Closed medical device with charged polymer coating

Abstract

A closure implant comprises an expandable frame configured to switch between a collapsed configuration and an expanded configuration. A closure member is disposed along at least a portion of the expandable frame. At least a portion of the closure implant is configured to repel fibrinogen. In some cases, the closure implant can be configured to be placed in the left atrial appendage (LAA) of a patient's heart.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application Serial No. 62 / 671,549, filed May 15, 2018, the entire contents of which are incorporated herein by reference. Technical Field

[0003] The present disclosure relates to closed medical devices. More specifically, the present disclosure relates to closed medical devices that can be used within the left atrial appendage (LAA). Background Art

[0004] The left atrial appendage (LAA) is a small organ attached to the left atrium of the heart, extending in a sac-like shape. In some cases, such as in patients with atrial fibrillation, the left atrial appendage may not contract properly with the left atrium, causing stagnant blood to accumulate inside it, which may lead to the formation of unwanted blood clots within the left atrial appendage. Thrombi formed in the left atrial appendage may break away from the area and enter the bloodstream. Thrombi that migrate through blood vessels may eventually block smaller blood vessels downstream, causing stroke or heart attack. Clinical studies have shown that most blood clots in patients with atrial fibrillation are found in the left atrial appendage.

[0005] As a treatment method, medical devices have been developed that are positioned in the left atrial appendage and deployed to close the opening of the left atrial appendage. Over time, the exposed surface across the opening of the left atrial appendage is covered with tissue (a process called endothelialization), effectively removing the left atrial appendage from the circulatory system and reducing or eliminating the number of thrombi that may enter the bloodstream from the left atrial appendage. There is a continuing need for an improved medical device and method to control the formation of thrombi in the left atrial appendage of patients with atrial fibrillation. Summary of the invention

[0006] The present disclosure provides designs, materials, manufacturing methods and use alternatives for closed medical devices. An exemplary closed implant comprises an expandable frame configured to switch between a collapsed configuration and an expanded configuration and a closed member arranged along at least a portion of the expandable frame. At least a portion of the closed implant is adapted to repel and / or attract fibrinogen.

[0007] Alternatively or additionally, the closure implant has a leading edge, and a region of the closure member proximal to the leading edge may be treated to repel fibrinogen.

[0008] Alternatively or additionally, the expandable framework includes a central structure, and regions of the closure members proximate the central structure may be treated to exclude fibrinogen.

[0009] Alternatively or additionally, at least a portion of the occlusive implant may be configured to have a negative charge at neutral pH.

[0010] Alternatively or additionally, at least a portion of the occlusive implant comprises a polymer that can be negatively charged at neutral pH.

[0011] Alternatively or additionally, at least a portion of the closure member may be coated with a polymer that is negatively charged at neutral pH.

[0012] Alternatively or additionally, a polymer that can be negatively charged at neutral pH can be sprayed onto the closure member.

[0013] Alternatively or additionally, a polymer that can be negatively charged at neutral pH can be physically blended with the material forming the closure member.

[0014] Alternatively or additionally, a polymer that can be negatively charged at neutral pH can be provided as a copolymer with the material forming the closure member.

[0015] Alternatively or additionally, the closure member may include a polymer coating covering at least a portion of the expandable frame, and the polymer coating may be positively charged at neutral pH to attract fibrinogen.

[0016] Alternatively or additionally, the closure member may be formed from polyethylene terephthalate (PET).

[0017] Alternatively or additionally, the expandable frame may include a plurality of anchoring members extending radially outward from the expandable frame.

[0018] Alternatively or additionally, the expandable frame and the plurality of anchoring members can be formed from a single tubular member.

[0019] Alternatively or additionally, the expandable frame in the expanded configuration can be configured to fit into the left atrial appendage (LAA) of the patient's heart.

[0020] Alternatively or additionally, a second portion of the closure implant that is not configured to repel fibrinogen may be configured to attract fibrinogen.

[0021] An exemplary medical implant for closing the left atrial appendage (LAA) of a patient's heart includes: an expandable frame configured to transition between a collapsed configuration and an expanded configuration; a closure member extending over and supported by at least a portion of the expandable frame; and a coating disposed on at least a portion of the closure member and configured to repel fibrinogen.

[0022] Alternatively or additionally, a coating configured to repel fibrinogen may include a polymer that is negatively charged at neutral pH.

[0023] Alternatively or additionally, the closure implant has a leading edge, and the coating configured to repel fibrinogen may extend over the leading edge.

[0024] Alternatively or additionally, the expandable framework may include a central structure, and the coating configured to repel fibrinogen may extend over the central structure.

