third pass of the weft yarn across the warp, skipping the given one of the warp yarns; and / or the method does not include cutting away a portion of third warp float.
[0751] Example 181. The method according to example 179, further comprising folding the fabric into a bi-layer fabric such that: the first directional barb protrudes obliquely from a first layer of the fabric, and / or the second directional barb protrudes obliquely from a second layer of the fabric.
[0752] Example 182. The method according to example 181, wherein folding comprises folding the fabric perpendicularly to a longitudinal axis of the fabric.
[0753] Example 183. The method according to example 181, wherein folding comprises folding the fabric perpendicularly to the warp yarns.
[0754] Example 184. The method according to example 181, wherein folding comprises folding the fabric such that the first directional barb and the second directional barb each protrude symmetrically from a respective layer of the fabric.
[0755] Example 185. The method according to example 181, wherein folding comprises folding the fabric such that the first directional barb and the second directional barb protrude at equal angles from a respective layer of the fabric.
[0756] Example 186. The method according to example 179, further comprising, prior to selectively cutting, distancing the first warp float and the second warp float from the face of the fabric by inserting: a first pin between the first warp float and the face of the fabric, and / or a second pin between the second warp float and the face of the fabric.
[0757] Example 187. The method according to example 186, wherein distancing the first warp float and the second warp float from the face of the fabric comprises inserting the first pin and the second pin in parallel.
[0758] Example 188. The method according to example 187, wherein distancing the first warp float and the second warp float from the face of the fabric comprises inserting the first pin and the second pin in parallel with the weft yarn.
[0759] Example 189. The method according to example 186, wherein shaping comprises shaping the first warp float and the second warp float into directional barbs that protrudeobliquely from the face of the fabric by advancing a blade along the first pin and the second pin to selectively cut away respective parts of the first warp float and the second warp float.
[0760] Example 190. The method according to example 189, wherein shaping comprises shaping the first warp float and the second warp float into directional barbs that protrude in opposite directions from the face of the fabric by advancing a blade along the first pin and the second pin to selectively cut away respective parts of the first warp float and the second warp float.
[0761] Example 191. The method according to example 189, wherein shaping comprises shaping the first warp float and the second warp float into directional barbs that protrude symmetrically from the face of the fabric by advancing a blade along the first pin and the second pin to selectively cut away respective parts of the first warp float and the second warp float.
[0762] Example 192. The method according to example 189, wherein shaping comprises shaping the first warp float and the second warp float into similarly shaped directional barbs that protrude from the face of the fabric by advancing a blade along the first pin and the second pin to selectively cut away respective parts of the first warp float and the second warp float.
[0763] Example 193. A method, comprising: weaving a fabric by interlacing a weft yarn with a warp that includes multiple warp yarns, the weaving comprising forming a warp float from a given one of the warp yarns by passing the weft yarn under the given one of the warp yarns on multiple consecutive passes of the weft yarn across the warp; and / or shaping the warp float into a directional barb that protrudes obliquely from a plane of the fabric by cutting away a portion of the warp float.
[0764] Example 194. The method according to example 193, further comprising sterilizing the weft yarn and the warp yarns.
[0765] Example 195. A method, comprising: weaving a fabric that defines a face by interlacing a weft yarn with a warp that includes multiple warp yarns, by passing the weft yarn: in a first pass along a width of the warp: over a first warp yarn, under a second warp yarn, over a third warp yarn, and / or in a second pass along the width of the warp: under the first warp yarn, the second warp yarn and the third warp yarn, such that the second warp yarn defines a warp float spanning a length of the face of the fabric; and / or shaping the warp float into a directional barb that protrudes obliquely from the face of the fabric by selectively cutting away a part of the warp float.
[0766] Example 196. The method according to example 195, further comprising sterilizing the weft yarn and the warp yarns.
[0767] Example 197. The method according to any one of examples 195–196, wherein the method does not comprise cutting away a portion of the first warp yarn.
[0768] Example 198. The method according to any one of examples 195–197, wherein the method does not comprise cutting away a portion of the third warp yarn.
[0769] Example 199. The method according to any one of examples 195–198, wherein cutting comprises selectively cutting away a portion of the second warp yarn, adjacent to the weft yarn.
[0770] Example 200. The method according to any one of examples 195–199, wherein cutting comprises selectively cutting away a portion of the second warp yarn, along a length of the weft yarn.
[0771] Example 201. A method for use at a real or simulated tissue of a real or simulated cardiovascular system of a subject, the method comprising, using a delivery tool: transluminally advancing an implant including a barbed fabric to the tissue, holding the fabric against the tissue such that barbs of the fabric penetrate the tissue, and / or while the barbs remain in the tissue, manipulating an adhesive to adhere the fabric to the tissue; and / or subsequently, removing the delivery tool from the subject.
[0772] Example 202. The method according to example 201, further comprising sterilizing the implant, the adhesive and the delivery tool.
[0773] Example 203. The method according to any one of examples 201–202, wherein: leaflets of a native valve of the cardiovascular system define the tissue, the implant includes a prosthetic valve, and / or holding the fabric comprises holding the fabric against the tissue such that barbs of the fabric penetrate the leaflets.
[0774] Example 204. The method according to any one of examples 201–202, wherein: the delivery tool includes a scaffold; and / or holding comprises, using the scaffold, pressing the fabric against the tissue such that the barbs penetrate the tissue.
[0775] Example 205. The method according to example 204, wherein holding comprises sandwiching the tissue between the scaffold and the fabric such that the barbs penetrate the tissue.
[0776] Example 206. The method according to example 204, wherein manipulating comprises manipulating the adhesive to adhere the fabric to the tissue while, using the scaffold, pressing the fabric against the tissue such that the barbs penetrate the tissue.
[0777] Example 207. The method according to example 204: further comprising, after pressing the fabric against the tissue such that the barbs penetrate the tissue, retracting thescaffold from the tissue; and / or subsequently manipulating the adhesive to adhere the fabric to the tissue while the barbs remain in the tissue.
