Coil-hydrogel hybrid patent ductus arteriosus (PDA) occluder device

Abstract

An occlusive coil-hydrogel hybrid device and methods of fabrication are disclosed. The hybrid device can be used to surgically close cardiovascular openings or malformations, such as a Patent Ductus Arteriosus (PDA). The hybrid device comprises a coil formed from a super-elastic shape-memory metal alloy and a hydrogel surrounding or integrated with the coil. The hydrogel is configured to swell in blood and to and promote endothelization. The hybrid device can be delivered through a small catheter, such as a 4- or 5-French gauge catheter.

Description

[0001] COIL-HYDROGEL HYBRID PATENT DUCTUS ARTERIOSUS (PDA) OCCLUDER DEVICE

[0002] CROSS-REFERENCE TO RELATED APPLICATION

[0003] This application claims priority to United States Provisional Application Number 63 / 670,406 that was filed on July 12, 2024. The entire content of the applications referenced above is hereby incorporated by reference herein.

[0004] FIELD

[0005] The present application generally relates to medical devices and, in particular, to a coil occluder device made of nitinol and a hydrogel that, when placed in the body, swells in blood to further aid in occlusion.

[0006] BACKGROUND

[0007] The ductus arteriosus is an essential fetal structure connecting the pulmonary artery with the descending thoracic aorta. The ductus arteriosus normally closes after birth. However, persistent patency of the ductus arteriosus is one of the most common congenital heart diseases and is referred to as Patent Ductus Arteriosus (PDA). The incidence of PDA is approximately 1 in 1,000 births, accounting for 10% of all congenital heart diseases.

[0008] Currently, there are mainly two categories of devices for transcatheter PDA closure: coils and vascular plug devices (such as Amplatzer devices). The shape and size of the PDA varies from patient to patient, and, therefore, none of the currently commercially available devices are ideal for all shapes and sizes of PDA. Coils have relatively high rates of residual leak and / or device embolization. Vascular plug devices cannot be delivered through small catheters and more often lead to complications such as aortic and / or pulmonary artery obstruction. Thus, there is a need for an improved PDA closure device that is configured to accommodate various PDA shapes and sizes and able to be delivered through a small catheter.

[0009] BRIEF SUMMARY

[0010] An occlusive coil-hydrogel hybrid device and methods of fabrication are disclosed. The hybrid device can be used as a vascular occluder to close malformations, such as a PDA. The hybrid device comprises a coil formed from a super-elastic shape-memory metal alloy (e.g., nitinol) and a hydrogel surrounding or integrated with the coil. The coil comprises a primary coil configured to form a secondary coil shaped to facilitate occlusion. The hydrogel is configured to swell in blood and to and promote endothelization. The hybrid device can be delivered through a small catheter, such as a 4- or 5 -French guide catheter.

[0011] Accordingly, certain embodiments of the invention provide a device for repairing or occluding a PDA. The device comprises a primary coil formed from a super-elastic wire. The primary coil is configured to form a secondary coil. The secondary coil comprises two two- dimensional spiral end plates and a central three-dimensional spiral helix portion. The device further comprises a hydrogel surrounding or integrated with at least one of the primary coil or the secondary coil. The hydrogel is configured to swell when exposed to fluid at physiological pH.

[0012] In certain embodiments, the super-elastic wire is nitinol.

[0013] In certain embodiments, the primary coil has an outer diameter of less than about 1 mm.

[0014] In certain embodiments, the primary coil is configured to allow the device to be delivered or implanted at a location of the cardiovascular defect using a 4-French or 5 -French catheter.

[0015] In certain embodiments, the cardiovascular defect is a Patent Ductus Arteriosus (PDA).

[0016] In certain embodiments, the hydrogel comprises an interpenetrating network (IPN) comprising at least two intertwined or crosslinked polymer networks. In certain embodiments, the IPN comprises crosslinked poly(acrylic acid) and crosslinked alginate. In certain embodiments, the IPN comprises crosslinked poly(acrylic acid) and crosslinked hyaluronic acid. In certain embodiments, the IPN comprises crosslinked poly(acrylic acid) and crosslinked chondroitin sulfate. In certain embodiments, the IPN comprises crosslinked poly(ethylene glycol) diacrylate and crosslinked alginate. In certain embodiments, the IPN comprises crosslinked poly(ethylene glycol) diacrylate and crosslinked hyaluronic acid. In certain embodiments, the IPN comprises crosslinked polyethylene glycol) diacrylate and crosslinked chondroitin sulfate.

