NL1008349C2 - Mandrel for making stented or stentless heart valve comprising a fibre reinforced composite material - Google Patents

Abstract

The mandrel comprises a cylindrical lower mandrel half-section with at least three sloping surfaces at its top end, and a cylindrical upper mandrel half-section containing a cavity with sloping side walls in its bottom end, the angles of these side walls corresponding to the angles of the sloping surfaces at the top end of the lower mandrel half-section. The bottom end of the upper mandrel half-section is provided with protuberances extending in the circumferential direction, the number and positions of which correspond to the cavity side walls. A mandrel used for making a synthetic, fibre-reinforced heart valve comprises an essentially cylindrical lower mandrel half-section with at least three sloping surfaces at its top end, and an essentially cylindrical upper mandrel half-section containing a cavity with sloping side walls in its bottom end, the angles of these side walls corresponding to the angles of the sloping surfaces at the top end of the lower mandrel half-section. The bottom end of the upper mandrel half-section is provided with protuberances extending in the circumferential direction, the number and positions of which correspond to the cavity side walls. Independent claims are also included for (a) two methods for making a synthetic, fibre-reinforced stentless heart valve using this mandrel, (b) a method for making a synthetic, fibre-reinforced stented heart valve using this mandrel, and (c) a synthetic, fibre-reinforced stentless heart valve comprising an essentially cylindrical tube with outwards protruding parts and leaflets on the inner wall, the leaflets containing reinforcing fibres (42) that extend into the tube material.

Description

98.5036 / OGR

Title: Mold and method for manufacturing a synthetic heart valve

The present invention generally relates to a synthetic unidirectional valve that is useful in applications where a fluid flows through a conduit. In particular, the present invention relates to such a valve which is intended to be implanted in a blood vessel. An important application of such a valve is as a replacement for a human aortic heart valve, for which reason the present invention will be explained in more detail hereinafter specifically for this application example. It is emphatically noted, however, that the principles of the present invention can also be applied in a different field of application, whereby the design of the valve may then have to be adapted to the relevant application.

As is known, blood is pumped through the heart into the aorta, during a cycle that has a first stage in which the heart fills with blood, and a second stage in which the heart squeezes to pump blood into the aorta. To prevent this blood from flowing back from the aorta to the heart in the next heart filling phase, a one-way valve is located at the entrance to the aorta. The construction of the natural heart valve is as follows. Three flexible membranes facing each other are attached to the aortic wall and are designated "leaflet". These leaflets can work together to close the valve. At each leaflet 25, the aortic wall has an outward bulge called the "Valsalva sinus". The valve is opened by blood with relatively high pressure in the heart, and closes when the pressure in the heart drops to a certain degree relative to the pressure in the sinus cavities behind the leaflets.

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When the valve is not functioning properly, the body is not properly supplied with blood. If the valve does not open properly, it will allow little blood to pass through, and it will take a lot of effort from the heart to push the blood through this valve. If the valve does not close properly, a lot of blood flows back to the heart! in, implying that the blood supply from the heart i is very inefficient. Causes of such failure can be, for example, a deposit of lime and / or cholesterol. In such cases it may be desirable or even necessary to replace the valve with a prosthesis.

Three different types of valve types have been developed - which can serve to replace the aortic valve: the mechanical 1: valve prosthesis, the biological valve prosthesis, and the - synthetic valve.

Mechanical valve prostheses are commercially available.

Typically, they comprise one or two movable disc or discs mounted relative to a valve seat, which abut or close in the closed position. lying on that seat. With mechanical 7): I valves, some major drawbacks are associated. Even in the fully opened state they cause a significant pressure drop, resulting in an excessive load on the heart. Furthermore, the mechanical cooperation between valve disc --- h and valve seat will cause damage to the red blood cells and blood ..... rz .. ..jj platelets, including resulting in hemolysis. The siV 25 main drawback, however, is that of mechanical valve prostheses. - "have a tendency to cause thrombosis, so that a patient equipped with a mechanical valve prosthesis will have to take anti-clotting medications for a lifetime.

::: iz Biological valve prostheses are typically made from 30 pig heart valves or from bovine pericardium. Their - -f - shape is very similar to the shape of the human heart valve, and the flow behavior of the blood flow also better matches the natural flow. There are two types: biological valve prostheses, which are referred to as "stented" and "stentless", respectively. With a stented valve 1 "TTSfj - * Γ ..... MIIEL .. _ 3, the three leaflets are attached to a rigid ring (the" stent "), which also serves to attach the prosthesis to the aortic wall. a stentless valve utilizes the three leaflets including a portion of the aorta where they are attached to 5. An important advantage of a stentless valve over a stented valve is that the flexible aortic wall can move when opening / closing. the valve, which allows the leaflets to transmit their load to the aorta in a more natural way and make them less susceptible to bending stress.

A drawback of a biological valve prosthesis is that in practice the life of such valves appears to be limited due to the occurrence of calcification and cracks in areas of the valve where high mechanical stresses occur. More recently, synthetic valves have been developed and researched. The shape of a synthetic valve corresponds to the natural shape of the heart valve, so that the flow behavior corresponds to the natural flow behavior, but the material is non-biological, so that rejection phenomena are avoided. Furthermore, an advantage of synthetic valves is that they have a greater freedom of design when tailoring such valves. In clinical practice, synthetic valves are already used, for example as part of a mechanical blood pump of a heart-lung machine / these have hitherto only been stented synthetic polyurethane valves. Stentless synthetic valves are being researched on a laboratory scale, but are not yet applied in practice. As a valve prosthesis in a human, synthetic valves have not hitherto been put into practice. The question of whether or not synthetic valves will prove successful as a prosthesis in a human depends largely on the strength and life of the leaflets. The leaflets of synthetic valves are made in the form of a plastic fleece. It has been found that the life of a synthetic leaflet can be extended considerably by applying reinforcing fibers therein.

