Valve with reduced tissue ingrowth and vascular nebula formation

Abstract

Disclosed herein is an implantable prosthetic valve that is configured to substantially reduce vascular nebula formation and / or uncontrolled tissue ingrowth along the implantable prosthetic valve. Methods of making such implantable prosthetic valves are also disclosed herein. Also disclosed herein are kits comprising one or more sutures configured to substantially reduce vascular nebula formation and / or uncontrolled tissue ingrowth along the implantable prosthetic valve.

Description

Valves with reduced inward tissue growth and pannus formation

[0001] Cross-reference to related applications

[0002] This application claims the benefit of U.S. Patent Application No. 63 / 582,837, filed September 14, 2023, the entire contents of which are incorporated herein by reference for all purposes. Technical Field

[0003] This application relates to various aspects of prosthetic valves with reduced tissue ingrown tissue and pannus formation. Background Technology

[0004] The human heart can suffer from a variety of valvular diseases. These valvular diseases can lead to significant dysfunction of the heart and eventually require the replacement of the natural valve with an artificial one. Many known artificial valves exist, along with numerous known methods for implanting these artificial valves into the human body.

[0005] When replacing a natural valve, the surgical implantation of a prosthetic valve typically requires open-heart surgery, during which the heart stops beating and the patient is placed on a cardiopulmonary bypass (a so-called "heart-lung machine"). In a common surgical procedure, the diseased natural valve leaflet is removed and the prosthetic valve is sutured to the surrounding tissue at the valve annulus. Due to the surgical trauma and the resulting duration of extracorporeal blood circulation, some patients do not survive the surgery or die shortly afterward. It is well known that the patient's risk increases with the amount of time required for extracorporeal circulation. Because of these risks, a large number of patients with defective natural valves are considered ineligible for surgery because their condition is too frail to withstand the procedure. Some estimates suggest that over 50% of subjects over 80 years of age with valvular stenosis are ineligible for valve replacement surgery.

[0006] Due to the drawbacks associated with conventional open-heart surgery, percutaneous and minimally invasive surgical approaches have garnered significant attention. In one technique, prosthetic valves are configured for implantation via catheter insertion in a far less invasive procedure. For example, U.S. Patent Nos. 5,411,522 and 6,730,118 (incorporated herein by reference for all purposes) describe contractile transcatheter heart valves that can be percutaneously introduced over a catheter in a compressed state and expanded at the desired location by balloon inflation or using a self-expanding frame or stent.

[0007] One of the challenges associated with implantable heart valves is the potential for tissue growth and pannus growth on the inner surface of the valve, which could lead to device malfunction.

[0008] Therefore, there is a need for valves and materials that can substantially reduce tissue growth and ensure a long device lifespan. This disclosure at least partially addresses these and other needs. Summary of the Invention

[0009] Various aspects of this disclosure relate to implantable prosthetic valves. Some aspects relate to an implantable prosthetic valve comprising an annular frame having an inner surface and an outer surface, and wherein the frame has an inflow end and an outflow end, and a central longitudinal axis extending from the inflow end to the outflow end. In such aspects, the implantable prosthetic valve may further include an inner skirt having an inner surface and an outer surface and positioned along the inner surface of the frame. Further, the implantable prosthetic valve may include an optional leaflet structure having an inner surface and an outer surface and located at the inner surface of the annular frame. Further still, the implantable prosthetic valve may also include an optional outer skirt having an inner surface and an outer surface and located at the outer surface of the annular frame. The implantable prosthetic valve disclosed herein includes one or more sutures, wherein the one or more sutures are configured to attach at least a portion of the inner skirt, at least a portion of the leaflet structure if present, and / or at least a portion of the outer skirt to at least the annular frame, and wherein the one or more sutures are configured to substantially reduce pannus formation and / or uncontrolled inward growth of tissue along the implantable prosthetic valve.

[0010] This document further discloses an implantable prosthetic valve comprising: an annular frame having an inner surface and an outer surface, wherein the frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end; an inner skirt having an inner surface and an outer surface and positioned along the inner surface of the frame; wherein the inner surface of the inner skirt includes a first pannus-limiting material; and an optional leaflet structure having an inner surface and an outer surface and located within the annular frame. The inner surface; and / or an optional outer skirt having an inner surface and an outer surface and located at the outer surface of the annular frame; and one or more sutures, wherein the one or more sutures are configured to attach at least a portion of the inner skirt, at least a portion of the leaflet structure if present, and / or at least a portion of the outer skirt to at least the annular frame, and wherein the one or more sutures are configured to substantially reduce pannus formation and / or uncontrolled inward tissue growth along the implantable prosthetic valve.

[0011] In some respects, the one or more sutures have a substantially cylindrical shape. In other respects, the one or more sutures have a substantially flat shape.

[0012] In some aspects, at least a portion of the surface of the one or more sutures has a coating comprising a pannus-limiting material. In such exemplary and non-limiting aspects, the pannus-limiting material includes thermoplastic polyurethane, modified thermoplastic polyurethane, polycarbonate polyurethane, polyether polyurethane, polyester polyurethane, fluoropolymers, fluorinated oligomers, polyethylene, modified inorganic backbone polymers, polyphosphazenes, polyacrylates, polysiloxanes, polyesters, any copolymers thereof, or any combination thereof.

[0013] This document also discloses aspects covering methods for manufacturing the disclosed implantable prosthetic valve. In one aspect, this document discloses a method for forming an implantable prosthetic valve, the method comprising: attaching at least a portion of an inner skirt to at least an annular frame using one or more sutures, such that the outer surface of the inner skirt is at least partially attached to the inner surface of the annular frame, wherein the one or more sutures are configured to substantially reduce pannus formation along the implantable prosthetic valve, and wherein the inner surface of the inner skirt faces an internal space formed by the annular frame; and wherein the annular frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end.

[0014] This article also discloses a method for preventing tissue inward growth, which involves inserting any of the implantable prosthetic valves disclosed herein into a patient.

[0015] This document also discloses a kit comprising one or more sutures configured to attach at least a portion of the inner skirt and / or at least a portion of the leaflet structure and / or at least a portion of the outer skirt to at least one frame of the implantable prosthetic valve, wherein the one or more sutures are configured to substantially reduce pannus formation and / or uncontrolled inward growth of tissue along the implantable prosthetic valve.

[0016] The foregoing and other features and advantages of this disclosure will become more apparent from the following detailed description with reference to the accompanying drawings. Attached Figure Description

[0017] Figure 1 illustrates an exemplary location of pannus growth in an exemplary prosthetic valve implanted in a patient.

[0018] Figures 2A and 2B show partial schematic diagrams of an exemplary implantable prosthetic valve with one or more sutures in an exemplary placement of one aspect.

[0019] Figure 3 illustrates an exemplary method for forming one or more sutures.

[0020] Figures 4A to 4C show photographs of exemplary sutures. Figure 4A shows a photograph of an untreated PET-based suture from one aspect. Figure 4B shows a photograph of a PET-based suture from one aspect configured to reduce pannus growth. Figure 4C shows a photograph of a PET-based suture from another aspect configured to reduce pannus growth.

[0021] Figures 5A and 5B show photographs of exemplary sutures from one aspect. Figure 5A shows a photograph of an untreated UHMWPE-based suture from one aspect. Figure 5B shows a photograph of a UHMWPE-based suture from one aspect configured to reduce pannus growth.

[0022] Figures 6A through 6E show SEM images of exemplary sutures from one aspect. Figure 6A shows an exemplary untreated suture. Figure 6B shows an exemplary suture treated to reduce pannus growth. Figure 6C shows a close-up image of the suture in Figure 6B. Figure 6D shows a suture treated in other aspects to further reduce pannus growth. Figure 6E shows a cross-section of the suture shown in Figure 6D.

[0023] Figures 7A to 7C illustrate schematic diagrams of one aspect of an exemplary method for forming sutures and other valve components configured to reduce pannus growth.

[0024] Figures 8A and 8B illustrate an exemplary implantable prosthetic heart valve of one aspect. Figure 8A shows a front view. Figure 8B shows a side view of the prosthetic heart valve of Figure 8A, with the outer skirt removed to show the inner skirt and valve structure mounted on the frame. Detailed Implementation

[0025] This disclosure can be more readily understood by referring to the following detailed description, examples, drawings, and claims, as well as the description preceding and following them. However, before disclosing and describing the articles, systems, and / or methods of this disclosure, it should be understood that, unless otherwise stated, this disclosure is not limited to the specific or exemplary aspects of the disclosed articles, systems, and / or methods, and therefore variations are naturally possible. It should also be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting.

[0026] The following description of this disclosure is provided as a teaching on what can be achieved in its best, currently known aspects. Therefore, those skilled in the art will recognize and understand that many changes can be made to various aspects of this disclosure as described herein, while still obtaining the beneficial results of this disclosure. It will also be apparent that some of the desired benefits of this disclosure can be obtained by selecting some features of this disclosure without utilizing others. Therefore, those skilled in the art will recognize that many modifications and changes to this disclosure are possible, and in some cases even desirable, and are part of this disclosure. Thus, the following description is again provided as an illustration of the principles of this disclosure, and not as a limitation thereof.

[0027] definition

[0028] As used in this application and claims, the singular forms “a,” “an,” and “the” include the plural forms unless the context clearly indicates otherwise. Thus, for example, reference to “suture” includes aspects having two or more such sutures unless the context clearly indicates otherwise.

[0029] It should also be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. As used in the specification and claims, the term "comprising" may include aspects that are "composed of" and "substantially composed of". Additionally, the term "include" means "comprise".

[0030] With respect to the terms “for example” and “such as” and their grammatical equivalents, unless otherwise expressly stated, the phrase “and not limited to” shall be understood as conforming to.

[0031] A range may be expressed herein as from “about” one specific value and / or to “about” another specific value. When such a range is expressed, the other side includes from one specific value and / or to another specific value. Similarly, when a numerical value is expressed as an approximation using the antecedent “about”, it will be understood that the specific value constitutes the other side. It should also be understood that the endpoints of each range are significant both relative to and independent of the other endpoint. Unless otherwise stated, the term “about” means within 5% (e.g., within 2% or 1%) of the specific value modified by the term “about”. It should also be understood that if the term “about 1” is disclosed, the term “1” is also disclosed.

[0032] Throughout this disclosure, various aspects of this disclosure may be presented in the form of ranges. It should be understood that the description in range form is merely for convenience and brevity and should not be construed as an immutable limitation on the scope of this disclosure. Therefore, the description of a range should be considered as having specifically disclosed all possible subranges and individual numerical values ​​within that range. For example, a description of a range such as 1 to 6 should be considered as having specifically disclosed subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., and individual numbers within that range, such as 1, 2, 2.7, 3, 4, 5, 5.3, 6, and any integers and partial increments therebetween. This applies regardless of the width of the range.

[0033] As used herein, the terms “optional” or “optionally” mean that an event or situation described below may or may not occur, and the description includes both the possibility that the event or situation occurs and the possibility that it does not occur.

[0034] Furthermore, the terms “link” and “association” generally mean an electrical, electromagnetic, and / or physical (e.g., mechanical or chemical) connection or link, and do not exclude the existence of intermediate elements between the linked or associated items.

[0035] It should be understood that when an element is referred to as “connected” or “linked” to another element, it may be directly connected or linked to the other element, or there may be intermediate elements. Conversely, when an element is referred to as “directly connected” or “directly linked” to another element, there are no intermediate elements. Other terms used to describe relationships between elements or layers should be interpreted in a similar manner (e.g., “between” vs. “directly between”, “adjacent” vs. “directly adjacent”, “on” vs. “directly above”).

[0036] It should be understood that although the terms "first," "second," etc., may be used herein to describe various elements, components, regions, layers, and / or parts, these elements, components, regions, layers, and / or parts should not be limited by these terms. These terms are used only to distinguish one element, component, region, layer, or part from another. Therefore, without departing from the teachings of the examples, the first element, component, region, layer, or part discussed below may be referred to as the second element, component, region, layer, or part.

