WO2015055652A1

WO2015055652A1 - Prosthesis seal

Info

Publication number: WO2015055652A1
Application number: PCT/EP2014/072019
Authority: WO
Inventors: Koby GVILI; Stéphane Delaloye; Youssef Biadillah; Lionel Flaction; Arnaud HUMAIR
Original assignee: Symetis Sa
Priority date: 2013-10-14
Filing date: 2014-10-14
Publication date: 2015-04-23

Abstract

A seal for a stented prosthesis for obstructing para-prosthesis leakage, the seal comprising a hollow sleeve for defining a space for swellable material that swells when contacted by at least a component of body fluid, at least a portion of the member comprising material permeable to at least some components of the body fluid. In some embodiments, the permeable material has a pore-size of less than about 0.005mm, optionally about or less than about 0.004mm. In some embodiments, the swellable material comprises polyethylene glycol film or micro-beads.

Description

PROSTHESIS SEAL

The present disclosure relates to the field of stents implantable in the body. Embodiments have been devised to address problems encountered in the field of stent-valves, for example, cardiac stent-valves (e.g. prosthetic heart valves). However, the concepts disclosed herein may have broader application to any stent or stented prosthesis where a seal is desired at an exterior surface of a stent.

Transcatheter valve implantation (for example, transcatheter aortic valve implantation (TAVI)) is an evolving technology for replacement valve therapy that (i) avoids the trauma of conventional open-chest surgery, and (ii) avoids the need for heart and lung bypass. In such a technique, a stent-valve loaded into a delivery catheter in a compressed condition of the stent-valve, is introduced to the desired site of implantation (for example, at the heart) via a percutaneous route or via minimally invasive surgery. The stent-valve is expanded into the implantation position from or by the delivery catheter, and the delivery catheter is then withdrawn.

Despite the successes of transcatheter stent-valves, technological challenges remain. One such challenge is preventing retrograde leakage of blood around the stent-valve (so called para-valve leakage). The above- noted stents form a friction fit with the native anatomy to anchor the stent- valve in position, and are round in cross-section. However, the native anatomy in which the stent is implanted is often off-round and is different from each person. Moreover, heavy calcification of the native anatomy may obstruct full deployment of any stent and make the native anatomy even more irregular. Thus, it can sometimes be difficult to provide a perfect sealing fit between the stent-valve and the surrounding anatomy. Para-valve leakage is believed to be one of the factors affecting long-term efficacy of the prosthetic valve, and possibly the life expectancy of the patient. One explanation is that the heart may have to work harder to compensate for some blood leaking retrograde at the entrance or exit of the heart. Therefore addressing para- valve leakage is a significant challenge.

It is known to incorporate an external skirt or cover as part of the stent- valve. For example, the skirt is made of compressible biocompatible material, such as pericardial tissue or PET. The thicker the material of the skirt, the more able the skirt is to occlude gaps and effect a seal. However, a disadvantage is that such skirts add to the bulk of the stent-valve. A thick skirt makes the stent-valve problematic to compress to a desirably small size for implantation.

US-A-2005/0137688 is understood to describe compliant sacs disposed around the exterior of a stent, that are said to provide a more efficient seal along an irregular interface. The sacs may be filled with an appropriate material, for example, water, blood, foam or a hydrogel. Different arrangement of sacs are proposed in principle, but this document neither describes any specific construction technique nor does it describe handling of the fill material.

US patent 5769882 is understood to describe an implantable expansible tubular vascular prosthesis carrying a form-in-place sealing layer for occluding at least a circumferential band at the interface between the prosthesis and the native tissue wall. In one example, the sealing layer comprises a hydrogel, arranged in a sleeve/cuff comprising a permeable membrane.

EP 1262201 is understood to describe an implantable vascular device having an external seal structure comprising a swellable hydrogel. In use, the hydrogel absorbs a mass of liquid so as to assume, as a result of the absorption, a certain degree of mechanical consistency. An example hydrogel has a polyvinyl alcohol (PVA) base, in combination with a polysaccharide.

WO-A-2008/070442 is understood to describe prosthetic heart valves, both expanding and non-expanding types, each having an anchoring sleeve that changes shape when the valve is implanted, to prevent migration of the valve. The anchoring sleeve is at least partly made of a material that swells due to absorption of body fluids. In examples, the sleeve is made of an inner material that swells upon contact with body fluids, and enclosed by a cover.