It is therefore desirable to provide a method by which fibers can be introduced into the valve in a predefined manner, and in particular into the leaflets of the valve.

Furthermore, it is desirable to provide a relatively simple method of manufacturing a stentless synthetic valve prosthesis, which makes it simple to give the valve, and in particular its leaflets, a predetermined desired shape.

An important object of the present invention is furthermore to provide a stentless synthetic valve with improved strength properties.

Another important object of the present invention is to provide an improved method of manufacturing synthetic stented or stentless valves.

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These and other aspects, features and benefits of the; The present invention will be further elucidated by: the following description with reference to the drawing, in which like reference numerals denote like or similar parts, and wherein:; Figures 1A-B illustrate the operation of a heart valve; : figure 2A schematically shows a perspective view of a "; ~ 25 synthetic stented valve;! =» «= 1¾ figure 2B schematically shows a longitudinal section of the synthetic: stented valve of figure 2A in the opened position;; figure 2C schematically shows a longitudinal "f - cross-section comparable with figure 2B of a variant of the valve of figure 2A; . Hyy the figures 3A-B schematically illustrate a device for the. manufacture of a synthetic valve; ....... ". Figures 4A-C illustrate different possible patterns of a fiber reinforcement; Figure 5 schematically shows a longitudinal section of a" gS 35 synthetic stentless valve; f

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: Figuur Figure 6 schematically shows a perspective view of a first mold for manufacturing a stentless valve; Figures 7A-C schematically illustrate different stages of use of the mold of Figure 6; Figures 8A-B schematically show a perspective view and a longitudinal section, respectively, of a second mold for manufacturing a stentless valve; Figures 9A-C schematically illustrate a preferred use of the mold of Figure 8.

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The construction of a natural heart valve 10 will now be discussed with reference to Figures 1A-B to explain its operation. Figure 1A schematically shows a perspective view of a cut-away portion of an aorta 15 with a valve 10, and Figure 1B schematically shows a longitudinal section thereof. The flow direction of blood is indicated by an arrow P. Three inner leaflets 3, which are generally in the form of a bag, are attached to the inner wall of the aorta 1 in the circumferential direction. At the location of the location of each leaflet 3, the aorta 1 has a bulge 2. Between these bulges 2 and the respective leaflets 3, respective spaces 4 are defined, which are referred to as "Valsalva sinus". These spaces are important for the proper functioning of the valve 10. When the heart (not shown for simplicity) squeezes to push blood into the aorta 1, the leaflets 3 diverge toward the wall of the valve. aorta 1, as indicated in the left half of Figure 1B; the valve 10 is then "open". When blood flow decreases at the end of a heartbeat-30 cycle, the flow pattern of the blood in the sinuses 4 will push the leaflets 3 off the aortic wall, so that the leaflets 3 touch each other to prevent backflow of blood, as indicated in the right half of figure 1B and in figure IA.

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Referring now to Figures 2-4, a description will be given of a method of manufacturing a synthetic valve 20 of the "stented" type.

Figure 2A schematically shows a perspective view of a synthetic stented valve 20, and Figure 2B schematically shows a longitudinal section of said valve 20. The stented valve: 20 comprises a rigid support ring 21 with a substantially circular round contour. The support ring 21 has a substantially flat bottom edge 22 and a top edge 23 with a corrugated contour, F defining three upwardly facing support posts 24, y the top edge 23 between two adjacent J support posts 24 having a substantially U-shaped contour has. Two adjacent support posts 24 and the U-shaped top edge portion 23 situated therebetween are one; flexible fleece ("leaflet") 25 attached. The dimensions of each! leaflet 25 are such that the free top edges 26 of the leaflets 25 can touch to define the closed state of the valve 20.

: π 20 Commercially available stented valves 20 are made of polyurethane, usually by dip-casting technique. Thereby, a prefabricated support ring 21 made of a plastic material is placed in a mold which is immersed in a polyurethane solution.

:; The mold is then dried in an oven. Alternatively, a polyurethane film can be cut to size to form separate leaflets i ...... i_z 25, which are then attached to the support ring 21.

- ~ l = Although these valves function well in themselves, they are; life too short, and there is a need for valves with an improved life. A stented valve according to the present. The invention has been improved in that it is provided with reinforcement. ; had fibers with a well-defined layout (pattern). The: ur :; Figures 3A-B schematically illustrate a method and an apparatus 30 for manufacturing such a fiber-reinforced stented valve according to the present invention. A 5 'ntgcrij

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r ~ vmmm · ". Support ring 21 is mounted on a substantially cylindrical mold 31, which is rotatably mounted in a subframe 32, which is tiltably disposed relative to a gutter-shaped reservoir 33, in which there is a quantity of plastic material 34 in solution, which hereinafter also referred to as "matrix material". As will be discussed in more detail later, the matrix material is preferably an EPDM rubber.