[0037] For ease of description, this document uses spatial relative terms such as “below,” “under,” “lower,” “above,” “upper,” “upward,” “downward,” “top,” “bottom,” etc., to describe the relationship of one element or feature to another, as shown in the figures. It will be understood that, in addition to the orientation depicted in the figures, the spatial relative terms are also intended to cover different orientations of the device during use or operation. For example, if the device in the figures is flipped, an element described as “below” or “under” other elements or features will be oriented “above” other elements or features. Thus, the term “below” can encompass both upward and downward orientations. The device may be oriented in other ways (rotated 90 degrees or in other orientations), and the spatial relative descriptors used herein will be interpreted accordingly.

[0038] Terms such as “proximal,” “farthest,” “radial outward,” “radial inward,” “external,” “internal,” and “side” describe the orientation and / or position of parts of a component or element within a consistent but arbitrary frame of reference, which becomes clear by referring to the text describing the component or element under discussion and the associated drawings. Such terms may include the words specifically mentioned above, their derivatives, and words with similar meanings.

[0039] As used herein, the term “and / or” includes any and all combinations of one or more of the associated listed items. It should also be understood that the term “and / or” includes situations where one or the other of the associated listed items is present, as well as aspects where two of the associated listed items are present or any combination of the associated listed items is present.

[0040] As used herein, the terms or phrases “effective,” “effective quantity,” or “condition effective for” refer to the quantity or condition that enables the realization of the function or property represented by the effective quantity or condition. As will be noted below, the exact quantity or specific condition required will vary depending on recognized variables, such as the materials used and the observed processing conditions. Therefore, it is not always possible to specify an exact “effective quantity” or “condition effective for”. However, it should be understood that a person skilled in the art can readily determine a suitable effective quantity using only routine experiments.

[0041] The terms "fiber" or "filament" are used interchangeably.

[0042] The terms “fiber” (or “filament”) and “material comprising multiple fibers (filaments)” are used herein in their broad and general sense and may refer to any type of natural or synthetic substance or material whose length is significantly greater than its width, including any elongated or relatively thin, elongated and / or filamentous sheets, filaments, ropes, yarns, ply yarns, strands, threads, cords, or portions thereof. Furthermore, “fiber” or “material comprising multiple fibers” may refer to a single filament or collectively to multiple filaments. Examples of materials comprising multiple fibers according to various aspects of this disclosure include, but are not limited to, any type of cloth, fabric, or textile. It should be understood that, in some non-limiting aspects, the term “material comprising multiple fibers” may refer to cloth, fabric, textile, or interlocking fiber material that may cover or form certain features of the disclosed apparatus.

[0043] As used herein, the term "fiber" includes fibers of extreme or infinite length (e.g., filaments) and fibers of short length (e.g., staple fibers). It should also be understood that filaments can be monofilaments, multifilaments, braided filaments, unbraided filaments, textured filaments, untextured filaments, etc.

[0044] As used herein, the term “substantially” means that the events or circumstances subsequently described have occurred completely, or that the events or circumstances subsequently described are generally, usually, or substantially likely to occur.

[0045] Furthermore, in some respects, the term “substantially” may refer to at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% of the said property, component, composition, or other condition, wherein “substantially” is used to characterize or otherwise quantify the quantity.

[0046] As used herein, the term “substantially”, such as in the context of “substantially identical” or “substantially similar”, means a method or system or component that is at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% similar to the method or system or component being compared.

[0047] While the operations of exemplary aspects of the disclosed methods may be described in a specific order for ease of presentation, it should be understood that the disclosed aspects may encompass an order of operations other than the specific order disclosed. For example, in some cases, the operations described in the order may be rearranged or performed simultaneously. Furthermore, the descriptions and disclosures provided in association with a particular aspect are not limited to that aspect and may be applied to any aspect disclosed.

[0048] Furthermore, for simplicity, the accompanying drawings do not illustrate the various ways in which the disclosed systems, methods, and apparatus can be combined with other systems, methods, and apparatuses (which will be readily apparent to those skilled in the art based on this disclosure). Additionally, this specification sometimes uses terms such as “produce” and “provide” to describe the disclosed methods. These terms are high-level abstractions of actual, executable operations. The actual operations corresponding to these terms may vary depending on the specific implementation and will be readily apparent to those skilled in the art based on this disclosure.

[0049] Implantable prosthesis devices

[0050] One of the challenges affecting the lifespan and overall performance of implantable prosthetic devices is the uncontrolled growth of tissue and pannus on the device's internal (luminal) surface. Pannus growth is a non-immune inflammatory response of the body to the implanted prosthesis. This growth can originate on any surface induced by blood turbulence. Typically, pannus growth begins in the suture area of ​​the valve and spreads from there. Currently available solutions to avoid this problem include dual antiplatelet therapy (DAPT). However, this solution requires patients to take two types of antiplatelet drugs for an extended period, and it only shows a decrease in the rate of pannus growth but does not eliminate it. In extreme cases, valve replacement is required, but it may not be suitable for all pannus-based failed valves.

[0051] Figure 1 illustrates an exemplary valve 1000 located within a patient's natural anatomical structure. It should be understood that the natural anatomical structure may include, for example, but not limited to, valve locations such as the aortic valve, mitral valve, tricuspid valve, and pulmonary valve, and their surrounding locations. An exemplary suture 1002 is used to attach the various portions of the valve to a frame 1003. In some non-limiting aspects, pannus growth may be observed around the area marked 1004. It should be understood that pannus growth may initiate in other portions of the valve's inner surface.

[0052] This disclosure relates to implantable prosthetic valves having one or more sutures configured to reduce pannus formation and other tissue growth. A partial schematic diagram of an exemplary implantable prosthetic device 2100 is shown in Figure 2A. More detailed schematic diagrams of exemplary valves are shown in Figures 8A and 8B and will be discussed herein.

[0053] One aspect disclosed herein is an implantable prosthetic valve 2100 comprising an annular frame 2040 having an inner surface 2041 (lumen) and an outer surface 2042 (distal lumen), wherein the frame has an inflow end portion 2020 and an outflow end portion 2030 and a central longitudinal axis 2050 extending from the inflow end portion to the outflow end portion. In other aspects, the implantable prosthetic valve further includes an inner skirt 2005 (partially shown in FIG. 2A) having an inner surface and an outer surface and positioned along the inner surface of the frame. In other aspects, the valve may optionally include a leaflet structure 2060 comprising one or more leaflets having an inner surface and an outer surface and located at the inner surface of the annular frame. In other aspects, the valve may optionally include an outer skirt. For example, as shown in FIG. 8A, an outer skirt 2009 has an inner surface and an outer surface and is located at the outer surface of the annular frame 2040. The outer skirt can also be attached to the frame with one or more stitches.

[0054] In other aspects, the implantable medical device disclosed herein includes one or more sutures 2002, 2004, 2006, 2008, 2010, 2012, and 2014, as shown, for example, in Figures 2A and 2B. The sutures shown in Figures 2A and 2B extend along various portions of the device. In other aspects, the sutures can be used to attach at least a portion of the inner skirt and / or, if present, at least a portion of the leaflet structure and / or at least a portion of the outer skirt to at least one frame of the implantable prosthetic valve. In yet another aspect, the sutures can be used to attach various components of the valve together. For example, suture 2002 extends along the vertical struts of the frame. Suture 2004 extends along the skirt joint. Sutures 2006, 2008, 2010, and 2012 extend along rows of struts in the frame, while suture 2014 extends along the tip of the leaflet 2060.

[0055] In other aspects, one or more sutures are configured to attach at least a portion of the inner skirt, at least a portion of the leaflet structure if present, and / or at least a portion of the outer skirt to at least an annular frame, and wherein one or more sutures are configured to substantially reduce pannus formation and / or uncontrolled inward tissue growth along the implantable prosthetic valve. It should be understood that, in some aspects, at least a portion of the above is located on the inner surface of the implantable prosthetic device. In other aspects, the one or more sutures disclosed herein are configured to substantially reduce pannus formation and / or uncontrolled inward tissue growth along the inner surface of the implantable prosthetic valve. It should also be understood that, in some aspects, having pannus-limiting material on the outer surface or at least in some portions of the outer surface of the implantable prosthetic device may be undesirable.

[0056] In other respects, one or more suture threads can have any desired form and shape. In some respects, one or more suture threads can be in the form of substantially cylindrical suture threads. It should be understood that in some respects, cylindrical suture threads can be monofilaments. However, in other respects, cylindrical suture threads can be multifilaments. In still other respects, if the suture thread is multifilament, such threads can be woven, textured, napped, twisted, or untwisted but bundled (chain yarns).

[0057] In some aspects, one or more sutures have a substantially flat form. In such exemplary and non-limiting aspects, flat sutures may exist as strips. However, in other aspects and as disclosed below, original napped, braided, and / or twisted sutures may be flattened by any method known in the art, such as, but not limited to, heat treatment. In still other aspects, flat sutures may have a planar shape. In still other aspects, flat sutures are substantially without sharp edges. However, in still other aspects, flat sutures may have substantially curved edges. However, in still other aspects, flat sutures may have any desired shape and / or edge shape.

[0058] In other aspects, at least a portion of the surface of one or more sutures has a coating comprising a pannus-limiting material. In still other aspects, substantially the entire surface of one or more sutures has a coating comprising a pannus-limiting material. It should be understood that, in such aspects, the pannus-limiting material may include thermoplastic polyurethane, modified thermoplastic polyurethane, polycarbonate polyurethane, polyether polyurethane, polyester polyurethane, fluoropolymers, fluorinated oligomers, polyethylene, modified inorganic backbone polymers, polyphosphazenes, polyacrylates, polysiloxanes, polyesters, any copolymers thereof, or any combination thereof.

[0059] In other aspects, any thermoplastic polyurethane known in the art can be used to form a coating. In some aspects, the thermoplastic polyurethane can be modified. For example, but not limited to, the thermoplastic polyurethane can be modified to include a fluorinated or organosilicon-containing portion incorporated into the polymer backbone. It should be understood that the phrase "incorporated into the polymer backbone" includes both portions present in the backbone and portions branching off from the backbone. In other aspects, modified thermoplastic polyurethane includes mixtures of thermoplastic polyurethane and compounds having a fluorinated portion and / or organosilicon.

[0060] In other respects, any inorganic main-chain polymer with the desired properties may be used. In some respects, the modified inorganic main-chain polymer may be modified with halogen-containing groups, phosphorus-containing groups, nitrogen-containing groups, or combinations thereof. In some respects, the modified inorganic main-chain polymer may include polyphosphazenes. It should be understood that halogen-containing groups may include groups containing fluorine, chlorine, bromine, iodine, or any combination thereof.

[0061] In other respects, polyethylene includes ultra-high molecular weight polyethylene (UHMWPE), low-density polyethylene (LDPE), high-density polyethylene (HDPE), or any combination thereof.

[0062] In other aspects, a coating is applied to one or more sutures before attaching at least a portion of the inner skirt and / or, if present, at least a portion of the leaflet structure and / or at least a portion of the outer skirt to at least the annular frame. It should be understood that the problem of uncontrolled pannus growth is particularly problematic on the inner surface of the implantable device. In some aspects, portions of the outer skirt that are intended to contact the patient's natural anatomy are configured to allow inward tissue growth. Therefore, the one or more sutures disclosed herein may be used only on portions of the outer skirt where tissue growth is not desired. Similarly, the one or more sutures disclosed herein may be used only on portions of the leaflet structure where inward tissue growth is not desired. However, in other aspects, the one or more sutures disclosed herein are used to create a desired pattern on any of the disclosed components, combining locations where inward tissue growth is desired with locations where inward tissue growth is not desired.