WO-A-2013/033791 is understood to describe expandable sealing means for endoluminal devices for controlled activation. The devices are said to have the benefits of a low profile mechanism for both self-expanding and balloon-expanding prostheses, contained, not open, release of the material, active conformation to the leak-sites such that leakage areas are filled without disrupting the physical and functional integrity of the prosthesis, and on- demand, controlled activation, that may not be pressure activated.

It would be desirable to address one or more of the issues mentioned above, and/or provide a technique for mitigating para-valve (or para-stent) leakage without substantially affecting other desirable characteristics.

The following presents a summary of the disclosure in order to provide a basic, non-limiting, understanding of some embodiments of the disclosure.

For example, in some embodiments of the present disclosure, a seal is provided for a prosthesis. The seal may be configured for obstructing para- prosthesis leakage. The prosthesis may, for example, be a stent-valve (for example, a cardiac stent-valve, such as an aortic stent-valve). The seal may comprise one or any combination of two or more of the following features, which are all optional. The list for optional features is bulleted by letters for reference only:

(a) In some embodiments, the seal comprises a hollow sleeve or cuff for defining a space for first material that swells when contacted by at least a component of body fluid (e.g. of blood), at least a portion of the hollow sleeve/cuff comprising second material permeable to at least some components of the body fluid.

(b) In some embodiments, at least a portion of (optionally all of) the second material has a pore size of about or less than about 0.004mm, optionally about or less than about 0.003mm, optionally about or less than about 0.002mm, optionally about or less than about 0.001 mm.

(c) In some embodiments, at least a portion of (optionally all of) the second material has a pore-size of between about 0.005mm and about 0.03mm. For example, the pore-size may be about or at least about 0.006mm, or optionally about or at least about 0.007mm, or about or at least about 0.008mm, or about or at least about 0.009mm, or about or at least about 0.01 mm.

(d) In some embodiments, at least a portion of (optionally all of) the second material has a pore-size of between about 0.005mm and about 0.01 mm. (e) In some embodiments, the second material has a pore size of about or less than about 0.04mm, optionally about or less than about 0.03mm, optionally about or less than about 0.025mm, optionally about or less than about 0.02mm, optionally about or less than about 0.015mm, optionally about or less than about 0.01 mm, optionally about or less than about 0.007mm, optionally about or less than about 0.006mm, optionally about or less than about 0.005mm, optionally about or less than about 0.004mm, optionally about or less than about 0.003mm, optionally about or less than about 0.002mm, optionally about or less than about 0.001 mm.

(f) In some embodiments, the pore size is about 0.002mm.

(g) In some embodiments, the second material comprises a film. In some embodiments, the film may have laser-perforations.

(h) In some embodiments, the second material comprises a fabric.

(i) In some embodiments, the second material has a thickness of less than about 0.1 mm, optionally less than about 0.09mm, optionally less than about 0.08mm, optionally less than about 0.07mm, optionally less than about 0.06mm, optionally less than about 0.05mm, optionally less than about 0.04mm, optionally less than about 0.03mm, optionally less than about 0.02mm, optionally less than about 0.01 mm.

(j) In some embodiments, the first material may comprise a hydrogel or a so-called super-absorbent material.

(k) In some embodiments, the first material is provided in the form of a thin film or a coating on a substrate. The thickness of the first material (optionally with or without substrate) may be about or less than about 0.010mm, optionally about or less than about 0.009mm, optionally about or less than about 0.008mm, optionally about or less than about 0.007mm, optionally about or less than about 0.006mm, optionally about or less than about 0.005mm, optionally about or less than about 0.004mm, optionally about or less than about 0.003mm, optionally about or less than about 0.002mm, optionally about or less than about 0.001 mm.

(I) In some embodiments, the first material is provided in the form of micro-beads (for example, microspheres). (m) In some embodiments, the first material comprises poly(ethylene glycol)-acrylate without an ester-bond and/or without an ester group (for example, poly(ethylene glycol)-acrylamide (PEG-acrylamide)).

(n) In some embodiments, the first material comprises one or more selected from: poly(ethylene glycol) (PEG); poly(ethylene glycol)-acrylate; poly(ethylene glycol)-diol (PEG-OH); poly(ethylene glycol)-diacrylate (PEG- diacrylate); poly(ethylene glycol)-acrylamide (PEG-acrylamide); poly(ethylene glycol)-diacrylamide (PEG-diacrylamide).

(o) In some embodiments, the first material comprises one or more selected from: poly(acrylic acid); sodium polyacrylate; polyacrylate; polyacrylamide; polyacrylamide copolymer; poly(ethylene oxide); poly(propylene oxide); poly(vinyl alcohol); polyvinyl pyrrolidinone; poly(hydroxyl ethyl methacrylate); poly (amino acids), Dextran; polysaccharides; ethylene maleic anhydride copolymer; carboxy-methyl- cellulose polyvinyl alcohol copolymers, polyacrylonitrile.