[0778] Example 208. The method according to example 204, wherein: the scaffold includes a shape-memory material having a compressed state and an expanded state; and / or the method further comprises: delivering the scaffold to the tissue while the scaffold is in the compressed state, deploying the scaffold such that the scaffold assumes the expanded state, and / or holding comprises holding the fabric against the tissue such that the barbs penetrate the tissue, while the scaffold is in the expanded state.
[0779] Example 209. The method according to example 208, wherein deploying comprises deploying the scaffold such that the scaffold engages the tissue as the scaffold transitions from the compressed state to the expanded state.
[0780] Example 210. The method according to example 204, wherein: the scaffold includes a leaflet-clip; holding comprises, using the leaflet-clip, holding the fabric against leaflets of a native valve of the cardiovascular system such that the barbs penetrate the leaflets; and / or manipulating comprises, while the barbs remain in the leaflets, manipulating the adhesive to adhere the fabric to the leaflets.
[0781] Example 211. The method according to example 210, wherein: the leaflet-clip includes a shape-memory material having a compressed state and an expanded state; and / or the method comprises deploying the leaflet-clip such that the leaflet-clip ensnares the leaflets, such that the barbs penetrate the leaflets, as the leaflet-clip transitions from the compressed state to the expanded state.
[0782] Example 212. The method according to example 210, wherein: the native valve defines an upstream side and a downstream side, and / or holding the fabric comprises holding the fabric against the leaflets on the upstream side of the native valve of the cardiovascular system such that the barbs penetrate an upstream of the leaflets.
[0783] Example 213. The method according to example 210, wherein: the native valve defines an upstream side and a downstream side, and / or holding the fabric comprises holding the fabric against the leaflets on the upstream side of the native valve of the cardiovascular system such that the barbs penetrate a downstream-facing surface of the leaflets.
[0784] Example 214. The method according to example 210, wherein: in the absence of the implant, the leaflets of the native valve deflect in an upstream direction and in a downstream direction, and / or holding the fabric comprises holding the fabric against the leaflets such that the barbs penetrate the tissue at an angle that inhibits deflection of the leaflets in the upstream direction.
[0785] Example 215. The method according to example 210, wherein holding the fabric comprises, using the delivery tool, holding the fabric against leaflets of the native valve such that the barbs penetrate: a first leaflet on a first side of the fabric, and / or a second leaflet on a second side of the fabric.
[0786] Example 216. The method according to any one of examples 201–215, wherein: the adhesive is a chemically-activated adhesive that is pre-disposed on the implant, and / or manipulating the adhesive comprises activating the adhesive by applying a chemical agent to the adhesive to adhere the fabric to the tissue.
[0787] Example 217. The method according to example 216, wherein: the adhesive is a protein-based bioadhesive, and / or manipulating the bioadhesive comprises activating the bioadhesive by applying a chemical agent that facilitates cross-linking of amino acid residues of the protein to adhere the fabric to the tissue.
[0788] Example 218. The method according to any one of examples 201–217, wherein: the adhesive is an energy-activated adhesive that is pre-disposed on the implant, and / or manipulating the adhesive comprises activating the adhesive by applying energy to the adhesive to adhere the fabric to the tissue.
[0789] Example 219. The method according to example 218, wherein activating comprises activating the adhesive by applying electromagnetic energy to the adhesive.
[0790] Example 220. The method according to example 218, wherein activating comprises activating the adhesive by applying heat to the adhesive.
[0791] Example 221. The method according to example 218, wherein activating comprises, using an extracorporeal energy-applicator, activating the adhesive by driving the extracorporeal energy-applicator to apply energy to the adhesive from outside of the subject.
[0792] Example 222. The method according to example 218, wherein activating comprises activating the adhesive to adhere the fabric to the tissue by applying energy to the adhesive from within the subject.
[0793] Example 223. The method according to example 222: further comprising, using the delivery tool, transluminally advancing an energy-applicator toward the tissue; and / or wherein activating comprises, using the energy-applicator, activating the adhesive to adhere the fabric to the tissue by applying energy to the adhesive from within the cardiovascular system.
[0794] Example 224. The method according to example 218, wherein activating comprises activating the adhesive by applying electrical current to the adhesive.
[0795] Example 225. The method according to example 224, wherein: the implant includes an implant-electrode; and / or applying electrical current to the adhesive comprises applying voltage to the implant-electrode such that current flows from the implant-electrode and through the adhesive, thereby activating the adhesive.
[0796] Example 226. The method according to example 225, wherein: the delivery tool includes a return electrode; and / or applying electrical current to the adhesive comprises applying voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive and to the return electrode, thereby activating the adhesive.
[0797] Example 227. The method according to example 225, wherein: the implant- electrode is a first implant-electrode; the implant further includes a second implant- electrode; and / or applying electrical current to the adhesive comprises applying voltage to: the first implant-electrode such that current flows from the first implant-electrode and through a first portion of the adhesive, thereby activating the first portion of the adhesive, and / or the second implant-electrode such that current flows from the second implant- electrode and through a second portion of the adhesive, thereby activating the second portion of the adhesive.
[0798] Example 228. The method according to any one of examples 201–227, wherein: the delivery tool includes an adhesive applicator, and / or manipulating the adhesive comprises, using the adhesive applicator, applying the adhesive to the fabric while the barbs remain in the tissue to adhere the fabric to the tissue.
[0799] Example 229. The method according to any one of examples 201–228, further comprising, subsequently to the step of applying the adhesive, activating the adhesive by applying a chemical agent to the adhesive to adhere the fabric to the tissue.
[0800] Example 230. The method according to example 229, wherein: the adhesive is a protein-based bioadhesive, and / or applying the chemical agent to the bioadhesive facilitates cross-linking of amino acid residues of the protein to adhere the fabric to the tissue.
[0801] Example 231. The method according to example 228, wherein manipulating the adhesive comprises, using an energy-applicator, activating the adhesive by applying energy to the adhesive while the barbs remain in the tissue to adhere the fabric to the tissue.
[0802] Example 232. The method according to example 231, wherein applying energy comprises applying electromagnetic energy to the adhesive while the barbs remain in the tissue to adhere the fabric to the tissue.