In order to apply a layer of the matrix material 34 to the mold 31 and to the supporting ring 21 placed thereon, the subframe 32 is tilted downwards around the mold 31 with the supporting ring 21 mounted thereon at least partly in the solution of the matrix material 34 (dotted position in Figure 3A), where the mold 31 is rotated about its longitudinal axis, driven by a motor 35. A layer of matrix material 34 is deposited on the support ring 21, and on surface parts of the mold 31 between the support posts 24 of the support ring 21 to form the leaflets 25. Then the subframe 32 is tilted up again to lift the mold 31 out of the bath 33 20, in order to allow the newly deposited layer of material 34 to dry. During this drying process, it is preferable to rotate the mold 31 to ensure a uniform thickness of the layer 34.

When the newly formed layer is dry, the above-mentioned process can be repeated to apply another layer to the previous one. The application of layers of matrix material is repeated until the layers together have reached a desired thickness. It has been found that four dipping steps are sufficient to achieve four layers with a joint thickness of 0.2 mm, which offers a good compromise between bending stresses and stiffness.

A fiber winding mechanism 40 is arranged next to the trough-shaped material bath 33. The fiber winding mechanism 40 comprises a supply spool 41 rotatably disposed about its longitudinal axis, with a continuous fiber 42 of sufficient length 8 wound thereon. The free end (not shown for simplicity) of the fiber 42 is attached to the mold 31 and / or (to the support ring 21 mounted thereon so that the fiber 42 is pulled off the mold 31 when the mold 31 is rotated. coils 41 and: 5 are wound around the mold 31 and the supporting ring 21 placed thereon. A guide 43 determines the axial position relative to the mold 31 where the fiber 42 is applied. The guide 43, which can for instance be designed as a needle with one eye, is movable along the axis of rotation of the = 31 jig 31, as indicated by the arrow P2 in Figure 3B, ™ for example, because the guide 43 is mounted on a spindle block 45 cooperating with a spindle 44. The spindle 44 " Ί is driven by a motor 46, which is controlled by

Is a programmable controller 47, such as, for example, a * i -..... | 15 computer or a microprocessor. The displacement mechanism for the guiding guide 43 n, formed in the illustrated = 4 by the motor 46 and spindle mechanism 44, 45, is controlled by the control member 47 such that the fiber 42 is wound on the valve 20 in a predetermined, k 20 desired pattern. Since the manner in which the controller 47 controls said displacement mechanism is not the subject of the present invention, while this will be sufficiently clear to one skilled in the art, this will not be explained in more detail here.

........ rt 25 The winding of the fiber 42 on the mold 31 and the supporting ring 21 7 "placed thereon takes place after first one or more layers of matrix material 34 have been applied with the above =====. Dipping procedure discussed The fiber 42 will then stick or stick to the previously applied layer of matrix material during winding, thereby fixing the desired pattern of the fiber = 42. To ensure good adhesion ..... Between the fiber 42 and the matrix material 34, the fiber - 42, is preferably wetted shortly before being wound: "f® ?! with a highly diluted matrix solution. This wetting solution should have a viscosity that is significantly lower fife i i''H. ^ 9 is then the viscosity of the matrix solution used for immersion in the bath 33; preferably the viscosity of the wetting solution is at least a factor 10 lower than that of the bath 33. It is also possible that the fiber 42 is wetted with pure solvent without matrix material.

It is desirable to press fiber 42 well into the underlying matrix material. For this purpose, and as shown, pressure means are preferably provided, which in the example shown are formed by a rotatable pressure cylinder 48 disposed adjacent to the rotating mold 31, which resilient biasing means (not shown for the sake of simplicity) on the fiber 42 exerts a pressing force in the direction of the mold 31.

After applying the fiber 42, in a layer which can comprise several turns, one or more layers of matrix material 34 can again be applied. Optionally, a layer of fiber material can then be applied again, and then again one or more layers of matrix material 34, etc. The valve is thus given a sandwich structure with one or more 20 layer-reinforced layers sandwiched between fiber-free layers, to ensure that only the matrix material in comes into contact with blood and tissue.

When the outer layer is dry, the molded product can be removed from the mold 31. After any post-processing 25 for tailoring the leaflets 25, the molded product is ready to be implanted as a stented valve prosthesis in, for example, an aorta.

A suitable material for the mold 31 is stainless steel. In order to be able to take it off from the mold 31 when the valve 20 is ready, the surface of the mold 31 has been treated with a suitable release agent, such as, for example, Teflon, to be non-adhesive for the material 34 used.

A suitable material for the pressure cylinder 48 is stainless steel. To prevent the pressure cylinder 48 from adhering to matrix material and / or fiber material, the surface of the pressure cylinder 48 has also been treated with, for example, Teflon.

A suitable material for the support ring 21 is plastic, or a metal such as, for example, stainless steel.

As mentioned, the control computer 47 is arranged to drive the guide conductor 43 such that the fiber 42 is applied in a predetermined pattern. Several patterns are possible, as illustrated in Figures 4A-C. These figures show a perspective view of different patterns, the shape of the support ring 21 being drawn.

~ The spatial dimensions are given in mm along the axes. Figure 4A illustrates a unidirectional pattern, the fiber 42 being arranged essentially in the form of adjacent circles (or, more accurately, a small pitch helix) so that at each point of the valve 20 the reinforcing fibers are are directed substantially tangentially with

- relative to the axis of rotation of the mold 31. Figure 4B

illustrates a substantially sinusoidal zigzag pattern, π in which the successive fiber windings intersect, so that the reinforcement fibers = j are oriented in multiple orientations substantially at each point of the valve 20. Figure 4C shows an AT! Leaflet oriented wave pattern with the tips and troughs of the successive windings aligned with each other and with the leaflets so that the fiber windings are symmetrical with respect to the leaflets and meet at the top ends of the the support posts 24 to appropriately transfer the forces occurring in the leaflets to the attachment points of the leaflets.