The seal may be defined independently of a prosthesis (for example, a stent-valve), or in combination with a prosthesis. The seal may be integral with the prosthesis or at least a component of the seal may be provided distinct from the prosthesis (for example in kit form). A sleeve for the seal may also be defined independently.

In a closely related aspect, the invention provides a seal for a stented prosthesis for obstructing para-prosthesis leakage, the seal comprising a hollow sleeve for receiving swellable material that swells when contacted by at least a component of body fluid, at least a portion of the member comprising material permeable to at least some components of the body fluid. In some embodiments, the permeable material has a pore-size of less than about 0.005mm, optionally about or less than about 0.004mm. In some embodiments, the swellable material comprises polyethylene glycol film or micro-beads.

Additional and/or independent embodiments and features of the disclosure are included in the claims.

Although certain features and aspects of the invention are highlighted in the foregoing disclosure and in the appended claims, protection is claimed for any novel concept described herein and/or illustrated in the drawings, whether or not emphasis is placed thereon.

Non-limiting embodiments of the invention are now described with reference to the accompanying drawings, in which:

Fig. 1 is a schematic drawing illustrating a stent-valve 10 with which some embodiments of the present disclosure are suitable to be used. The figure is broken along a centre-line of the stent-valve. The stent-structure is shown to the right, and a profile showing the position of the valve, skirt and seal, is shown to the left.

Fig. 2 is a schematic illustration of a first example seal structure for the stent-valve of Fig. 1 ;

Fig. 3 is a schematic illustration of a second example seal structure for the stent-valve of Fig. 1 ;

Fig. 4 is a schematic illustration of a third example seal structure for the stent-valve of Fig 1 ;

Fig. 5 is a graph showing experimental test results illustrating variation of swelling factor Qv over time, for different pore sizes of permeable membrane;

Fig. 6 is a schematic illustration of a swellable material film;

Fig. 7 is a schematic illustration of swellable material on a carrier substrate;

Fig. 8 is a schematic illustration of swellable material microbeads sandwiched between cover sheets;

Fig. 9 is a schematic illustration of free swellable material microbeads captive in a sleeve;

Fig. 10 is a schematic illustration of swellable material in plug form; and

Fig. 1 1 is a schematic illustration of swellable material in slug form.

Referring to Fig. 1 , a stented prosthesis according to some embodiments is illustrated in the form of a stent-valve 10. A seal 40 (described further below) may be provided for sealing against surrounding tissue when the stent-valve 10 is implanted. The stent-valve 10 may be cardiac stent-valve, for example, an aortic stent-valve, a mitral stent-valve, a pulmonary stent-valve or a tricuspid stent-valve, for implantation at the respective valve position in a human heart. Details of an optional example of stent-valve construction are firstly described, following which details of example seals and seal construction are described in detail.

The stent-valve 10 may optionally comprise biological tissue (for example, pericardium (such as porcine pericardium and/or bovine pericardium) and/or natural cardiac valve leaflets (for example, natural porcine cardiac valve leaflets, optionally attached to a portion of natural cardiac wall tissue). The biological tissue may be fixed, for example, using glutaraldehyde.

The stent-valve 10 may be compressible to a radially compressed condition for delivery using a delivery catheter, and be expandable to an operative or expanded condition (as shown) at implantation. The stent-valve 10 may comprise a stent 12 carrying a plurality of leaflets defining a valve 14 (the position of which is depicted schematically by the bounding phantom lines). Various geometries of stent 12 may be used. In some embodiments, the stent 10 may include one of more of: a lower tubular or crown portion 16 (e.g. defining an inlet section), an upper crown portion 18, a plurality of upstanding commissural supports 20, and a plurality of stabilization arches 22. The stent 12 may have opposite first and second extremities. The lower tubular crown portion 16 may define a first extremity of the stent. The upper crown portion 16 may have a free edge or free crown extremity that is positioned between (e.g. and spaced from) both extremities. The free edge or crown extremity may face towards one of the stent extremities. The upper crown portion 16 may be defined by The commissural supports 20 may optionally be spaced from both extremities. The stabilization arches 22 may extend between the commissural supports 22 and the second stent extremity. The stabilization arches 22 may define the second stent extremity (e.g. the tips and/or arch-apexes of the stabilization arches 22 may define the second stent extremity). The stabilization arches 22 may arch over, and interconnect, the commissural supports 20. Additionally or alternatively to any of the above, the stabilization arches 22 may be bendable or capable of flexing, relative to the commissural supports 20, substantially independently of one another.