[0017] In certain embodiments, the hydrogel is modified with at least one bioactive molecule to promote endothelization. In certain embodiments, the bioactive molecule is an integrin- interacting peptide. In certain embodiments, the integrin-interacting peptide is selected from the group consisting of: RGD, REDV (SEQ ID NO:1), and / or YIGSR (SEQ ID NOG). In certain embodiments, the bioactive molecule is vascular endothelial growth factor (VEGF), and / or a VEGF-mimetic peptide such as KLTWQELYQLKYKGI (QK) (SEQ ID NOG).

[0018] Certain embodiments of the invention provide a first method of fabricating a nitinol- hydrogel hybrid device for repairing or occluding a cardiovascular defect. The method comprises injecting a liquid hydrogel precursor into a sealed cylindrical mold; triggering gelation of the liquid hydrogel precursor to produce a hydrogel tube; removing the hydrogel tube from the cylindrical mold; and fitting the hydrogel tube around a primary coil formed from a nitinol wire.

[0019] Certain embodiments of the invention provide a second method of fabricating a nitinol- hydrogel hybrid device for repairing or occluding a cardiovascular defect. The method comprises inserting a sacrificial rod into a primary coil formed from a nitinol wire, the sacrificial rod comprising at least one of a hydrogel initiator, initiator activator, or crosslinker; soaking the sacrificial rod and the primary coil in a hydrogel precursor solution; removing the hydrogel precursor solution after a specified period of time; and removing the sacrificial rod from the primary coil.

[0020] Certain embodiments of the invention provide a method of modifying a hydrogel surface to promote endothelization. The method comprises immobilizing an integrin-interacting peptide, VEGF, or a VEGF-mimetic peptide on the hydrogel surface.

[0021] Other objects, features, and advantages of the present invention will be apparent to one of skill in the art from the following detailed description and figures.

[0022] BRIEF DESCRIPTION OF THE FIGURES

[0023] The present application can be understood by reference to the following drawings, wherein like reference numerals represent like elements. The drawings are merely exemplary to illustrate certain features that may be used singularly or in combination with other features and the present application should not be limited to the embodiments shown.

[0024] FIG. 1A is a side view of an embodiment of a nitinol wire used in accordance with the present disclosure.

[0025] FIG. IB is a side view of a primary coil formed from the nitinol wire of FIG. 1A.

[0026] FIG. 1C is an isometric view of a secondary coil formed from the nitinol primary coil of FIG. IB.

[0027] FIG. ID is a side view of the nitinol secondary coil of FIG. 1C.

[0028] FIG. IE is an isometric view of a nitinol-hydrogel hybrid device formed using the nitinol secondary coil of FIGS. 1C and ID.

[0029] FIG. IF is a side view of the nitinol-hydrogel hybrid device of FIG. IE when the hydrogel is swollen.

[0030] FIG. 2 illustrates a first method of making a nitinol-hybrid device in accordance with the present disclosure.

[0031] FIG. 3 illustrates a second method of making a nitinol-hybrid device in accordance with the present disclosure. FIG. 4 illustrates a third method of making a nitinol-hybrid device in accordance with the present disclosure.

[0032] FIG. 5A illustrates a method of chemically modifying a hydrogel surface presenting carboxyl groups with a peptide not containing lysine residues in accordance with the present disclosure.

[0033] FIG. 5B illustrates a method of chemically modifying a hydrogel surface presenting carboxyl groups with a peptide containing lysine residues in accordance with the present disclosure.

[0034] FIG. 5C illustrates a method of chemically modifying a hydrogel surface presenting acrylate groups in accordance with the present disclosure.

[0035] DETAILED DESCRIPTION

[0036] The present disclosure describes an occlusive coil-hydrogel hybrid device. The hybrid device can be used to surgically close vascular openings or vascular malformations, such as a Patent Ductus Arteriosus (PDA). The hybrid device can also be used to repair other vascular defects, including, for example, atrial septal defects, patent foramen ovale, fistulas, and other arterio-venous malformations. The hybrid device includes a coil formed in whole or in part from nitinol or another super-elastic shape-memory metal alloy. The coil comprises a primary coil configured to form a secondary coil shaped to facilitate occlusion. The hybrid devices further include hydrogel surrounding or integrated with the coil. The hydrogel is configured to swell in blood to provide more volume for complete occlusion. The hydrogel is further configured to promote endothelization. The hybrid device can be delivered through a small catheter, such as a 4- or 5 -French guide catheter.