[0025] Another exemplary medical implant for closing a left atrial appendage (LAA) of a patient's heart includes an expandable frame configured to transition between a collapsed configuration and an expanded configuration and a closure member extending over and supported by at least a portion of the expandable frame. A first coating configured to repel fibrinogen is disposed on a first portion of the closure member, and a second coating configured to attract fibrinogen is disposed on a second portion of the closure member.

[0026] The above summary of some embodiments is not intended to describe each disclosed embodiment or every implementation of the present disclosure. The following figure descriptions and detailed description more particularly exemplify these embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] The present disclosure may be more fully understood upon consideration of the following detailed description taken in conjunction with the accompanying drawings, in which:

[0028] Figure 1 is a plan view of an exemplary closure implant;

[0029] Figure 2 An exemplary closure implant positioned in a heart is shown;

[0030] Figure 3 An exemplary closure implant positioned in the left atrial appendage is shown;

[0031] Figure 4 is a plan view of an exemplary closure implant;

[0032] Figure 5 is a plan view of an exemplary closure implant;

[0033] Figure 6 is a plan view of an exemplary closure implant;

[0034] Figure 7 is a plan view of an exemplary closure implant;

[0035] Figure 8 is a plan view of an exemplary closure implant;

[0036] Fig. 9 is a plan view of an exemplary embolic device; and,

[0037] Fig.10 It is along Fig. 9 A cross-sectional view of an exemplary embolic device taken along line 10-10.

[0038] Although the present disclosure is suitable for various modifications and alternative forms, its details have been shown by the examples in the drawings and will be described in detail. However, it should be understood that it is not intended to limit the present disclosure to the specific embodiments described. On the contrary, the present invention covers all modifications, equivalents and alternatives that fall within the spirit and scope of the present disclosure. DETAILED DESCRIPTION

[0039] For the following defined terms, these definitions shall apply unless a different definition is given in the claims or elsewhere in this specification.

[0040] All numerical values ​​assumed herein are modified by the term "approximately", whether or not explicitly stated. The term "approximately" generally refers to a range of numbers that one skilled in the art considers to be equivalent to the value (e.g., having the same function or result). In many cases, the term "approximately" may include numbers rounded to the nearest significant figure.

[0041] The recitation of numerical ranges by endpoints includes all numbers within that range (eg 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5).

[0042] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. As used in this specification and the appended claims, the term "or" is generally employed in its sense including "and / or" unless the content clearly dictates otherwise.

[0043] Note that references in the specification to "an embodiment," "some embodiments," "other embodiments," etc., indicate that the described embodiment may include one or more specific features, structures, and / or characteristics. However, such a description does not necessarily mean that all embodiments include the specific features, structures, and / or characteristics. In addition, when specific features, structures, and / or characteristics are described in conjunction with one embodiment, it should be understood that, unless explicitly stated to the contrary, these features, structures, and / or characteristics may also be used in conjunction with other embodiments, whether or not explicitly described.

[0044] The following detailed description should be read with reference to the drawings, in which similar elements in different drawings are numbered the same. The drawings, which are not necessarily to scale, depict illustrative embodiments and are not intended to limit the scope of the invention.

[0045] The occurrence of thrombus in the left atrial appendage (LAA) during atrial fibrillation may be caused by stagnation of blood pool in the LAA. The pooled blood may still be pumped out of the left atrium by the left ventricle, but the effect is poor due to the irregular contraction of the left atrium caused by atrial fibrillation. Therefore, the filling of the left ventricle may depend primarily or only on the suction effect generated by the left ventricle, rather than actively supporting blood flow through the contracting left atrium and left atrial appendage. However, the contraction of the left atrial appendage may be out of sync with the cycle of the left ventricle. For example, the contraction of the left atrial appendage may be up to 180 degrees out of phase with the left ventricle, which may create significant resistance to the desired blood flow. In addition, the geometry of most left atrial appendages is complex and highly variable, with large irregular surface areas and narrow openings or pores compared to the depth of the left atrial appendage. These aspects and other aspects, alone or in various combinations, may lead to high flow resistance to blood outflow from the left atrial appendage.

[0046] In order to reduce the occurrence of thrombosis in the left atrial appendage and prevent thrombi from entering the bloodstream from the left atrial appendage, it may be necessary to develop a medical device and / or closure implant that seals the left atrial appendage from the heart and / or circulatory system, thereby reducing the risk of stroke caused by thrombolytic substances entering the bloodstream from the left atrial appendage. In some cases, fibrinogen circulating in the blood contributes to the formation and growth of thrombi. An exemplary medical device and / or closure implant for sealing the left atrial appendage is disclosed herein.