In use, the lower portion 16 of the stent 12 may be configured to be deployed after the other regions of the stent 12. For example, the arches 22, the supports 20 and the upper crown 18 may be deployed at least partly before the lower portion 16 (in that order, or in reverse order, or in a different order). At least once the upper crown 18 has been at least partly deployed, the stent 12 may be urged and/or displaced in the direction of arrow 24 to seat the upper crown 18 against native leaflets at the implantation site. Deploying the lower portion 16 last fixes the stent 12 in its final position.

The lower portion 16, and optionally a portion of the upper crown 18, may be formed by a lattice structure of the stent. The lattice structure may define cells or apertures or interstices, for example, generally diamond- shaped apertures (although in some embodiments not strictly diamond- shaped).

The native leaflets may generally overlap a portion 26 of the stent. The native valve annulus may overlap a portion 28 of the stent.

Optionally, regardless of the stent geometry, the stent-valve 10 may further include an inner skirt 30 communicating with the leaflets 14 and carried on an interior of the stent 12. Optionally the inner skirt 30 is coupled directly to the leaflets 14. Additionally or alternatively, the stent-valve 10 may further comprise an outer skirt 32 carried on an exterior of the stent 12. When both skirts are provided, the skirts may partially overlap. The skirts may be offset. In some embodiments, one skirt (e.g. the outer skirt 32) extends further towards a lower extremity of the stent 12 than the other (e.g. inner skirt 30). Additionally or alternatively, one skirt (e.g. the inner skirt 30) extends further towards an upper extremity of the stent 12 than the other (e.g. outer skirt 32). The skirts may be of any suitable flexible and/or compliant material, for example, fabric (e.g. of PET of PEEK) or film (e.g. of PET of PEEK), or of biological tissue (e.g. of pericardium). The skirts may be of the same specific material, or of the same type of material (e.g. biological tissue, fabric, film), or of different types of material. In some examples described below, the outer skirt 32 may of fabric or film; the inner skirt may be of fabric, film or of biological material as desired.

Optionally, the inner skirt 30 and the outer skirt 32 may be attached directly to each other along at least one substantially continuous or discontinuous line of attachment. The attachment may, for example, be by one of more of: suturing, welding, fusion, adhesive. The line of attachment may optionally extend around the entire circumference of the stent-valve. The attachment may mitigate risk of leakage of blood in the spaces of the stent between the inner and outer skirts 30 and 32.

Optionally, for example with the stent geometry described above, at least the outer skirt 32 is positioned to leave the upper crown 18 substantially unobscured by the outer skirt 32. Such an arrangement may assist good blood flow to the coronary arteries (for example, in the case of a stent-valve for the aortic valve).

In some embodiments, regardless of the stent geometry, the lower portion 16 has an extremity formed with a substantially zig-zag shape. The zig-zag shape may comprise lower apexes 16a and upper apexes 16b. The upper apexes 16b may be masked in Fig. 1 by the superimposed presentation of both the frontmost and rearmost cells of the lattice structure. The zig-zag shape may be substantially continuous around the circumference of the stent 12. The outer skirt 32 may have a peripheral edge having a zig-zag shape that matches substantially the zig-zag shape of the extremity of the lower portion 16. Such an arrangement can avoid excessive material at the extremity, and thereby facilitate crimping of the stent-valve 10. At the same time, the outer skirt 32 covers (for example, complete) open cells of the lattice structure down to the stent extremity to reduce risk of blood leakage through the apertures of the cells. The outer skirt 32 can also provide a layer of material over the struts of the stent, thereby to cushion the engagement between the stent and the sensitive native heart tissue.

Regardless of the stent geometry, the valve 14 may comprise biological tissue, for example, pericardium (such as porcine pericardium or bovine pericardium) or natural cardiac valve leaflets (for example, natural porcine cardiac valve leaflets, optionally attached to a portion of natural cardiac wall tissue). Other biological or non-biological material could also be used for the valve 14, as desired.

The stent 12 may optionally be of a self-expanding type that is compressible (e.g. crimped) to the compressed configuration for loading into a delivery catheter (not shown) having a sheath for constraining the stent 12 in the compressed configuration for delivery to the site of implantation. In use, by removal of the constraining effect of the sheath, the stent 12 self-expands to or towards the operative configuration. A self-expanding stent may, for example, be of shape-memory material, for example, shape-memory metal alloy, for example, a nickel-titanium alloy, for example, nitinol. Additionally or alternatively, the stent 12 may be configured to be expanded by application of a foreshortening force from the delivery catheter and/or by application of an (e.g. radially) expanding force from the delivery catheter, such as by using an expansion balloon.

