Adaptive seal for heart valves

Abstract

An adaptive seal includes an attachment configured to attach to a replacement heart valve to close gaps between the replacement heart valve and a patient's own and surrounding structure to reduce or to prevent paravalvular leakages.

Description

ADAPTIVE SEAL FOR HEART VALVESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 513,368, filed July 13, 2023, which is incorporated by reference herein in its entirety.TECHNICAL FIELD

[0002] The present invention relates to the methods, manufacture, and use of an adaptive seal for prosthetic heart valves. More specifically, the invention relates to the methods, manufacture and use of an adaptive seal that may be used to prevent leakage, with a focus on paravalvular leakage.BACKGROUND

[0003] Paravalvular leaks (PVL) refers to backflow of blood through gaps between an artificial heart valve and the native valves and tissues because of a lack of proper sealing. PVL remains to be an issue with replacement heart valves causing increased mortality risk due to stroke, or silent death post treatment. Factors contributing to PVL include calcified native valves, elliptical annuli, improper valve sizing, and suboptimal deployment in cases of transcatheter heart valves. PVL occurs at high rates (between 30-50%) in transcatheter aortic valve replacements (TAVR) patients. Given the fact that even mild PVL is associated with increased mortality, any new TAVR should be designed to reduce and prevent paravalvular leakage. The most recent iteration of the SAPIEN valve, the SAPIEN 3 Ultra (available from Edwards Lifesciences LLC, headquartered in Irvine, California, U.S.A.) uses a texturized polyethylene terephthalate textile skirt that has high porosity to achieve a high frictional coefficient. This textile is sutured in the lower annulus part of the valve. This skirt is 40% taller than the previous SAPIEN 3 valve, which increases the contact with the annulus and reduces PVL in vivo. Among 101 patients treated with this valve, 10.8% had mild PVL compared to 36.5% with SAPIEN 3 30-day post TAVR evaluation. The credit was given to the tall texturized outer skirt. Therefore, a properly designed annular skirt can reduce PVL and protect the annulus by reducing the radial force of valve expansion from crimping. New technologies are emerging with innovation in skirt material selection and design. For example, Triskele valve (developed by University College London, UCL cardiovascular Engineering1SUBSTITUTE SHEET (RULE 26)Laboratory) has a sealing cuff and skirt, Accurate neo2™ (available from Boston Scientific Corporation headquarted in Watertwon, Massachusetts, U.S.A.) has hydrogel, and NaviGate (available from NaviGate Cardiac Structures, Inc.) has polyester microfiber fabric. Polyester microfiber yarns have micropores, and the fibers are in micron range diameter. Therefore, this promotes tissue ingrowth to reduce the gap between the valve and annulus. Hydrogels conform to the shape of the annulus and prevent PVL but could cause valve migration due to a reduced frictional co-efficient. While there are multiple approaches to reducing PVL, it is clear that reduction of PVL is a necessary design feature of all TAVRs due to the severity of outcomes when PVL is prevalent.SUMMARY

[0004] In accordance with the purposes of the disclosed materials and methods, as embodied and broadly described herein, the disclosed invention, in one aspect, relates to a swelling compound-based adaptive seal for heart valves, as well as methods of using and making the same. The adaptive seal comprises chemical elements that actively swell upon contact with biological fluids, such as blood, when implanted. This seal can be employed in (i) surgical heart valves or (ii) transcatheter heart valves.

[0005] In one embodiment, an adaptive seal includes an attachment configured to attach to a replacement heart valve to close gaps between the replacement heart valve and a patient’s own and surrounding structure to reduce or to prevent paravalvular leakages.

[0006] In one embodiment, a replacement heart valve includes a stent frame and an adaptive seal attached to the stent frame. The adaptive seal is configured to close gaps between the replacement heart valve and a patient’s own and surrounding structure to reduce or to prevent paravalvular leakages.