[0047] Figure 1 An exemplary closed implant 10 is shown. Implant 10 can include an expandable frame 12. In some cases, expandable frame 12 includes a central structure 13 at which a plurality of individual elements 15 forming the expandable frame are brought together. Closed implant 10 can also include a closure member 14 disposed on, over, around, or covering at least a portion of the expandable frame 12. In some embodiments, closure member 14 can be disposed on, over, around, or covering at least a portion of an outer surface (or outwardly facing surface) of expandable frame 12. Figure 1 It is further shown that the closure member 14 can extend only partially along the longitudinal extent of the expandable frame 12. However, this is not limiting. On the contrary, the closure member 14 can extend to any extent along the longitudinal extent of the expandable frame (e.g., the entire longitudinal extension of the expandable frame 12).

[0048] In some embodiments, the closure member 14 is permeable or impermeable to blood and / or other fluids (e.g., water). In some embodiments, the closure member 14 may include a woven, braided and / or knitted material, a fiber, a sheet material, a fabric, a polymeric membrane, a metal or polymer mesh, a porous filter-like material, or other suitable construction. In some cases, the closure member 14 may be formed of a polymeric material. A suitable polymeric material is polyethylene terephthalate (PET), which is a thermoplastic polyester. In some embodiments, the closure member 14 may prevent thrombi (i.e., blood clots, etc.) from passing through the closure member 14 and leaving the left atrial appendage into the bloodstream. In some embodiments, the closure member 14 may promote endothelialization after implantation, thereby effectively removing the left atrial appendage from the patient's circulatory system. Some suitable but non-limiting examples of materials for the closure member 14 will be discussed below.

[0049] Figure 1 It is further shown that the expandable frame 12 can include a plurality of anchoring members 16 disposed around the periphery of the expandable frame 12. The plurality of anchoring members 16 can extend radially outward from the expandable frame 12. In some embodiments, at least some of the plurality of anchoring members 16 can each have and / or include a main body portion and an end portion protruding circumferentially from the main body portion, such as Figure 1 Some suitable but non-limiting examples of materials for the expandable frame 12 and / or the plurality of anchoring members 16 are discussed below.

[0050] In some examples, the expandable frame 12 and the plurality of anchoring members 16 can be integrally formed and / or cut from a single member. In some embodiments, the expandable frame 12 and the plurality of anchoring members 16 can be integrally formed and / or cut from a single tubular member and subsequently formed and / or heat-set to the desired shape in the expanded configuration. In some embodiments, the expandable frame 12 and the plurality of anchoring members 16 can be integrally formed and / or cut from a single flat member and then rolled or formed into a tubular structure and subsequently formed and / or heat-set to the desired shape in the expanded configuration. Some exemplary means and / or methods of manufacturing and / or forming the expandable frame 12 include laser cutting, machining, punching, stamping, electrical discharge machining (EDM), chemical dissolution, etc., and other means and / or methods are also contemplated.

[0051] like Figure 1 As shown, the plurality of anchoring members 16 disposed along the expandable frame 12 may include two rows of anchoring members 16. However, this is not limiting. Instead, the expandable frame 12 may include a single row of anchoring members 16. In other examples, the expandable frame 12 may include more than two rows of anchoring members 16. For example, in some cases, the expandable frame 12 may include 1, 2, 3, 4, or more rows of anchoring members 16.

[0052] Figure 2 It is shown that the closure implant 10 may be inserted and advanced through a body cavity via a closure implant delivery system 20 . Figure 2 Further shown is the closure implant 10 delivered and positioned within the left atrial appendage 50. In some cases, the closure implant delivery system 20 can include a delivery catheter 24 that is guided toward the left atrium to a location adjacent to the left atrial appendage 50 via various chambers and cavities of the heart (e.g., the inferior vena cava, the right atrium, etc.).

[0053] The delivery system 20 may include a hub member 22 coupled to a proximal region of a delivery catheter 24. The clinician may manipulate the hub member 22 to guide the distal end region of the delivery catheter 24 to a position adjacent to the left atrial appendage 50. In some embodiments, the closed implant delivery system may include a core wire 18. In addition, the proximal end of the expandable frame 12 may be configured to releasably attach, combine, couple, engage, or otherwise connect to the distal end of the core wire 18. In some embodiments, the end region of the expandable frame 12 may include a threaded insert coupled thereto. In some embodiments, the threaded insert may be configured and / or adapted to be coupled, coupled, mated, or otherwise engaged with a threaded member disposed at the distal end of the core wire 18. Other means of releasably coupling and / or engaging the proximal end of the expandable frame 12 to the distal end of the core wire 18 are also contemplated.