[0063] In other aspects, portions of various valve components, such as at least a portion of the inner skirt and / or, if present, at least a portion of the leaflet structure and / or at least a portion of the outer skirt, may include a coating comprising a pannus-limiting material. As described above, it should be understood that the portion of the outer skirt facing the natural anatomy is configured to allow tissue growth inward. Where a particular application requires, the disclosed aspects allow for the formation of valve components having portions with and without pannus-limiting material. For example, the outer skirt may have an inner skirt cap and an outer skirt cap in which it is desired to prevent tissue growth inward. In such aspects, a pannus-limiting material as disclosed herein may be deposited on the cap to limit growth transfer from the outside to the inside, thereby forming a growth-free zone. It should also be understood that the aspects disclosed herein relate to an outer skirt and / or leaflet structure substantially without pannus-limiting material.

[0064] In other respects, if pannus-restricting material is only required at specific locations, the inner skirt, outer skirt, or other parts of the leaflet valve can be masked before the pannus-restricting material is applied to create the desired pattern.

[0065] In some aspects, this document discloses an implantable prosthetic valve comprising: an annular frame having an inner surface and an outer surface, wherein the frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end; an inner skirt having an inner surface and an outer surface and positioned along the inner surface of the frame; wherein the inner surface of the inner skirt includes a first pannus-limiting material; and an optional leaflet structure having an inner surface and an outer surface and located within the annular frame. The inner surface of the frame; and / or an optional outer skirt having an inner surface and an outer surface and located at the outer surface of the annular frame; and one or more sutures, wherein the one or more sutures are configured to attach at least a portion of the inner skirt, at least a portion of the leaflet structure if present, and / or at least a portion of the outer skirt to at least the annular frame, and wherein the one or more sutures are configured to substantially reduce pannus formation and / or uncontrolled inward tissue growth along the implantable prosthetic valve.

[0066] In other aspects, implantable devices containing leaflet structures are disclosed. However, in other aspects, implantable devices containing an outer skirt are disclosed. In such aspects, the outer skirt is circumferentially located on the outer surface of the annular frame. Likewise, it should be understood that, if desired, pannus-limiting material may be disposed on specific portions of the outer skirt. However, if it is desired that the outer skirt allows for inward tissue growth, pannus-limiting material is generally not disposed on such portions.

[0067] In some respects, one or more sutures may include polyester, polyethylene, ultra-high molecular weight polyethylene, silicone, polyurethane, polytetrafluoroethylene, polyether ether ketone (PEEK), fluoropolymers, or natural tissue or combinations thereof.

[0068] In other respects, one or more threading threads may comprise multifilament threads. Similarly, as discussed herein, multifilaments may be braided, twisted, napped, flat-bundled, textured, or any combination thereof. In such respects, the thread may comprise two or more filaments having a thickness of about 0.02 mm to about 0.5 mm, including exemplary values ​​of about 0.03 mm, about 0.04 mm, about 0.05 mm, about 0.06 mm, about 0.07 mm, about 0.1 mm, about 0.12 mm, about 0.15 mm, about 0.17 mm, about 0.2 mm, about 0.22 mm, about 0.25 mm, about 0.27 mm, about 0.3 mm, about 0.32 mm, about 0.35 mm, about 0.37 mm, about 0.4 mm, about 0.42 mm, about 0.45 mm, and about 0.47 mm. It should be understood that the thickness can have any value between any two of the foregoing values ​​or fall within the range formed by any two of the foregoing values. For example, but not limited to, the thickness can be about 0.05 mm to about 0.5 mm, about 0.1 mm to about 0.5 mm, about 0.2 mm to about 0.5 mm, about 0.3 mm to about 0.5 mm, about 0.02 mm to about 0.4 mm, about 0.02 mm to about 0.3 mm, about 0.02 mm to about 0.2 mm, about 0.02 mm to about 0.1 mm, about 0.02 mm to about 0.05 mm, etc.

[0069] However, in other respects, the suture may have sizes from about 10-0 to about 4, including exemplary values ​​of about 9-0, about 8-0, about 7-0, about 6-0, about 5-0, about 4-0, about 3-0, about 2-0, about 0, about 1, about 2, and about 3 based on USP (United States Pharmacopeia) units. This size may be converted to metric sizes of size numbers from about 0.2 to about 6, including exemplary values ​​of about 0.3, about 0.4, about 0.5, about 0.7, about 1, about 1.5, about 2, about 3, about 3.5, about 4, and about 5. However, in other respects, the suture may have an average diameter of about 0.02 mm to about 0.7 mm, including exemplary values ​​of about 0.03 mm, about 0.04 mm, about 0.05 mm, about 0.06 mm, about 0.07 mm, about 0.1 mm, about 0.12 mm, about 0.15 mm, about 0.17 mm, about 0.2 mm, about 0.22 mm, about 0.25 mm, about 0.27 mm, about 0.3 mm, about 0.32 mm, about 0.35 mm, about 0.37 mm, about 0.4 mm, about 0.42 mm, about 0.45 mm, about 0.47 mm, about 0.5 mm, about 0.52 mm, about 0.55 mm, about 0.57 mm, about 0.6 mm, about 0.62 mm, about 0.65 mm, and about 0.67 mm. It should be understood that the suture may have any average diameter falling between or within the range formed by any two of the foregoing values. For example, but not limited to, the suture may have an average diameter of about 0.05 mm to about 0.7 mm, about 0.1 mm to about 0.7 mm, about 0.2 mm to about 0.7 mm, about 0.3 mm to about 0.7 mm, about 0.5 mm to about 0.7 mm, about 0.02 mm to about 0.5 mm, about 0.02 mm to about 0.4 mm, about 0.02 mm to about 0.3 mm, about 0.02 mm to about 0.2 mm, about 0.02 mm to about 0.1 mm, about 0.02 mm to about 0.05 mm, etc.

[0070] It should also be understood that each filament in the thread may have the same thickness or different thicknesses. It should also be understood that the overall roughness of the suture may depend on the filament diameter.

[0071] Exemplary sutures are illustrated in Figures 4A-4C, 5A-5B, and 6A-6E. For example, Figure 4A shows a PET-based suture having a cylindrical shape and no coating on its surface. It can be seen that the suture is the surface of the suture, which has a significant roughness that can affect its surface area. Figure 4B shows the application of the pannus-limiting material disclosed herein to virtually all surfaces of a PET-based suture. It can be seen that the coating covers the suture and reduces the surface area by reducing roughness. Figure 4C shows a suture that has first been rinsed and then coated with one of the materials disclosed herein. Figures 5A and 5B show UHMWPE-based sutures, one without any treatment and the other coated with the material disclosed herein. Variations in surface roughness are also observed.

[0072] Figures 6A through 6E show SEM images of such exemplary sutures. For example, Figure 6A shows an untreated suture. Figures 6B and 6C show sutures with the coating disclosed herein, while Figure 6D shows a coated suture that has been smoothed and heat-treated to further reduce the surface area of ​​the suture and lower its roughness. Figure 6E shows a cross-section of a coated suture with a coating thickness of 6002.

[0073] In other respects, at least a portion of the inner skirt and / or, if present, at least a portion of the leaflet structure and / or at least a portion of the outer skirt, as well as one or more sutures, substantially have no roughness greater than about 0.5 μm, about 1 μm, 0.5 μm, about 0.1 μm, about 90 nm, about 50 nm, or about 30 nm. Not wishing to be bound by any theory, since tissue cells are approximately 10 μm to 15 μm in size and can reach up to about 40 μm, it is assumed that any surface roughness below 5 μm will not be detected by cells and will not induce cell growth.

[0074] In yet another aspect, the surface of one or more sutures is substantially free of turbulence-induced surface morphology that would cause pannus formation. In yet another aspect, at least a portion of the inner skirt is substantially free of turbulence-induced surface morphology that would cause pannus formation. In yet another aspect, at least a portion of the leaflet structure is substantially free of turbulence-induced surface morphology that would cause pannus formation. In yet another aspect, at least a portion of the outer skirt is substantially free of turbulence-induced surface morphology that would cause pannus formation.

[0075] In further aspects, the sutures and the inner surface of the inner skirt (and at least a portion of the outer surface) form a smooth profile, the sutures being used to attach it to at least the frame. It should be understood that, in such aspects, the overall morphology of the inner surface of the inner skirt and the sutures has no deep edges. In other aspects, the surfaces of the sutures and the inner skirt (at least a portion of the inner surface and at least a portion of the outer surface) are configured to form a smooth profile that substantially lacks any “pockets” or “grooves” formed between the sutures and the surfaces of the inner skirt. An exemplary photograph of such a profile can be seen in Figure 7C, where the sutures 7014 and the inner skirt 7024 form a smooth profile. It should also be understood that the sutures and at least some portions of any present leaf-like structures, as well as at least some portions of the surface of the outer skirt, form a profile similar to that of the sutures and the surfaces of the inner skirt.

[0076] In other aspects, the coatings disclosed herein may have a thickness of about 50 nm to about 150 μm, including about 100 nm, about 150 nm, about 200 nm, about 250 nm, about 300 nm, about 350 nm, about 400 nm, about 450 nm, about 500 nm, about 550 nm, about 600 nm, about 650 nm, about 700 nm, about 750 nm, about 800 nm, about 850 nm, about 900 nm, about 950 nm, about 1 μm, about 5 μm, about 10 μm, about 15 μm, about 20 μm, about 25 μm, about 30 μm, about 35 μm, about 40 μm, about 45 μm, about 50 μm, about 55 μm, about 60 μm, about 65 μm, about 70 μm, about 75 μm, about 80 μm, about 85 μm, about 90 μm, about 90 μm, about 100 nm, about 150 nm, about 200 nm, about 250 nm, about 70 μm, about 75 μm, about 80 μm, about 85 μm, about 90 μm, about 100 nm, about 150 nm, about 200 nm, about 200 nm, about 200 nm, about 700 nm, about 75 μm, about 80 μm, about 85 μm, about 90 μm, about 100 nm, about 150 nm, about 200 nm, about 200 nm, about 200 nm, about 200 nm, about 700 nm, about 75 μm, about 80 μm, about 85 μm, about 90 μm, about 100 nm, about Exemplary values ​​are given for approximately 95 μm, 100 μm, 105 μm, 110 μm, 115 μm, 120 μm, 125 μm, 130 μm, 135 μm, 140 μm, and 145 μm. In other aspects, the coating thickness may have any value between any two of the foregoing values, or fall within any range formed by any two of the foregoing values. For example, but not limited to, the thickness of the coating can be about 50 nm to about 100 μm, about 50 nm to about 50 μm, about 50 nm to about 10 μm, about 50 nm to about 1 μm, about 50 nm to about 900 nm, about 50 nm to about 500 nm, about 50 nm to about 200 nm, about 50 nm to about 100 nm, about 100 nm to about 150 μm, about 200 nm to about 150 μm, about 500 nm to about 150 μm, about 1 μm to about 150 μm, about 10 μm to about 150 μm, about 50 μm to about 150 μm, about 100 μm to about 150 μm, etc.

[0077] In other respects, the implantable prosthetic valves disclosed herein are radially constrictible to a constricted configuration and radially expandable to an expanded configuration. Exemplary implantable prosthetic valves are disclosed in Figures 2A, 8A, and 8B.

[0078] For example, Figure 8A shows a side plan view of an exemplary prosthetic heart valve 2100 having an inflow end 2020 and an outflow end 2030 according to one aspect. The prosthetic heart valve 2100 is described, for example, in U.S. Patent No. 10,463,484 entitled “Prosthetic HeartValve Having Leaflet Inflow Below Frame,” which is incorporated herein by reference. The illustrated prosthetic valve 2100 is suitable for implantation in a natural aortic valve annulus, but in other aspects, it may be suitable for implantation in other natural valve annulus of the heart (mitral, pulmonary, and tricuspid valves). The prosthetic valve 2100 may have one or more of the following components: a frame 2040, a leaflet (or valve) structure 2060, and an inner skirt 2005. The valve 2100 may also include an outer skirt 2009.