[0007] In one embodiment, the adaptive seal is provided, comprising swelling chemical compounds enclosed in fabric components, or a fabric pouch. This pouch is attached either to the bottom of a transcatheter valve stent frame or incorporated in the sewing rings for surgical valves. Upon contact with blood, the swelling compounds increase in size, occupying space in the gaps between the valve prosthesis and native tissue through which PVL occurs. In regions without gaps,2SUBSTITUTE SHEET (RULE 26)the swelling elements are compressed by radial force without damaging surrounding structures. The swelling occurs within a short period of time after entering the body, reducing PVL immediately post deployment. The fabric material allows for endothelialization and tissue ingrowth, creating a long-term reliable seal. It also ensures stable positioning of the prosthetic valve, minimizing the risk of dislodging or migration, especially in transcatheter heart valves.

[0008] In some embodiments, the fabric pouch comprises two different fabric types: (i) inner fabric in contact with the device frame, and (ii) outer fabric in contact with native tissue. The inner fabric can be woven or knit to be highly elastic and porous, allowing part of the blood flowing through the valve to contact the swelling elements and trigger the adaptive sealing mechanism. The outer fabric, which is in contact with native tissue, can be texturized and non-porous to provide high friction upon deployment. The non-porosity ensures that none of the swelling elements break off and embolize into the bloodstream. Additionally, the outer fabric dampens the radial force exerted on surrounding structure to prevent damage.

[0009] In some embodiments, the swelling elements and fabric components are non-toxic, and do not induce adverse immune responses in the patient.

[0010] In some embodiments, the adaptive seal along with the swelling elements and fabric pouch, can be crimped, expanded and delivered via a transcatheter approach.

[0011] In some embodiments, the swelling elements degrade over time, allowing a reliable seal with tissue ingrowth and endothelialization to form before complete degradation. This degradation does not produce harmful toxins or debris in the bloodstream.

[0012] In some embodiments, the swelling elements have a gradual swelling profde, reaching complete expansion over the period required for device deployment or implantation.

[0013] In some embodiments, the swelling elements can be individually packed, or manufactured together and then packed. The swelling elements can vary in size, shape, material and degradation profile. Inside the fabric pouch, the swelling elements can either be packed in a single layer, or multiple layers with different arrangements.

[0014] In some embodiments, the swelling elements can be made from hydrogel materials3SUBSTITUTE SHEET (RULE 26)due to their ability to swell in contact with liquids, filling gaps, and their easy deformability to stay compressed in regions with no gaps. Hydrogels offer a variety of sizes, shapes, and materials, making them a good choice for swelling elements. These elements can also be crosslinked, with the crosslinking method varied based on the required material, size, shape, swelling, and degradation profiles.

[0015] In one example, an adaptive seal in provided wherein the swelling elements are gelatin beads, crosslinked with EDC (l-ethyl-3-(3-dimethylaminopropl)carbodiimide) and NHS (N-hydroxysuccinimide). The inner fabric used is highly porous and stretchable polyester fabric, e g., Dacron® fabric, and outer fabric used is a texturized polyester fabric, e.g., Dacron® fabric. The gelatin beads are synthesized by extruding a 20% w / v solution of gelatin into oil. The beads are recovered, washed and dried, and then crosslinked in a solution of 20 millimolar (mM) EDC and 20 mM NHS for six hours at room temperature.

[0016] In some embodiments, the gelatin beads can be crosslinked with methacrylamide, oxidated hyaluronic acid or dextran dialdehyde.

[0017] Additional advantages will be set forth in part in the description that follows, and in part will be obvious from the description or may be learned by practice of the aspects described below. The advantages described below will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are by example and explanatory only and are not restrictive.BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The accompanying figures, which are incorporated in and constitute a part of this specification, illustrate several aspects described below.

[0019] FIG. 1 shows a schematic diagram of an exemplary adaptive seal attached to a transcatheter aortic heart valve.

[0020] FIG. 2 shows a schematic layout of an exemplary adaptive seal with its different components.4SUBSTITUTE SHEET (RULE 26)

[0021] FIG. 3 shows an exemplary schematic demonstrating how paravalvular leakage occurs in heart valves.