[0054] Figure 3 The left atrial appendage closure implant 10 is shown via a delivery catheter 24 (as shown in the above reference Figure 2 The implant 10 may be configured to be in a collapsed configuration and an expanded configuration. For example, in some cases, the closed implant may be in a collapsed configuration during delivery via a closed implant delivery system, and once deployed from the closed implant delivery system, the closed implant may be expanded to an expanded configuration. Figure 3 Also shown are several areas of the closure implant 10 that tend to attract fibrinogen and therefore promote the growth of thrombus. In some cases, the central structure 13 tends to be an area that attracts fibrinogen and therefore promotes the growth of thrombus. The closure implant 10 includes a front edge 17 that tends to be an area that attracts fibrinogen and therefore promotes the growth of thrombus.

[0055] also, Figure 3 The expandable frame 12 is shown to be plastic so that in the expanded configuration, it substantially conforms to and / or sealingly engages the shape and / or geometry of the sidewall of the left atrial appendage. In some embodiments, the closure implant 10 can be expanded to a size, range, or shape that is less than or different than the maximum unconstrained range, as determined by the surrounding tissue and / or sidewall of the left atrial appendage. In addition, Figure 3 The expandable frame 12 is shown to be held fixed adjacent the left atrial appendage by one or more anchoring members 16 .

[0056] Furthermore, it will be appreciated that elements of the expandable frame 12 may be customized to increase the flexibility and plasticity of the expandable frame 12 and / or closure implant 10, thereby allowing the expandable frame 12 and / or closure implant 10 to conform to the tissue surrounding it, rather than forcing the tissue to conform to the expandable frame 12 and / or closure implant 10. Additionally, in some instances, it may be desirable to design the above-described closure implant 10 to include various features, components, and / or configurations that improve the sealing ability of the closure implant within the left atrial appendage.

[0057] In some cases, at least a portion of the closure implant 10 can be treated or otherwise configured to selectively repel fibrinogen so as to selectively reduce thrombosis relative to certain portions of the closure implant 10. In some cases, at least a portion of the closure implant 10 can be treated or otherwise configured to selectively attract fibrinogen so as to selectively promote thrombosis relative to certain portions of the closure implant 10. Figure 4 A closure implant 110 is shown. Figures 5 to 8 Examples are provided of how the closure implant 110 may be configured to selectively repel and / or attract fibrinogen.

[0058] exist Figure 4 In some embodiments, the closure implant 110 includes an expandable frame 112. In some cases, the expandable frame 112 includes a central structure 113 at which a plurality of individual elements 15 forming the expandable frame are brought together. The closure implant 110 may also include a closure member 114 disposed on, above, around, or covering at least a portion of the expandable frame 112. In some embodiments, the closure member 114 may be disposed on, above, around, or covering at least a portion of an outer (or outwardly facing) surface of the expandable frame 112. Figure 4 It is further shown that the closure member 114 can extend only partially along the longitudinal extent of the expandable frame 112. However, this is not limiting. Instead, the closure member 114 can extend to any extent along the longitudinal extent of the expandable frame (e.g., the entire longitudinal extent of the expandable frame 112). In some cases, the expandable frame 112 can include a plurality of closure members 114 that are provided with ... Figure 1 ) describes various features

[0059] In some embodiments, the closure member 114 may be permeable or impermeable to blood and / or other fluids (e.g., water). In some embodiments, the closure member 114 may include a woven, braided and / or knitted material, a fiber, a sheet material, a fabric, a polymeric membrane, a metal or polymer mesh, a porous filter-like material, or other suitable construction. In some cases, the closure member 114 may be formed of a polymeric material. A suitable polymeric material is polyethylene terephthalate (PET), which is a thermoplastic polyester. In some embodiments, the closure member 114 may prevent thrombi (i.e., blood clots, etc.) from passing through the closure member 114 and leaving the left atrial appendage to enter the bloodstream. In some embodiments, the closure member 114 may promote endothelialization after implantation, thereby effectively removing the left atrial appendage from the patient's circulatory system. Some suitable but non-limiting examples of materials for the closure member 14 will be discussed below.

[0060] In some examples, expandable frame 112 can be integrally formed and / or cut from a single member. In some embodiments, expandable frame 112 can be integrally formed and / or cut from a single tubular member, and subsequently formed and / or heat-set into the desired shape in the expanded configuration. In some embodiments, expandable frame 112 can be integrally formed and / or cut from a single flat member, then rolled or formed into a tubular structure, and subsequently formed and / or heat-set into the desired shape in the expanded configuration. Some exemplary means and / or methods of manufacturing and / or forming expandable frame 112 include laser cutting, machining, punching, stamping, electrical discharge machining (EDM), chemical dissolution, etc., and other means and / or methods are also considered.