[0803] Example 233. The method according to example 231, wherein: the energy- applicator is an extracorporeal energy-applicator; and / or activating comprises, using the extracorporeal energy-applicator, activating the adhesive by applying energy to the adhesivefrom outside of the subject while the barbs remain in the tissue to adhere the fabric to the tissue.
[0804] Example 234. The method according to example 231: further comprising, using the delivery tool, transluminally advancing the energy-applicator toward the tissue; and / or wherein activating comprises, using the energy-applicator, activating the adhesive by driving the energy-applicator to apply energy to the adhesive from within the cardiovascular system.
[0805] Example 235. The method according to example 231, wherein activating comprises activating the adhesive by applying electrical current to the adhesive while the barbs remain in the tissue.
[0806] Example 236. The method according to example 235, wherein: the implant includes an implant-electrode; and / or applying electrical current to the adhesive comprises applying voltage to the implant-electrode such that current flows from the implant-electrode and through the adhesive, thereby activating the adhesive.
[0807] Example 237. The method according to example 236, wherein: the delivery tool includes a return electrode; and / or applying electrical current to the adhesive comprises applying voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive and to the return electrode, thereby activating the adhesive.
[0808] Example 238. The method according to example 236, wherein: the implant- electrode is a first implant-electrode; the implant further includes a second implant- electrode; and / or applying electrical current to the adhesive comprises applying voltage to: the first implant-electrode such that current flows from the first implant-electrode and through a first portion of the adhesive, thereby activating the first portion of the adhesive, and / or the second implant-electrode such that current flows from the second implant- electrode and through a second portion of the adhesive, thereby activating the second portion of the adhesive.
[0809] Example 239. A method for use at a tissue of a simulated cardiovascular system of a subject, the method comprising: using a delivery tool: transluminally advancing an implant including a barbed fabric to the tissue, holding the fabric against the tissue such that barbs of the fabric penetrate the tissue, and / or while the barbs remain in the tissue, manipulating an adhesive to adhere the fabric to the tissue; and / or subsequently, removing the delivery tool from the subject.
[0810] Example 240. A system for use at a tissue of a cardiovascular system of a subject, the system comprising: a fabric defining barbs that protrude from a face of the fabric; an adhesive; and / or a transluminally advanceable delivery tool: comprising a scaffold, configured to temporarily restrain the face of the fabric against the tissue such that the barbspenetrate the tissue, and / or configured to: adhere the fabric to the tissue by manipulating the adhesive, and / or transluminally withdraw the scaffold from the subject.
[0811] Example 241. The system according to example 240, wherein at least one of the fabric, the adhesive and the delivery tool is sterile.
[0812] Example 242. The system according to any one of examples 240–241, wherein the adhesive is pre-disposed on the fabric.
[0813] Example 243. The system according to any one of examples 240–241, wherein the delivery tool further comprises an adhesive applicator.
[0814] Example 244. The system according to any one of examples 240–243, wherein the fabric is bioabsorbable.
[0815] Example 245. The system according to any one of examples 240–244, wherein the scaffold is configured to temporarily restrain the face of the fabric against the tissue by sandwiching the tissue between the scaffold and the fabric, such that the barbs penetrate the tissue.
[0816] Example 246. The system according to any one of examples 240–245, wherein the delivery tool is configured to adhere the fabric to the tissue by manipulating the adhesive while the scaffold restrains the face of the fabric against the tissue such that the barbs penetrate the tissue.
[0817] Example 247. The system according to any one of examples 240–246, wherein the delivery tool is configured to: adhere the fabric to the tissue by manipulating the adhesive while the scaffold restrains the face of the fabric against the tissue such that the barbs penetrate the tissue, and / or subsequently, transluminally withdraw the scaffold from the subject, leaving the fabric adhered to the tissue.
[0818] Example 248. The system according to any one of examples 240–247, wherein the delivery tool further comprises an adhesive applicator, configured to apply the adhesive to the fabric while the scaffold restrains the face of the fabric against the tissue such that the barbs penetrate the tissue.
[0819] Example 249. The system according to any one of examples 240–248, wherein the fabric and the scaffold are configured such that penetration of the tissue by the barbs, while the scaffold restrains the face of the fabric against the tissue, is such that upon release of the tissue by the scaffold, the barbs retain the fabric in contact with the tissue.
[0820] Example 250. The system according to any one of examples 240–249, wherein: leaflets of a native valve of the cardiovascular system defines the tissue, and / or the scaffoldcomprises a leaflet-clip, configured to temporarily restrain the face of the fabric against the leaflets such that the barbs penetrate the leaflets.
[0821] Example 251. The system according to example 250, wherein the fabric and the scaffold are configured such that penetration of the leaflets by the barbs, while the scaffold restrains the face of the fabric against the leaflets, is such that upon release of the leaflets by the scaffold, the barbs retain the fabric in contact with the leaflets during a cardiac cycle of the cardiovascular system.
[0822] Example 252. The system according to any one of examples 240–251, wherein: the adhesive is a chemically-activated adhesive, the system further comprises an activator, and / or the delivery tool comprises a nozzle, configured to chemically activate the adhesive by applying the activator to the adhesive.
[0823] Example 253. The system according to example 252, wherein: the adhesive is a mussel foot protein-based bioadhesive, and / or the activator is configured to activate the bioadhesive by cross-linking amino acid residues of the mussel foot protein.
[0824] Example 254. The system according to any one of examples 240–251, wherein: the adhesive is an energy-activated adhesive, and / or the system further comprises an energy-applicator, configured to adhere the fabric to the tissue by applying energy to the adhesive.
[0825] Example 255. The system according to example 254, wherein the energy- applicator is an extracorporeal energy-applicator, configured to activate the adhesive by applying energy to the adhesive from outside of the subject.
[0826] Example 256. The system according to example 254, wherein the delivery tool comprises the energy-applicator, which is configured to adhere the fabric to the tissue by applying energy to the adhesive from within the cardiovascular system.