The seal 40 may be configured for sealing against surrounding native tissue when the stent-valve 10 is implanted. In some embodiments, the seal 40 may be provided as an integral part of the stent-valve 10. Alternatively, in some embodiments, at least a component of the seal 40 may be provided as a separate item from the stent-valve (optionally provided together as a kit, for example, within a common container or package). The at least one component may, for example, be mountable to the stent-valve 10 prior to implantation, or it may be introduced (e.g. injected) into a portion of the stent- valve. The at least one component may be mounted/introduced as part of a pre-implantation preparation process.

The seal 40 may be arranged or arrangeable at any suitable position on the stent 12. With the example stent geometry described above, in some embodiments, the seal 40 may be arranged between the upper crown portion 18 and the lower crown or tubular potion 16. In some embodiments, the seal 40 may be positioned optionally closer to the upper crown portion 18, alternatively optionally closer to the lower crown or tubular portion 16, alternatively optionally midway between the extremities of the two crown portions 16 and 18, alternatively optionally at a waist or trunk section between the two crown portions 16 and 18. In some embodiments, regardless of the stent geometry, the seal 40 is carried on the exterior of the stent 12.

As mentioned above, in some embodiments, the (e.g. lower or inlet) periphery of the stent 12 has a substantially zig-zag shape. The zig-zag shape may comprise lower apexes 16a and upper apexes 16b. The upper apexes may be masked in Fig. 1 by the superimposed presentation of both the frontmost and rearmost cells of the lattice structure. The zig-zag shape may be substantially continuous around the circumference of the stent 12. The seal 40 may be arranged or arrangeable to be positioned only between the upper crown 18 and the upper apexes 16b. For example, the seal 40 does not extend to occupy space between the upper apexes 16b and the lower apexes 16a. Positioning the seal 40 clear of the lower apexes 16a can reduce the bulk of material at the extremity, and facilitate crimping. Additionally or alternatively, the seal may be positioned so as not to cover the upper crown 18. Leaving the upper crown 18 clear may enhance blood flow to coronary arteries (for example, in the case of a replacement valve for the aortic valve position).

Referring to Figs. 2-4, the seal 40 may comprise a hollow sleeve and/or cuff 42. Either term "sleeve" or "cuff (or also "sleeve/cuff') may be used. The sleeve/cuff 42 may define a space for receiving swellable material 44 that swells when contacted by at least a component of body fluid (e.g. of blood) to distend the hollow sleeve/cuff 42.

In some embodiments, the sleeve/cuff may be arranged to extend substantially in a circumferential direction around the stent 12.

The swellable material 44 may expand by absorbing at least a component of body fluid (e.g. of blood) or other liquids that contact the material 44. Such a seal 40 may initially be very compact in form, yet may expand significantly when contacted by blood, to fill gaps between the stent- valve 10 and any irregularities in the surrounding tissue. It is desirable that the material 44 have a relatively large swelling factor, in order to be able to fill leak sites at the interface around the prosthesis. The material 44 may comprise a hydrogel and/or a super-absorbent material. Examples of suitable swellable (e.g. absorptive) material 44 may be any of the hydrogels referred to in the aforementioned patents and applications: US 5769882, EP 1262201 , WO-A-2008/070442, US 2007/0060998, WO-A-2010/083558. Other examples are described below.

In some embodiments, the sleeve/cuff may be arranged to substantially contain the swellable material 44 captive within the sleeve/cuff. A pore size of a permeable portion of the sleeve/cuff 42 may be smaller than a particle size of the swellable material, and/or the particle size of the swellable material may be less than about 0.005mm. Such a small particle size has very little embolism risk, and is much smaller than would be trapped by, for example, most current embolic protection filters. The sleeve/cuff 42 may comprise flexible material. The sleeve/cuff 42 may comprise material that is elastically stretchable, and/or material that is substantially non-elastically-stretching. In some embodiments, the sleeve/cuff 42 may be an integral part of, or attached integrally to, one of the skirts 30, 32, for example, the outer skirt 32. Referring to Fig. 2, the sleeve/cuff 42 may be in the form of a tubular band integrally attached to the outer skirt 32. Referring to Fig. 3, the sleeve/cuff 42 may be formed as, or by, an annular pocket between layers of the outer skirt 32. Alternatively, in some embodiments, the sleeve/cuff 42 may be distinct from one or both of the skirts 30, 32. For example, referring to Fig. 4, the sleeve/cuff 42 may be received, or receivable within a channel defined on or within the outer skirt 32.

