GB2046165A

GB2046165A - Shaping Biomaterial

Info

Publication number: GB2046165A
Application number: GB7912721A
Authority: GB
Original assignee: Individual
Current assignee: Individual
Priority date: 1979-04-11
Filing date: 1979-04-11
Publication date: 1980-11-12
Also published as: GB2046165B

Abstract

A method of shaping biomaterial in which, during treatment with a chemical treatment fluid, it is constrained by shaping forces, to provide ease and permanence of shaping. In the preferred application a cusped valve (1) of biomaterial mounted on an approximately matching stent (2) is treated with a fixative liquid (17) to fix the biomaterial of the valve (1), the valve (1) being subjected, during the treatment with fluid (17) to forces such as to constrain its biomaterial to remove dimensional inaccuracies in the valve, (e.g. fit of the valve on its stent and/or shape of the valve cusps), preferably while holding the valve in its closed condition. The valve can be a natural valve or one fabricated from biomaterial. The containing forces can be applied hydrostatically or by means of dies, for example. <IMAGE>

Description

SPECIFICATION Shaping Biomaterial This invention relates to a method of shaping biomaterial and to the product of such a method, and is especially, although not exclusively, concerned with a method of making a stemtmounted replacement cardiac valve, which method involves shaping of biomaterial, as well as valves obtained thereby.

Replacement cardiac valves for human beings have now been in use for several years.

The replacement valve may either be entirely of synthetic materials, or may comprise a cusped valve of natural tissue. In the latter case, the natural tissue valve is usually mounted on a support structure which is known as a stent, and which generally comprises a metal or plastics material structure having a cloth covering. The valve formed of natural tissue may be a natural cusped valve (e.g. an aortic or pulmonary valve) of human or animal origin; or alternatively it may be a valve which has been fabricated, to have a shape similar to that of a natural cusped valve, from tissue from a human being or other animal.

however, it has proved very difficult to fabricate an efficiently sealing cusped valve from animal tissue.

Great effort has been devoted to developing the shape of valve stents, with a view to making the shape such that it will cause the least possible change in the morphological shape of the valve when it is mounted on the stent, because any distortion of the original shape will adversely affect the ability of the cusps of the valve to seal against each other, and can make the valve grossly incompetent. It will be appreciated that where the valve is fabricated from animal tissue it is very difficult to make the valve accurately to predetermined dimensions, so that it will exactly fit a given valve stent.Also, as no two natural valves of a given type (aotic, pulmonary, etc.) are of identical geometrical configuration (in much the same way as no two human faces are of identical configuration), it will be appreciated that the problem of suitably matching natural valves to stents is also an extremely difficult one.

The present invention provides, in its broadest aspect, a method of shaping biomaterial, the method comprising treating biomaterial with a chemical treatment fluid, the biomaterial being subjected, during the treatment with chemical treatment fluid, to forces such as to constrain the biomaterial into the required shape. We have found that applying the forces during the treatment with chemical treatment fluid can enable one to provide a surprising amount of shaping (both stretching and contraction) of the biomaterial, and furthermore that after the treatment the applied shape can be retained to a surprising degree.

The biomaterial may, for example, be tissue (e.g. skin or pericardium) from a human being or other animal.

Especially good results can be obtained when the chemical treatment fluid is a fixative fluid which fixes the biomaterial; the fixative fluid may be a liquid, for example a fixative liquid comprising glutaraldehyde; and we prefer that the fixative fluid should be circulated during the fixing treatment. In accordance with this embodiment, any fixing of the biomaterial prior to the application of said forces should have been incomplete. However, we prefer that the biomaterial should be substantially unfixed prior to the application of said forces; we have found that this enables maximum shaping of the biomaterial to be obtained.

In accordance with the presently preferred application, the method of the invention is a method of making a stent-mounted replacement cardiac valve and comprises providing a cusped valve of biomaterial mounted on an approximately matching valve stent, and treating the mounted valve with the chemical treatment fluid, the valve being subjected, during the treatment with said fluid, to forces such as to constrain the biomaterial of the valve to remove dimensional inaccuracies in the valve. Preferably the valve is held in its closed condition during the application of said forces.Thus, we have made the surprising discovery that it is possible in accordance with this aspect of the invention to remove dimensional inaccuracies in the valve especially as regards its fit on the valve stent and/or the shape of the valve cusps) while at the same time not substantially detracting from the ability of the vaive cusps to effect the required seal, if chemical treatment such as fixing of the biomaterial of the valve is carried out while the valve is mounted on the stent, forces being applied to the valve so as to produce the required shaping while holding the valve in its closed condition.

We have found that where the valve is a natural one, a convenient procedure for applying said forces to the stent-mounted valve is to arrange that there is a constant pressure drop in said fluid across the valve from its outlet side to its inlet side. By this procedure the natural valve can be forced into intimate contact with the stent while at the same time keeping the cusps in their closed condition so that their sealing ability will not be lost. The pressure drop may be between 5 and 200 mm of Hg, and preferably is between 80 and 120 mm of Hg.

