AU2006260681A1

AU2006260681A1 - Artificial graft tubing

Info

Publication number: AU2006260681A1
Application number: AU2006260681A
Authority: AU
Inventors: Colin Gerald Caro
Original assignee: Veryan Medical Ltd
Current assignee: Veryan Medical Ltd
Priority date: 2005-06-24
Filing date: 2006-06-26
Publication date: 2006-12-28
Also published as: EP1898835A1; US20090293574A1; WO2006136861A1; CA2613401A1; JP2008543470A; IL188229A0

Description

WO 2006/136861 PCT/GB2006/002354 Artificial Graft Tubin The invention relates to methods of making artificial graft tubing and the 5 graft tubing made by the methods. We have previously proposed that the flow pattern in arteries including the swirling pattern induced by their non-planar geometry operates to inhibit the development of vascular diseases such as thrombosis, atherosclerosis and intimal hyperplasia. 10 It is known from WO 95/09585 to provide a vascular prosthesis comprising a length of generally hollow tubing having openings at both ends thereof and including a non-planar curved portion so as to induce swirl flow in blood flowing through the curved portion. As explained in that publication, the swirl flow induced by skewing of the blood flow within the non-planar curved portion improves flow 15 characteristics and reduces the potential for deposit build-up and vascular disease including intimal hyperplasia. It is explained in Caro et al. (1998) J. Physiol. 513P, 2P how non-planar geometry of tubing inhibits flow instability. Further aspects of how swirl flow is beneficial are explained in J.R. Soc. Interface (2005) 2, 261-266. 20 It is known from WO 2004/082534 to make artificial helical grafts by winding a tube of flexible material round a mandrel so that the tube adopts a shape in which its longitudinally extending cavity has a helical centre line, and thermosetting the tube so that it retains, at least partly, the helical shape. In one method, shown in Figures 12A - 12E, the mandrel consists of a rigid rod, shaped 25 into a helix. In another method, shown in Figures 13A and 13B, the mandrel consists of a straight steel rod onto which a steel wire has been wound and secured in a helical manner. In both cases, because the graft material is soft and flexible, it is necessary to support the flexible tube during winding round the mandrel so that it retains its cross-sectional shape during this process. A support consisting of silicone 30 rubber tubing inside the flexible graft tube is proposed. This method thus requires an extra component, in addition to the mandrel external of the flexible tube. Moreover, care has to be taken in order to ensure that the flexible tube adopts the WO 2006/136861 PCT/GB2006/002354 -2 correct geometry so that the eventual graft has the intended helical pitch and amplitude. The initial winding of the flexible tube onto the mandrel must be accurately carried out, and it then needs to be retained in the correct position along its length during the thermosetting process. 5 According to a first aspect of the invention, there is provided a method of making artificial graft tubing, comprising providing a helical mandrel having a centre line following a substantially helical path, providing a generally tubular wall having a longitudinally extending cavity, positioning the helical mandrel inside the tubular wall so that the longitudinally extending cavity has a centre line following a 10 substantially helical path, and causing the tubular wall to retain, at least partly, the shape with the longitudinally extending helical cavity. Such a mandrel is beneficial in properly defining the desired helical shape which the tubular wall is to adopt, e.g. in terms of helix angle and amplitude. The tubular wall is in effect automatically caused to comply with the predetermined 15 shape of the mandrel. Such a mandrel can also maintain the desired cross-sectional shape of the longitudinally extending cavity. A close fit of the mandrel within the tubular wall can ensure this, for example a fit in which the diameter of the mandrel is at least 90 per cent of the internal diameter of the tubular wall, more preferably 95 per cent. 20 In general, the tubular wall has its shape modified from a basic initial shape, preferably a substantially cylindrical shape, to the helical shape, by being placed on the mandrel. Thus a pre-existing tubular wall has its shape modified by the internally positioned mandrel. The "internal" mandrel may be made by rapid prototype laser sintering of e.g. stainless steel, or by milling a cylindrical rod of e.g. 25 stainless steel. The graft tubing made by the methods disclosed herein is suitable for in vivo use, in the human or animal body. It is suitable for use as a prosthesis to carry a flow of bodily fluid, e.g. blood. The tubing may for example be used as a vascular prosthesis. It may be used as a vascular access graft of the type which is to be 30 punctured with a needle to allow blood to be withdrawn and returned for e.g. dialysis. The tubing may therefore carry the body fluid directly, in contact with the inside wall of the tubing.