[0061] exist Figure 5 , it can be seen that a negatively charged region 120 is arranged near the central structure 113 relative to the closing member 114. In some cases, providing a negatively charged region 120 in this block helps to repel fibrinogen, which tends to be negatively charged at neutral pH values. It should be understood that by repelling fibrinogen in the block around the central structure 113, this can reduce or eliminate the formation of thrombi that would otherwise form in the block. Since the rest of the closing member 114 does not include a negatively charged region 120, thrombi and other tissue growth can be allowed. In some cases, the negatively charged region 120 can be formed by a polymer that is negatively charged at a neutral pH, such as a polymer found in the bloodstream. In this case, the neutral pH can be defined as ranging from 7.35 to 7.45, which is typically the range in which the human body maintains blood pH.

[0062] In some cases, the negatively charged region 120 can be formed by spraying a negatively charged polymer at a neutral pH onto the closed member 114. In some cases, the polymer can be physically mixed into the material forming the closed member 114 instead. In some instances, the polymer can be formed as a copolymer with the material forming the closed member 114 instead. In some cases, for example, the closed member 114 can be formed by polyethylene terephthalate (PET). The negatively charged polymer at a neutral pH can be poly (acrylic acid), carboxymethyl cellulose, polystyrene sulfonate, quaternized poly (4-vinyl pyridine) and other polymers. In some cases, a negatively charged surfactant can be used, such as a siloxane surfactant.

[0063] exist Figure 6 In FIG. 1 , it can be seen that the negatively charged region 122 is provided relative to the closing member 114. The negatively charged region is Figure 5 The negatively charged region 120 is shown to span a larger area. It should be understood that the negatively charged region 122 spans the central structure 113 and will become the front edge (refer to Figure 3 In some cases, since the closure implant 110 can be considered radially symmetrical, there may not be a good way to specify its rotational position relative to the left atrial appendage (LAA) 50, such as Figure 3 As shown, a negatively charged region 122 having the dimensions shown may mean that the leading edge 17 is covered regardless of the rotational orientation of the implant closure implant 110 .

[0064] In some cases, the negatively charged region 122 can be formed by spraying a negatively charged polymer at a neutral pH onto the closed member 114. In some cases, the polymer can be physically mixed into the material forming the closed member 114 instead. In some cases, the polymer can be formed as a copolymer with the material forming the closed member 114 instead. In some cases, for example, the closed member 114 can be formed by polyethylene terephthalate (PET). The negatively charged polymer at a neutral pH can be poly (acrylic acid), carboxymethyl cellulose, polystyrene sulfonate, quaternized poly (4-vinyl pyridine) and other polymers. In some cases, a negatively charged surfactant can be used, such as a siloxane surfactant.

[0065] In some cases, it may be desirable to promote the formation of a thrombus in a specific area of ​​the occlusive implant 110. Figure 7In the embodiment of the present invention, the closure implant 110 includes a positively charged region 130. In some cases, providing a positively charged region 130 in this block helps to attract fibrinogen, which tends to be negatively charged at a neutral pH. It should be understood that by attracting fibrinogen to the periphery 140 of the closure implant 110, this can promote the formation of thrombus, thereby promoting endothelialization. In some cases, it is desirable to promote endothelialization starting from the periphery 140 and extending inwardly.

[0066] In some cases, the positively charged region 130 can be formed by spraying a polymer that is positively charged at a neutral pH onto the closed member 114. In some cases, the polymer can be physically mixed into the material that forms the closed member 114 instead. In some cases, the polymer can be formed as a copolymer with the material that forms the closed member 114 instead. In some cases, for example, the closed member 114 can be formed of polyethylene terephthalate (PET). The polymer that is positively charged at a neutral pH can be one or more of isopropyl acrylamide, polysulfone, silicone, dialkyl quaternary ammonium compound, poly (DMEMA-b-PDMEMA-Co-BMA-Co-PAA), etc.

[0067] In some cases, such as Figure 8 As shown, it may be desirable to prevent endothelialization on some portions of the closure implant 110 and promote endothelialization on other portions of the closure implant 110. Figure 8 In the embodiment of the present invention, it can be seen that the closed implant 110 includes a negatively charged region 120 and a positively charged region 130. Although the negatively charged region 120 and the positively charged region 130 are shown as discrete regions, it should be understood that in some cases, there may be a more gentle gradient in charge, that is, the negatively charged region 120 can change from a high negative charge portion to a low negative charge portion. The positively charged region 120 can change from a high positive charge region to a low positive charge portion. These are just examples.