[0022] FIG. 4 shows a schematic representation of the mechanism with which the adaptive seal swells and fills in the gaps to reduce paravalvular leakage

[0023] FIG. 5 shows a schematic layout of different configurations in which swelling layers can be assembled

[0024] FIG. 6 shows a schematic layout of a fabric pouch of an adaptive seal

[0025] FIG. 7 shows results of an in vitro kinematic swelling test for gelatin beads.

[0026] FIG. 8 shows an in vitro demonstration of an adaptive sealing mechanism.

[0027] FIG. 9 shows an exemplary adaptive seal prototype sutured onto a transcatheter aortic valve replacement.

[0028] FIG. 10 shows a deployed adaptive seal prototype in a 3D printed anatomical aortic root.

[0029] FIG. 11 shows an exemplary fabric pouch design and attachment technique using a single layer of fabric.

[0030] FIG. 12 shows two exemplary designs of the fabric pouches using two fabric materialsDETAILED DESCRIPTION

[0031] The disclosed embodiments are directed to an adaptive sealing mechanism that can be attached to prosthetic heart valves. In particular, an adaptive sealing mechanism, capable of swelling once in contact with fluid such as blood or any other biological fluid, attached to a transcatheter aortic valve replacement (hereinafter “TAVR”) is provided as shown in FIG. 1. Although a TAVR will be described herein, it should be apparent to one of skill in the art that the adaptive seal can be attached to any kind of heart valve replacement, whether it is implanted surgically through open heart surgery or delivered minimally invasively via the transcatheter5SUBSTITUTE SHEET (RULE 26)approach. The disclosed embodiments are not limited to use in the aortic valve position, but can also be used in the mitral, tricuspid and pulmonary positions. As shown in FIG. 1, an adaptive seal 10 disclosed herein may be attached to a metallic stent frame 11 of a TAVR 15. The adaptive seal 10 is attached such that it does not obstruct leaflets 12, 13, 14 of the TAVR 15, or affect the TAVR’ s hemodynamic performance. The leaflets 12, 13, 14 can be made of either animal derived tissues, polymers or metallic.

[0032] Referring now to FIG. 2, it illustrates various components of the adaptive seal 10 including an attachment 19 including a layer of swelling elements 20 capable of swelling, enclosed within a fabric pouch consisting of an outer layer 21 and an inner layer 22. The swelling elements 20 are made of compounds that are capable of swelling upon contact with a fluid, such as blood or any other biological fluid. This swelling causes the swelling elements 20 to increase in size (volume). FIG. 3 shows an exemplary deployed TAVR frame 30 in a native aortic root or an annulus 31. Based on patient anatomy, calcified native leaflets, deployment parameters of the TAVR, there may exist gaps 32 between the deployed TAVR frame 30 and the annulus 31. These gaps 32 allow for backflow of blood, referred to as paravalvular leaks. The swelling elements 20 swell into these gaps 32 to create a physical barrier for blood and prevent any blood from flowing through the gaps 32 as shown in FIG. 4 The swelling elements 20 may include a plurality of chemical elements that can vary in dimensions, swelling rates, swelling profiles and materials. It should be noted that these swelling elements 20 may be packed in fabric pouches, e.g., the outer and inner layers 21 and 22 made of fabric pouches in various configurations as shown in FIG. 5. In some embodiments, the swelling elements 20 are configured to provide for a seal that can adapt its shape (based on the swelling mechanism) to different anatomies. In some embodiments, the swelling elements 20 are individual elements enclosed in the fabric component (e.g., the fabric pouch). In some embodiments, the swelling elements 20 are multiple elements fabricated together and enclosed in the fabric component (e.g., the fabric pouch).