[0079] In some aspects, the prosthetic valve 2100 may include a leaflet structure 2060. In some aspects, the leaflet structure may include one or more leaflets, each of which may be arranged to contract in a tricuspid configuration. In some aspects, the edges of the leaflet structure 2060 may have an undulating, curved fan-shaped shape. Furthermore, due to the fan-shaped shape, wrinkles and ripples at the ventral side of each leaflet, which may lead to early calcification in these areas, can be eliminated or at least minimized. In other aspects, the leaflets may have a variety of other shapes and / or configurations. However, it should be understood that the leaflets of the leaflet structure do not need to have a V-shaped or fan-shaped inflow edge, but rather each leaflet may have a square or rectangular shape defining a straight inflow edge.

[0080] As shown in Figures 2A, 8A, and 8B, the leaflet 2060 can be secured to the frame 2040 using one or more sutures 2014 disclosed herein. The frame 2040 can be made of any of a variety of suitable malleable expandable materials known in the art (e.g., stainless steel, cobalt-chromium, etc.) or self-expanding materials (e.g., nitinol). When made of a malleable expandable material, the frame 2040 can be coiled into a radially compressed state on the delivery catheter and then expanded in the patient via an inflatable balloon or equivalent expansion mechanism. When made of a self-expanding material, the frame 2040 can be coiled into a radially compressed state and restrained in a compressed state by insertion into a sheath or equivalent mechanism of the delivery catheter. Once inside the body, the valve can be advanced from the delivery sheath, which allows the valve to expand to its functional size. Suitable malleable expandable materials that can be used to form the frame 2040 include, but are not limited to, stainless steel, nickel-based alloys (e.g., cobalt-chromium or nickel-cobalt-chromium alloys), polymers, or combinations thereof. In certain aspects, the 2040 frame can be made from nickel-cobalt-chromium-molybdenum alloys, such as the MP35N™ alloy (a trade name by SPS Technologies), which is equivalent to the UNS R30035 alloy (covered by ASTM F562-02). The MP35N™ / UNS R30035 alloy contains 35 wt% nickel, 35 wt% cobalt, 20 wt% chromium, and 10 wt% molybdenum. In using MP35N as the frame material, less material is required to achieve the same or better resistance to radial and crushing forces, fatigue resistance, and corrosion resistance. Furthermore, because less material is required, the frame's curl profile can be reduced, thus providing a lower profile valve assembly for percutaneous delivery to the body's treatment site.

[0081] In other respects, the frame 2040 can have other configurations or shapes.

[0082] The leaflets can be sewn together to form leaflet structure 2060, which can then be secured to frame 2040. It should be understood that when the leaflets are sewn together, each leaflet may include any of the sutures disclosed herein, if desired. However, it is also disclosed herein that one or more sutures are used to secure the leaflet structure within the valve, when different from what is disclosed. In other exemplary and non-limiting aspects, the leaflets of leaflet structure 2060 may be secured to each other on adjacent sides to form a fusion portion 2011 of the leaflet structure. It should be understood that the sutures disclosed herein can also be used to form such fusion portions. However, in other aspects, sutures different from those disclosed herein may also be used.

[0083] In another exemplary aspect, one or more leaflets of the leaflet structure 2060 may be attached to the inner skirt 2005 using sutures 2014. The sutures 2014 may trace the curvature of the bottom edge of the leaflet structure 2060 and are collectively referred to as fan lines.

[0084] The inner skirt 2005 may have multiple functions, including assisting in securing the leaflet structure 2060 and / or the outer skirt 2009 to the frame 2040, and aiding in forming a good seal between the valve 2100 and the natural valve annulus by preventing blood flow below the lower edge of the leaflet. It should be understood that any skirt configuration / construction known in the art may be used. For example, but not limited to, the skirt configuration / construction may include woven, knitted, woven, and / or nonwoven textiles. The inner skirt 2005 may comprise a tough, tear-resistant material, such as polyethylene terephthalate (PET), but various other synthetic or natural materials may be used. The skirt thickness is ideally less than 6 mils or 0.15 mm, and ideally less than 4 mils or 0.10 mm, and even more ideally about 2 mils or 0.05 mm, and even more ideally about 1.1 mils or 0.03 mm. In certain aspects, the skirt 2005 may have a variable thickness; for example, the skirt may be thicker at its edges than at its center. In one embodiment, the skirt 2005 may comprise a PET skirt having a thickness of about 0.07 mm at its edges and about 0.06 mm at its center. A thinner skirt can provide better curling performance while still providing a good valve-like seal. In other aspects, the inner skirt 2005 may have any of the coatings disclosed herein. In some aspects, only the inner surface of the inner skirt 2005 may have the coatings disclosed herein. In other aspects, both surfaces of the inner skirt may have the same coating.

[0085] Additionally and / or alternatively, as shown in FIG8B, the inner skirt 2005 may include a first portion 2015 (also referred to as the supported portion) extending circumferentially around the central longitudinal axis of the prosthetic valve along the inner surface of the frame 2040 and a second portion (also referred to as the unsupported portion 2013) at the inflow end 2020 of the prosthetic valve 2100. The unsupported portion 2013 is not supported by the frame 2040. The unsupported portion 2013 is capable of extending circumferentially around the central longitudinal axis of the prosthetic valve to form an unsupported circumference at the inflow end 2020.

[0086] In some respects and as described herein, the prosthetic valve may also include an outer skirt 2009. The outer skirt 2009 may be laser-cut or otherwise formed from a robust material, such as woven PET, but other synthetic or natural materials may also be used. The outer skirt 2009 may be secured at the inflow end of the prosthetic valve to the lower edge of the inner skirt 2005, such as by any of the sutures disclosed herein. However, other methods of securing the outer skirt are also available, such as welding and / or adhesives. In certain respects, the lower edge of the outer skirt 2009 may be tightly sutured or otherwise secured (e.g., by welding or adhesives) to the inner skirt 2005. In some respects, only the desired portion of the outer skirt may have the pannus-limiting material disclosed herein. In some respects, the outer surface of the outer skirt is configured to allow tissue to grow inward. If it is desired not to form a tissue growth zone, the disclosed coatings or sutures may be used to achieve this goal.

[0087] The absence of a frame or other rigid metal component along the inflow end portion of the prosthetic valve advantageously reduces mechanical compression of the natural valve annulus (e.g., the aortic valve annulus) and the left ventricular outflow tract (when implanted in the aortic position), thus reducing the risk of trauma to surrounding tissues.

[0088] Any sutures described herein may be present in the kit. In some aspects, the kit may include any one or more sutures disclosed herein that are configured to attach the inner skirt and / or leaflet structure and / or outer skirt to the framework of the implantable prosthetic valve, wherein the one or more sutures are configured to substantially reduce pannus formation and / or uncontrolled inward growth of tissue along the implantable prosthetic valve.

[0089] In other aspects, the kit may include one or more sutures having a substantially cylindrical form, a substantially flat form, or a combination thereof. In other aspects, the kit may include one or more sutures, wherein at least a portion of the surface of the one or more sutures has a coating comprising a pannus-limiting material. However, in other aspects, substantially the entire surface of the one or more sutures has a coating comprising a pannus-limiting material.

[0090] As disclosed herein, the pannus-limiting material may include any of the thermoplastic polyurethanes, modified thermoplastic polyurethanes, polycarbonate polyurethanes, polyether polyurethanes, polyester polyurethanes, fluoropolymers, fluorinated oligomers, polyethylene, modified inorganic backbone polymers, polyphosphazenes, polyacrylates, polysiloxanes, polyesters, any copolymers thereof, or any combination thereof.

[0091] In other respects, one or more sutures present in the kit may include polyester, polyethylene, ultra-high molecular weight polyethylene, silicone, polyurethane, polytetrafluoroethylene, polyether ether ketone (PEEK), fluoropolymers, or natural tissue or combinations thereof.

[0092] It should be understood that these kits can be used in any known application requiring the connection of two or more components. For example, but not limited to, kits including one or more sutures disclosed herein can be used to connect or attach fabric or tissue to a frame of a prosthetic valve, or to or attach to each other, or to or attach to any other desired component. In other aspects, the one or more sutures present in the kits disclosed herein are configured to connect various components of an article.

[0093] method

[0094] This disclosure also relates to a method of manufacturing a prosthetic valve, the method comprising attaching at least a portion of an inner skirt to at least an annular frame using one or more sutures, such that the outer surface of the inner skirt is at least partially attached to the inner surface of the annular frame, wherein the one or more sutures are configured to substantially reduce pannus formation along the implantable prosthetic valve, and wherein the inner surface of the inner skirt faces the internal space formed by the annular frame. In other aspects, and as shown above, the annular frame has an inflow end and an outflow end, and a central longitudinal axis extending from the inflow end to the outflow end. In some aspects, any one or more of the sutures disclosed herein may be used. In some aspects, the one or more sutures are configured to substantially reduce pannus formation along the implantable prosthetic valve.

[0095] In other aspects, a method of manufacturing a prosthetic valve includes attaching at least a portion of a leaflet structure having an inner surface and an outer surface to at least an annular frame using one or more sutures. In yet another aspect, the method may include attaching at least a portion of an outer skirt to at least an annular frame using one or more sutures.

[0096] As described above, one or more sutures can be provided in a substantially cylindrical form or in a flat form. In other respects, the suture can have flattened portions and substantially cylindrical portions. In some respects, the suture can be provided as a band. However, in other respects, a substantially cylindrical suture can be flattened to form a flat suture.

[0097] In some respects, one or more sutures are flattened before attaching the inner skirt to at least the annular frame. However, in other respects, one or more sutures are flattened before attaching at least a portion of the leaflet structure to at least the annular frame. And in still other respects, one or more sutures are flattened before attaching at least a portion of the outer skirt to at least the annular frame.

[0098] In other respects, flattening can be performed by any method known in the art. For example, in some respects, the substantially cylindrical suture may first be treated to substantially remove surface roughness, and then flattened. However, in other respects, the substantially cylindrical suture may be flattened without any pretreatment. In some respects, the flattening of one or more sutures includes passing one or more sutures between at least two hot presses at temperatures of about 120°C to about 210°C (including exemplary values ​​of about 130°C, about 140°C, about 150°C, about 160°C, about 170°C, about 180°C, about 190°C, and about 200°C) and pressures of about 0.5 MPa to about 5 MPa (including exemplary values ​​of about 0.8 MPa, about 1 MPa, about 1.2 MPa, about 1.5 MPa, about 1.8 MPa, about 2 MPa, about 2.2 MPa, about 2.5 MPa, about 2.8 MPa, about 3 MPa, about 3.2 MPa, about 3.5 MPa, about 3.8 MPa, about 4 MPa, about 4.2 MPa, about 4.5 MPa, and about 4.8 MPa).

[0099] In one, and non-limiting, aspect, one or more sutures have substantially no surface roughness. In yet another aspect, one or more sutures have substantially no roughness greater than about 10 μm, about 5 μm, about 1 μm, 0.5 μm, about 0.1 μm, about 90 nm, about 50 nm, or about 30 nm.

[0100] In other aspects, the method disclosed herein includes forming a first coating on one or more sutures, wherein the first coating comprises a pannus-limiting material. This method 3000 is schematically illustrated in Figure 3. First, 3002 one or more sutures are cleaned. It should be understood that cleaning can be performed by any method known in the art. For example, but not limited to, the sutures can be cleaned with an alcohol (such as isopropanol) and then dried at room temperature. In other aspects, the step of forming the first coating includes immersing one or more sutures 3004 in a first solution comprising a first concentration of a first pannus-limiting material for a first predetermined time. In some aspects, the desired coating may be formed after the insertion step 3004. However, in other aspects, the method further includes removing one or more sutures from the first solution and immersing one or more sutures in a second solution comprising a second concentration of a second pannus-limiting material for a second predetermined time 3006.

[0101] In other aspects, the method may also include additional n sequences 3008, each sequence comprising the step of inserting one or more sutures into a solution containing a certain concentration of pannus-limiting material for a predetermined time. In such aspects, n can be 1 to 10, including exemplary values ​​2, 3, 4, 5, 6, 7, 8, and 9.

[0102] In some respects, the first concentration of the first solution is lower than the second concentration of the second solution. However, it should be understood that the first concentration may also be greater than the second concentration. In yet other respects, the concentration of the pannus-restricting material in each of the n sequences may be the same as or different from the first concentration.