At least a portion of the sleeve/cuff 42 may be permeable, and may comprise material (e.g. second material) having pores therein or therethrough. The pore size (e.g. diameter or other transverse dimension of the pores representative or pore size) may be about or less than about 0.04mm, optionally about or less than about 0.03mm, optionally about or less than about 0.025mm, optionally about or less than about 0.02mm, optionally about or less than about 0.015mm, optionally about or less than about 0.01 mm, optionally about or less than about 0.007mm, optionally about or less than about 0.006mm, optionally about or less than about 0.005mm, optionally about or less than about 0.004mm, optionally about or less than about 0.003mm, optionally about or less than about 0.002mm, optionally about or less than about 0.001 mm.

Experimental testing results indicate that the swelling size of the material 44 (which may generally be proportional to the weight of absorbed fluids), may depend on the pore size of the permeable material used for the sleeve/cuff 42. The swelling size may be represented by the value Qv, being a ratio of volume increase (after swelling / before swelling). Volume increase was determined from measurement of weight before and after swelling, the volume increase being proportional to the mass of absorbed fluids. A simulated body fluid was used for the experimental testing.

Surprisingly, the test results may indicate that a relatively small pore size may provide increased swelling compared to a relatively larger pore size. For example, Fig. 5 illustrates the results of one experimental test to assess the significance of pore size to the swelling factor Qv. In Fig. 5, the vertical axis denotes Qv, and the horizontal axis denotes time in hours (starting upon exposure to liquid). Line A represents the value of Qv measured in one example for a pore size of 0.002mm, lines B represent Qv measured in two equivalent cases but for a pore size of 0.006mm, lines C represent Qv measured in two equivalent cases but for a pore size of 0.027mm. Also in the same graph, lines D represent the degree of swelling of the 0.002mm pore size permeable material in isolation (without swellable material 44) to verify that no fluid is significantly entrapped in the permeable material.

In Fig. 5, it can be seen that line A (0.002mm pore size) indicates greatest swelling. Lines B (0.006mm pore size) are slightly inferior, and line C (0.027mm) provides least swelling in this test condition.

The reason for the results is still being investigated. Generally it might be expected that a large pore size might provide best access of body fluid components into the swellable material 42, and thus optimum swelling. One reason why a relatively small pore size might provide unexpectedly better results is that, despite the higher resistance of smaller pores, body fluid components might pass initially relatively quickly through the permeable material by virtue of osmosis. Thereafter, the body fluid components may be physically trapped within the sleeve/cuff 42, and thus available to be absorbed by the swellable material 44. This is in contrast to a relatively large pore size that does not obstruct the body fluid components from leaving the interior of the sleeve/cuff 42.

Additionally or alternatively, a further factor may be the small pore size limiting loss of hydrogel particles (even small particles) through the permeable wall, either before or upon swelling.

Various materials may be used for the permeable portion of the sleeve/cuff 42 (or for the sleeve/cuff as a whole). Example materials include polyesters (for example, polyethylene terephthalate or PET), and/or polyaryletherketones (for example, polyether ether ketone or PEEK), and/or polyurethanes (PU), and/or nylon, and/or polyvinylidene difluoride (PVDF). The material may comprise a film, optionally with perforations formed therein (for example, by laser perforation), or a woven or non-woven fabric. The experimental measurements illustrated in Fig. 5 were based on a laser- perforated PEEK membrane material for the sleeve/cuff 42.

A further test using a PVDF membrane with a pore size of about 0.0045mm (45 microns), also exhibited greater swelling factor Qv than values in Fig. 5, although with a thicker membrane material than, for example, PEEK film.

As mentioned above, various materials may be used for the swellable material 44. One further example is poly(ethylene glycol) ("PEG"), for example a PEG hydrogel. Specific PEG examples include PEG-diol ("PEG- OH") (for example, at 3.4kDA and/or 10kDa and/or 20kDa and/or 35 kDa), or PEG-diacrylate ("PEG-DA"; for example, at 10kDa and/or 20kDa and/or 35kDa), or PEG-acrylamide (for example, at 10kDA and/or 20kDa and/or 35kDa), or PEG-diacrylamide (for example, at 10kDA and/or 20kDa and/or 35kDa). A further example is polyacrylic acid ("PAA"). Specific examples include PAA (for example at 1 .8kDa, and/or 500 to 1000kDa), or sodium polyacrylate (for example 170kDa).