A: The sine pattern of Figure 4B has the advantage that the fiber 42 forms a network which gives the composite (matrix plus fiber reinforcement) substantially homogeneous strength properties in axial and tangential direction. This will prevent propagation of any cracks in the leaflets.

; A drawback, however, is that the voltage drop is less than 35 in a unidirectional pattern.

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The cartridges of Figures 4A and 4C provide good reinforcement against circumferential load. The pattern of figure 4C offers the advantage over the unidirectional pattern of figure 4C, that the flexibility of the 5 leaflets is slightly better.

However, when loaded in the axial direction, the fiber hardly contributes to increased strength in the cartridges of Figures 4A and 4C. It is therefore recommended to combine such a pattern with another pattern. This can be achieved according to the present invention by applying successive layers of a fiber reinforcement, the control computer 47 being programmed to apply the different fiber reinforcement layers according to different patterns. In particular, a combination of the sine pattern of Figure 4B with the leaflet-oriented wave pattern of Figure 4C appears to offer good strength properties. However, it has been found that with such a combination the stiffness of the leaflets 25 becomes rather high. The present invention therefore proposes, instead of using a winding according to the sine pattern of Figure 4B, to apply a layer of matrix material which is provided with a large number of relatively short pieces of fiber 42, which fiber pieces in the matrix material have a random orientation, whereby a reasonably homogeneous reinforcement in axial and tangential direction is achieved, without unacceptably reducing the flexibility of the leaflets. According to the present invention this can be achieved in a relatively simple manner by adding a certain amount of such fiber pieces 30, with an appropriate concentration, to the liquid matrix material 34 in the matrix bath 33.

In an experiment, favorable results were obtained with nylon fiber pieces about 6 mm long and about 0.02 mm thick. However, other suitable materials and dimensions are also possible.

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In principle, it would suffice to provide fiber reinforcement solely on the basis of fiber pieces added to the matrix solution. This would then have the advantage that the parts discussed above; 5 41 to 48 can be omitted for the application of a continuous fiber winding. On the other hand, short fiber pieces are less efficient as reinforcement than continuous fibers, and the fiber ends form locations for crack initiation.

As already mentioned, commercially available synthetic stented valves are made of polyurethane. However, according to the present invention, a matrix material is preferably a rubber, preferably an ethylene-propylene-diene monomer (EPDM) rubber. In a successful experiment, a commercially available EPDM rubber with the following composition was used: 55% ethylene, 40.5% propylene, 4.5% dicyclopentadiene (DCPD). This material rj was found to have a Young's modulus of about 1.5 HPa.

1.1. To prepare a bath 33 with a liquid matrix material, a solution was prepared of 30 g of -% the said EPDM rubber in 400 g of xylene (C0H4 (CH3) -). To an i; solution to obtain a uniform viscosity, the '? solution mixed at a temperature of about 80 ° C for about 12 hours. After cooling to room temperature, 25 dibenzoyl peroxide was added to act as a crosslinker. 1 wt% was found to be sufficient. It will be understood, however, that other materials can be used as a crosslinker.

A fiber material which has proved to be very suitable in combination with the said EPDM rubber is high-performance polyethylene fiber (HP-PE). This fiber has, among other things, a high -... longitudinal Young's modulus and a low density. In a successful experiment, an HP-PE fiber was used with tfSj about 0.06 mm thick and a Young's modulus of about 30 GPa. For a further discussion of processes for F rm * "T * TSb | ΚΊ ·) || r 'mmm 13 the manufacture of such a fiber, see Ton Peijs," High-performance Polyethylene Fibers in Structural Composites ", thesis of the Technical University Eindhoven, 1993.

After a desired number of layers of matrix material have been deposited on the mold 31, depending on the nature of the matrix material used, the matrix material must be fixed in the obtained shape before the manufactured product can be removed from the mold. In said preferred example wherein the matrix material is a rubber, the rubber must be vulcanized. To this end, the mold 31 was placed in an oven and kept at a temperature of about 120 ° C for about 2-3 hours.

In the procedure discussed above, in which the mold 31 has a substantially cylindrical shape, a valve 20 is obtained with a configuration which is also substantially cylindrical, that is to say that in the tension-free state the leaflets 25 are oriented essentially along the cylinder jacket of the mold 31 used, so that the valve is completely open in that stress-free state (see Figure 2B). With such a valve, however, there is a fairly high tendency for blood to flow back. In order to reduce that tendency, it is preferable to make the valve 20 such that it is partially or preferably even completely closed in the tension-free rest position. To this end, the mold 31 could be given a shape that corresponds to the desired rest position of the leaflets 25. For minor deviations from the fully open position this is still possible, although the winding process becomes complicated because it becomes difficult or even impossible. to press the fiber 42 with a pressure cylinder 48. However, it is not possible to make a valve in this way with an (almost) completely closed rest position.

The present invention also offers a solution to this problem. According to the present invention, a stented 14 valve is manufactured according to the procedure described above, in which the mold 31 is substantially cylindrical, or at most has a small degree of constriction for the leaflets to be formed, so that the wrapping process can be performed in the manner described are performed using a pressure cylinder 48. Then the valve is vulcanized, but the vulcanization process is interrupted after 1 - 2.5 hours before full vulcanization is achieved. The incompletely vulcanized valve is then taken off from the mold 31. The leaflets 25 are then pressed inwards to assume a fully or partially closed position. While the leaflets 25 are held in this position, the valve 20 is subjected to an additional vulcanization process of 0.5-2 hours to complete the vulcanization. As a result of this additional vulcanization, the leaflets 25 retain their in-pressed position even when released. Thus, it turned out to be possible to manufacture a fiber-reinforced stented valve which is closed in the tension-free rest position.