[0103] In some respects, the first solution, the second solution, and the solution at each of the n sequences may be maintained at room temperature or may be heated if necessary. In other respects, the first predetermined time, the second predetermined time, or the predetermined time at each of the n sequences may be the same or different. It should be understood that the first predetermined time, the second predetermined time, or the predetermined time at each of the n sequences may be selected to achieve the desired result, and may be from about 1 second to about 5 minutes, including exemplary values ​​of about 2 seconds, about 3 seconds, about 4 seconds, about 5 seconds, about 6 seconds, about 7 seconds, about 8 seconds, about 9 seconds, about 10 seconds, about 15 seconds, about 20 seconds, about 25 seconds, about 30 seconds, about 35 seconds, about 40 seconds, about 45 seconds, about 50 seconds, about 55 seconds, about 1 minute, about 1.5 minutes, about 2 minutes, about 2.5 minutes, about 3 minutes, about 3.5 minutes, about 4 minutes, and about 4.5 minutes. In other respects, the first predetermined time, the second predetermined time, or the predetermined time in each of the n sequences may have any value between any two of the foregoing values, or may fall within a range formed by any two of the foregoing values. For example, the first predetermined time, the second predetermined time, or the predetermined time in each of the n sequences may be about 10 seconds to about 5 minutes, about 30 seconds to about 5 minutes, about 1 minute to about 5 minutes, about 2 minutes to about 5 minutes, about 1 second to about 4 minutes, about 1 second to about 2 minutes, about 1 second to about 1 minute, about 1 second to about 30 seconds, etc.

[0104] In other aspects, the first light-limiting material, the second light-limiting material, and the light-limiting materials in each of the n sequences may be the same or different, and are selected from light-limiting materials including thermoplastic polyurethane, modified thermoplastic polyurethane, polycarbonate polyurethane, polyether polyurethane, polyester polyurethane, fluoropolymers, fluorinated oligomers, polyethylene, modified inorganic backbone polymers, polyphosphazenes, polyacrylates, polysiloxanes, polyesters, any copolymers thereof, or any combination thereof. However, in another aspect, the modified thermoplastic polyurethane includes thermoplastic polyurethane having fluorine and / or organosilicon incorporated into the polymer backbone. In still other aspects, the modified thermoplastic polyurethane includes a mixture of thermoplastic polyurethane and compounds having fluorinated portions and / or organosilicon. In yet another aspect, the modified inorganic backbone polymer is modified with halogen-containing groups, phosphorus-containing groups, nitrogen-containing groups, or combinations thereof. In other aspects, polyethylene includes ultra-high molecular weight polyethylene (UHMWPE), low-density polyethylene (LDPE), high-density polyethylene (HDPE), or any combination thereof. It should be understood that the first solution, the second solution, and / or the solution in each of the n sequences may also include a solvent. Any solvent known in the art may be used. More specifically, the choice of solvent may depend on the selection of the pannus-limiting material. In some aspects, the solvent may be selected from dimethylacetamide (DMA), tetrahydrofuran (THF), dimethylformamide (DMF), dimethyl sulfide (DMSO), hexafluoro-2-propanol (HFIP), ethyl acetate, butyl acetate, methyl ethyl ketone, acetone, cyclohexanone, or any combination thereof.

[0105] In other aspects, the concentration of the first concentration, the second concentration, and / or the concentration in each of the n sequences can be from about 1 wt% to about 50 wt% of the pannus-restricting material, including exemplary values ​​of about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, about 10 wt%, about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, and about 45 wt%. In other aspects, the concentration of the first concentration, the second concentration, and / or the concentration in each of the n sequences can have any value between any two of the foregoing values. In yet another aspect, the concentration in the first concentration, the second concentration, and / or the concentration in each of the n sequences can be about 5 wt% to about 50 wt%, about 10 wt% to about 50 wt%, about 20 wt% to about 50 wt%, about 30 wt% to about 50 wt%, about 1 wt% to about 40 wt%, about 1 wt% to about 30 wt%, about 1 wt% to about 20 wt%, about 1 wt% to about 10 wt%, etc. In step 3010, the coated suture is dried to remove any residual solvent, washed with purified water, and dried at room temperature. It should be understood that the suture formed by the method disclosed herein has a coating that is substantially free of any residual solvent. In yet another aspect, in step 3020, the coated suture may be smoothed and heat-treated. In such an aspect, one or more sutures are smoothed to substantially remove surface roughness before attaching at least a portion of the inner skirt and / or at least a portion of the leaflet structure and / or at least a portion of the outer skirt to at least the annular frame.

[0106] In this respect, the smoothing step includes heat-treating one or more sutures having the first coating at a temperature of about 120°C to about 210°C (including exemplary values ​​of about 130°C, about 140°C, about 150°C, about 160°C, about 170°C, about 180°C, about 190°C, and about 200°C) and a pressure of about 0.5 MPa to about 2.5 MPa (including exemplary values ​​of about 0.8 MPa, about 1 MPa, about 1.2 MPa, about 1.5 MPa, about 1.8 MPa, about 2 MPa, and about 2.2 MPa). In other respects, the temperature may be any value falling within any two of the foregoing values, or may fall within a range formed by any two of the foregoing values. For example, the temperature can be about 150°C to about 210°C, about 170°C to about 210°C, about 170°C to about 210°C, about 200°C to about 210°C, about 120°C to about 200°C, about 120°C to about 170°C, about 120°C to about 150°C, etc. In other aspects, the pressure can be any value falling within any two of the foregoing values, or can fall within a range formed by any two of the foregoing values. For example, the pressure can be about 0.7 MPa to about 2.5 MPa, about 1 MPa to about 2.5 MPa, about 1.2 MPa to about 2.5 MPa, about 1.5 MPa to about 2.5 MPa, about 1.7 MPa to about 2.5 MPa, about 2 MPa to about 2.5 MPa, about 0.5 MPa to about 2 MPa, about 0.5 MPa to about 1.5 MPa, about 0.5 MPa to about 1 MPa, etc.

[0107] In other aspects, the surface smoothing step may include placing a suture in a cylinder located between two hot presses and passing the suture through the cylinder multiple times (e.g., 1 to 10 times), wherein each pass ensures that the suture is exposed to the desired temperature and pressure for a desired duration, such as any time from about 1 second to about 5 minutes, including exemplary values ​​of about 2 seconds, about 3 seconds, about 4 seconds, about 5 seconds, about 6 seconds, about 7 seconds, about 8 seconds, about 9 seconds, about 10 seconds, about 15 seconds, about 20 seconds, about 25 seconds, about 30 seconds, about 35 seconds, about 40 seconds, about 45 seconds, about 50 seconds, about 55 seconds, about 1 minute, about 1.5 minutes, about 2 minutes, about 2.5 minutes, about 3 minutes, about 3.5 minutes, about 4 minutes, and about 4.5 minutes. In other aspects, the desired time may have any value between any two of the foregoing values, or may fall within a range formed by any two of the foregoing values. For example, the desired time could be approximately 10 seconds to approximately 5 minutes, approximately 30 seconds to approximately 5 minutes, approximately 1 minute to approximately 5 minutes, approximately 2 minutes to approximately 5 minutes, approximately 1 second to approximately 4 minutes, approximately 1 second to approximately 2 minutes, approximately 1 second to approximately 1 minute, approximately 1 second to approximately 30 seconds, etc.

[0108] In other respects, the first coating formed on one or more sutures is substantially stable. It should be understood that the first coating is expected to produce a substantially nonspecific material that can migrate into the patient's natural anatomy. However, it should also be understood that if any particles form, their concentration and size are substantially below those that would cause a stroke or embolism-related risk to the patient. In other respects, it should be understood that, as disclosed herein, smoothing of the first coating is also intended to substantially reduce or even completely eliminate the formation of any particles. In other respects, annealing of the first coating may be performed to substantially reduce particle formation. In such exemplary and non-limiting aspects, annealing is performed at temperatures from about 60°C to about 150°C, including exemplary values ​​of about 70°C, about 80°C, about 90°C, about 100°C, about 110°C, about 120°C, about 130°C, and about 140°C, for a duration of about 3 minutes to about 15 minutes, including exemplary values ​​of about 4 minutes, about 5 minutes, about 6 minutes, about 7 minutes, about 8 minutes, about 10 minutes, about 11 minutes, about 12 minutes, about 13 minutes, and about 14 minutes. In other aspects, the temperature may have any value falling within any two of the foregoing values, or may fall within a range formed by any two of the foregoing values. For example, the temperature may be about 60°C to about 150°C, about 70°C to about 150°C, about 80°C to about 150°C, about 100°C to about 150°C, about 60°C to about 100°C, about 60°C to about 70°C, etc. In other respects, time may have any value falling within any two of the aforementioned values, or may fall within a range formed by any two of the aforementioned values. For example, time may be about 5 minutes to about 15 minutes, about 7 minutes to about 15 minutes, about 10 minutes to about 15 minutes, about 5 minutes to about 12 minutes, about 5 minutes to about 10 minutes, about 5 minutes to about 7 minutes, etc.

[0109] Alternatively, a method for forming an implantable prosthetic valve may include immersing an annular frame having at least a portion of the attached inner skirt in a mixture comprising a pannus-limiting material present at a predetermined concentration for a predetermined time to form a second coating. The steps of this method 7000 are schematically illustrated in Figures 7A and 7B. For example, the inner skirt is first attached 7002 to at least the annular frame with one or more sutures. In one aspect, the sutures are not treated prior to the attachment step. In other aspects, the sutures are treated to form a first coating with the pannus-limiting material. In step 7004, the skirt and sutures are cleaned and dried, and then immersed in the mixture 7006 at least once.

[0110] In other aspects, the method may include m sequences 7008, each sequence comprising the step of immersion in a further mixture having a further predetermined concentration of a further predetermined concentration of a further predetermined concentration for a further predetermined time, wherein m is 1 to 10 (including 2, 3, 4, 5, 6, 7, 8, and 9), and wherein at least one of the following applies: the further predetermined concentration of the material in each of the m sequences is the same or different; the further predetermined concentration of the material in each of the m sequences is the same or different; and / or the further predetermined time of the material in each of the m sequences is the same or different.

[0111] Similarly, it should be understood that any of the pannus-restricting materials disclosed above may be used. In other aspects, the mixture may include any of the solvents disclosed above.

[0112] In other aspects, additional predetermined times in each of the m sequences can be selected to achieve the desired result, and can be from about 1 second to about 5 minutes, including exemplary values ​​of about 2 seconds, about 3 seconds, about 4 seconds, about 5 seconds, about 6 seconds, about 7 seconds, about 8 seconds, about 9 seconds, about 10 seconds, about 15 seconds, about 20 seconds, about 25 seconds, about 30 seconds, about 35 seconds, about 40 seconds, about 45 seconds, about 50 seconds, about 55 seconds, about 1 minute, about 1.5 minutes, about 2 minutes, about 2.5 minutes, about 3 minutes, about 3.5 minutes, about 4 minutes, and about 4.5 minutes. In other aspects, the time can have any value between any two of the foregoing values, or can fall within a range formed by any two of the foregoing values. For example, the time can be approximately 5 seconds to approximately 5 minutes, approximately 10 seconds to approximately 5 minutes, approximately 30 seconds to approximately 5 minutes, approximately 1 minute to approximately 5 minutes, approximately 2 minutes to approximately 5 minutes, approximately 1 second to approximately 4 minutes, approximately 1 second to approximately 2 minutes, approximately 1 second to approximately 1 minute, approximately 1 second to approximately 30 seconds, etc.

[0113] In other aspects, the additional predetermined concentration in each of the m sequences can be from about 1 wt% to about 50 wt%, including exemplary values ​​of about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, about 10 wt%, about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, and about 45 wt% of the pannus-limiting material. In other aspects, the concentration can have any value between any two of the foregoing values, or can fall within the range formed by any two of the foregoing values. For example, the concentration can be from about 5 wt% to about 50 wt%, from about 10 wt% to about 50 wt%, from about 20 wt% to about 50 wt%, from about 30 wt% to about 50 wt%, from about 1 wt% to about 40 wt%, from about 1 wt% to about 30 wt%, from about 1 wt% to about 20 wt%, etc.