[0037] Referring now to the drawings wherein like reference numerals are used to identify like elements in the various views, FIG. 1A illustrates an embodiment of a nitinol wire 10. In an embodiment, the nitinol wire 10 has a transition temperature below normal body temperature (e.g., about 37 degrees Celsius). In an embodiment, the nitinol wire 10 has a transition temperature below normal room temperature (e.g., about 20 degrees Celsius). FIG. IB illustrates the nitinol wire 10 formed into a primary coil 12 with an outer diameter d. In an embodiment, the outer diameter d can be 1.00 mm or smaller (e.g., 1.00 mm, 0.95 mm, 0.90 mm, or 0.85 mm). Importantly, the outer diameter d of the primary coil 12 can determine the size of the catheter used to deliver the hybrid device, regardless of the dimensions of the fully formed device or the dimensions of the defect to be treated. For example, when the outer diameter d of the primary coil is 1.00 mm, a hybrid device made of this primary coil 12 can be delivered with a 4- or 5-French gauge catheter (hydrogel is very thin before swelling in blood). Thus, the occlusive coil-hydrogel hybrid devices described herein can have a large range of dimensions when fully assembled (e.g., into secondary coil, tertiary coil, etc.), but can be still delivered with the same small catheter (e.g., a 4- or 5-French gauge catheter). Consequently, physicians do not need to decide what size catheter to use based on the size of the device or the defect to be treated. In addition, this allows for smaller vascular access in small patients and also avoids vascular access related complications.

[0038] The primary coil 12 can be formed into a secondary coil 14, as shown in FIG. 1C. In an embodiment, the secondary coil 14 comprises two nitinol coil spiral end plates 16A, 16B and a central nitinol coil spiral helix portion 18. The secondary coil 14 can have varied dimensions to treat defects having different shapes and sizes. As shown in FIG. ID, DI is the outer diameter of widest, central section of the three-dimensional spiral helix portion 18. As further shown in FIG. ID, the spiral helix portion 18 can include progressively smaller diameter secondary coils toward the junction with each spiral end plate 16A, 16B. D2 is the outer diameter of the two- dimensional spiral end plates 16A, 16B. D3 is the distance between the spiral end plates 16A, 16B (i.e., the length of the spiral helix portion 18). In some embodiments, DI can be 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, or 20 mm. In some embodiments, D2 can be Dl+1 mm, Dl+2 mm, or Dl+3 mm. In some embodiments, D3 can be 3, 4, 5, 6, 8, or 10 mm.

[0039] Referring to FIGS. IE and IF, the central nitinol coil spiral helix portion 18 of the secondary coil 14 can be coated or wrapped with hydrogel. In some embodiments, the hydrogel wraps around the primary coil 12 in the central spiral helix portion 18. In some embodiments, the hydrogel can be placed inside the primary coil 12 in the central spiral helix portion 18. In FIG. IE, dry hydrogel 20A is shown coating spiral helix portion 18. When exposed to fluid, such as blood, the hydrogel can swell (e.g., by more than 10 times in volume compared to its dry state). The swollen hydrogel 20B is shown in FIG. IF.

[0040] In an embodiment, one end of the primary coil 12 includes a detachment element (not shown) to allow device deployment at the surgical site. Deployment systems based on mechanical detachment, such as interlocking arms or Ferrule type detachment systems, can be used. Alternatively, other detachment methods, such as electrolytic detachment, can be used.

[0041] In an embodiment, radiopaque marker bands made from platinum, platinum-iridium alloy, gold, or tantalum can be incorporated into the nitinol primary coil 12 to ensure proper deployment and function of the device (e.g., via post-placement imaging). Alternatively, select locations of the nitinol primary coil 12 can be coated with radiopaque materials to provide marking for peri- and post-operative visualization.