[0068] In some cases, embolic devices may include positively charged polymers to attract fibrinogen. Embolic devices may be used in situations where it is desirable to block blood flow through a particular blood vessel. For example, this may be done when a particular blood vessel provides blood flow to a tumor and it is desirable to kill the tumor or at least reduce its growth. Fig. 9An embolic device 150 is shown, which is generally in the shape of an expanded configuration of a coil (as shown). It will be appreciated that the embolic device 150 is schematically shown as a coil. In some cases, the embolic device 150 can have a more complex structure. For example, the embolic device 150 can be formed of a wire or thread that is coiled into a primary coil, which is then formed into a secondary coil. Further details about the structure of the embolic device 150 can be found in U.S. Patent No. 6,984,240, the disclosure of which is incorporated herein by reference in its entirety.

[0069] from Fig.10 As can be seen in the cross-section shown, the embolic device 150 can include a central member 152 coated with a positively charged polymer 154. In some cases, the positively charged polymer 154 (which can be considered to be positively charged at neutral pH) can act as a closure member by attracting fibrinogen. Illustrative but non-limiting examples of materials that can be used to form the central member 152 include metals such as platinum, stainless steel, zinc, nickel, cobalt, aluminum and aluminum alloys, and Illustrative but non-limiting examples of polymers that are positively charged at neutral pH and can be used are isopropylacrylamide, polysulfones, silicones, dialkyl quaternary ammonium compounds, block polymers such as poly(DMEMA-b-PDMEMA-Co-BMA-Co-PAA), and the like.

[0070] Materials that can be used for the various components of the medical devices disclosed herein may include those materials commonly associated with medical devices. However, this is not intended to limit the devices and methods described herein, as the discussion can be applied to other components of the closure implants 10, 110 disclosed herein.

[0071] The closure implant 10, 110 or portions thereof and the embolic device 150 may be made of metal, metal alloy, polymer (some examples of polymers are disclosed below), metal-polymer composite, ceramic, combinations thereof, or the like, or other suitable materials. Some examples of suitable polymers may include polytetrafluoroethylene (PTFE), tetrafluoroethylene (ETFE), fluorinated ethylene propylene (FEP), polyoxymethylene (POM, available from DuPont, for example). ), polyether block esters, polyurethanes (e.g., polyurethane 85A), polypropylene (PP), polyvinyl chloride (PVC), polyether esters (e.g., available from DSM Engineering Plastics) ), ether or ester based copolymers (e.g., butene / poly(alkylene ether) phthalate and / or other polyester elastomers such as those available from DuPont ), polyamides (e.g., available from Bayer Or available from Elf Atochem ), elastic polyamides, block polyamide / ether, polyether block amide (PEBA, for example, can be ), ethylene vinyl acetate copolymer (EVA), silicone, polyethylene (PE), high-density polyethylene (HDPE), polyester, Marex high-density polyethylene, Marex low-density polyethylene, linear low-density polyethylene (e.g. ), ultra-high molecular weight (UHMW) polyethylene, polypropylene, polybutylene terephthalate (PBT), polyethylene terephthalate (PET), polytrimethylene terephthalate, polyethylene naphthalate (PEN), polyetheretherketone (PEEK), polyimide (PI), polyetherimide (PEI), polyphenylene sulfide (PPS), polyphenylene oxide (PPO), poly(p-phenylene terephthalamide) (e.g. ), polysulfone, nylon, nylon-12 (e.g., available from EMS American Grilon) ), perfluoro(propyl vinyl ether) (PFA), ethylene vinyl alcohol, polyolefins, polystyrene, epoxy resins, polyvinylidene chloride (PVdC), poly(styrene-b-isobutylene-b-styrene) (e.g., SIBS and / or SIBS 50A), polycarbonate, ionomers, biocompatible polymers, other suitable materials, or mixtures, combinations, copolymers, polymer / metal composites thereof, etc. In some embodiments, the sheath can be blended with a liquid crystal polymer (LCP).