[0033] The swelling rate can be adjusted based on the type and combination of swelling elements 20, depending on their intended use. For instance, for transcatheter heart valves, the swelling elements 20 might have a slower swelling rate. This slower rate ensures that the attached adaptive seal 10 on transcatheter heart valves can be accurately positioned and deployed through a catheter. The swelling elements 20 may also be chosen such that they degrade after sufficient6SUBSTITUTE SHEET (RULE 26)tissue ingrowth and stabilization has taken place in the gaps 32 and a reliable seal has been formed. The swelling elements 20 can be made of natural materials like hyaluronan, gelatin, starch, carrageenan, chitin, chitosan, cyclodextrin, guar gum, cellulose and / or synthetic materials like poly (vinyl alcohol), poly (acrylic acid), poly-N-isopropyl acrylamide, polyethylene glycol (PEG) / polyethylene oxide, poly(acrylic acid-coacrylamide), polyaniline, poly (lactic-co-glycolic acid), PEG block polylactide, PEG block polyglycolide, PEG block polylactide-co-glycolide, polyurethane, or a combination thereof.

[0034] The swelling elements 20 may be enclosed in a fabric pouch formed between the outer layer 21 and the inner layer 22. The inner layer 22 may be attached to the frame of the heart valve, via one or more mechanisms 60 such as suturing, sewing, welding, thermoforming, adhesives, vacuum sealing, or a combination thereof, as shown in FIG. 6 The fabric used for the inner layer 22 may be highly porous to allow for fluid to enter the adaptive seal and activate the swelling mechanism. The inner layer 22 can be attached to the outer layer 21 via any one or more of the mechanisms 60. The mechanism 60 may be any suitable mechanism configured to allow stable positioning of the replacement heart valve without a risk of dislodging or valve migration.

[0035] The outer layer 21 may be made from a high texturized and / or non-porous fabric to allow for high friction during deployment and valve positioning. The outer layer 21 may serve as a covering to prevent the swelling elements 20 from breaking off from the adaptive seal 10 into a bloodstream. The fabric layers, e.g., the outer layer 21 and the inner layer 22 may also serve as a facilitator for healthy endothelialization and tissue ingrowth for a reliable seal. Different fabric materials can be used for either of the layers such as polyester, polyethylene terephthalate, expanded polytetrafluoroethylene, polytetrafluoroethylene, polypropylene, silicone, or a combination thereof. The fabric pouch may be made from different types of fabrics. For example, the outer layer 21 may be made of one fabric material and the inner layer 22 may be made of another fabric material different from that of the outer layer 21.

[0036] The inner fabric 22 is configured to contact a metallic valve frame of the heart replacement valve. The inner fabric 22 may be a woven or knit fabric that is highly elastic and porous. For example, the inner fabric 22 may have a Young’s Modulus or an Elastic Modulus in a suitable range, making it highly elastic for the application. For example, the inner fabric 22 may7SUBSTITUTE SHEET (RULE 26)have a porosity in a suitable range making it sufficiently porous for the application. The outer fabric 21 is configured to contact the patient’s native tissue. The outer fabric 22 may be made of a texturized fabric that is configured to provide high friction upon deployment and allow for tissue ingrowth. For example, the outer fabric 22 may have a friction coefficient in a suitable range making it sufficiently textured for the application.

[0037] Example Device

[0038] An exemplary procedure to form crosslinked gelatin beads in adaptive seal for heart valves is described below.

[0039] Step 1 : preparing a 20% w / v (gram pf solute / 100 milliliter of solution) of gelatin in boiling deionized water (DI H2O). Step 1 may include: (a) measuring 20 ml DI H2O with graduated cylinder and add magnetic stir bar to beaker; (b) boiling 20 ml DI H2O in a 100- millimeter (ml) beaker; (c) stirring boiling water (vigorously); (d) adding 4 gram (g) gelatin to 20 ml boiling DI H2O; (e) stirring the reaction until the gelatin is completely dissolved (this should take no more than a few minutes; when fully dissolved, the solution is clear; (f) allowing the solution a minute to cool, but do not let it cool to the point that it becomes too viscous to push through the syringe; and (g) recording weight of gelatin, volume of DI H2O, how long gelatin took to dissolve, and how long the gelatin was allowed to cool.