[0042] Several methods can be used to add the hydrogel coating or tube to the nitinol coil to create the occlusive coil-hydrogel hybrid device described above with respect to FIGS. 1A-1F. FIG. 2 illustrates a first method of fabricating a nitinol-hydrogel hybrid device by sleeving a presynthesized hydrogel tube on a nitinol coil (shown in FIG. 2 as a primary coil). In this method, a hydrogel tube wrapping a nitinol coil can be pre-synthesized using either a mold-based or a mold-free process. In the mold-based process, a liquid hydrogel precursor is added into a sealed mold surrounding a rod template. Next, gelation is triggered, for example, by exposing the liquid gel precursor to a temperature change or irradiation. After gelation is completed, the synthesized hydrogel tube is removed from the mold. In the mold-free process, an initiator, initiator activator, and / or crosslinker required for gelation are encapsulated into a sacrificial rod, which is then soaked in a hydrogel precursor solution that does not contain the initiator, initiator activator, and / or crosslinker. The encapsulated initiator, initiator activator, and / or crosslinker diffuse out to trigger gelation reaction, and the reaction can be terminated by removing the remaining hydrogel precursor. The hydrogel thickness is controlled by the reaction time, which determines the diffusion distance of the initiator, initiator activator, and / or crosslinker. The sacrificial rod is then removed to yield a hydrogel tube. One example of the sacrificial material is Pluronic F127, which forms a gel at room or higher temperatures and becomes a liquid at 4°C. Another example of the sacrificial material is gelatin solution, which forms a gel at room or lower temperatures and becomes a liquid when the temperature is above 40°C. A hydrogel tube pre-synthesized via either the mold-based or the mold-free process is sleeved onto a nitinol coil device, a procedure that can be readily performed due to the super-elastic property of the nitinol material and the tough property of the hydrogel.

[0043] FIG. 3 illustrates another method of fabricating the occlusive coil-hydrogel hybrid device described above with respect to FIGS. 1A-1F. This second method is a mold-free, in-situ synthesis of a hydrogel tube wrapping around a nitinol coil. This method is particularly relevant for pediatric devices, which have small dimensions. The thin wall thickness of hydrogel tubes used in such small devices can make it challenging to fabricate coil-hydrogel hybrid devices using the first method described above with respect to FIG. 2, which involves sleeving a presynthesized hydrogel tube around a nitinol coil. Therefore, the present inventors developed the alternative mo Id- free, in-situ method shown in FIG. 3. In this method, an initiator, initiator activator, and / or crosslinker required for gelation are encapsulated into a sacrificial material, which is placed inside the nitinol coil. Then the nitinol coil and the sacrificial material are soaked in a hydrogel precursor solution that does not contain the initiator, initiator activator, and / or crosslinker. The encapsulated initiator, initiator activator, and / or crosslinker diffuse out to trigger gelation reaction, and the reaction can be terminated by removing the remaining hydrogel precursor. The wall thickness of the in-situ formed hydrogel tube is controlled by the reaction time, which determines the diffusion distance of the initiator, initiator activator, and / or crosslinker. After a desired hydrogel tube is in-situ synthesized, the sacrificial material is removed, yielding a hybrid device with the hydrogel tube wrapping the nitinol coil. One example of the sacrificial material is Pluronic Fl 27, which forms a gel at room or higher temperatures and becomes a liquid at 4°C. Another example of the sacrificial material is gelatin solution, which forms a gel at room or lower temperatures and becomes a liquid when the temperature is above 40°C.

[0044] FIG. 4 illustrates a third method of fabricating the occlusive coil-hydrogel hybrid device described above with respect to FIGS. 1A-1F. In this method, the hybrid device is fabricated through inserting a dried hydrogel rod into the core area of the nitinol primary coil. The nitinol secondary coil is straightened into the primary coil using its superelasticity. The two ends of the primary coil are held apart by a force. A dried hydrogel rod is inserted into the core area of the straightened primary coil. The force is then released to allow the shape of the secondary coil to recover. After deployment, or delivery of the hybrid device to the surgical site, the hydrogel swells to reach outside the primary coil, expanding through the gaps between the turns of the primary coil.