[0827] Example 257. The system according to example 256, wherein the energy- applicator is configured to adhere the fabric to the tissue by applying electromagnetic energy to the adhesive from within the cardiovascular system.
[0828] Example 258. The system according to example 256, wherein the energy- applicator is configured to adhere the fabric to the tissue by applying heat to the adhesive from within the cardiovascular system.
[0829] Example 259. The system according to example 256, wherein the energy- applicator is configured to adhere the fabric to the tissue by applying electrical current to the adhesive from within the cardiovascular system.
[0830] Example 260. The system according to example 259, wherein: the system comprises an implant that includes the fabric and an implant-electrode; and / or the energy- applicator is configured to apply electrical current to the adhesive by applying voltage to the implant-electrode such that current flows from the implant-electrode and through the adhesive, thereby activating the adhesive.
[0831] Example 261. The system according to example 260, wherein the implant- electrode is disposed on the face of the fabric.
[0832] Example 262. The system according to example 260, wherein the implant- electrode is embedded within the adhesive on the face of the fabric.
[0833] Example 263. The system according to example 260, wherein: the delivery tool comprises a return electrode; and / or the energy-applicator is configured to apply electrical current to the adhesive by applying voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive and to the return electrode, thereby activating the adhesive.
[0834] Example 264. The system according to example 260, wherein: the implant- electrode is a first implant-electrode; the implant further comprises a second implant- electrode; and / or the energy-applicator is configured to apply electrical current to the adhesive by applying voltage to: the first implant-electrode such that current flows from the first implant-electrode and through a first portion of the adhesive, thereby activating the first portion of the adhesive, and / or the second implant-electrode such that current flows from the second implant-electrode and through a second portion of the adhesive, thereby activating the second portion of the adhesive.
[0835] Example 265. The system according to any one of examples 240–264, wherein: the scaffold comprises a shape-memory material having a compressed state and an expanded state, and / or the delivery tool is configured to: deliver the scaffold to the tissue while the scaffold is in the compressed state, and / or deploy the scaffold at the tissue such that the scaffold engages the tissue as the scaffold transitions from the compressed state to the expanded state.
[0836] Example 266. The system according to example 265, wherein the delivery tool is configured to deploy the scaffold at the tissue such that the scaffold restrains the face of the fabric against the tissue such that the barbs penetrate the tissue, as the scaffold transitions from the compressed state to the expanded state.
[0837] Example 267. The system according to example 266, wherein: leaflets of a native valve of the cardiovascular system defines the tissue, the scaffold comprises a leaflet-clip, and / or the delivery tool is configured to deploy the leaflet-clip at the leaflets such that,during a cardiac cycle of the cardiovascular system, the leaflet-clip restrains the face of the fabric against the leaflets such that the barbs penetrate the leaflets as the leaflet-clip transitions from the compressed state to the expanded state.
[0838] Example 268. The system according to example 265, wherein: the delivery tool comprises a catheter, configured to house the scaffold while the scaffold is in the compressed state, and / or the delivery tool is configured to retract the scaffold into catheter such that the scaffold transitions from the expanded state to the compressed state, prior to transluminally withdraw the scaffold from the subject.
[0839] Example 269. The system according to any one of examples 240–268, wherein the fabric is a woven fabric comprising: a weft yarn, and / or multiple warp yarns, including: first warp yarns extending from a first end of the fabric to a second end of the fabric, and / or second warp yarns, each of the second warp yarns being cut in a manner that defines at last one of the barbs.
[0840] Example 270. The system according to example 269, wherein each of the second warp yarns comprises steel.
[0841] Example 271. The system according to example 269, wherein each of the second warp yarns comprises nitinol.
[0842] Example 272. The system according to example 269, wherein each of the second warp yarns comprises nylon.
[0843] Example 273. The system according to example 269, wherein each of the second warp yarns is a monofilament yarn.
[0844] Example 274. The system according to example 269, wherein each of the first warp yarns is a polyfilament yarn.
[0845] Example 275. The system according to example 269, wherein the weft yarn is a polyfilament yarn.
[0846] Example 276. The system according to example 269, wherein each of the second warp yarns comprises a polyester resin.
[0847] Example 277. The system according to any one of examples 269–276, wherein the first warp yarns have a different composition from the second warp yarns.
[0848] Example 278. The system according to example 277, wherein the weft yarn has a different composition from the first warp yarns and the second warp yarns.
[0849] Example 279. The system according to example 277, wherein the weft yarn has the same composition as the first warp yarns.
[0850] Example 280. The system according to any one of examples 240–279, wherein the fabric comprises a laminate disposed on a back of the fabric.
[0851] Example 281. The system according to example 280, wherein the laminate comprises a high weight polyethylene.
[0852] Example 282. The system according to example 280, wherein the laminate comprises a thermoplastic polyurethane.
[0853] Example 283. The system according to example 280, wherein the laminate has the same composition as at least one of the barbs.
[0854] Example 284. A system for use at a heart of a subject, the system comprising: an implant comprising, on an exterior of the implant, a fabric manufactured via the method of example 139; and / or a delivery tool, configured to secure the implant to tissue of the heart by pressing the fabric against the tissue such that the barbs penetrate the tissue.
[0855] Example 285. The system according to example 284, wherein the implant comprises a prosthetic heart valve.
[0856] Example 286. A system for use in a heart of a subject, the system comprising: an implant, the implant comprising: an implant body, an energy-activated adhesive, disposed at the implant body, and / or an implant-electrode that is disposed at the adhesive; and / or a delivery tool, configured to: transluminally position a contact-portion of the implant at a tissue of the heart while electrically connected to the implant-electrode, using the implant- electrode, detect contact between the contact-portion and the tissue, and / or activate the adhesive to adhere the implant body to the tissue by driving the implant-electrode to apply energy to the adhesive.
[0857] Example 287. The system according to example 286, wherein at least one of the implant and the delivery tool is sterile.
[0858] Example 288. The system according to any one of examples 286-287, wherein the implant-electrode is disposed at the contact-portion.