[0040] Step 2: placing 30-40 ml vegetable oil in a second 100 ml beaker. Step 3: drawing the gelatin solution into the syringe. Step 4: slowly pushing out droplets of the gelatin solution into the vegetable oil forming gelatin beads. Different size beads can be generated by using needles of different diameters.

[0041] Step 5: allowing the beads to cool for about 10-20 minutes, or any suitable time to cool, e.g., to about the room temperature. Step 6 rinsing beads thoroughly with DI H2O to remove all oil. Step 7: placing beads in water for about 1 hour to allow residual oil to separate from the surface. Step 8: rinsing beads again. Step 9: drying beads in a vacuum oven overnight and recording dry weight the following day.

[0042] Step 10: preparing 20 millimolar (mM) solution of NHS and EDC (calculations are made at 40 mM as the final concentration when mixed is 20 mM). Step 10 may include: (a) placing8SUBSTITUTE SHEET (RULE 26)magnetic stir bar in 100 ml beaker; (b) adding 25 ml DI H2O to 100 ml beaker; (c) heating DI H2O to 37 °C; (d) repeating steps (a)-(c) to generate two beakers of 25 ml DI H2O at 37 °C; (e) adding 0.115 g NHS to one beaker and allow to completely dissolve; (f) adding 0.155 g EDC to second beaker and allowing to completely dissolve; (g) fixing the two solutions and immediately adding gelatin beads; (h) allowing the gelatin beads to crosslink for about 6 hours (no heat is applied; beads will melt / stick together if heat is applied); (i) removing the beads from the solution after about 6 hours and rinsing the EDC / NHS solution off of the beads; (j) drying the beads overnight in the vacuum oven; and (k) recording weight of dry crosslinked beads.

[0043] It should be noted that although beads are given as an example above, the swelling elements 20 may be in any suitable shapes, e g., beads, spheres, irregular shape, etc. The swelling elements 20 may be in any suitable sizes.

[0044] Kinematic swelling study of an adaptive seal using gelatin beads

[0045] Provided below is an example of an adaptive seal attached to the bottom of a polymeric TAVR. The adaptive seal uses crosslinked gelatin beads encapsulated in polyethylene terephthalate (PET, i.e., Dacron®) or other textile to generate a dynamic seal that rapidly reduces paravalvular regurgitation upon deployment. The DST runs around the outside annulus of the valve and consists of three parts: (1) an outer layer of texturized polyethylene terephthalate (PET / Dacron®) that provides high friction upon deployment and allows for tissue ingrowth; (2) crosslinked gelatin or other swellable beads that quickly expands and reduces paravalvular leakage by 26% within 30 minutes of deployment, and (3) an inner layer of stable Dacron® woven fabric or other suitable textile which is stitched to the outer layer using highly elastic and porous Dacron® knit fabric or other suitable textile. The textile patch encapsulates the beads while allowing for movement of the beads to fill up paravalvular gaps in patient-specific anatomies. The beads can be made from gelatin, polyethylene glycol (as known as polyethylene oxide), hyaluronic acid, or other swellable gel materials. The swellable beads rapidly expand upon deployment physically blocking paravalvular leakage (PVL) while the soft nature of the gelatin in the beads prevents unnecessary force on the inner annulus of deployment. It should be noted that crosslinked gelatin, used in the DST, is a biomaterial used in a wide range of applications including cell growth, drug encapsulation, and surface coatings. The beads are synthesized by excreting a 20% w / v solution9SUBSTITUTE SHEET (RULE 26)of gelatin into oil. The beads are recovered, washed, and dried before crosslinking in a solution of 20 mM EDC (l-ethyl-3 -(-3 -dimethylaminopropyl) carbodiimide hydrochloride) and 20 mM NHS(N-Hydroxysuccinimide) for about six hours at room temperature. Finally the beads are dried and weighed. This concentration of EDC and NHS crosslinking allows the beads to approach their maximum swelling ratio over the course of approximately one hour. This is so the beads can be crimped and deployed without significant expansion in the catheter while also expanding over a relatively short period of time once deployed to prevent PVL. The attachment 19, the swelling elements 20, and the fabric component (e.g., the outer layer 22 and the inner layer 21) are crimped and configured to be expanded and delivered via a transcatheter approach. A kinetic swelling study in water demonstrates that the beads swell over 900% of their original volume in 1 hour and that the beads reach a maximum swelling ratio of approximately 1000% over the course of 1 hour and 15 minutes.