[0072] Some examples of suitable metals and metal alloys include: stainless steel, such as 304V, 304L, and 316LV stainless steel; mild steel; nickel-titanium alloys, such as linear elastic and / or superelastic nitinol; other nickel alloys, such as nickel-chromium-molybdenum alloys (e.g., UNS: N06625, such as UNS: N06022, such as UNS: N10276, such as other alloys, etc.), nickel-copper alloys (e.g., UNS: N04400, such as etc.), nickel-cobalt-chromium-molybdenum alloys (e.g., UNS: R30035, such as etc.), nickel-molybdenum alloys (e.g., UNS: N10665, such as ALLOY ), other nickel-chromium alloys, other nickel-molybdenum alloys, other nickel-cobalt alloys, other nickel-iron alloys, other nickel-copper alloys, other nickel-tungsten alloys or tungsten alloys, etc.; cobalt-chromium alloys; cobalt-chromium-molybdenum alloys (for example, UNS: R30003, such as etc.); platinum-rich stainless steel; titanium; combinations thereof; or any other suitable material.

[0073] In at least some embodiments, part or all of the closure implant 10,110 and / or the embolic device 150 may also be doped with, made of or additionally include radiopaque materials. Radiopaque materials are understood to be materials that can produce relatively bright images on a fluoroscopic examination screen or another imaging technique during a medical procedure. This relatively bright image helps the user determine its position. Some examples of radiopaque materials may include but are not limited to gold, platinum, palladium, tantalum, tungsten alloys, polymeric materials loaded with radiopaque fillers, etc. In addition, other radiopaque marker bands and / or coils may also be incorporated into the design of the medical device 10 to achieve the same result.

[0074] In some embodiments, a degree of magnetic resonance imaging (MRI) compatibility is imparted to the closure implant 10, 110 and / or the embolic device 150. For example, the closure implant 10, 110 and / or the embolic device 150 may include materials that do not significantly distort images and produce significant artifacts (e.g., gaps in the image). For example, certain ferromagnetic materials may not be suitable because they may produce artifacts in MRI images. The closure implant 10, 110 and / or the embolic device 150 may also be made of materials that can be imaged by MRI machines. Some materials that exhibit these properties include, for example, tungsten, cobalt-chromium-molybdenum alloys (e.g., UNS: R30003 such as etc.), nickel-cobalt-chromium-molybdenum alloys (e.g., UNS: R30035, etc.) etc.), Nitinol, etc. and other materials.

[0075] In certain embodiments, closed implant 10,110 (and its variant, system or parts disclosed herein) can include textile material.Some examples of suitable textile material can include synthetic yarn, which can be flat, shaped, twisted, textured, pre-contracted or non-contracted.The biocompatible yarn suitable for synthesis in the present disclosure includes but is not limited to polyester, including polyethylene terephthalate (PET) polyester, polypropylene, polyethylene, polyurethane, polyolefin, ethylene polymer, polymethyl acetate, polyamide, ethylene naphthalate derivatives, natural silk and polytetrafluoroethylene.In addition, at least one synthetic yarn can be metal yarn or glass or ceramic yarn or fiber.Useful metal yarn includes made of stainless steel, platinum, gold, titanium, tantalum or nickel-cobalt-chromium-based alloy or containing these yarns of stainless steel, platinum, gold, titanium, tantalum or nickel-cobalt-chromium-based alloy.Yarn can further include carbon, glass or ceramic fiber.Ideally, yarn is made of thermoplastic material, including but not limited to polyester, polypropylene, polyethylene, polyurethane, polynaphthalene, polytetrafluoroethylene etc. The yarns may be multifilament, monofilament or spun yarn types. The type and denier of the yarn selected may be selected based on the manner in which the biocompatible and implantable prosthesis is to be formed, and more specifically, may be selected based on the vascular structure having the desired properties.

[0076] In some embodiments, the closure implant 10, 110 (and variations, systems or components thereof disclosed herein) may include and / or be treated with a suitable therapeutic agent. Some examples of suitable therapeutic agents may include antithrombotic agents (such as heparin, heparin derivatives, urokinase and PPack (dextrorotatory phenylalanine proline arginine chloromethyl ketone)); antiproliferative agents (such as enoxaparin, angiopeptide, monoclonal antibodies capable of blocking smooth muscle cell proliferation, hirudin and acetylsalicylic acid); anti-inflammatory agents (such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine and mesalazine); anti-tumor / antiproliferative / anti-mitotic agents (such as paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin and thymidine kinase inhibitors); anesthetics (such as lidocaine, bupivacaine and ropivacaine); anticoagulants (such as D-Phe-Pr o-Arg chloromethyl ketone, compounds containing RGD peptides, heparin, antithrombin compounds, platelet receptor antagonists, antithrombin, antibodies, antiplatelet receptor antibodies, aspirin, prostaglandin inhibitors, platelet inhibitors and tick antiplatelet peptides); vascular cell growth promoters (such as growth factor inhibitors, growth factor receptor antagonists, transcription activators and transformation promoters); vascular cell growth inhibitors (such as growth factor inhibitors, growth factor receptor antagonists, transcription repressors, transformation repressors, replication inhibitors, inhibitory antibodies, antibodies against growth factors, bifunctional molecules composed of growth factors and cytotoxins, bifunctional molecules composed of antibodies and cytotoxins); cholesterol-lowering agents; vasodilators; and agents that interfere with endogenous vascular mechanisms of action.