WO 2006/136861 PCT/GB2006/002354 -3 Alternatively, the tubing may be positioned externally of natural tubing of the human or animal body e.g. an intact or grafted blood vessel. The tubing may thus act as an external sheath or stent to the natural tubing which carries the body fluid flow. When the graft tubing is used externally of natural tubing, during 5 deployment it will sometimes be desirable to cut the graft tubing longitudinally to facilitate insertion of the natural tubing. The cut may be repaired by stitching or the like, if medically indicated. Preferably, the tubular wall is thermoset so as to retain, at least partially, the shape with the longitudinally extending cavity. Because an internal mandrel is used, 10 the tubular wall can be exposed evenly to the external heating conditions during thermosetting. In a preferred embodiment, the tubular wall is made of ePTFE. In this case, where thermosetting is used to cause the helical shape to be retained, the tubular wall may be heated to a temperature in the range of 340 to 380'C, more preferably 15 350 to 370*C, for a period in the range of 10 to 30 minutes, more preferably 15 to 25 minutes, in order to achieve thermosetting in the helical shape. In a most preferred method the tubular wall is heated to 360*C for 20 minutes. It is known to provide PTFE grafts of cylindrical form which are externally supported by helically wound polymer filaments. The purpose of such support is to 20 reduce the likelihood of kinking, when for example the graft is implanted across a joint. The helix angle (i.e. the angle to the longitudinal axis of the graft) of the filament of such externally supported grafts is of the order of 80* or more. We have found that this type of graft is a suitable starting material for carrying out the method of the present invention. Preferably, therefore, the tubular wall comprises a helically 25 wound support. The support is preferably provided externally of the tubular wall. The helix angle of the helically wound support is preferably at least 700. The helically wound support may be in the form of a tape or a wrap. In certain preferred methods, an elongate member is applied to the tubular wall so as to extend longitudinally thereof, when the tubular wall is supported by the 30 mandrel. Such an elongate member is provided to assist in reducing any tendency for the helical graft to be straightened out and thereby cause reduction in helical amplitude. Such a tendency to straighten out may occur due to internal WO 2006/136861 PCT/GB2006/002354 -4 pressurisation by a fluid, for example in response to arterial pressure, or axial extension if the graft is used in the vicinity of a joint, or a combination of the two. A further cause of straightening out may be during deployment, when the graft may be "stretched". 5 In the manufacturing methods described in WO 2004/082534, a helical reinforcing portion for resisting such straightening out is applied to the tube when it is in a cylindrical condition, before it is deformed and thermoset in the helical condition. It can however be difficult accurately to apply the helical reinforcing portion to the tube in its initial cylindrical form, particularly when it is made of a 10 relatively flexible material. Similar methods are described in WO 2004/082520 in relation to the manufacture of tubing for placement externally of a body fluid flow conduit, such as a blood vessel. However in the embodiments of the invention involving the use of an elongate reinforcing member, because the tubular wall is internally supported by the 15 mandrel, application of the elongate member to the tubular wall is facilitated. The internal mandrel allows pressure to be applied to the tubular wall by the elongate member without causing deformation. The elongate member may be in the form of a strip, bead, thread, filament or the like. It may have a width (i.e. its dimension in the circumferential direction of 20 the tubular wall) which is wide or narrow. One or more elongate members may be provided. More than one elongate member may be useful to provide additional resistance to the extensibility of the graft tubing. The elongate member may be applied to extend substantially only longitudinally of the tubular wall. This would mean that the elongate member 25 would effectively be on only one "side" of the tubular wall. If located on the outside of the tubular wall, it would be visible all along that side, without disappearing behind the tubular wall. Preferably, the elongate member has a circumferential component as well as a longitudinal component. In a preferred embodiment, therefore, the elongate 30 member is applied to extend both circumferentially and longitudinally of the tubular wall. The elongate member would then have its own helix angle and corresponding pitch. It is generally desirable that the helix angle of the elongate member is not too WO 2006/136861 PCT/GB2006/002354 -5 great, because with larger helix angles the resistance to axial extension of the graft tubing provided by the elongate member tends to reduce. The helix angle is preferably less than about 70', as measured relative to the overall axial direction of the graft tubing (i.e. relative to the axis about which the helical centre line of the 5 longitudinally extending cavity revolves). For example the helix angle may be between about 300 and 40'. It is preferred that the elongate member is applied to extend helically along the tubular wall with a pitch approximately greater than or equal to the pitch of the helical centre line of the longitudinally extending cavity (i.e. a helix angle less than 10 or equal to that of the helical centre line), more preferably with a pitch substantially equal to the pitch of the helical centre line. The elongate member may be applied to the tubular wall in various ways, for example by use of an appropriate adhesive or by stitching. The elongate member may be attached to the tubular wall intermittently, providing the attachment points 15 or regions are sufficient in number and density for the elongate member to assist the tubular wall in retaining the helical shape. Preferably, the elongate member is attached to the tubular wall continuously along its length. The elongate member is most preferably bonded to the tubular wall, for example by a heating step. This could involve a thermally activated adhesive, or the use of a material to form the 20 tubular wall and/or the elongate member which softens or melts during heating to form a bond. In a preferred method, the elongate member may be secured to the mandrel or tubular wall at one end and may then be subjected to longitudinal tension whilst being helically applied to the tubular wall, ensuring a degree of contact pressure 25 between the elongate member and the tubular wall. The elongate member may be applied after an initial thermosetting step, with a further heating or adhesion step being carried out to bond the elongate member to the tubular wall. Preferably, however there is a single heating step serving both to bond the elongate member to the tubular wall and to thermoset the tubular wall to 30 retain, at least partly, the shape with the longitudinally extending cavity. Thus, relatively inextensible graft tubing may be made with a single heating step.