[0859] Example 289. The system according to any one of examples 286-288, wherein the adhesive is disposed at the contact-portion.
[0860] Example 290. The system according to any one of examples 286-289, wherein the delivery tool is configured to, responsively to detecting contact between the contact- portion and the tissue, move the implant-electrode toward the tissue.
[0861] Example 291. The system according to any one of examples 286-290, wherein the implant-electrode is embedded within the adhesive.
[0862] Example 292. The system according to any one of examples 286-291, wherein the delivery tool is configured to automatically drive the implant-electrode to apply energy to the adhesive, responsively to detecting contact between the contact-portion and the tissue.
[0863] Example 293. The system according to any one of examples 286-292, wherein the delivery tool is configured to provide a notification, responsively to detecting contact between the contact-portion and the tissue.
[0864] Example 294. The system according to any one of examples 286-293, wherein: the contact-portion is a first contact-portion of the implant; the implant-electrode is a first implant-electrode disposed at the first contact-portion; the implant further comprises a second implant-electrode disposed at a second contact-portion of the implant; and / or the delivery tool is configured to: adhere the first contact-portion to the tissue by driving the first implant-electrode to apply energy to adhesive at the first contact-portion, and / or adhere the second contact-portion to the tissue by driving the second implant-electrode to apply energy to adhesive at the second contact-portion.
[0865] Example 295. The system according to any one of examples 286-294, wherein: the implant-electrode is a first implant-electrode; the implant further comprises a second implant-electrode; and / or the delivery tool is configured to activate the adhesive by driving the first implant-electrode such that energy flows from the first implant-electrode, through the adhesive, to the second implant-electrode.
[0866] Example 296. The system according to any one of examples 286-295, wherein: the implant-electrode comprises: an activation-electrode configured to apply energy to the adhesive, and / or a sensing-electrode that is configured to receive a signal indicative of contact between the contact-portion and the tissue; and / or the delivery tool is configured to: drive the sensing-electrode to receive the signal indicative of contact between the contact- portion and the tissue, and / or activate the adhesive to adhere the implant body to the tissue by driving the activation-electrode to apply energy to the adhesive.
[0867] Example 297. The system according to any one of examples 286-296, wherein: the implant-electrode is a first implant-electrode, at a first portion of the adhesive; the implant further comprises a second implant-electrode, at a second portion of the adhesive; and / or the delivery tool is adjustable to selectively drive one of the implant-electrodes, to apply energy to a selected portion of the adhesive.
[0868] Example 298. The system according to example 297, wherein: the contact- portion is a first contact-portion, at which the first implant-electrode is disposed, and / or the implant defines a second contact-portion, at which the second implant-electrode is disposed.
[0869] Example 299. The system according to any one of examples 286-298, wherein: the system further comprises a return electrode configured to remove energy from the subject; and / or the delivery tool is configured to adhere the implant body to the tissue by driving the implant-electrode such that energy flows from the implant-electrode, through the adhesive to the return electrode, thereby activating the adhesive.
[0870] Example 300. The system according to example 299, wherein the delivery tool comprises the return electrode.
[0871] Example 301. The system according to example 299, wherein the implant comprises the return electrode.
[0872] Example 302. The system according to example 299, wherein: the delivery tool is configured to, using the implant-electrode, detect contact between the contact-portion and the tissue by driving the implant-electrode to apply energy through the tissue and to the return electrode.
[0873] Example 303. The system according to example 299, wherein: the return electrode is a first return electrode;
[0874] the system further comprises a second return electrode; and / or the delivery tool is configured to, using the implant-electrode, detect contact between the contact-portion and the tissue by driving the implant-electrode to apply energy through the tissue and to the second return electrode.
[0875] Example 304. The system according to example 303, wherein the delivery tool comprises the first return electrode.
[0876] Example 305. The system according to example 303, wherein the implant comprises the first return electrode.
[0877] Example 306. The system according to example 303, wherein the second return electrode is configured to contact a skin surface of the subject while the contact-portion is positioned at the tissue of the heart.
[0878] Example 307. The system according to example 299, wherein the system has: a bioimpedance-measuring mode in which the delivery tool drives the implant-electrode such that energy flows from the implant-electrode, through the tissue and to the return electrode; and / or an adhesive-curing mode in which the delivery tool drives the implant-electrode such that energy flows from the implant-electrode, through the adhesive to the return electrode.
[0879] Example 308. The system according to example 307, wherein the deliver tool is configured to drive the implant-electrode to apply greater amount of energy to the adhesivewhile the system is in the adhesive-curing mode than while the system is in the bioimpedance-measuring mode.
[0880] Example 309. The system according to any one of examples 286-308, wherein the delivery tool is operable to transition between: a navigation mode in which the implant- electrode receives endogenic electrical signals within the heart; and / or an adhesive-curing mode in which the delivery tool drives the implant-electrode such that energy flows from the implant-electrode, through the adhesive to the return electrode.
[0881] Example 310. The system according to example 309, wherein the system is configured to, responsively to the received endogenic electrical signals, calculate a location of the implant-electrode.
[0882] Example 311. The system according to any one of examples 286-310: further comprising an external power supply, and / or wherein the implant comprises a terminal that is configured to receive the energy from the power supply, and to direct the energy to the implant-electrode.
[0883] Example 312. The system according to example 311 wherein the delivery tool is configured to transluminally transmit energy from the power supply, via a wired connection with the terminal, to the implant.
[0884] Example 313. The system according to example 311, wherein the power supply is configured to transmit energy via a wireless connection with the terminal, to the implant.
[0885] Example 314. The system according to any one of examples 286-313, wherein: the contact-portion defines a tissue-engaging element, and / or the delivery tool is configured to mechanically attach the implant to the tissue via the tissue-engaging element, prior to driving the implant-electrode to apply energy to the adhesive.
[0886] Example 315. The system according to example 314, wherein: the tissue- engaging element comprises a clip; and / or the delivery tool is configured to mechanically attach the implant to the tissue by closing the clip on the tissue, prior to driving the implant- electrode to apply energy to the adhesive.