In an alternative procedure the cusped valve may be fabricated from biomaterial such as animal tissue (e.g. skin or pericardium), and this may be done by mounting a piece of the biomaterial about the periphery of a suitably shaped valve stent so that the peripheral portions of the biomaterial at the outlet end of the valve can come together to form the closure cusps of the valve. When fabricating a valve in this manner, not only is it virtually impossible to make the valve fit the stent exactly, but also the cusps in practice always contain at least some dimensional inaccuracies such as wrinkles and areas which require to be stretched. It will be appreciated that such inaccuracies interfere with the movement and sealing of the cusps.In accordance with the invention, application of forces during the chemical treatment of the biomaterial of the stent-mounted fabricated valve can constrain the biomaterial to remove such inaccuracies as well as to improve the fit of the valve to its stent. A preferred method of applying the forces in this embodiment is to arrange that the cusped valve is sandwiched, in its closed condition, between a pair of complementary dies.

Alternatively, the forces may be applied by holding the cusped valve against a mould surface, for example by with drawing ambient fluid (normally air) through the mould surface (e.g. by a vacuum moulding technique).

In order that the invention be more fully understood, some preferred embodiments in accordance therewith will now be described with reference to the accompanying drawings, wherein: Figure 1 is a diagrammatic perspective view of an unfixed natural cusped valve mounted on a valve stent; Figure 2 is a diagrammatic. partially sectional view of the mounted valve of Figure 1 being subjected, in accordance with the invention, to pressure while being treated with a chemical fixative fluid; and Figure 3 is a diagrammatic perspective view of a cusped valve which has been fabricated from animal tissue, mounted on a stent, and ready to be sandwiched between a pair of complementary dies.

We will first describe, with reference to Figures 1 and 2 of the drawings, a method, in accordance with the invention, of making a replacement cardiac valve using a natural cusped valve, e.g. an aortic valve from a pig. A stent is selected to match the valve as closely as possible, and the valve, which initially includes the aortic root, is dissected to match the outline shape of the stent and is mounted on the stent by positioning it within the lumen of the stent and attaching it to the stent by suturing. This stage is illustrated in Figure 1, which shows the valve 1 mounted on the stent 2.The stent 2 is a cloth-covered metal or plastics structure, and has three cusp supporting members 3, 4 and 5 and a suture ring 6, and the dissected valve 1 comprises cusps 7, 8 and 9 (shown in their closed position), the valve 1 being attached to the stent 2 by sutures 10 along the outlet periphery of the valve and by additional sutures along its inlet periphery, the latter sutures not being visible in the drawing. It should be noted that at this stage the tissue of the valve 1 is not completely fixed (and may, in fact, be unfixed).

Next, the stent 2, together with the valve 1, is mounted in the apparatus shown in Figure 2. The apparatus comprises a generally cylindrical open ended chamber 11, the stent-mounted valve being mounted within the chamber 11, so as to substantially to seal the lower open end as schematically indicated at 12. The chamber 11 terminates at its lower end within an open ~container 13, and is provided at its upper end with a header tank 14. A duct 15 communicates between the interiors of the container 13 and the header tank 14, and a duct 16 communicates between the interior of the container 1 3 and the interior of the chamber 11, terminating in the latter adjacent to the outlet side of the valve 1.

Chamber 11, container 13, header tank 14 and ducts 15 and 16 contain a chemical fixative liquid 17, and the duct 16 includes in its length a suitable pump (e.g. a roller pump), indicated at 18, which, when steady state flow conditions are reached, pumps liquid 17 from the container 13 through the duct 16 to a position within chamber 11 adjacent to the outlet end of the valve 1, displacing extra liquid 1 7 into the header tank 14, whence liquid 17 flows under gravity through duct 15 into the container 13, and then through the body of liquid within the container 13 to the intake end of the duct 1 6. Thus it will be seen that the liquid 17 is kept in constant circulation past the inlet and outlet sides of the valve 1.

It will also be seen that the pressure of the liquid 1 7 at the outlet side of the valve 1 is substantially greater than at the inlet side, so that there is a substantial pressure drop in the fixative liquid 17 across the valve 1 from its outlet side to its inlet side. This pressure drop is preferably about 100 mm Hg. We have found that after seven days' treatment in the apparatus shown in Figure 2, the tissue of valve 1 becomes fixed and permanently moulded into a good fit on the stent 2, without adversely affecting the ability of the cusps 3, 4 and 5 to provide the required seal.