[0045] The hydrogel used in the presently disclosed occlusive coil-hydrogel hybrid device includes an interpenetrating network (IPN). The IPN contains at least two intertwined networks formed from one or more of the following polymers or their copolymers: poly(acrylic acid), polyacrylamide, poly( ethylene glycol), poly(ethylene glycol) diacrylate, poly(2-hydroxyethyl methacrylate), poly(hydroxypropyl methacrylate), poly(sulfobetaine methacrylate), poly(sulfobetaine acrylamide), poly(carboxybetaine methacrylate), poly(N-hydroxyethyl acrylamide), poly(2-hydroxyethyl acrylate), poly(2-acrylamido-2-methylpropanesulfonic acid), poly(vinyl Alcohol), poly(N-isopropylacrylamide), alginate, hyaluronic acid, chondroitin sulfate, agarose, cellulose, carboxymethylcellulose, hydroxyethyl cellulose, dextran, collagen, gelatin, and / or fibrinogen.

[0046] In an embodiment, the hydrogel comprises an IPN comprising crosslinked poly(acrylic acid) and crosslinked alginate.

[0047] In an embodiment, the hydrogel comprises an IPN comprising crosslinked poly(acrylic acid) and crosslinked hyaluronic acid.

[0048] In an embodiment, the hydrogel comprises an IPN comprising crosslinked poly(acrylic acid) and crosslinked chondroitin sulfate.

[0049] In an embodiment, the hydrogel comprises an IPN comprising crosslinked poly(ethylene glycol) diacrylate and crosslinked alginate.

[0050] In an embodiment, the hydrogel comprises an IPN comprising crosslinked poly(ethylene glycol) diacrylate and crosslinked hyaluronic acid. In an embodiment, the hydrogel comprises an IPN comprising crosslinked poly(ethylene glycol) diacrylate and crosslinked chondroitin sulfate.

[0051] The hydrogel used in the presently disclosed occlusive coil-hydrogel hybrid device can be modified with bioactive molecules to promote endothelization. Since the occlusive properties of the coil-hydrogel hybrid device are enhanced by the hydrogel and do not rely on thrombus formation like some currently available commercial products, which have the risk of embolization, endothelization of the device could reduce thrombus formation and the risk of embolization without sacrificing the occlusive properties. The bioactive molecules used to promote endothelization can include one or more of the following: integrin-interacting peptides (such as RGD, REDV (SEQ ID NO:1), and YIGSR (SEQ ID NO:2)), vascular endothelial growth factor (VEGF), or the VEGF-mimetic peptide KLTWQELYQLKYKGI (QK) (SEQ ID NOG).

[0052] As shown in FIGS. 5A-5C, various chemical approaches can be used to modify the hydrogel surface to promote endothelization. FIG. 5A illustrates a process of modifying a hydrogel surface presenting carboxyl groups with a peptide not containing lysine residues. Examples of hydrogels presenting carboxyl groups include hydrogels containing poly(acrylic acid). Examples of peptides not containing lysine residues include RGD, REDV (SEQ ID NO: 1), YIGSR (SEQ ID NOG) peptides. Such peptides do not have primary amines in their side chains, and each peptide contains one primary amine at the N-terminus. These peptides are immobilized on the hydrogel surface by derivatizing the surface with N-(3- dimethylaminopropyl)-N’ -ethylcarbodiimide hydrochloride (EDC) and N-hydroxy succinimide (NHS), followed by covalent immobilization of the peptide through amine -NHS reaction.

[0053] FIG. 5B illustrates a process of modifying a hydrogel surface presenting carboxyl groups with a peptide containing lysine residues. Examples of hydrogels presenting carboxyl groups include hydrogels containing poly(acrylic acid). An example of a peptide containing lysine residues is the QK peptide. Peptides such as this contain a primary amine in their side chain. To immobilize these peptides, the hydrogel surface presenting carboxyl groups is sequentially derivatized with EDC, NHS, and a bifunctional compound containing amine at one end and maleimide at the other end; this is followed by covalent immobilization of the peptide through a thiol-maleimide reaction.

[0054] FIG. 5C illustrates a process of modifying a hydrogel surface presenting acrylate groups. Examples of hydrogels presenting acrylate groups include hydrogels containing poly(ethylene glycol) diacrylate. In this process, the hydrogel surface is allowed to react with glycidyl acrylate through irradiation at 365 nm to introduce epoxy groups. A peptide that does not contain lysine residues (such as RGD, REDV (SEQ ID NO:1), or YIGSR (SEQ ID NO:2)) is immobilized on the hydrogel surface through an amine-epoxy reaction. To immobilize a peptide that contains lysine residues (such as QK), the epoxy-bearing surface is further derivatized with a bifunctional compound containing amine at one end and maleimide at the other end; this is followed by immobilization of the peptide through a thiol-maleimide reaction.