In some embodiments, a PEG hydrogel may be of a type not containing (or in which at least a substantial portion or at least the majority does not contain) an ester group and/or ester bond. Avoiding an ester group/bond may reduce a liability of the PEG hydrogel to hydrolysis in the presence of an aqueous medium. In contrast, some PEG hydrogels may, in some cases, undergo slow hydrolysis in the presence of an aqueous medium if the cross-linking moieties contain ester bonds. An example of a PEG hydrogel containing an ester group/bond is PEG-DA. Examples of PEG hydrogel not containing an ester group and/or ester bond may include certain PEG-acrylates. Examples of PEG hydrogel not containing an ester group and/or ester bond may include acrylamide-based PEGs, for example, PEG- acrylamide and PEG-diacrylamide. An acrylamide-based PEG may have very similar swelling characteristics to PEG-DA, except that the acrylamide-based PEG may provide even longer-term stability. PEG-acrylamide or PEG- diacrylamide may be substituted for PEG-DA in all of the examples herein.

An example method of hydrogel production is as follows:

(a) providing a mixture of:

(i) polymer component(s) to be polyermized; (ii) buffer solution (e.g. phosphate buffered saline);

(iii) polymerization initiator (e.g. photoinitiator).

In some embodiments, use of photoinitiation to polymerize the hydrogel may provide the effects of (i) at least partial sterilization of the hydrogel as part of manufacturing process, during irradiation (e.g. UV-light irradiation), and/or (ii) avoiding use of a chemical initiator, which can sometimes result in undesirable residual chemicals remaining within the hydrogel, and which might not be fully compatible with the intended use of the hydrogel within the human blood stream.

In one example, the phosphate buffered saline ("PBS"; for example

150mM or 300mM) is added to a pre-weighed dry polymer powder at the desired concentration (percent weight per volume, %w/v). For example, a 15%w/v concentration is prepared by adding 150mg dry polymer powder to 10ml PBS. A photoinitiator (for example, "Irgacure 2959" from BASF, but many other commercially available photoinitiators are suitable) is added, such that the final concentration of the solution is about 0.1 %w/v.

The solution is mixed (for example, by shaking), and degassed (for example by centrifugation; for example centrifugation for 5 minutes at 2500rpm).

(b) The solution is "shaped" by applying the solution onto or into a desired form that will determine the shape of the hydrogel article. Example forms are discussed further below.

(c) Thereafter, the solution is cross-linked, for example by exposure to suitable radiation to which the photoinitiator is sensitive. In some embodiments, the radiation may be ultra-violet ("UV") radiation. An example light wavelength may be about 365nm. Other wavelengths may be used to suit the absorption characteristics of the photoinitiator that is used. The irradiation power and/or exposure duration may be adjusted according to the size and/or thickness of the article being formed, and/or the radiation transparency of the form used to shape the hydrogel article.

(d) Optionally the hydrogel is dried. For example, the hydrogel may be dried using an air dryer for about 10 minutes.

The material 44 may be provided in film form, for example a self- supporting film as in Fig. 6, or as a coating (optionally filmlike coating) on a substrate 48, as in Fig. 7. Alternatively, the material 44 may be provided in micro-bead form, for example, carried by or between one or more covers 50 as in Fig. 8, or free microbeads captive only within the sleeve 42 as in Fig. 9. Alternatively, the material 44 may be provided in slug-form (e.g. Fig. 10) or plug-form (e.g. Fig. 1 1 ).

By way of example, a film form (e.g. about 30 micron in thickness) may be produced by preparing first and second microscope slides sandwiching a predetermined small quantity of the polymerizable solution. For example, about 250 microlitres of solution may be used and/or the film may have a thickness of about 30 microns. In some embodiments, at least one of the slides may be prepared with polyethylene film. In some embodiments, additionally or alternatively, at least one of the slides may be prepared with a hydrophobic film or coating. For example, the hydrophobic coating may a plastic paraffin film (for example, Parafilm from Pechiney Plastic Packaging Company), or another hydrophobic material. The slides may be exposed to UV-radiation (for example, of about 365 nm wavelength, about 12W nominal power for about 3 minutes). Thereafter, the slides may be separated, and optionally dried.

Also by way of example, a micro-bead form may be produced by loading the polymerizable solution into a pen needle (e.g. of about 30 Gauge). Micro-beads may be dispensed from the pen needle onto a hydrophobic surface (for example, a super-hydrophobic polytetrafluoroethylene sheet) using air pressure, forming micron-sized micro-beads. Cross-linking is achieved by exposure to radiation (for example, about 365 nm wavelength, about 12W nominal power for about 30 seconds). The beads are optionally dried.