[0887] Example 316. A method for use with a real or simulated heart of a real or simulated subject, the method comprising, using a delivery tool, transluminally: advancing an implant to the heart, the implant including: an implant body defining a contact-portion, an energy-activated adhesive, disposed at the implant body, and / or an implant-electrode, electrically connected to the delivery tool; positioning the contact-portion at a real or simulated tissue of the heart; and / or while the contact-portion remains positioned at the tissue: driving the implant-electrode to detect contact between the contact-portion and thetissue, and / or activating the adhesive to adhere the implant body to the tissue by driving the implant-electrode to apply energy to the adhesive.
[0888] Example 317. The method according to example 316, further comprising sterilizing the implant and the delivery tool.
[0889] Example 318. The method according to any one of examples 316-317, further comprising, responsively to detecting contact between the contact-portion and the tissue, mechanically attaching the implant to the tissue.
[0890] Example 319. The method according to any one of examples 316-318, wherein positioning the contact-portion at the tissue comprises positioning the implant-electrode at the tissue.
[0891] Example 320. The method according to any one of examples 316-319, further comprising, responsively to detecting contact between the contact-portion and the tissue, repositioning the implant.
[0892] Example 321. The method according to any one of examples 316-320, further comprising providing a notification, responsively to detecting contact between the contact- portion and the tissue.
[0893] Example 322. The method according to any one of examples 316-321, wherein: the implant-electrode is a first implant-electrode; the implant further includes a second implant-electrode; and / or activating the adhesive comprises driving the first implant- electrode such that energy flows from the first implant-electrode, through the adhesive, to the second implant-electrode.
[0894] Example 323. The method according to any one of examples 316-322, wherein driving the implant-electrode comprises, responsively to detecting contact between the contact-portion and the tissue, driving the implant-electrode to apply energy to the adhesive.
[0895] Example 324. The method according to example 323, wherein driving the implant-electrode comprises automatically driving the implant-electrode to apply energy to the adhesive, responsively to detecting contact between the contact-portion and the tissue.
[0896] Example 325. The method according to any one of examples 316-324, further comprising operating the delivery tool to, via the implant-electrode, detect endogenic electrical signals within the heart.
[0897] Example 326. The method according to example 325, further comprising, responsively to the detected endogenic electrical signals, calculating a location of the implant-electrode.
[0898] Example 327. The method according to any one of examples 316-326, wherein: activating the adhesive to adhere the implant body to the tissue by driving the implant- electrode comprises: driving a first implant-electrode to apply energy to a first portion of the adhesive, and / or driving a second implant-electrode to apply energy to a second portion of the adhesive.
[0899] Example 328. The method according to example 327, wherein: driving the first implant-electrode comprises driving the first implant-electrode to apply energy to the first portion of the adhesive at a first contact-portion of the implant, and / or driving the second implant-electrode comprises driving the second implant-electrode to apply energy to the second portion of the adhesive at a second contact-portion of the implant.
[0900] Example 329. The method according to any one of examples 316-328, further comprising, responsively to detecting contact between the contact-portion and the tissue, moving the implant-electrode toward the tissue.
[0901] Example 330. The method according to example 329, wherein moving the implant-electrode toward the tissue comprises mechanically attaching the implant to the tissue.
[0902] Example 331. The method according to example 329, wherein moving the implant-electrode toward the tissue comprises sandwiching the tissue between the contact- portion and the implant-electrode.
[0903] Example 332. The method according to any one of examples 316-331, wherein driving the implant-electrode comprises applying electrical energy to the implant-electrode.
[0904] Example 333. The method according to example 332, wherein: driving the implant-electrode to detect contact between the contact-portion and the tissue comprises applying a lower voltage to the implant-electrode; and / or driving the implant-electrode to apply energy to the adhesive comprises applying a higher voltage to the implant-electrode.
[0905] Example 334. The method according to example 333, wherein: the implant- electrode includes an activation-electrode and a sensing-electrode;
[0906] driving the implant-electrode to detect contact between the contact-portion and the tissue comprises applying the lower voltage to the sensing-electrode; and / or driving the implant-electrode to apply energy to the adhesive comprises applying the higher voltage to the activation-electrode.
[0907] Example 335. The method according to any one of examples 316-334, wherein: driving the implant-electrode to detect contact between the contact-portion and the tissue comprises driving the implant-electrode to apply energy through the tissue to a first returnelectrode; and / or driving the implant-electrode to apply energy to the adhesive comprises driving the implant-electrode to apply energy through the adhesive to a second return electrode.
[0908] Example 336. The method according to example 335, wherein the method further comprises, prior to activating the adhesive: ungrounding the first return electrode, and / or grounding the second return electrode.
[0909] Example 337. The method according to example 335, further comprising placing the first return electrode in contact with a skin surface of the subject.
[0910] Example 338. The method according to example 335, further comprising placing the first return electrode within the subject.
[0911] Example 339. The method according to any one of examples 316-338, wherein: the method further comprises, using the delivery tool, transmitting energy from an external power supply to a terminal of the implant; and / or via the terminal, directing the energy to the implant-electrode.
[0912] Example 340. The method according to example 339, wherein: transmitting comprises transluminally transmitting energy from the external power supply, via a wired connection, to the terminal; and / or the method further comprises, subsequently to activating the adhesive: severing the wired connection, and / or withdrawing the delivery tool from the subject.
[0913] Example 341. The method according to example 339, wherein transmitting comprises wirelessly transmitting energy from the external power supply to the terminal.
[0914] Example 342. A method for use with a simulated heart of a subject, the method comprising, using a delivery tool, transluminally: advancing an implant to the heart, the implant including: an implant body defining a contact-portion, an energy-activated adhesive, disposed at the implant body, and / or an implant-electrode, electrically connected to the delivery tool; positioning the contact-portion at a tissue of the heart; and / or while the contact-portion remains positioned at the tissue: driving the implant-electrode to detect contact between the contact-portion and the tissue, and / or activating the adhesive to adhere the implant body to the tissue by driving the implant-electrode to apply energy to the adhesive.