[0055] Although at least one embodiment of a coil-hydrogel hybrid PDA occluder device, as well as methods of fabrication thereof, have been described above with a certain degree of particularity, those skilled in the art could make numerous alterations to the disclosed embodiments without departing from the spirit or scope of this disclosure. All directional references (e.g., upper, lower, upward, downward, left, right, leftward, rightward, top, bottom, above, below, vertical, horizontal, clockwise, and counterclockwise) are only used for identification purposes to aid the reader's understanding of the present disclosure, and do not create limitations, particularly as to the position, orientation, or use of the disclosure. Joinder references (e.g., attached, coupled, connected, and the like) are to be construed broadly and can include intermediate members between a connection of elements and relative movement between elements. As such, joinder references do not necessarily infer that two elements are directly connected and in fixed relation to each other. It is intended that all matter contained in the above description or shown in the accompanying drawings shall be interpreted as illustrative only and not limiting. Changes in detail or structure can be made without departing from the spirit of the disclosure as defined in the appended claims.

[0056] Various embodiments are described herein to various apparatuses, systems, and / or methods. Numerous specific details are set forth to provide a thorough understanding of the overall structure, function, manufacture, and use of the embodiments as described in the specification and illustrated in the accompanying drawings. It will be understood by those skilled in the art, however, that the embodiments may be practiced without such specific details. In other instances, well-known operations, components, and elements have not been described in detail so as not to obscure the embodiments described in the specification. Those of ordinary skill in the art will understand that the embodiments described and illustrated herein are nonlimiting examples, and thus it can be appreciated that the specific structural and functional details disclosed herein may be representative and do not necessarily limit the scope of the embodiments, the scope of which is defined solely by the appended claims.

[0057] Reference throughout the specification to “various embodiments,” “some embodiments,” “one embodiment,” or “an embodiment,” or the like, means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, appearances of the phrases “in various embodiments,” “in some embodiments,” “in one embodiment,” or “in an embodiment,” or the like, in places throughout the specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. Thus, the particular features, structures, or characteristics illustrated or described in connection with one embodiment may be combined, in whole or in part, with the features structures, or characteristics of one or more other embodiments without limitation given that such combination is not illogical or non-functional.

[0058] It will be appreciated that the terms “proximal” and “distal” may be used throughout the specification with reference to a clinician manipulating one end of an instrument used to treat a patient. The term “proximal” refers to the portion of the instrument closest to the clinician and the term “distal” refers to the portion located furthest from the clinician. It will be further appreciated that for conciseness and clarity, spatial terms such as “vertical,” “horizontal,” “up,” and “down” may be used herein with respect to the illustrated embodiments. However, surgical instruments may be used in many orientations and positions, and these terms are not intended to be limiting and absolute.

[0059] The terms “about” and “approximately” may be used throughout the specification when referring to a measurable value, such as an amount, a distance, a temporal duration, and the like. The terms “about” and “approximately” are meant to encompass variations of ±20% or ±10%, in certain embodiments ±5%, in certain embodiments ±1%, in certain embodiments ±0.1% from the specified value, as such variations are appropriate in accordance with the present disclosure.

[0060] Any patent, publication, or other disclosure material, in whole or in part, that is said to be incorporated by reference herein is incorporated herein only to the extent that the incorporated materials does not conflict with existing definitions, statements, or other disclosure material set forth in this disclosure. As such, and to the extent necessary, the disclosure as explicitly set forth herein supersedes any conflicting material incorporated herein by reference. Any material, or portion thereof, that is said to be incorporated by reference herein, but which conflicts with existing definitions, statements, or other disclosure material set forth herein will only be incorporated to the extent that no conflict arises between that incorporated material and the existing disclosure material.

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A device for repairing or occluding a cardiovascular defect, the device comprising: a primary coil formed from a super-elastic wire, wherein the primary coil is configured to form a secondary coil, the secondary coil comprising two two-dimensional spiral end plates and a central three-dimensional spiral helix portion; and a hydrogel surrounding or integrated with at least one of the primary coil or the secondary coil, wherein the hydrogel is configured to swell when exposed to fluid.

2. The device of claim 1, wherein the super-elastic wire is nitinol.

3. The device of claim 1 or 2, wherein the primary coil has an outer diameter of about 1 mm or less.

4. The device of any one of claims 1-3, wherein the primary coil is configured to be delivered or implanted at a location of the cardiovascular defect using a guide catheter.