[0114] In some respects, the immersion sequence is repeated with minimal dwell time in between. However, in other respects, after each immersion step, the frame with the skirt attached by one or more sutures can be at least partially dried before the next immersion step. In step 7010, when the desired thickness of the second coating is achieved, the frame with the attached skirt attached by one or more sutures is air-dried to ensure removal of all residual solvent. In step 7012, the frame with the attachments attached by one or more sutures is thoroughly washed and air-dried. Again, it should be understood that the second coating formed by the method disclosed herein is substantially stable. It should be understood that the second coating is expected to produce a substantially nonspecific material that can migrate into the patient's natural anatomy. However, in other respects, it should be understood that if any particles are formed, their concentration and size are substantially below the concentration or size that could lead to a stroke or embolism-related risk in the patient. In still other respects, annealing of the second coating may be performed to substantially reduce particle formation. In such exemplary and non-limiting aspects, annealing is performed at temperatures from about 60°C to about 150°C, including exemplary values ​​of about 70°C, about 80°C, about 90°C, about 100°C, about 110°C, about 120°C, about 130°C, and about 140°C, for a duration of about 3 minutes to about 15 minutes, including exemplary values ​​of about 4 minutes, about 5 minutes, about 6 minutes, about 7 minutes, about 8 minutes, about 10 minutes, about 11 minutes, about 12 minutes, about 13 minutes, and about 14 minutes. In other aspects, the annealing temperature may have any value falling within any two of the foregoing values, or may fall within a range formed by any two of the foregoing values. For example, the annealing temperature may be about 60°C to about 150°C, about 70°C to about 150°C, about 80°C to about 150°C, about 100°C to about 150°C, about 60°C to about 100°C, about 60°C to about 70°C, etc. In other respects, time may have any value falling within any two of the aforementioned values, or may fall within a range formed by any two of the aforementioned values. For example, time may be about 5 minutes to about 15 minutes, about 7 minutes to about 15 minutes, about 10 minutes to about 15 minutes, about 5 minutes to about 12 minutes, about 5 minutes to about 10 minutes, about 5 minutes to about 7 minutes, etc.

[0115] The process is schematically illustrated in Figure 7B. A frame 7010, having a skirt 7004 attached by one or more sutures 7006, is inserted into the mixture 7002 for a desired time. In some respects, the frame 7010 having the skirt 7004 attached by one or more sutures 7006 can be rotated by any device 7008 to ensure that the formed second coating is uniform. In some respects, the mixture 7002 can be at room temperature. In other respects, the mixture 7002 can be heated.

[0116] In other aspects, if at least a portion of the leaflet structure and / or at least a portion of the outer skirt has already been attached to at least the annular frame, and a second coating is not required on these surfaces, the leaflet structure and / or outer skirt may be masked prior to the immersion step. Masking may be performed to ensure that no material is present on the leaflets and / or outer skirt. It should be understood that if there are portions on the leaflet structure and / or outer skirt requiring a second coating, masking may be appropriate, but only the portions not requiring a coating may be hidden. However, in other aspects, the method may include attaching at least a portion of the leaflet structure and / or at least a portion of the outer skirt to at least the annular frame using one or more sutures after the second coating has been formed. In such exemplary and non-limiting aspects, the sutures used for attaching at least a portion of the leaflet structure and / or at least a portion of the outer skirt may have a first coating. However, in other aspects, the sutures used for attaching at least a portion of the leaflet structure and / or at least a portion of the outer skirt may be flat.

[0117] In other respects, one or more sutures may be treated according to any of the methods disclosed herein.

[0118] In other aspects, the first and / or second coatings formed by the methods disclosed herein may have a thickness of about 50 nm to about 150 μm, including about 100 nm, about 150 nm, about 200 nm, about 250 nm, about 300 nm, about 350 nm, about 400 nm, about 450 nm, about 500 nm, about 550 nm, about 600 nm, about 650 nm, about 700 nm, about 750 nm, about 800 nm, about 850 nm, about 900 nm, about 950 nm, about 1 μm, about 5 μm, about 10 μm, about 15 μm, about 20 μm, about 25 μm, about 30 μm, about 35 μm, about 40 μm, about 45 μm, about 50 μm, about 55 μm, about 60 μm, about 65 μm, about 70 μm, about 75 μm, about 80 μm, about 85 ... Exemplary values ​​are given for approximately 90 μm, 95 μm, 100 μm, 105 μm, 110 μm, 115 μm, 120 μm, 125 μm, 130 μm, 135 μm, 140 μm, and 145 μm. In other respects, the thickness of the first and / or second coating may have any value between any two of the foregoing values ​​or fall within any range formed by any two of the foregoing values. For example, but not limited to, the thickness of the first and / or second coating can be about 50 nm to about 100 μm, about 50 nm to about 50 μm, about 50 nm to about 10 μm, about 50 nm to about 1 μm, about 50 nm to about 900 nm, about 50 nm to about 500 nm, about 50 nm to about 200 nm, about 50 nm to about 100 nm, about 100 nm to about 150 μm, about 200 nm to about 150 μm, about 500 nm to about 150 μm, about 1 μm to about 150 μm, about 10 μm to about 150 μm, about 50 μm to about 150 μm, about 100 μm to about 150 μm, etc.

[0119] This article also discloses a method for preventing tissue inward growth, which involves inserting any of the implantable prosthetic valves disclosed herein into a patient.

[0120] Exemplary aspects

[0121] Example 1: An implantable prosthetic valve comprising: an annular frame having an inner surface and an outer surface, wherein the frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end; an inner skirt having an inner surface and an outer surface and positioned along the inner surface of the frame; an optional leaflet structure having an inner surface and an outer surface and located at the inner surface of the annular frame; and / or an optional outer skirt having an inner surface and an outer surface and located at the outer surface of the annular frame; and one or more sutures, wherein the one or more sutures are configured to attach at least a portion of the inner skirt, at least a portion of the leaflet structure (if present), and / or at least a portion of the outer skirt to at least the annular frame, and wherein the one or more sutures are configured to substantially reduce pannus formation and / or uncontrolled inward tissue growth along the implantable prosthetic valve.

[0122] Example 2: As in any of the embodiments herein, specifically Example 1, the implantable prosthetic valve, wherein one or more sutures have a substantially cylindrical form.

[0123] Example 3: An implantable prosthetic valve as described in any of the embodiments herein, specifically Example 1, wherein one or more sutures have a substantially flattened form.

[0124] Example 4: As in any of the embodiments herein, specifically the implantable prosthetic valves of Examples 1 to 3, wherein at least a portion of the surface of one or more sutures has a coating comprising a pannus-limiting material.

[0125] Example 5: As in any of the embodiments herein, specifically Example 4, the implantable prosthetic valve wherein the substantially entire surface of one or more sutures has the coating comprising the pannus-limiting material.

[0126] Example 6: As in any of the examples herein, specifically Examples 4 to 5, the implantable prosthetic valve, wherein the pannus-limiting material includes thermoplastic polyurethane, modified thermoplastic polyurethane, polycarbonate polyurethane, polyether polyurethane, polyester polyurethane, fluoropolymers, fluorinated oligomers, polyethylene, modified inorganic backbone polymers, polyphosphazene, polyacrylate, polysiloxane, polyester, any copolymers thereof, or any combination thereof.

[0127] Example 7: An implantable prosthetic valve as described in any of the embodiments herein, specifically Example 6, wherein the modified thermoplastic polyurethane comprises a thermoplastic polyurethane having fluorine and / or silicone incorporated into the polymer backbone.

[0128] Example 8: An implantable prosthetic valve as described in any of the embodiments herein, specifically Example 6, wherein the modified thermoplastic polyurethane comprises a mixture of thermoplastic polyurethane and compounds having a fluorinated portion and / or organosilicon.

[0129] Example 9: As in any of the examples herein, specifically Example 6, the implantable prosthetic valve, wherein the modified inorganic backbone polymer is modified with halogen-containing groups, phosphorus-containing groups, nitrogen-containing groups, or combinations thereof.

[0130] Example 10: An implantable prosthetic valve as described in any of the embodiments herein, specifically Example 6, wherein the polyethylene includes ultra-high molecular weight polyethylene (UHMWPE), low-density polyethylene (LDPE), high-density polyethylene (HDPE), or any combination thereof.

[0131] Example 11: As in any of the embodiments herein, specifically Examples 4 to 10, the implantable prosthetic valve, wherein the coating is applied to the one or more sutures before attaching at least a portion of the inner skirt and / or, if present, at least a portion of the leaflet structure and / or at least a portion of the outer skirt to at least the annular frame.

[0132] Example 12: As in any of the embodiments herein, specifically Examples 4 to 10, the implantable prosthetic valve, wherein the coating is applied to the one or more sutures after at least a portion of the inner skirt and / or, if present, at least a portion of the leaflet structure and / or at least a portion of the outer skirt is attached to at least the annular frame.

[0133] Example 13: As in any of the embodiments herein, specifically Example 12, the implantable prosthetic valve wherein at least a portion of the inner skirt and / or at least a portion of the leaflet structure, if present, and / or at least a portion of the outer skirt comprises the coating containing the pannus-limiting material.

[0134] Example 14: An implantable prosthetic valve as described in any of the embodiments herein, specifically Examples 1 to 13, wherein at least a portion of the inner skirt and / or, if present, at least a portion of the leaflet structure and / or at least a portion of the outer skirt, and the one or more sutures have a roughness substantially no greater than about 0.5 μm.

[0135] Example 15: An implantable prosthetic valve as described in any of the embodiments herein, specifically Examples 1 to 14, wherein the at least portion of the inner skirt and / or, if present, the at least portion of the leaflet structure and / or the at least portion of the outer skirt, as well as the one or more sutures, substantially do not cause pannus formation in the turbulence-induced surface morphology.

[0136] Example 16: An implantable prosthetic valve as described in any of the embodiments herein, specifically Examples 1 to 15, wherein at least a portion of the inner skirt and / or, if present, at least a portion of the leaflet structure and / or at least a portion of the outer skirt, together with the one or more sutures, form a substantially uniform surface profile.

[0137] Example 17: An implantable prosthetic valve as described in any of the examples herein, specifically Examples 4 through 16, wherein the coating has a thickness of about 50 nm to about 150 μm.

[0138] Example 18: An implantable prosthetic valve as described in any of the embodiments herein, specifically Examples 1 to 17, wherein the leaflet structure is present.

[0139] Example 19: An implantable prosthetic valve as described in any of the embodiments herein, specifically Examples 1 to 18, wherein the outer skirt is present and circumferentially located on the outer surface of the annular frame.

[0140] Example 20: An implantable prosthetic valve as described in any of the embodiments herein, specifically Examples 1 to 19, wherein the implantable prosthetic valve is radially constrictible to a constricted configuration and radially expandable to an expanded configuration.

[0141] Example 21: An implantable prosthetic valve as described in any of the examples herein, specifically Examples 1 to 20, wherein the one or more sutures comprise polyester, polyethylene, ultra-high molecular weight polyethylene, silicone, polyurethane, polytetrafluoroethylene, polyetheretherketone (PEEK), fluoropolymers, or natural tissue or combinations thereof.

[0142] Example 22: A method of forming an implantable prosthetic valve, the method comprising: attaching at least a portion of an inner skirt to at least an annular frame with one or more sutures, such that the outer surface of the inner skirt is at least partially attached to the inner surface of the annular frame, wherein the one or more sutures are configured to substantially reduce pannus formation along the implantable prosthetic valve, and wherein the inner surface of the inner skirt faces an internal space formed by the annular frame; and wherein the annular frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end.

[0143] Example 23: The method described in particular Example 22, as in any of the embodiments herein, includes attaching at least a portion of a leaflet structure having an inner and outer surface to at least the annular frame using the one or more sutures.