[0077] Although the above discussion is generally directed to closure implants for the left atrial appendage of the heart, the above features can also be used for other types of medical implants in which a fabric or membrane is attached to a frame or support structure, including but not limited to implants for treating aneurysms (e.g., abdominal aortic aneurysms, thoracic aortic aneurysms, etc.), replacement valve implants (e.g., replacement heart valve implants, replacement aortic valve implants, replacement mitral valve implants, replacement vascular valve implants, etc.) and / or other types of closure devices (e.g., atrial septal occluders, cerebral aneurysm occluders, peripheral artery occluders, etc.). Other useful applications of the disclosed features are also contemplated.

[0078] It should be understood that the present disclosure is in many respects illustrative only. Changes may be made in detail, particularly in shape, size, and arrangement of steps, without exceeding the scope of the present disclosure. This may include the use of any feature of an example embodiment used in other embodiments, where appropriate. Of course, the scope of the present disclosure is defined by the language of the appended claims.

Claims

1. A closed implant, comprising: an expandable frame configured to transition between a collapsed configuration and an expanded configuration; and a closure member disposed along at least a portion of the expandable frame; wherein the proximal portion of the closure member comprises a negatively charged region adapted to repel fibrinogen, wherein the distal portion of the closure member comprises a positively charged region adapted to attract fibrinogen, Therein, the negatively charged regions and the positively charged regions are discrete regions of the closing member separated from each other by uncharged regions.

2. The closure implant according to claim 1, wherein: The closure implant has a leading edge, and the negatively charged region of the closure member is disposed adjacent the leading edge.

3. The closure implant according to claim 1, wherein: The expandable frame includes a central structure, and the negatively charged region of the closure member is disposed adjacent to the central structure.

4. The closure implant according to claim 1, wherein: At least a portion of the occlusive implant is configured to carry a negative charge at neutral pH.

5. The closure implant according to claim 1, wherein: At least a portion of the occlusive implant includes a polymer that is negatively charged at neutral pH.

6. The closure implant according to claim 5, wherein: A polymer that is negatively charged at neutral pH covers at least a portion of the closure member.

7. The closure implant according to claim 1, wherein: The occlusive implant includes a polymer coating covering at least a portion of the expandable frame, and the polymer coating is positively charged at neutral pH to attract fibrinogen.

8. The closure implant according to any one of claims 1 to 6, wherein: The closure member is formed from polyethylene terephthalate (PET).

9. The closure implant according to any one of claims 1 to 6, wherein: The expandable frame is configured to fit into a left atrial appendage (LAA) of a patient's heart in an expanded configuration.

10. A medical implant for closing a left atrial appendage (LAA) of a patient's heart, the medical implant comprising: an expandable frame configured to transition between a collapsed configuration and an expanded configuration; a closure member extending over and supported by at least a portion of the expandable frame; a first coating configured to repel fibrinogen, the first coating disposed on a proximal portion of the closure member; as well as a second coating configured to attract fibrinogen, the second coating being disposed on a distal portion of the closure member, Wherein, a portion of the closing member disposed between the first coating layer and the second coating layer is free of the first coating layer and the second coating layer.

11. The medical implant according to claim 10, wherein: The first coating configured to repel fibrinogen includes a negatively charged polymer at neutral pH.

12. The medical implant according to claim 10, wherein: The medical implant has a leading edge, and the first coating configured to repel fibrinogen extends over the leading edge.

13. The medical implant according to claim 10, wherein: The expandable framework includes a central structure, and the first coating configured to repel fibrinogen extends over the central structure.

14. A medical implant for closing a left atrial appendage (LAA) of a patient's heart, the medical implant comprising: an expandable frame configured to transition between a collapsed configuration and an expanded configuration; a closure member extending over and supported by at least a portion of the expandable frame; a first coating disposed on a proximal portion of the closure member, the first coating having a negative charge at neutral pH configured to repel fibrinogen; as well as a second coating disposed on the distal portion of the closure member, the second coating having a positive charge at neutral pH configured to attract fibrinogen, Wherein, a middle portion of the closing member disposed between the proximal portion and the distal portion is neither positively nor negatively charged.

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