A second embodiment of the invention will now be described, with reference to Figure 3. In this embodiment, the cusped valve is formed from a substantially rectangular piece of unfixed biological material, e.g. pericardium, which is cut to suit a valve stent 23 which, like the stent 2 employed in the previous embodiment, is a cloth covered metal or plastics structure, and has three cusp-supporting members 24, 25 and 26, and a suture ring 27. The piece of biomaterial 26 is mounted around the outer (or, alternatively, the inner) periphery of the cusp-supporting members 24, 25 and 26, so that its ends meet and overlap slightly at one of the cusp-supporting members, in this case member 26. The biomaterial (now in generally tubular form) is then attached to the stent by means of a line of sutures 29a running up the centre of the outer surface of the cuspsupporting member 24, a similar line of sutures 29b on the cusp-supporting member 26 (the latter line serving also to join the aforementioned ends of the biomaterial), and a further similar line (not shown) on the cusp-supporting member 25, and a line of sutures 30 around the base of the biomaterial 28.The outline shapes of the cuspsupporting members 24. 25 and 26 are such that when the three lengths of biomaterial between the three members 24, 25 and 26 are subjected to pressure such as would allow reverse flow of fluid through the valve (i.e. in the general direction from the top right hand corner to the bottom left hand corner in Fig 3), the three lengths come together to the position shown in Fig. 3, and thus form the three valve cusps; these cusps are shown at 32, 33 and 34 in Fig. 3. At this stage they are generally spherical, but are inexactly formed, and have several wrinkles, as indicated diagrammatically at 35.

In order to perform this embodiment of the invention, two dies are required, and these are indicated at 36 and 37. Die 36 has a male mould surface 38 comprising three areas 38a, 38b and 38c having the final, generally spherical, shape required for cusps 32. 33 and 34. Die 37 has a female mould surface 39 which is complementary to surface 38. Suitable dies are disclosed in U.S.

Patent Specification No. 3,655,306.

The dies 36 and 37 are clamped together so as to sandwich the stent-mounted biomaterial valve between them at a pressure similar to that employed in the previous embodiment, and the resulting assembly is immersed in a chemical fixative liquid comprising glutaraldehyde. The fixative liquid is preferably gently agitated to produce circulation about the pericardium tissue.

After about seven days, the assembly is removed from the fixative liquid and the dies 36 and 37 are unclamped from the stent-mounted valve. It is found that the biomaterial 28 has been moulded and fixed so that the valve formed from it is a good fit on the stent 23 and its cusps 32, 33 and 34 are wrinkle-free and form a good seal in the closed position.

Claims

1. A method of shaping biomaterial, the method comprising treating biomaterial with a chemical treatment fluid, the biomaterial being subjected, during the treatment with chemical treatment fluid, to forces such as to constrain the biomaterial into the required shape.

2. A method according to claim 1, wherein said biomaterial is animal tissue.

3. A method, according to claim 1 or claim 2 wherein said chemical treatment fluid is a fixative fluid which fixes said biomaterial.

4. A method according to claim 3, wherein said biomaterial is substantially unfixed prior to the application of said forces.

5. A method according to claim 3 or claim 4, wherein said fixative fluid is a liquid.

6. A method according to claim 5, wherein said fixative fluid comprises glutaraldehyde.

7. A method according to any one of claims 1 to 6, wherein said fluid is circulated during said treatment.

8. A method according to any one of claims 1 to 6, the method being a method of making a stent-mounted replacement cardiac valve, and comprising providing a cusped valve of biomaterial mounted on an approximately matching valve stent, and treating the mounted valve with the chemical treatment fluid, the valve being subjected, during the treatment with said fluid, to forces such as to constrain the biomaterial of the valve to remove dimensional inaccuracies in the valve.

9. A method according to claim 8, wherein said valve is held in its closed condition during the application of said forces.

10. A method according to claim 8 or claim 9, wherein said valve is a natural one, and said forces are applied by arranging that there is pressure drop in said fluid across the valve from its outlet side to its inlet side.

11. A method according to claim 10, wherein said pressure drop is between 5 and 200 mm of Hg.

12. A method according to claim 11, wherein said pressure drop is between 80 and 120 mm of Hg.

13. A method according to claim 8 or claim 9 wherein said cusped valve is formed of a piece of biomaterial mounted about the periphery of a suitably shaped stent so that the peripheral portions of the biomaterial at the outlet end of thevalve can come together to form the closure cusps of the valve.

14. A method according to claim 13, wherein said biomaterial is animal tissue.

15. A method according to claim 14, wherein said animal tissue is skin.

16. A method according to claim 14, wherein said animal tissue is pericardium.

17. A method according to any one of claims 13 to 16, wherein said forces are applied by arranging that said cusped valve is sandwiched, in its closed condition, between a pair of complementary dies.

18. A method according to any one of claims 13 to 16, wherein said forces are applied by holding said cusped valve against a mould surface.

19. A method according to claim 18, wherein said cusped valve is held against said mould surface by withdrawing the ambient fluid through the mould surface.

20. A method of making a stent-mounted replacement cardiac valve, the method being substantially as hereinbefore described with reference to Figures 1 and 2 of the accompanying drawings.

21. A method of making a stent-mounted replacement cardiac valve, the method being substantially as hereinbefore described with reference to Figure 3 of the accompanying drawings.

22. A stent-mounted replacement cardiac valve whenever made by a method according to any one of claims 1 to 21.

23. Each and every novel invention hereinbefore disclosed.