5. The device of any one of claims 1-4, wherein the cardiovascular defect is a Patent Ductus Arteriosus (PDA).

6. The device of any one of claims 1-5, wherein the hydrogel comprises an interpenetrating network (IPN) comprising at least two intertwined or crosslinked polymer networks.

7. The device of claim 6, wherein the at least two intertwined or crosslinked polymer networks are formed from one or more polymers or copolymers selected from the group consisting of: poly(acrylic acid), polyacrylamide, polyethylene glycol), poly(ethylene glycol) diacrylate, poly(2 -hydroxyethyl methacrylate), poly(hydroxypropyl methacrylate), poly(sulfobetaine methacrylate), poly(sulfobetaine acrylamide), poly(carboxybetaine methacrylate), poly(N-hydroxyethyl acrylamide), poly(2 -hydroxyethyl acrylate), poly(2- acrylamido-2-methylpropanesulfonic acid), poly(vinyl Alcohol), poly(N-isopropylacrylamide), alginate, hyaluronic acid, chondroitin sulfate, agarose, cellulose, carboxymethylcellulose, hydroxyethyl cellulose, dextran, collagen, gelatin, and / or fibrinogen.

8. The device of claim 6 or 7, wherein the IPN comprises crosslinked poly(acrylic acid) and crosslinked alginate.

9. The device of claim 6 or 7, wherein the IPN comprises crosslinked poly(acrylic acid) and crosslinked hyaluronic acid.

10. The device of claim 6 or 7, wherein the IPN comprises crosslinked poly(acrylic acid) and crosslinked chondroitin sulfate.

11. The device of claim 6 or 7, wherein the IPN comprises crosslinked poly(ethylene glycol) diacrylate and crosslinked alginate.

12. The device of claim 6 or 7, wherein the IPN comprises crosslinked poly(ethylene glycol) diacrylate and crosslinked hyaluronic acid.

13. The device of claim 6 or 7, wherein the IPN comprises crosslinked poly(ethylene glycol) diacrylate and crosslinked chondroitin sulfate.

14. The device of any one of claims 1-13, wherein the hydrogel is modified with at least one bioactive molecule to promote endothelization.

15. The device of claim 14, wherein the at least one bioactive molecule is an integrin- interacting peptide.

16. The device of claim 15, wherein the integrin-interacting peptide is selected from the group consisting of: RGD, REDV (SEQ ID NO: 1), and / or YIGSR (SEQ ID NO:2).

17. The device of claim 14, wherein the at least one bioactive molecule is vascular endothelial growth factor (VEGF) and / or VEGF-mimetic peptide KLTWQELYQLKYKGI (QK) (SEQ ID NO:3).

18. A method of fabricating a nitinol-hydrogel hybrid device for repairing or occluding a cardiovascular defect, the method comprising: injecting a liquid hydrogel precursor into a sealed cylindrical mold;triggering gelation of the liquid hydrogel precursor to produce a hydrogel tube; removing the hydrogel tube from the cylindrical mold; and fitting the hydrogel tube around a primary coil formed from a nitinol wire.

19. A method of fabricating a nitinol-hydrogel hybrid device for repairing or occluding a cardiovascular defect, the method comprising: soaking a sacrificial rod in a hydrogel precursor solution, the sacrificial rod comprising at least one of a hydrogel initiator, initiator activator, or crosslinker; removing the hydrogel precursor solution after a specified period of time; removing the sacrificial rod to yield a hydrogel tube; and fitting the hydrogel tube around a primary coil formed from a nitinol wire.

20. The method of claim 18 or 19, wherein the hydrogel tube comprises an interpenetrating network (IPN) comprising at least two intertwined or crosslinked polymer networks.

21. The method of claim 20, wherein the at least two intertwined or crosslinked polymer networks are formed from one or more polymers or copolymers selected from the group consisting of: poly(acrylic acid), polyacrylamide, polyethylene glycol), poly(ethylene glycol) diacrylate, poly(2 -hydroxyethyl methacrylate), poly(hydroxypropyl methacrylate), poly(sulfobetaine methacrylate), poly(sulfobetaine acrylamide), poly(carboxybetaine methacrylate), poly(N-hydroxyethyl acrylamide), poly(2 -hydroxyethyl acrylate), poly(2- acrylamido-2-methylpropanesulfonic acid), poly(vinyl Alcohol), poly(N-isopropylacrylamide), alginate, hyaluronic acid, chondroitin sulfate, agarose, cellulose, carboxymethylcellulose, hydroxyethyl cellulose, dextran, collagen, gelatin, and / or fibrinogen.