The holding of the leaflets 25 in the completely or partially closed position can be carried out using a mold or the like. However, it is sufficient to open the valve Z-; with its straight side edge 22 down, and then place pressure members (small, loose weights) on the leaflets 25. These weights can for instance be made of plastic or stainless steel; because the valve 20 is already vulcanized to a certain degree, these weights will no longer adhere to the surface of the leaflets 25.

Figure 2C illustrates a variant of the valve 20, wherein - some design details have been implemented which further reduce the tendency for blood reflux to occur. The ends of the support posts 24 are made as narrow as possible, as indicated at A. The length of the leaflets 25 measured in the axial direction is greater than that of the -4 "support posts 24, that is, the leaflets 25 are ; 35 passing above the support posts 24, as indicated under B. Furthermore, 3 'I * ...... H ... fV./, • ....... it ·; : t'l f .....

15, the top edges of the leaflets 25 are somewhat parabolic or sinusoidal, as indicated at C. As a result of these measures, the leaflets 25 move inward more easily and are more likely to touch, and a larger overlap area or have a "coaptation area".

A stented valve 20 is intended for implantation in an aorta 1, in situations where the aorta itself still has sufficient quality. However, it is possible that the aorta itself is affected to such an extent, for example by calcification, that the aortic wall cannot contribute to the proper functioning of the valve prosthesis. Furthermore, it is seen as a drawback of stented valves in general that the rigid support ring 21 does not move with the moving leaflets 25, so that the stress load of the leaflets is quite high. Therefore, there is also a need for a fiber-reinforced stentless valve. Such a valve, and methods of making such a valve, will be discussed below with reference to Figures 5-9.

Figure 5 schematically shows a longitudinal section of a stentless valve 50. The stentless valve 50 is designed to mimic a piece of aorta 1 with a natural valve 10 (see Figures 1A-B), and includes a flexible tube 51 with a predetermined length of about 3-5 cm. At its lower end 56 and its upper end 57, the tube 51 has a substantially circular cross-section, the diameter of which corresponds to the diameter of an aorta. In a central section, the tube 51 has a larger diameter in that the tube 51 has a few, preferably three, protrusions 52. On the inside of the tube 51, corresponding to the protuberances 52, leaflets 55 are formed, the function of which corresponds to the function of the previously discussed leaflets 25 of the stented valve 20. The material of the flexible tube 51 and the leaflets 55 similarly to the stented valve 20, is preferably the EPDM rubber discussed above.

The manufacture of a stentless valve 50 is more complicated than the manufacture of a stented valve 20, because 5 must be defined between the leaflets 55 and the tube bulges 52 sinus cavities 54, which implies that the leaflets 55 and the tube bulges 52 must not be glued together. to be. According to an important aspect of the present invention, a stentless valve 50 is made in two stages, with a portion of the lower tube wall 56 being made with the leaflets 55 in the first stage, and a portion of the upper one in the second stage tube wall 57 with the protuberances 52, taking steps to prevent sticking of leaflets and tube wall, as will be explained below with reference to Figures 6 and 7A-C.

Figure 6 schematically shows a perspective view of; ; a mold 60 'usable in the manufacture of the stentless valve 50. In a manner similar to that discussed above with respect to the mold 31, the mold 60 may be made of stainless steel. The mold 60 is generally in the form of a cylinder 61 with a circular cross-section, and is: i = on its cylinder mantle surface 63 provided with three, substantially circumferentially adjacent, mutually identical, -25. optionally contacting loot-shaped thickenings 62, the shape of which corresponds to the shape of the protrusions 52 to be formed in the tube 51. In the center of its end faces 64, the cylinder 61 has a recess 65 for clamping in an immersion device. 30 to facilitate. These depressions 30 can be defined by a central bore.

Figures 7A-C show the mold 60 during successive stages of manufacturing the stentless valve 50, partly in elevation and partly in section.

; To manufacture the stentless valve 50, the I-iSJ 35 mold 60, instead of the said mold 31, is mounted in the * "· -TTPn r 'VniR'i" "" "" WWl »' * ' With reference to Figs. 3A-B, apparatus discussed, with the said support ring 21, of course, is omitted.

In a first manufacturing step, using the rotate-and-dip technique already discussed, a layer of matrix material is applied to the mold 60, which layer is dried. In a similar manner as discussed above with respect to a stented valve, a fiber 42 is wound on the mold 60 in a desired pattern, and said first step is repeated until the layers applied on the mold 60 have a combined thickness that is is sufficient for the thickness of the leaflets 55. A thickness of 0.2 mm, which can be achieved with, for example, four dipping steps, is sufficient. These layers are collectively referred to in Figures 7A-C as first layer 71.

The part of the first layer 71, at least a part thereof, which is located on the thickenings 62, will start to function as leaflets 55. These leaflet parts of the first layer 71 are indicated with the reference numeral 75. It is located below the leaflet parts 75, and thereon contiguous portion of the first layer 71 is indicated by the reference numeral 73, 20, while the portion of the first layer 71 located above the leaflet parts 75 is indicated by the reference numeral 74.