WO 2006/136861 PCT/GB2006/002354 -6 A preferred method comprises shaping a tubular wall by positioning a helical mandrel inside it, whereby the tubular wall adopts a helical shape, applying an elongate member to the tubular wall when it is supported by the helical mandrel, whereby the elongate member extends longitudinally of the tubular wall, and heating 5 the helical mandrel, tubular wall and elongate member to cause thermosetting of the tubular wall and bonding thereto of the elongate member. In one preferred embodiment, the tubular wall and the elongate member are made of ePTFE. They may for example be heated to a temperature in the range of 330 to 350'C for a period in the range of 10 to 15 minutes, in order to achieve 10 thermosetting in the helical shape and bonding of the elongate member to the tubular wall. Preferred values are 340'C and 10 minutes. The application of an elongate member to a tubular wall after its shape has been modified to a helical form is considered to be of independent patentable significance. According to a second aspect of the invention, therefore, there is 15 provided a method of making artificial graft tubing, the method comprising providing a generally tubular wall having a longitudinally extending cavity, shaping the tubular wall so that the longitudinally extending cavity has a centre line following a substantially helical path, causing the tubular wall to retain, at least partly, the shape with the longitudinally extending helical cavity, and thereafter 20 applying to the tubular wall an elongate member so as to extend longitudinally thereof. By applying the elongate member to the tubular wall once it has adopted a helical condition, it can better accept the application of the elongate member. Since the elongate member extends longitudinally of the tubular wall it tends 25 to reduce the axial extensibility of the graft tubing. If the length of the graft tubing is increased, this involves a reduction in the amplitude of the helical centre line of the longitudinally extending cavity and a corresponding increase in the pitch of the helix. Such a straightening out effect is reduced by the provision of the elongate member. 30 The step of causing the tubular wall to retain, at least partly, the helical shape may comprise thermosetting the tubular wall. Accordingly, one preferred method comprises a first heating step in which the tubular wall is thermoset in the helical WO 2006/136861 PCT/GB2006/002354 -7 shape, and a second heating step, carried out after the elongate member has been applied to the tubular wall, in which the elongate member is bonded to the tubular wall. The temperature to which the tubular wall is heated in the first heating step is preferably lower than that to which it is heated in the second heating step. 5 The shaping of the tubular wall so that its longitudinally extending cavity has a helical centre line may be carried out in a number of ways, not necessarily being restricted to the use of an internal mandrel. In one preferred method, the tubular wall is shaped by being wound round a mandrel. Such a mandrel is "external" of the tubular wall. The material from which the tubular wall is made may be quite soft 10 and flexible and so can present difficulties if it is to be wound round e.g. a cylindrical mandrel whilst retaining its own cross-sectional shape. Preferably therefore the mandrel has a substantially helical groove in which the tubular wall is at least partly received. Such a groove can serve as a support for the tubular wall both during its initial shaping to the helical shape and during the step in which the 15 tubular wall is caused at least partly to retain the helical shape. It can further provide a support during application of the elongate member to the tubular wall, if the tubular wall remains on the mandrel during that step. The helical groove is preferably such as to provide some support to opposite sides of the tubular wall. It is preferably shaped to correspond to that part of the 20 external surface of the tubular wall which contacts the groove. This may be beneficial in minimising tooling marks left on the tubular wall by the mandrel. In the case of a circular cross-sectional shaped tubular wall, the groove may thus have a part-circular cross-sectional shape. The groove may have a pair of side walls spaced apart by a base wall. In the latter case, the tubular wall may engage the first 25 side wall, the base wall, and the second side wall, so as to be properly supported. The side and base walls may be curved or straight. In the above method of shaping the tubular wall by winding round a mandrel, an internal support may be used inside the tubular wall to help it retain its cross sectional shape. Preferably, however, no internal support is used. 30 The helically shaped tubular wall may be removed from the mandrel before the elongate member is applied. Preferably however the elongate member is applied to the tubular wall when it is supported by the mandrel. This can assist in applying WO 2006/136861 PCT/GB2006/002354 -8 the elongate member correctly, for example in terms of a desired helix angle. If for example the tubular wall has been shaped by being wound round a mandrel, the elongate member may be applied with the same helix angle as the tubular wall by contacting it with the radially outermost portion of the tubular wall in its wound 5 condition. In the case of a helical mandrel inserted inside the tubular wall, the mandrel provides a support for that part of the tubular wall to which the elongate member is applied. This arrangement therefore facilitates application of the elongate member extending generally longitudinally only, or with helix angles other than the same helix angle as the tubular wall. 10 Preferably the elongate member is applied externally of the tubular wall. Therefore the elongate member will have a minimal effect on the cross-sectional shape of the longitudinally extending cavity. When the graft tubing is in use and carries a flow of bodily fluid, either directly or as a sheath to a natural vessel, it is desirable to avoid any internal ribs or grooves, because these may lead to flow 15 disturbances including flow stagnation in the region of the rib or groove. By applying the elongate member externally of the tubular wall, any internal projection caused by the elongate member can be substantially avoided, particularly if the radially inward pressure on the tubular wall when the elongate member is applied is minimised. 20 The various other features described herein in relation to graft tubing manufacture may be used in combination with the second aspect of the invention, individually or in any combination. The use of a mandrel having a substantially helical groove to make artificial graft tubing is considered to be of patentable significance in its own right. 25 According to a third aspect, therefore, the invention provides a method of making artificial graft tubing, the method comprising providing a mandrel having a substantially helical groove, providing a generally tubular wall having a longitudinally extending cavity, positioning the tubular wall at least partly in the groove so that the longitudinally extending cavity has a centre line following a 30 substantially helical path, and causing the tubular wall to retain, at least partly, the shape with the longitudinally extending helical cavity.