[0915] The present disclosure is not limited to the examples that have been particularly shown and described hereinabove. Rather, the scope includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description.
Claims
WHAT IS CLAIMED IS:
1. A system for use with a heart of a subject, the system comprising: a catheter, transluminally advanceable to the heart; a bioink comprising a biomaterial; and a bioprinter: housing the bioink, comprising a nozzle that is transluminally advanceable via the catheter to the heart, wherein the system is configured to, while the nozzle extends from a distal portion of the catheter, extrude the bioink from the nozzle into the heart such that the biomaterial assumes a three-dimensional implant- shape.
2. The system according to claim 1, wherein at least one of the catheter, the nozzle and the bioink is sterile.
3. The system according to any one of claims 1–2, wherein the system is configured to, while the nozzle extends from a distal portion of the catheter, extrude the bioink from the nozzle into the heart such that the biomaterial: assumes a three-dimensional implant-shape, and adheres to tissue of the heart.
4. The system according to any one of claims 1–3, wherein the bioprinter is configured to, after extruding the bioink from the nozzle into the heart, fixate the biomaterial such that the biomaterial retains the implant-shape.
5. The system according to claim 4, wherein the bioprinter is configured to, after extruding the bioink from the nozzle into the heart, fixate the biomaterial such that the biomaterial: adheres to tissue of the heart, and retains the implant-shape.
6. The system according to any one of claims 1–5, wherein the system further comprises a fixator that is: transluminally advanceable via the catheter to the heart, and configured to fixate the biomaterial such that the biomaterial retains the implant- shape.
7. The system according to claim 6, wherein the fixator is configured to fixate the biomaterial such that the biomaterial: retains the implant-shape, andadheres to tissue of the heart.
8. A method for use with a simulated heart of a subject, the method comprising, using a delivery tool, transluminally: advancing an implant to the heart, the implant including: an implant body, an adhesive, pre-disposed on the implant, and an energy-applicator; positioning the implant in the heart such that the adhesive contacts tissue of the heart; and activating the adhesive by driving the energy-applicator to apply energy to the adhesive, thereby adhering the implant body to tissue of the heart.
9. A system for use in a heart of a subject, the system comprising: an implant, the implant comprising: an implant body, an adhesive, pre-disposed on the implant body, and an activator; and a delivery tool, configured to: transluminally deliver the implant to the heart, and position the adhesive in contact with tissue of the heart, and while the adhesive remains in contact with the tissue, activate the adhesive to adhere the implant body to the tissue by applying the activator to the adhesive.
10. The system according to claim 9, wherein at least one of the implant and the delivery tool is sterile.
11. The system according to any one of claims 9-10, wherein: the adhesive is a mussel foot protein-based bioadhesive, and the activator is configured to activate the bioadhesive by cross-linking amino acid residues of the mussel foot protein.
12. A system for use at a tissue of a cardiovascular system of a subject, the system comprising: a fabric defining barbs that protrude from a face of the fabric; an adhesive; and a transluminally advanceable delivery tool: comprising a scaffold, configured to temporarily restrain the face of the fabric against the tissue such that the barbs penetrate the tissue, andconfigured to: adhere the fabric to the tissue by manipulating the adhesive, and transluminally withdraw the scaffold from the subject.
13. The system according to claim 12, wherein at least one of the fabric, the adhesive and the delivery tool is sterile.
14. The system according to any one of claims 12–13, wherein the adhesive is pre- disposed on the fabric.
15. The system according to any one of claims 12–13, wherein the delivery tool further comprises an adhesive applicator.
16. The system according to any one of claims 12–15, wherein the fabric is bioabsorbable.
17. The system according to any one of claims 12–16, wherein the scaffold is configured to temporarily restrain the face of the fabric against the tissue by sandwiching the tissue between the scaffold and the fabric, such that the barbs penetrate the tissue.
18. The system according to any one of claims 12–17, wherein the delivery tool is configured to adhere the fabric to the tissue by manipulating the adhesive while the scaffold restrains the face of the fabric against the tissue such that the barbs penetrate the tissue.
19. The system according to any one of claims 12–18, wherein the delivery tool is configured to: adhere the fabric to the tissue by manipulating the adhesive while the scaffold restrains the face of the fabric against the tissue such that the barbs penetrate the tissue, and subsequently, transluminally withdraw the scaffold from the subject, leaving the fabric adhered to the tissue.
20. The system according to any one of claims 12–19, wherein the delivery tool further comprises an adhesive applicator, configured to apply the adhesive to the fabric while the scaffold restrains the face of the fabric against the tissue such that the barbs penetrate the tissue.
21. The system according to any one of claims 12–20, wherein the fabric and the scaffold are configured such that penetration of the tissue by the barbs, while the scaffold restrains the face of the fabric against the tissue, is such that upon release of the tissue by the scaffold, the barbs retain the fabric in contact with the tissue.
22. The system according to any one of claims 12–21, wherein: leaflets of a native valve of the cardiovascular system defines the tissue, andthe scaffold comprises a leaflet-clip, configured to temporarily restrain the face of the fabric against the leaflets such that the barbs penetrate the leaflets.
23. The system according to claim 22, wherein the fabric and the scaffold are configured such that penetration of the leaflets by the barbs, while the scaffold restrains the face of the fabric against the leaflets, is such that upon release of the leaflets by the scaffold, the barbs retain the fabric in contact with the leaflets during a cardiac cycle of the cardiovascular system.
24. The system according to any one of claims 12–23, wherein: the adhesive is a chemically-activated adhesive, the system further comprises an activator, and the delivery tool comprises a nozzle, configured to chemically activate the adhesive by applying the activator to the adhesive.
25. The system according to claim 24, wherein: the adhesive is a mussel foot protein-based bioadhesive, and the activator is configured to activate the bioadhesive by cross-linking amino acid residues of the mussel foot protein.
26. The system according to any one of claims 12–23, wherein: the adhesive is an energy-activated adhesive, and the system further comprises an energy-applicator, configured to adhere the fabric to the tissue by applying energy to the adhesive.