In a second step, said part 73 of the first layer 71 is covered with, for example, Teflon tape 72 (Figure 7A).

In a third step, the mold 60 is kept at a temperature of about 120 ° C for, for example, 2-3 hours.

Thereby, the uncovered parts 75 and 74 of the first layer 71 are selectively vulcanized in an otherwise customary manner, while vulcanization of the covered part 73 of the first layer 71 is prevented by that teflon cover 72.

After completion of this first vulcanization step, the teflon tape 72 is removed in a fourth step, as is the said (now vulcanized) part 74 of the first layer 71, for example by cutting it away. Thus, only the said (unvulcanized) portion 73 of 18 leaves the first layer 71 on the mold 60, as well as the said (now vulcanized) leaflet portion 75 of the first layer 71, as illustrated in Figure 7B.

Then, in a fifth step, the thickenings 62 and the portion above of the cylinder jacket 63 are covered with teflon tape 76, as illustrated in Figure 7C.

Then, the mold 60 covered with teflon tape 76 is placed back into the device 30, and in a sixth step the dipping procedure resumed for single layer application; Rubber 34 and possibly fiber 42, which layers become together? designated as second matrix layer 77. A suitable thickness of this second matrix layer 77 is about 0.4 mm, which can be achieved with about 8 dipping steps. Since the previously applied rubber member 73 is unvulcanized, it adheres well to the second rubber layer 77 now to be applied thereto, thereby forming a good aortic base 56. The second rubber layer 77, which is applied over the said leaflet part 75, will remain free from that leaflet part 75, thanks to the teflon tape 76 situated between the two layers. When the desired thickness is reached, the mold 60 is with - * the rubber applied thereon placed in the oven in a seventh step before undergoing a second vulcanization step. The rubber can then be removed from the mold 60, and; the teflon tape 76 can be removed, and the product is ready to be implanted as a stentless valve prosthesis, after being cut to a desired length if desired.

Thus, valve 60 is formed into two separate .4 rubber-positive shafts, each followed by a vulcanization phase.

During each of the rubber deposition phases, several dipping steps are carried out, before applying several rubber layers to each other. In a similar manner as discussed above in connection with the stented valve 20, iiJL. by means of a computer - controlled winding device, between. two consecutive rubber layers, a pattern of reinforcement: 35 fibers 42 applied in the leaflets 55, pressing * Τ ’" * · * 'TW1! - τ'ϊπ ^ immm r'fT! i f! n i: A Q 4

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It is better to do this manually because, because of the contours of the thickenings 62, a pressure roller 48 does not give an adequate result. The patterns to be applied can be the same as the patterns already discussed above, and need not be discussed again in this place. Likewise, reinforcement fibers can be applied in the rubber layer 77 of the bulge 52.

A drawback of this mold 60 is that the leaflets 55 are fully open in a tension-free state. However, for the same reason as discussed above with regard to the stented valve 20, it is desirable to be able to make a stentless valve the leaflets of which are fully or partially closed in their stress-free condition. According to the present invention, this result can be achieved in a relatively simple manner with a two-part mold 80 to be discussed hereinafter with reference to Figures 8A-B. This mold 80 comprises two substantially cylindrical mold halves 81 and 82, of which Fig. 8A schematically shows a perspective view and figure 8B shows schematically a longitudinal section. A first mold half 81, which will also be referred to as "lower" mold half, is provided with three obliquely oriented surfaces 84 near an upper end 83, the shape of which corresponds to the desired shape of the leaflets 55. A second mold half 82, which will also are referred to as "upper" mold half, near a lower end 85 is provided with three bosses 86, which correspond to the bosses 62 of the mold 60. Furthermore, a recess 87 is arranged in the bottom end 85 of the upper mold half 82, with inclined walls 88 aligned with said thickenings 86, the shape of which corresponds to that of said faces 84 of the lower mold half 81. Thus, the two mold halves 81 and 82 fit together, defining together an outer configuration that corresponds to that of the previously discussed template 60.

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The mold halves 81 and 82 are preferably, as shown, provided with central bores 91 and 92, through which a carrier shaft can be fitted about the mold halves axially. fix with respect to each other.

The use of the divided mold 80 will now be explained, referring again to Figure 3. In a first step, the lower mold half 81 is placed in the device 30, in place of the mold 31, and on that mold half 81 single (e.g. two) layers of matrix material i; 10, preferably the aforementioned EPDM rubber, by carrying out the immersion method already discussed.

In a second step, a layer of reinforcing fibers r5 42 is applied by winding the fiber 42, in particular on said surfaces 84 defining the leaflets to be formed, r 15, in a pattern which may be equal to one of the cartridges illustrated in Figures 4A-C. Possibly; then one (or more) layers of matrix material are applied again, according to the first step.

Γ 1 “In a third step, the top mold half 82 is placed in the device 30, in place of the mold 31, and is placed on -: ·; ...... 'f = the outer surface of that mold half 82 at applied at least one layer of matrix material, by performing the dipping method already discussed. Hereby, said cavity 87. covered with, for example, a plug fitting in the cavity (for reasons of simplicity, not shown for simplicity).

It will be understood that the order of performing the first and second steps on the one hand and the third step on the other is irrelevant. Furthermore, it will be clear that it is possible to perform the third step simultaneously with, for example, perform the first step.

In a fourth step, it is placed on the end face 89 of the ..... -t- -; . . lower mold half 81 deposited matrix material removed.