Also by way of example, a plug or slug form may be produced by injecting the polymerizable solution into a mold. The mold may, for example, be of silicone. An example dimension for the mold interior is a diameter of about 5mm, and a depth of about 2mm. Cross-linking is achieved by exposure to radiation (for example, about 365 nm wavelength, about 12W nominal power for about 90 seconds). The slug/plug form is optionally dried. It will be appreciated that the foregoing description is merely illustrative of example embodiments of the invention. Many modifications and equivalents may be used within the scope and/or principles of the invention.

Claims

1 . A seal for a stented prosthesis and configured for obstructing para- prosthesis leakage, the seal comprising a hollow sleeve defining a space for first material that swells when contacted by at least a component of body fluid, at least a portion of the sleeve comprising a second material permeable to at least some components of the body fluid.

2. The seal of claim 1 , wherein at least a portion of the second material has a pore-size of less than about 0.005mm, optionally about or less than about 0.004mm, optionally about or less than about 0.003mm, optionally about or less than about 0.002mm, optionally about or less than about 0.001 mm.

3. The seal of claim 1 , wherein at least a portion of the second material has a pore-size of between about 0.005mm and about 0.03mm, optionally between about 0.005mm and about 0.01 mm.

4. The seal of claim 3, wherein at least a portion of the second material has a pore-size of about or at least about 0.006mm, or optionally about or at least about 0.007mm, or about or greater than about 0.008mm, or about or at least about 0.009mm, or about or at least about 0.01 mm.

5. The seal of claim 4, wherein the pore size is not greater than about 0.01 mm.

6. The seal of any preceding claim, wherein the second material comprises one or more selected from: polyester; polyethylene; polyethylene terephthalate; polyaryletherketone; polyether ether ketone; polyurethane; nylon; and/or polyvinylidene difluoride.

7. The seal of any preceding claim, wherein the second material comprises at least one selected from: polyethylene terephthalate; polyether ether ketone.

8. The seal of any preceding claim, wherein the second material comprises at least one selected from: film; fabric.

9. The seal of any preceding claim, wherein the first material comprises poly(ethylene glycol) hydrogel without an ester-bond and/or without an ester group.

10. The seal of any preceding claim, wherein the first material comprises poly(ethylene glycol)-acrylate without an ester-bond and/or without an ester group.

1 1 . The seal of any preceding claim, wherein the first material comprises acrylamide-based poly(ethylene glycol).

12. The seal of any preceding claim, wherein the first material comprises one or more selected from: poly(ethylene glycol) (PEG); poly(ethylene glycol)- acrylate; poly(ethylene glycol)-diol (PEG-OH); poly(ethylene glycol)-diacrylate (PEG-diacrylate); poly(ethylene glycol)-acrylamide (PEG-acrylamide); poly(ethylene glycol)-diacrylamide (PEG-diacrylamide).

13. The seal of any preceding claim, wherein the first material comprises one or more selected from: poly(acrylic acid); sodium polyacrylate; polyacrylate; polyacrylamide; polyacrylamide copolymer; poly(ethylene oxide); poly(propylene oxide); polyvinyl alcohol); polyvinyl pyrrol idinone; poly(hydroxyl ethyl methacrylate); poly (amino acids), Dextran; polysaccharides; ethylene maleic anhydride copolymer; carboxy-methyl- cellulose polyvinyl alcohol copolymers, polyacrylonitrile.

14. The seal of any preceding claim, wherein the first material is provided in the form of: a film; and/or mirco-beads.

15. A stent-valve comprising a stent component supporting a plurality of leaflets defining a prosthetic valve, the stent-valve further comprising a seal as defined in any preceding claim.

16. A kit comprising a seal as defined in any of claims 1 to 14, and a stent- valve, the stent-valve comprising a stent component supporting a plurality of leaflets defining a prosthetic valve.

17. The kit according to claim 16, wherein the seal is fittable to the stent- valve prior to implantation in a body.

18. A sleeve for a seal for a stented prosthesis, the sleeve configured for containing first material that swells when contacted by at least a component of body fluid, at least a portion of the member comprising a second material permeable to at least some components of the body fluid.

19. The sleeve of claim 18, wherein the second material has a pore-size of less than about 0.005mm, optionally about or less than about 0.004mm, optionally about or less than about 0.003mm, optionally about or less than about 0.002mm, optionally about or less than about 0.001 mm.