22. A method of fabricating a nitinol-hydrogel hybrid device for repairing or occluding a cardiovascular defect, the method comprising: inserting a sacrificial rod into a primary coil formed from a nitinol wire, the sacrificial rod comprising at least one of a hydrogel initiator, initiator activator, or crosslinker; soaking the sacrificial rod and the primary coil in a hydrogel precursor solution; removing the hydrogel precursor solution after a specified period of time; and removing the sacrificial rod from the primary coil.

23. The method of claim 22, wherein the nitinol-hydrogel hybrid device comprises a hydrogel tube surrounding the primary coil.

24. The method of claim 23, wherein the hydrogel tube comprises an interpenetrating network (IPN) comprising at least two intertwined or crosslinked polymer networks.

25. The method of claim 24, wherein the at least two intertwined or crosslinked polymer networks are formed from one or more polymers or copolymers selected from the group consisting of: poly(acrylic acid), polyacrylamide, polyethylene glycol), poly(ethylene glycol) diacrylate, poly(2 -hydroxyethyl methacrylate), poly(hydroxypropyl methacrylate), poly(sulfobetaine methacrylate), poly(sulfobetaine acrylamide), poly(carboxybetaine methacrylate), poly(N-hydroxyethyl acrylamide), poly(2 -hydroxyethyl acrylate), poly(2- acrylamido-2-methylpropanesulfonic acid), poly(vinyl Alcohol), poly(N-isopropylacrylamide), alginate, hyaluronic acid, chondroitin sulfate, agarose, cellulose, carboxymethylcellulose, hydroxyethyl cellulose, dextran, collagen, gelatin, and / or fibrinogen.

26. A method of fabricating a nitinol-hydrogel hybrid device for repairing or occluding a cardiovascular defect, the method comprising: straightening a secondary coil into a primary coil formed from a nitinol wire; holding each end of the primary coil apart by a force; inserting a dried hydrogel rod into a core area of the primary coil; and releasing the force to allow the secondary coil to reform.

27. The method of claim 26, wherein the hydrogel rod comprises an interpenetrating network (IPN) comprising at least two intertwined or crosslinked polymer networks.

28. The method of claim 27, wherein the at least two intertwined or crosslinked polymer networks are formed from one or more polymers or copolymers selected from the group consisting of: poly(acrylic acid), polyacrylamide, polyethylene glycol), poly(ethylene glycol) diacrylate, poly(2 -hydroxyethyl methacrylate), poly(hydroxypropyl methacrylate), poly(sulfobetaine methacrylate), poly(sulfobetaine acrylamide), poly(carboxybetaine methacrylate), poly(N-hydroxyethyl acrylamide), poly(2 -hydroxyethyl acrylate), poly(2- acrylamido-2-methylpropanesulfonic acid), poly(vinyl Alcohol), poly(N-isopropylacrylamide), alginate, hyaluronic acid, chondroitin sulfate, agarose, cellulose, carboxymethylcellulose, hydroxyethyl cellulose, dextran, collagen, gelatin, and / or fibrinogen.

29. A method of modifying a hydrogel surface to promote endothelization, the method comprising immobilizing a bioactive molecule on the hydrogel surface.

30. The method of claim 29, wherein the hydrogel surface comprises at least one of a carboxyl group or an acrylate group.

31. The method of claim 29 or 30, wherein the bioactive molecule is an integrin-interacting peptide that does not include lysine residues.

32. The method of claim 29 or 30, wherein the bioactive molecule is an integrin-interacting peptide that includes lysine residues.

33. The method of claim 31, wherein the integrin-interacting peptide is selected from the group consisting of: RGD, REDV (SEQ ID NO: 1), and / or YIGSR (SEQ ID NO:2) .

34. The method of claim 29, wherein the bioactive molecule is vascular endothelial growth factor (VEGF), and / or VEGF-mimetic peptide KLTWQELYQLKYKGI (QK) (SEQ ID NO:3).

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