: In a fifth step, the lower and upper mold halves -.- 4¾¾ halves 81 and 82 are secured together, with the inner surfaces -35 * 35 88 of the upper mold half 82 practically against the outer surfaces - J <\ / 21 84 of the lower mold half 81 abut only separated by the matrix layers applied to those outer surfaces 84 with the reinforcing fiber 42. The lower and upper mold halves 81 and 82 are pressed axially tightly together, the matrix material on the outer surfaces 84 of the lower mold half 81 defines the leaflets 55.

In a sixth step, the total mold 80 is placed in the device 30, and, optionally after one or more dipping steps for applying one or more layers of matrix-10 material on the mantle surface of the mold 80 and on the thickenings 86, fiber material 42 wound on the mold 80, in particular in the areas of the thickenings 86.

Then, in a seventh step, one or more dipping steps are carried out for applying one or more layers of matrix material, until the layers of the matrix material applied to the outer surface of the mold 80 together have reached a sufficient thickness. A suitable value for this thickness is, for example, 0.4 mm, which can be achieved with a total of about 8 dipping steps.

In an eighth step, the entire mold 80 is placed in an oven to vulcanize the matrix material applied thereon, after which the vulcanized matrix material can be removed from the mold. The molded product is now ready for implantation as a stentless valve prosthesis after any post-treatment for cutting the tubular sections 56, 57 to size.

Thus, by using a split mold, it is possible to pre-select the position of the leaflets 55 in the tension-free state, independently of the shape of the protuberances 52, by choosing the shape of the faces 84, This shape can be nearly cylindrical, in line with the cylinder shell of the lower mold half 81, to ensure that the leaflets have the largest possible surface area. On the other hand, it is desirable to give the leaflets a half-35 closed position. A possible compromise is that the 0 G 83 4 9 surfaces 84 are substantially flat, or are slightly convexly curved.

22, A further preferred detail of the present invention will now be discussed with reference to Figures 8-9. In fact, in the stentless valve 50 fabricated according to the procedure discussed above, three different matrix layers can be distinguished, as exaggerated in the partial longitudinal section of Figure 9A. A first matrix layer 101 is formed by the matrix material which is applied to the first mold half 81 during the first and second steps. A second matrix layer 102 is formed by the f 'm matrix material which is formed during the third step. is applied to the second mold half 82. A third matrix layer 103 is formed by the matrix material applied to the coupled mold halves during the sixth and seventh steps. From the foregoing discussion, it will be apparent that the reinforcing fibers 42 of the leaflets 55 are contained only in the first matrix layer 101. For improved strength of adhesion between leaflets 55 and bulge 52, it is preferred that at least some fibers 42 of the leaflets 55 continue from the first matrix layer 101 into the third matrix layer 103, especially towards the downstream side of the leaflet attachments, ie the wall sections 57 located above the protuberances 52 in FIG. 5. achieving this significant improvement, the present argues; The invention is a simple modification of the wrapping procedure to be performed during the second step. Instead of continuously wrapping the fiber 42 in, as discussed above; the desired pattern, the winding process is regularly repeated. stopped, and the fiber 42 is cut. The part of the fiber 42 already wound on the lower mold half 81 has thus received a first free end 111, and the part of the fiber still wound on the stock reel 41 42 has been given a second free end 112. That first free end

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23 111, which may have a length of the order of one to a few centimeters, is now laid down on the lower mold half 81 such that it leaves the lower mold half 81 near an intersection 113 between the end face 89 of the mold half 81 and two adjacent planes 84, and substantially located in a plane 84, and pointing outwardly with respect to the lateral surface of the mold 81, as clearly shown in the side view of Figure 9B.

Winding of the fiber 42 is now resumed, with the second free end 112 of the fiber 42 approaching the mold 81 in one of said intersection points 113 in a similar manner to the first free end 111, as also shown in Figure 9B. This may involve the same intersection points 113, or just two different ones.

Optionally, it is possible that the fiber 42 is not cut, but the two said ends are left together to define a loop.

This step of interrupting continuous winding and advancing a fiber end at an intersection 113 is repeated several times, so that at the end of the second step, an intermediate results at each intersection 113 of multiple outwardly pointing fiber ends 111, 112. The number of outwardly projecting fiber ends per cutting point 113 is preferably 10 or more.

When performing the fourth step, in which the upper mold half 82 is placed on the lower mold half 81, care is taken that the protruding fiber ends 111, 112 do not get between the two mold halves 81, 82. During or after coupling of the two mold halves 81, 82, these protruding fiber ends 111, 112 are laid out in a flaring pattern on the second matrix layer 102 on the lateral surface 93 and / or the thickenings 86 of the second mold half 82, as outlined in the side view of figure 9C, and pressed into that layer. Only then, in the fifth step, is the third matrix layer 103 applied, with any reinforcement 24 fibers 42 being wound up in a layer over said fiber ends 111, 112. As a variant, the third matrix layer 103 can be provided with short fiber pieces, as has already been discussed above.

; It will be apparent to a person skilled in the art that the scope of the present invention is not limited to the scope of the invention

B

The foregoing discussed examples, but that various modifications and modifications thereof are possible without departing from the scope of the invention as defined in the appended claims. For example, it will be apparent that if the possibility of making said Γ: loose fiber ends 111, 112 is omitted, it is not necessary to

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When the upper mold half 82 is provided with a second matrix layer 102 acting as an adhesive layer for said fiber ends 111, 112, so that the said third step can be skipped, it will further be apparent that the part-74 to be removed the matrix layer 71 can be removed before the material is vulcanized.