[0046] FIG. 7 illustrate exemplary results of the kinetic swelling study and images of the beads during swelling. After examining the swelling ratio of the beads, a prototype DST is assembled and deployed in a 3D-printed, patient-specific, calcified aortic root model using balloon expansion.

[0047] FIG 8 shows how gaps 80 between the aortic root model 81 are filled upon swelling of the adaptive seal 10. The DST quickly fills extra annular gaps and reducing PVL upon deployment. The swelling elements 20 are chosen to provide a gradual swelling profile such that the swelling elements 20 reach a complete expansion over a period of time required for the replacement heart valve to be deployed in place.

[0048] In vitro testing of an adaptive seal with gelatin beads

[0049] FIG. 9 shows an image of a TAVR with an example adaptive seal 10 attached using sutures 90. The adaptive seal 10 includes gelatin beads and polyester fabric 91 covering as shown in FIG 9.

[0050] The TAVR with the attached adaptive seal 10 may bed deployed in a 3D printed anatomical aortic root 100 as seen in FIG 10. The aortic root is mounted in the pulsatile flow loop and tested under adult physiological conditions. Paravalvular leakage is examined over the course10SUBSTITUTE SHEET (RULE 26)of 90 minutes with the initial measurement taken nine minutes after deployment. At this point the beads have not swollen significantly; however 21 minutes later the beads have swollen significantly, reducing the RF from 35% (9 minutes post deployment) to 26% (30 minutes post deployment) demonstrating the functionality of both the beads as a method to reduce PVL and the polyethylene terephthalate a functional pocket to contain the beads upon deployment. At 90 minutes post deployment PVL is reduced to 23%.

[0051] Fabric pouch design, assembly and attachment

[0052] Provided herein are examples of fabric pouches that are designed to hold the swelling elements 20. The first example is simple rectangular pouch that uses a single piece of 100% polyester fabric and is stitched onto a metallic stent frame of a polymeric TAVR device as shown in FIG. 11 in images A, B, and C. The fabric is stitched onto the stent using sewing needles and sewing threads for preliminary prototyping. The bottom layer of the stent is attached to individual struts of the stent, while the top layer of the fabric is stitched on the inside of only specific struts, to ensure no damage and / or obstruction to the leaflets.

[0053] The second example of the fabric pouch design provided uses a combination of knit (inner layer) 120 and terry fabric (outer layer) 121. The first iteration is shown in FIG. 12 in images A and B wherein rectangular pieces of fabric are assembled onto a TAVR stent. The second iteration as shown in images C and D involves cutting the fabric according to the strut design to make a more suitable fabric pouch that can be assembled onto the stent.

[0054] It should be noted that the adaptive seal 10 includes the attachment 19 that may be attached to the replacement heart valve at a different position depending on the type of replacement heart valve. In one example, if the replacement heart valve is a transcatheter heart valve, the attachment 19 is configured to sit or attach to a bottom of a frame of the transcatheter heart valve. In another example, if the replacement heart valve is a surgical heart valve, the attachment 19 is configured to sit or attach along a sewing ring for the surgical heart valve.

[0055] Definitions

[0056] As used herein, “comprising” is to be interpreted as specifying the presence of the stated features, integers, steps, or components as referred to, but does not preclude the presence or11SUBSTITUTE SHEET (RULE 26)addition of one or more features, integers, steps, or components, or groups thereof. Moreover, each of the terms “by,” “comprising,” “comprises,” “comprised of,” “including,” “includes,” “included,” “involving,” “involves,” “involved,” and “such as” are used in their open, non-limiting sense and may be used interchangeably. Further, the term “comprising” is intended to include examples and aspects encompassed by the terms “consisting essentially of’ and “consisting of.” Similarly, the term “consisting essentially of’ is intended to include examples encompassed by the term “consisting of.”