[0144] Example 24: The method described in any of the embodiments herein, specifically Example 22 or 23, the method comprising attaching at least a portion of the outer skirt to at least the annular frame using the one or more stitches.

[0145] Example 25: The method described in any of the embodiments herein, specifically Examples 22 to 24, wherein one or more sutures are flattened before attaching the at least portion of the inner skirt to at least the annular frame.

[0146] Example 26: The method described in any of the embodiments herein, specifically Examples 23 to 25, wherein one or more sutures are flattened prior to attaching at least a portion of the leaflet structure to at least the annular frame.

[0147] Example 27: The method described in any of the embodiments herein, specifically Examples 24 to 26, wherein one or more stitches are flattened before attaching the at least portion of the outer skirt to at least the annular frame.

[0148] Example 28: The method described in any of the embodiments herein, specifically Examples 25 to 27, wherein the flattening of the one or more sutures includes passing the one or more sutures between at least two hot presses at a temperature of about 120°C to about 210°C and a pressure of about 0.5 MPa to about 5 MPa.

[0149] Example 29: As in any of the embodiments herein, specifically the methods described in Examples 22 to 28, the one or more sutures have substantially no surface roughness.

[0150] Example 30: The method described in any of the embodiments herein, specifically Examples 22 to 29, wherein one or more sutures have a first coating comprising a pannus-restricting material.

[0151] Example 31: The method described in any of the embodiments herein, specifically Example 30, wherein forming the first coating includes inserting one or more sutures into a first solution for a first predetermined time, wherein the first solution contains a first concentration of a first pannus-restricting material.

[0152] Example 32: The method described in any of the embodiments herein, specifically in Example 31, wherein the step of forming the first coating further includes inserting the one or more sutures into a second solution for a second predetermined time, wherein the second solution contains a second concentration of a second pannus-restricting material.

[0153] Example 33: The method described in any of the embodiments herein, specifically Example 32, wherein the method further includes an additional n sequences, each sequence comprising the step of inserting the one or more sutures into a solution containing a certain concentration of pannus-limiting material for a predetermined time, and wherein n is 1 to 10.

[0154] Example 34: The method described in any of the embodiments herein, specifically Examples 30 to 33, wherein the first concentration is lower than the second concentration, or wherein the first concentration is higher than the second concentration.

[0155] Example 35: The method described in any of the embodiments herein, specifically Examples 33 to 34, wherein the first predetermined time, the second predetermined time, or the predetermined time in each of the n sequences is the same or different.

[0156] Example 36: The method described in any of the embodiments herein, specifically Examples 33 to 35, wherein the concentration of the pannus-restricting material in each of the n sequences is the same as or different from the first concentration.

[0157] Example 37: The method described in any of the embodiments herein, specifically Examples 33 to 36, wherein the concentration of the pannus-restricting material in each of the n sequences is the same or different.

[0158] Example 38: The method described in any of the embodiments herein, specifically Examples 33 to 37, wherein the first pannus-restricting material, the second pannus-restricting material, and the pannus-restricting material in each of the n sequences are the same or different, and are selected from the pannus-restricting materials comprising thermoplastic polyurethane, modified thermoplastic polyurethane, polycarbonate polyurethane, polyether polyurethane, polyester polyurethane, fluoropolymers, fluorinated oligomers, polyethylene, modified inorganic backbone polymers, polyphosphazene, polyacrylate, polysiloxane, polyester, any copolymers thereof, or any combination thereof.

[0159] Example 39: The method described in any of the embodiments herein, specifically in Example 38, wherein the modified thermoplastic polyurethane comprises a thermoplastic polyurethane having fluorine and / or silicone incorporated into the main chain of the polymer structure.

[0160] Example 40: The method described in any of the embodiments herein, specifically in Example 38, wherein the modified thermoplastic polyurethane comprises a mixture of thermoplastic polyurethane and a compound having a fluorinated portion and / or an organosilicon.

[0161] Example 41: The method described in any of the embodiments herein, specifically Example 38, wherein the modified inorganic main-chain polymer is modified with halogen-containing groups, phosphorus-containing groups, nitrogen-containing groups, or combinations thereof.

[0162] Example 42: The method described in any of the embodiments herein, specifically Example 38, wherein the polyethylene comprises ultra-high molecular weight polyethylene (UHMWPE), low-density polyethylene (LDPE), high-density polyethylene (HDPE), or any combination thereof.

[0163] Example 43: The method described in any of the embodiments herein, specifically Examples 22 to 42, wherein one or more sutures are smoothed to substantially remove surface roughness before attaching at least a portion of the inner skirt and / or at least a portion of the leaflet structure and / or at least a portion of the outer skirt to at least the annular frame.

[0164] Example 44: The method described in any of the embodiments herein, specifically Example 43, wherein the smoothing step includes heat-treating the one or more sutures at a temperature of about 120°C to about 210°C and a pressure of about 0.5 MPa to about 2.5 MPa.

[0165] Example 45: The method described in any of the embodiments herein, specifically Example 22, wherein the method includes immersing the annular frame having the attached inner skirt in a mixture containing a pannus-restricting material present at a predetermined concentration for a predetermined time to form a second coating.

[0166] Example 46: The method described in particular, as in any of the embodiments herein, specifically Example 45, wherein the method comprises m sequences, each sequence comprising the step of immersion in a further mixture having a further predetermined concentration of a further predetermined concentration of a further predetermined concentration for a further predetermined time, wherein m is 1 to 10, and wherein at least one of the following applies: the further predetermined concentration of ...

[0167] Example 47: In any of the embodiments herein, specifically the method of Example 46, wherein the additional pannus-restricting material in each of the m sequences is selected from thermoplastic polyurethane, modified thermoplastic polyurethane, polycarbonate polyurethane, polyether polyurethane, polyester polyurethane, fluoropolymers, fluorinated oligomers, polyethylene, modified inorganic backbone polymers, polyphosphazene, polyacrylates, polysiloxanes, polyesters, any copolymers thereof, or any combination thereof.

[0168] Example 48: The method described in any of the embodiments herein, specifically Example 47, wherein the modified thermoplastic polyurethane comprises a thermoplastic polyurethane having fluorine and / or silicone incorporated into the main chain of the polymer structure.

[0169] Example 49: The method described in any of the embodiments herein, specifically Example 47, wherein the modified thermoplastic polyurethane comprises a mixture of thermoplastic polyurethane and a compound having a fluorinated portion and / or an organosilicon.

[0170] Example 50: The method described in any of the embodiments herein, specifically Example 47, wherein the modified inorganic main-chain polymer is modified with halogen-containing groups, phosphorus-containing groups, nitrogen-containing groups, or combinations thereof.

[0171] Example 51: The method described in any of the embodiments herein, specifically Example 47, wherein the polyethylene comprises ultra-high molecular weight polyethylene (UHMWPE), low-density polyethylene (LDPE), high-density polyethylene (HDPE), or any combination thereof.

[0172] Example 52: The method described in any of the embodiments herein, specifically Examples 45 to 51, wherein if at least a portion of the leaflet structure and / or at least a portion of the outer skirt is attached to at least the annular frame, the at least a portion of the leaflet structure and / or the at least a portion of the outer skirt is masked prior to the immersion step.

[0173] Example 53: The method described in any of the embodiments herein, specifically Examples 45 to 51, further comprising attaching at least a portion of the leaflet structure and / or at least a portion of the outer skirt to at least the annular frame using the one or more sutures.

[0174] Example 54: The method described in any of the embodiments herein, specifically in Examples 45 to 53, wherein the one or more sutures are processed according to any one of claims 22 to 44 prior to the attachment step.

[0175] Example 55: The method described in any of the embodiments herein, specifically Examples 24 to 54, wherein the at least portion of the inner skirt and / or the at least portion of the leaflet structure and / or the at least portion of the outer skirt, as well as the one or more sutures, have a roughness substantially no greater than about 0.5 μm.

[0176] Example 56: The method described in any of the embodiments herein, specifically Examples 24 to 55, wherein the at least portion of the inner skirt and / or the at least portion of the leaflet structure and / or the at least portion of the outer skirt, as well as the one or more sutures, substantially do not cause pannus formation in the turbulence-induced surface morphology.

[0177] Example 57: The method described in any of the embodiments herein, specifically Examples 24 to 56, wherein at least a portion of the inner skirt and / or at least a portion of the leaflet structure and / or at least a portion of the outer skirt, together with the one or more sutures, form a substantially uniform surface profile.

[0178] Example 58: The method described in any of the embodiments herein, specifically Examples 22 to 57, wherein the first and / or second coating has a thickness of about 50 nm to about 150 micrometers.

[0179] Example 59: A method for preventing tissue inward growth, the method comprising inserting any of the examples herein, specifically Examples 1 to 21, into a patient.

[0180] Example 60: A kit comprising one or more sutures configured to attach at least a portion of the inner skirt and / or at least a portion of the leaflet structure and / or at least a portion of the outer skirt to at least one frame of an implantable prosthetic valve, wherein the one or more sutures are configured to substantially reduce pannus formation and / or uncontrolled inward tissue growth along the implantable prosthetic valve.

[0181] Example 61: The kit described in any of the embodiments herein, specifically Example 60, wherein the kit includes one or more sutures having a substantially cylindrical form, a substantially flat form, or a combination thereof.

[0182] Example 62: The kit described in any of the embodiments herein, specifically Examples 60 to 61, wherein at least a portion of the surface of one or more sutures has a coating comprising a pannus-limiting material.

[0183] Example 63: The kit described in any of the embodiments herein, specifically Examples 60 to 62, wherein the substantially entire surface of one or more sutures has the coating comprising the pannus-limiting material.

[0184] Example 64: The kit described in any of the embodiments herein, specifically Examples 60 to 63, wherein the pannus-limiting material comprises thermoplastic polyurethane, modified thermoplastic polyurethane, polycarbonate polyurethane, polyether polyurethane, polyester polyurethane, fluoropolymer, fluorinated oligomer, polyethylene, modified inorganic backbone polymer, polyphosphazene, polyacrylate, polysiloxane, polyester, any copolymer thereof, or any combination thereof.

[0185] Example 65: The kit described in any of the embodiments herein, specifically Example 64, wherein the modified thermoplastic polyurethane comprises a thermoplastic polyurethane having fluorine and / or silicone incorporated into the polymer structure backbone.

[0186] Example 66: The kit described in any of the embodiments herein, specifically Example 64, wherein the modified thermoplastic polyurethane comprises a mixture of thermoplastic polyurethane and a compound having a fluorinated portion and / or an organosilicon.

[0187] Example 67: The kit described in any of the embodiments herein, specifically Example 64, wherein the modified inorganic backbone polymer is modified with halogen-containing groups, phosphorus-containing groups, nitrogen-containing groups, or combinations thereof.

[0188] Example 68: The kit described in any of the embodiments herein, specifically Example 64, wherein the polyethylene includes ultra-high molecular weight polyethylene (UHMWPE), low-density polyethylene (LDPE), high-density polyethylene (HDPE), or any combination thereof.

[0189] Example 69: The kit described in any of the embodiments herein, specifically Examples 60 to 68, wherein the one or more sutures comprise polyester, polyethylene, ultra-high molecular weight polyethylene, silicone, polyurethane, polytetrafluoroethylene, polyether ether ketone (PEEK), fluoropolymers, or natural tissue or combinations thereof.

[0190] Example 70: An implantable prosthetic valve comprising: an annular frame having an inner surface and an outer surface, wherein the frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end; an inner skirt having an inner surface and an outer surface and positioned along the inner surface of the frame; wherein the inner surface of the inner skirt includes a first pannus-limiting material; an optional leaflet structure having an inner surface and an outer surface and located at the inner surface of the annular frame; and / or an optional outer skirt having an inner surface and an outer surface and located at the outer surface of the annular frame; and one or more sutures, wherein the one or more sutures are configured to attach at least a portion of the inner skirt, at least a portion of the leaflet structure (if present), and / or at least a portion of the outer skirt to at least the annular frame, and wherein the one or more sutures are configured to substantially reduce pannus formation and / or uncontrolled inward tissue growth along the implantable prosthetic valve.