27. The system according to claim 26, wherein the energy-applicator is an extracorporeal energy-applicator, configured to activate the adhesive by applying energy to the adhesive from outside of the subject.
28. The system according to claim 26, wherein the delivery tool comprises the energy-applicator, which is configured to adhere the fabric to the tissue by applying energy to the adhesive from within the cardiovascular system.
29. The system according to claim 28, wherein the energy-applicator is configured to adhere the fabric to the tissue by applying electromagnetic energy to the adhesive from within the cardiovascular system.
30. The system according to claim 28, wherein the energy-applicator is configured to adhere the fabric to the tissue by applying heat to the adhesive from within the cardiovascular system.
31. The system according to claim 28, wherein the energy-applicator is configured to adhere the fabric to the tissue by applying electrical current to the adhesive from within the cardiovascular system.
32. The system according to claim 31, wherein: the system comprises an implant that includes the fabric and an implant-electrode; and the energy-applicator is configured to apply electrical current to the adhesive by applying voltage to the implant-electrode such that current flows from the implant-electrode and through the adhesive, thereby activating the adhesive.
33. The system according to claim 32, wherein the implant-electrode is disposed on the face of the fabric.
34. The system according to claim 32, wherein the implant-electrode is embedded within the adhesive on the face of the fabric.
35. The system according to claim 32, wherein: the delivery tool comprises a return electrode; and the energy-applicator is configured to apply electrical current to the adhesive by applying voltage to the implant-electrode such that current flows from the implant-electrode, through the adhesive and to the return electrode, thereby activating the adhesive.
36. The system according to claim 32, wherein: the implant-electrode is a first implant-electrode; the implant further comprises a second implant-electrode; and the energy-applicator is configured to apply electrical current to the adhesive by applying voltage to: the first implant-electrode such that current flows from the first implant- electrode and through a first portion of the adhesive, thereby activating the first portion of the adhesive, and the second implant-electrode such that current flows from the second implant-electrode and through a second portion of the adhesive, thereby activating the second portion of the adhesive.
37. The system according to any one of claims 12–36, wherein: the scaffold comprises a shape-memory material having a compressed state and an expanded state, and the delivery tool is configured to:deliver the scaffold to the tissue while the scaffold is in the compressed state, and deploy the scaffold at the tissue such that the scaffold engages the tissue as the scaffold transitions from the compressed state to the expanded state.
38. The system according to claim 37, wherein the delivery tool is configured to deploy the scaffold at the tissue such that the scaffold restrains the face of the fabric against the tissue such that the barbs penetrate the tissue, as the scaffold transitions from the compressed state to the expanded state.
39. The system according to claim 38, wherein: leaflets of a native valve of the cardiovascular system defines the tissue, the scaffold comprises a leaflet-clip, and the delivery tool is configured to deploy the leaflet-clip at the leaflets such that, during a cardiac cycle of the cardiovascular system, the leaflet-clip restrains the face of the fabric against the leaflets such that the barbs penetrate the leaflets as the leaflet-clip transitions from the compressed state to the expanded state.
40. The system according to claim 37, wherein: the delivery tool comprises a catheter, configured to house the scaffold while the scaffold is in the compressed state, and the delivery tool is configured to retract the scaffold into catheter such that the scaffold transitions from the expanded state to the compressed state, prior to transluminally withdraw the scaffold from the subject.
41. The system according to any one of claims 12–40, wherein the fabric is a woven fabric comprising: a weft yarn, and multiple warp yarns, including: first warp yarns extending from a first end of the fabric to a second end of the fabric, and second warp yarns, each of the second warp yarns being cut in a manner that defines at last one of the barbs.
42. The system according to claim 41, wherein each of the second warp yarns comprises steel.
43. The system according to claim 41, wherein each of the second warp yarns comprises nitinol.
44. The system according to claim 41, wherein each of the second warp yarns comprises nylon.
45. The system according to claim 41, wherein each of the second warp yarns is a monofilament yarn.
46. The system according to claim 41, wherein each of the first warp yarns is a polyfilament yarn.
47. The system according to claim 41, wherein the weft yarn is a polyfilament yarn.
48. The system according to claim 41, wherein each of the second warp yarns comprises a polyester resin.
49. The system according to any one of claims 41–48, wherein the first warp yarns have a different composition from the second warp yarns.
50. The system according to claim 49, wherein the weft yarn has a different composition from the first warp yarns and the second warp yarns.
51. The system according to claim 49, wherein the weft yarn has the same composition as the first warp yarns.
52. The system according to any one of claims 12–51, wherein the fabric comprises a laminate disposed on a back of the fabric.
53. The system according to claim 52, wherein the laminate comprises a high weight polyethylene.
54. The system according to claim 52, wherein the laminate comprises a thermoplastic polyurethane.
55. The system according to claim 52, wherein the laminate has the same composition as at least one of the barbs.
56. A system for use at a heart of a subject, the system comprising: an implant comprising, on an exterior of the implant, a fabric manufactured via the method of claim 139; and a delivery tool, configured to secure the implant to tissue of the heart by pressing the fabric against the tissue such that the barbs penetrate the tissue.
57. The system according to claim 56, wherein the implant comprises a prosthetic heart valve.
58. A system for use in a heart of a subject, the system comprising: an implant, the implant comprising:an implant body, an energy-activated adhesive, disposed at the implant body, and an implant-electrode that is disposed at the adhesive; and a delivery tool, configured to: transluminally position a contact-portion of the implant at a tissue of the heart while electrically connected to the implant-electrode, using the implant-electrode, detect contact between the contact-portion and the tissue, and activate the adhesive to adhere the implant body to the tissue by driving the implant-electrode to apply energy to the adhesive.
Citation Information
Patent Citations
Multi-portion replacement heart valve prosthesis
US10639143B2
Prosthetic spacer device for heart valve
US11051940B2
Annuloplasty ring with intra-ring anchoring
US8715342B2
Closed band for percutaneous annuloplasty
US8926697B2
Implant-adhering techniques
US20220313438A1
Cited By
System for determining implant-tissue contact
US20250009461A1