[0057] As used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a compound,” “a composition,” or “a disorder” includes, but is not limited to, two or more such compounds, compositions, or disorders, and the like.

[0058] It should be noted that ratios, concentrations, amounts, and other numerical data can be expressed herein in a range format. It can be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint and independently of the other endpoint. It is also understood that there are a number of values disclosed herein and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Ranges can be expressed herein as from “about” one particular value and / or to “about” another particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it can be understood that the particular value forms a further aspect. For example, if the value “about 10” is disclosed, then “10” is also disclosed.

[0059] When a range is expressed, a further aspect includes from the one particular value and / or to the other particular value. For example, where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure, e.g., the phrase “x to y” includes the range from ‘x’ to ‘y’ as well as the range greater than ‘x’ and less than ‘y’. The range can also be expressed as an upper limit, e.g., ‘about x, y, z, or less’ and should be interpreted to include the specific ranges of ‘about x’, ‘about y’, and ‘about z’ as well as the ranges of Tess than x’, less than y’, and Tess than z’. Likewise, the phrase ‘about x, y, z, or greater’ should be interpreted to include the specific ranges of ‘about x’, ‘about y’, and12SUBSTITUTE SHEET (RULE 26)‘about z’ as well as the ranges of ‘greater than x’, greater than y’, and ‘greater than z’. In addition, the phrase “about ‘x’ to ‘y’,” where ‘x’ and ‘y’ are numerical values, includes “about ‘x’ to about J)?

[0060] It is to be understood that such a range format is used for convenience and brevity, and, thus, should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. To illustrate, a numerical range of “about 0.1% to 5%” should be interpreted to include not only the explicitly recited values of about 0.1% to about 5%, but also include individual values (e.g., about 1%, about 2%, about 3%, and about 4%) and the sub-ranges (e.g., about 0.5% to about 1.1%; about 5% to about 2.4%; about 0.5% to about 3.2%, and about 0.5% to about 4.4%, and other possible sub-ranges) within the indicated range.

[0061] As used herein, the terms “about,” “approximate,” “at or about,” and “substantially” mean that the amount or value in question can be the exact value or a value that provides equivalent results or effects as recited in the claims or taught herein. That is, it is understood that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact but may be approximate and / or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art such that equivalent results or effects are obtained. In some circumstances, the value that provides equivalent results or effects cannot be reasonably determined. In such cases, it is generally understood, as used herein, that “about” and “at or about” mean the nominal value indicated ±10% variation unless otherwise indicated or inferred. In general, an amount, size, formulation, parameter, or other quantity or characteristic is “about,” “approximate,” or “at or about” whether or not expressly stated to be such. It is understood that where “about,” “approximate,” or “at or about” is used before a quantitative value, the parameter also includes the specific quantitative value itself unless specifically stated otherwise. As used herein, the term “substantially free,” when used in the context of a composition or component of a composition that is substantially absent, is intended to refer to an amount that is then about 1 % by weight or less, e.g., less than about 0.5 % by weight, less than about 0.1 % by weight, less than about 0.05 % by weight, or less than about 0.01 % by weight of the stated material, based on the total weight of the composition.13SUBSTITUTE SHEET (RULE 26)

Claims

CLAIMS1. An adaptive seal, comprising: an attachment configured to attach to a replacement heart valve to close gaps between the replacement heart valve and a patient’s own and surrounding structure to reduce or to prevent paravalvular leakages.

2. The adaptive seal of claim 1, wherein the replacement heart valve is a transcatheter heart valve and the attachment is configured to attach to a bottom of a frame of the transcatheter heart valve.

3. The adaptive seal of claim 1, wherein the replacement heart valve is a surgical heart valve and the attachment is configured to attach along a sewing ring for the surgical heart valve.

4. The adaptive seal of claim 1, wherein the attachment comprises swelling elements configured to expand into the gaps between the replacement heart valve and the patient’s native tissue to reduce or prevent the paravalvular leakages.