WO 2006/136861 PCT/GB2006/002354 -9 As described above, such a helical groove can provide support to the tubular wall during its positioning at least partly in the groove and also when it is caused at least partly to retain a helical shape. In general, the tubular wall as a whole will be positioned at least partly in the helical groove. Thus, at least in a preferred 5 embodiment, the centre line of the longitudinally extending helical cavity extends along the groove. Such a mandrel may be used with or without an elongate member to assist in resisting axial extension. The various other features described herein in relation to graft tubing manufacture may be used in combination with the third aspect of the invention, 10 individually or in any combination. In all aspects of the invention, the tubular member may be made of various biocompatible materials. Woven or non-woven fabrics may be used, preferably made of polymeric material. One suitable material is expanded polytetrafluoroethylene (ePTFE), either alone or in combination with other polymers 15 or additives. Another suitable biocompatible material is polyester, for example a knitted polyester yarn such as polyethyleneterephthalate, known as Dacron (trade mark). The elongate member, if provided, may also be made of various biocompatible materials, for example those described above. One suitable material 20 for the elongate member may be polypropylene. The tubular wall may be of the type externally reinforced with multiple circular reinforcements or with helically wound (with a very large helix angle, close to 900) reinforcement. The reinforcement may be in the form of a tape, strip, wrap or the like, so that it is suitable for being made into a vascular access graft which in 25 use will be repeatedly punctured laterally by a needle. Another form of reinforcement is a bead or the like which protrudes radially outwardly from the tubular wall, usually with a longitudinal spacing between adjacent bead circles or windings. This type of tubing is used in prostheses subject to external bending forces, for example going across joints such as the knee, and the bead helps to 30 maintain a circular cross-section. In some cases, a bead or the like is used in addition to a tape , strip, wrap or the like.