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Claims (15)

A mold (80) for use in a method of manufacturing a synthetic fiber-reinforced stentless heart valve (50), comprising: a substantially cylindrical lower mold half (81) having at least three obliquely at an upper end (83). placed faces (84); a substantially cylindrical top mold half (82) provided at a bottom end (85) with a recess (87) with inclined side walls (88) corresponding to said oblique planes (84), and which is at the bottom end (85) provided on its cylinder face in circumferential side-by-side bosses (86) corresponding in number and position to said side walls (88). A method of manufacturing a synthetic fiber-reinforced stentless heart valve (50) using said mold (80) according to claim 1, comprising the steps of: a) providing a reservoir (33) with a solution of matrix material ( 34); c) rotating immersion of the lower mold half (81) in the reservoir (33) at least once in rotation to apply at least one layer of matrix material (101) to the lower mold half (81), in particular to the said oblique 25 surfaces (84) of the lower mold half (81); d) winding at least one layer of fiber material (42) according to a suitable pattern on said inclined surfaces (84) of the lower mold half (81); e) mounting the top and bottom mold halves (81, 82) together; f) rotating the immersed mold halves (81, 82) in the reservoir (33) at least once in a rotating manner. for applying at least one layer of matrix material (103) to the outer surfaces of the mold halves (81, 82); g) winding at least one layer of fiber material (42) according to a suitable pattern on the thickenings (86) of the | Top mold half (82); h) form-fixing the cast iron material applied to the mold. The method of claim 2, further comprising at least one rotary rotation immersion of the top mold half (82) into the reservoir (33) for applying at least one layer of matrix material (102) to the top mold half (82); wherein during step (d) the fiber to be wound (42) is cut several times to form loose fiber ends (111, 112), and said fiber ends (111, 112) during or after! E "step (e) are deposited in a fan-shaped pattern on said layer of matrix material (102) on the cylindrical shell surface (93) and / or the bosses (86) of the upper mold half; j (82). 7 1 20; A method of manufacturing a synthetic 1 ....... fiber-reinforced stentless heart valve (50) comprising the steps. i of: "S a) providing a mold (60) having a substantially cylindrical contour, which is provided on its cylinder face (63) - h of at least three, circumferentially adjacent. thickenings (62); ; b) providing a reservoir (33) with a solution of matrix material (34); C) rotating immersion of the mold (60) in the reservoir (33) at least once in rotation to apply at least one layer of matrix material (71) to the mold; d) winding at least one layer of fiber material (42) according to a suitable pattern on a part (75) of the layer of ms 35 matrix material (71) on the mold; e) covering (72) a portion (73) of the applied matrix material (71); f) vulcanizing the uncovered portion (74, 75) of the applied matrix material (71); G) removing a portion (74) of the vulcanized matrix material; h) removing said covering (72), and covering at least the remaining vulcanized fiber-reinforced matrix material (75); I) Rotatingly dipping the mold (60) into the reservoir (33) at least once to apply at least one layer of matrix material (77) to the mold. The method of claim 4, wherein after step (i) at least one layer of fiber material (42) is wound onto said layer (77) in a suitable pattern. A method of manufacturing a synthetic fiber-reinforced stented heart valve (20), comprising the steps of 20: a) providing a substantially cylindrical mold (31); b) placing a support ring (21) on the mold (31), said support ring (21) being substantially cylindrical, and having a corrugated contour at a top edge (23) with three or more support posts (24); c) providing a reservoir (33) with a solution of matrix material (34); d) rotating the mold (31) with the support ring (21) with the support ring (21) in the reservoir (33) at least once while applying at least one layer of matrix material (34) to the mold and the support ring; e) winding at least one layer of fiber material (42) according to a suitable pattern on the support ring (21); f) partially vulcanizing the matrix material (34); y ') f' "-T · g) removing the support ring (21) and the partially vulcanized matrix material (34) from the mold (31); h) at least partially folding in leaflets (25) formed between the support posts (24) of the support ring (21); - i) completing the vulcanization, retaining the leaflets (25) in the folded-in condition. A method according to claim 6, wherein the free edges (26) of the leaflets (25) are made parabolic or sinusoidal. The method of claim 6 or 7, wherein the length of 44 the leaflets (25) is greater than that of the support posts (24) of the support ring (21) F I ? A method according to any one of claims 2-8, wherein the matrix material is an EPDM rubber, and the molding fixation is performed by vulcanization. A method according to any one of claims 2-9, wherein the fiber 4_ (42) is wetted just before winding with the solvent used in the reservoir (33). 7 " A method according to any one of claims 2-9, wherein the fiber M3 25 (42) is wetted just before winding with a solution of the matrix material whose viscosity is lower than that of the matrix material (34) in the reservoir (33). A method according to any one of claims 2-11, wherein a certain amount of fiber pieces is added to the -30 reservoir (33) with matrix material (34). A method according to any one of claims 2-12, wherein the application of a fiber reinforcement (42) is done in two or more layers with mutually different patterns. inn 'T T * rfï F' nun? vmf M r "nmf i * ^ r 'W | Synthetic fiber-reinforced stentless heart valve (50), comprising a substantially cylindrical tube (51) with outwardly protruding portions (52) and leaflets (55) attached to the inner wall, which leaflets (55) are provided with 5 reinforcing fibers (42 ) that extend from the leaflets (55) into the material of the tube (51). The heart valve of claim 14, wherein the tube (51) includes its own fiber reinforcement (42). "£ O"