5. The adaptive seal of claim 4, wherein the attachment further comprises a fabric component configured to enclose the swelling elements and attach to the replacement heart valve.

6. The adaptive seal of claim 5, wherein the swelling elements are configured to expand and fill in the gaps whilst enclosed by the fabric component.

7. The adaptive seal of claim 5, wherein the swelling elements are individual elements enclosed in the fabric component.

8. The adaptive seal of claim 5, wherein the swelling elements are multiple elements fabricated together and enclosed in the fabric component.

9. The adaptive seal of claim 5, wherein the attachment, the swelling elements, and the fabric component are crimped and are configured to be expanded and delivered via a transcatheter14SUBSTITUTE SHEET (RULE 26)approach.

10. The adaptive seal of claim 5, wherein the fabric component is configured to facilitate healthy endothelialization and tissue ingrowth to create a long term, reliable seal for the replacement heart valve that reduces or prevents paravalvular leakage.

11. The adaptive seal of claim 5, wherein the fabric component comprises an inner fabric configured to contact a metallic valve frame of the replacement heart valve, the inner fabric is a woven or knit fabric that is highly elastic and porous.

12. The adaptive seal of claim 5, wherein the fabric component comprises an outer fabric configured to contact the patient’ s native tissue, the outer fabric is a texturized fabric that provides high friction upon deployment and allows for tissue ingrowth.

13. The adaptive seal of claim 5, wherein the fabric component comprises an inner fabric with a sufficient porosity to allow for a part of blood to come in contact with the swelling elements.

14. The adaptive seal of claim 5, wherein the fabric component is made from two different types of fabrics.

15. The adaptive seal of claim 4, wherein the swelling elements are made from hydrogel materials comprising gelatin and / or polyethylene oxide.

16. The adaptive seal of claim 4, wherein the swelling elements are made of gelatin crosslinked using one or more of EDC (l-ethyl-3-(3-dimethylaminopropyl)carbodiimide), NHS (N- hydroxysuccinimide), methacrylamide, oxidated hyaluronic acid, and dextran dialdehyde.

17. The adaptive seal of claim 4, wherein the swelling elements are in a form of spheres or beads.

18. The adaptive seal of claim 4, wherein the swelling elements are configured to degrade over15SUBSTITUTE SHEET (RULE 26)time without producing any toxic waste products in a bloodstream.

19. The adaptive seal of claim 4, wherein the swelling elements have a degradation profile matching a time period needed for sufficient endothelialization and tissue ingrowth to take place.

20. The adaptive seal of claim 4, wherein the swelling elements do not pose a threat of embolization into a bloodstream.

21. The adaptive seal of claim 4, wherein the swelling elements have a gradual swelling profile such that the swelling elements reach a complete expansion over a period of time required for the replacement heart valve to be deployed in place.

22. The adaptive seal of claim 4, wherein the swelling elements are made of materials comprising hyaluronan, gelatin, starch, carrageenan, chitin, chitosan, cyclodextrin, guar gum, cellulose and / or synthetic materials like poly (vinyl alcohol), poly (acrylic acid), poly-N-isopropyl acrylamide, polyethylene glycol (PEG) / polyethylene oxide, poly(acrylic acid-coacrylamide), polyaniline, poly (lactic-co-glycolic acid), PEG block polylactide, PEG block polyglycolide, PEG block polylactide-co-glycolide, polyurethane, or a combination thereof.

23. The adaptive seal of claim 1 is configured to allow stable positioning of the replacement heart valve without a risk of dislodging or valve migration.

24. The adaptive seal of claim 1 is configured to reduce subsequent regurgitation fraction of the replacement heart valve immediately post-implantation / deployment of the replacement heart valve.

25. A replacement heart valve comprising: a stent frame; and an adaptive seal attached to the stent frame, wherein the adaptive seal is configured to close gaps between the replacement heart valve and a patient’s own and surrounding structure to reduce or to prevent paravalvular leakages.16SUBSTITUTE SHEET (RULE 26)

Images