[0191] Example 71: An implantable prosthetic valve as described in any of the embodiments herein, specifically Example 70, wherein one or more sutures have a substantially cylindrical form.

[0192] Example 72: An implantable prosthetic valve as described in any of the embodiments herein, specifically Example 70, wherein one or more sutures have a substantially flattened form.

[0193] Example 73: As in any of the embodiments herein, specifically Examples 70 to 72, the implantable prosthetic valve wherein at least a portion of the surface of one or more sutures has a coating comprising a pannus-limiting material.

[0194] Example 74: An implantable prosthetic valve as described in any of the embodiments herein, specifically Example 73, wherein the substantially entire surface of one or more sutures has the coating comprising the pannus-limiting material.

[0195] Example 75: As in any of the embodiments herein, specifically Examples 70 to 74, an implantable prosthetic valve, wherein at least a portion of the surface of one or more sutures has a coating including a second pannus-limiting material.

[0196] Example 76: An implantable prosthetic valve as described in any of the embodiments herein, specifically Example 75, wherein the first pannus limiting material and the second pannus limiting material are the same or different, and are selected from thermoplastic polyurethane, modified thermoplastic polyurethane, polycarbonate polyurethane, polyether polyurethane, polyester polyurethane, fluoropolymers, fluorinated oligomers, polyethylene, modified inorganic backbone polymers, polyphosphazene, polyacrylate, polysiloxane, polyester, any copolymers thereof, or any combination thereof.

[0197] Example 77: An implantable prosthetic valve as described in any of the embodiments herein, specifically Example 76, wherein the modified thermoplastic polyurethane comprises a thermoplastic polyurethane having fluorine and / or silicone incorporated into the polymer structural backbone.

[0198] Example 78: An implantable prosthetic valve as described in any of the embodiments herein, specifically Example 76, wherein the modified thermoplastic polyurethane comprises a mixture of thermoplastic polyurethane and compounds having a fluorinated portion and / or organosilicon.

[0199] Example 79: An implantable prosthetic valve as described in any of the embodiments herein, specifically Example 76, wherein the modified inorganic backbone polymer is modified with halogen-containing groups, phosphorus-containing groups, nitrogen-containing groups, or combinations thereof.

[0200] Example 80: An implantable prosthetic valve as described in any of the embodiments herein, specifically Example 76, wherein the polyethylene comprises ultra-high molecular weight polyethylene (UHMWPE), low-density polyethylene (LDPE), high-density polyethylene (HDPE), or any combination thereof.

[0201] Given the many possible aspects to which the principles of the disclosed content can be applied, it should be recognized that the aspects shown are merely some examples of this disclosure and should not be considered as limiting the scope of this disclosure. Rather, the scope of this disclosure is defined by the following claims. Therefore, we claim protection for all content within the scope and spirit of these claims as part of our disclosure.

Claims

1. An implantable prosthetic valve, said implantable prosthetic valve comprising: An annular frame having an inner surface and an outer surface, wherein the frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end; An inner skirt having an inner surface and an outer surface and positioned along the inner surface of the frame; An optional leaflet structure having an inner surface and an outer surface and located at the inner surface of the annular frame; And / or an optional outer skirt having an inner surface and an outer surface and located at the outer surface of the annular frame, and one or more sutures, wherein the one or more sutures are configured to attach at least a portion of the inner skirt, at least a portion of the leaflet structure if present, and / or at least a portion of the outer skirt to at least the annular frame, and wherein the one or more sutures are configured to substantially reduce pannus formation and / or uncontrolled inward tissue growth along the implantable prosthetic valve.

2. The implantable prosthetic valve as described in claim 1, wherein: The one or more sutures are substantially cylindrical in shape, or the one or more sutures are substantially flat in shape.

3. The implantable prosthetic valve as described in any one of claims 1 to 2, wherein at least a portion of the surface of the one or more sutures has a coating comprising a pannus-limiting material.

4. The implantable prosthetic valve of claim 3, wherein the pannus limiting material comprises thermoplastic polyurethane, modified thermoplastic polyurethane, polycarbonate polyurethane, polyether polyurethane, polyester polyurethane, fluoropolymer, fluorinated oligomer, polyethylene, modified inorganic main chain polymer, polyphosphazene, polyacrylate, polysiloxane, polyester, any copolymer thereof, or any combination thereof.

5. The implantable prosthetic valve of claim 4, wherein the modified thermoplastic polyurethane comprises: Thermoplastic polyurethane having fluorine and / or organosilicon incorporated in the main chain of the polymer structure, or a mixture of thermoplastic polyurethane and a compound having a fluorine-containing portion and / or organosilicon.

6. The implantable prosthetic valve of claim 4, wherein the modified inorganic main chain polymer is modified with halogen-containing groups, phosphorus-containing groups, nitrogen-containing groups, or combinations thereof.

7. The implantable prosthetic valve of any one of claims 3 to 6, wherein the coating is applied to the one or more sutures before attaching at least a portion of the inner skirt and / or, if present, at least a portion of the leaflet structure and / or at least a portion of the outer skirt to at least the annular frame, or after attaching at least a portion of the inner skirt and / or, if present, at least a portion of the leaflet structure and / or at least a portion of the outer skirt to at least the annular frame.

8. The implantable prosthetic valve of claim 7, wherein at least a portion of the inner skirt and / or at least a portion of the leaflet structure, if present, and / or at least a portion of the outer skirt comprises the coating containing the pannus-limiting material.

9. The implantable prosthetic valve of any one of claims 1 to 8, wherein the at least portion of the inner skirt and / or, if present, the at least portion of the leaflet structure and / or the at least portion of the outer skirt, and the one or more sutures, have substantially no roughness greater than about 0.5 μm; and / or wherein the at least portion of the inner skirt and / or, if present, the at least portion of the leaflet structure and / or the at least portion of the outer skirt, and the one or more sutures, have substantially no turbulence-induced surface morphology that causes pannus formation; and / or wherein the at least portion of the inner skirt and / or, if present, the at least portion of the leaflet structure and / or the at least portion of the outer skirt, and the one or more sutures together form a substantially uniform surface profile.

10. The implantable valve according to any one of claims 3 to 9, wherein the coating has a thickness of about 50 nm to about 150 μm.

11. The implantable valve according to any one of claims 1 to 10, wherein the one or more sutures comprise polyester, polyethylene, ultra-high molecular weight polyethylene, silicone, polyurethane, polytetrafluoroethylene, polyetheretherketone (PEEK), fluoropolymers, or natural tissue or combinations thereof.

12. A method for forming an implantable prosthetic valve, the method comprising: At least a portion of the inner skirt is attached to at least an annular frame using one or more sutures, such that the outer surface of the inner skirt is at least partially attached to the inner surface of the annular frame, wherein the one or more sutures are configured to substantially reduce pannus formation along the implantable prosthetic valve, and wherein the inner surface of the inner skirt faces the internal space formed by the annular frame; and wherein the annular frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end.

13. The method of claim 12, the method comprising attaching at least a portion of the leaflet structure having an inner surface and an outer surface to at least the annular frame using the one or more sutures.

14. The method of claim 12 or 13, wherein the method comprises attaching at least a portion of the outer skirt to at least the annular frame using the one or more stitches.

15. The method of any one of claims 12 to 14, wherein the one or more sutures are flattened before attaching the at least portion of the inner skirt to at least the annular frame, and / or wherein the one or more sutures are flattened before attaching the at least portion of the leaflet structure to at least the annular frame, and / or wherein the one or more sutures are flattened before attaching the at least portion of the outer skirt to at least the annular frame, and wherein flattening the one or more sutures comprises passing the one or more sutures between at least two hot presses at a temperature of about 120°C to about 210°C and a pressure of about 0.5 MPa to about 5 MPa.

16. The method of any one of claims 12 to 15, wherein the one or more sutures have a first coating comprising a pannus-limiting material, and wherein forming the first coating comprises immersing the one or more sutures in a first solution for a first predetermined time, wherein the first solution comprises a first concentration of the first pannus-limiting material.

17. The method of claim 16, wherein the step of forming the first coating further comprises inserting the one or more sutures into a second solution for a second predetermined time, wherein the second solution contains a second concentration of a second pannus-restricting material.

18. The method of claim 17, wherein the method further comprises an additional n sequences, wherein each sequence comprises the step of inserting the one or more sutures into a solution containing a certain concentration of pannus-limiting material for a predetermined time, and wherein n is 1 to 10.

19. The method of claim 18, wherein the first pannus-restricting material, the second pannus-restricting material, and the pannus-restricting material in each of the n sequences are the same or different, and are selected from pannus-restricting materials including thermoplastic polyurethane, modified thermoplastic polyurethane, polycarbonate polyurethane, polyether polyurethane, polyester polyurethane, fluoropolymers, fluorinated oligomers, polyethylene, modified inorganic backbone polymers, polyphosphazene, polyacrylate, polysiloxane, polyester, any copolymers thereof, or any combination thereof.

20. The method of any one of claims 12 to 19, wherein the one or more sutures are smoothed to substantially remove surface roughness before attaching at least a portion of the inner skirt and / or at least a portion of the leaflet structure and / or at least a portion of the outer skirt to at least the annular frame, and wherein the smoothing step includes heat-treating the one or more sutures at a temperature of about 120°C to about 210°C and a pressure of about 0.5 MPa to about 2.5 MPa.

21. The method of claim 12, wherein the method comprises immersing the annular frame having the attached inner skirt in a mixture comprising a pannus-limiting material present at a predetermined concentration for a predetermined time to form a second coating, and wherein the method comprises m sequences, wherein each sequence comprises the step of: immersing in a further mixture having a further pannus-limiting material at a further predetermined concentration for a further predetermined time, wherein m is 1 to 10, and wherein at least one of the following applies: the further pannus-limiting material in each of the m sequences is the same. Or different; the additional predetermined concentrations in each of the m sequences are the same or different; and / or the additional predetermined times in each of the m sequences are the same or different; and wherein the additional pannus-restricting material in each of the m sequences is selected from thermoplastic polyurethane, modified thermoplastic polyurethane, polycarbonate polyurethane, polyether polyurethane, polyester polyurethane, fluoropolymers, fluorinated oligomers, polyethylene, modified inorganic main-chain polymers, polyphosphazene, polyacrylate, polysiloxane, polyester, any copolymers thereof, or any combination thereof.

22. The method of claim 21, wherein if at least a portion of the leaflet structure and / or at least a portion of the outer skirt is attached to at least the annular frame, then the at least a portion of the leaflet structure and / or the at least a portion of the outer skirt is masked prior to the immersion step.

23. A method for preventing tissue inward growth, the method comprising inserting an implantable prosthetic valve as described in any one of claims 1 to 11 into a patient.

24. A kit comprising one or more sutures configured to attach at least a portion of an inner skirt and / or at least a portion of a leaflet structure and / or at least a portion of an outer skirt to at least one frame of an implantable prosthetic valve, wherein the one or more sutures are configured to substantially reduce pannus formation and / or uncontrolled inward tissue growth along the implantable prosthetic valve by having at least a portion of the surface of the one or more sutures coated with a pannus-limiting material.

25. An implantable prosthetic valve, said implantable prosthetic valve comprising: An annular frame having an inner surface and an outer surface, wherein the frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end; An inner skirt having an inner surface and an outer surface and positioned along the inner surface of the frame; wherein the inner surface of the inner skirt includes a first pannus-restricting material; An optional leaflet structure having an inner surface and an outer surface and located at the inner surface of the annular frame; And / or an optional outer skirt having an inner surface and an outer surface and located at the outer surface of the annular frame, and one or more sutures, wherein the one or more sutures are configured to attach at least a portion of the inner skirt, at least a portion of the leaflet structure if present, and / or at least a portion of the outer skirt to at least the annular frame, and wherein the one or more sutures are configured to substantially reduce pannus formation and / or uncontrolled inward tissue growth along the implantable prosthetic valve.

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