WO 2006/136861 PCT/GB2006/002354 -10 A tubular wall with circular or helically wound reinforcement is a suitable starting point for the methods described herein, for example the method using an internal mandrel to modify the shape of the tubular wall. In the embodiments of the invention including such reinforcement, where an elongate member is additionally 5 provided, the elongate member is applied in addition to the circular or helical reinforcement. The reinforcement, having a relatively large helix angle (e.g. 70 degrees or more), can provide properties such as the ability to be neatly punctured, or resistance to lateral compression or kinking. The elongate member, having a relatively small helix angle (e.g. less than 40 degrees), is intended to resist axial 10 extension of the graft tubing and hence any tendency for reduction in the helical amplitude. In this specification, the amplitude of the helix refers to the extent of displacement from a mean position to a lateral extreme, so, in the case of a tubular wall having a longitudinally extending cavity with a helical centre line, the 15 amplitude is one half of the full lateral width of the helical centre line. The graft tubing may be made with substantially the same amplitude and helix angle along its length. There may be small variations when the graft tubing is in use, caused by elongation or contraction of the graft tubing due to tensile loading or caused by torsional loading. However, there may be circumstances in which it is 20 desired to make the graft tubing with a variable helix angle and/or amplitude, either to suit the space constraints or to optimise the flow conditions. This can be achieved by suitably customising a mandrel, whether of the external or internal type. For reasons of manufacturing simplicity, it may be preferred for the graft tubing to be made with the longitudinal cavity having a substantially constant cross 25 sectional area along its length. Again, there may be variations in use caused by loading on the graft tubing. The cross-sectional shape of the cavity in the graft tubing as manufactured is preferably circular. The helical tubular wall may form just part of the overall length of the graft tubing or it may extend over substantially its entire length. 30 The helical tubular wall may undergo a fraction of one complete turn, for example one quarter, one half or three quarters of a turn. Preferably, the helical tubing portion undergoes at least one turn, more preferably at least a plurality of WO 2006/136861 PCT/GB2006/002354 - 1.1 turns. Repeated turns of the helix along the tubular wall will tend to ensure that the swirl flow is generated and maintained. The invention also extends to graft tubing made by the methods described herein, and to use of such graft tubing in the human or animal body. 5 The graft tubing made by the methods disclosed herein may be used in various biomedical applications e.g. in various arteries (such as in the femoral, coronary and renal arteries), in veins, and in non-cardiovascular applications such as in the gastro-intestinal (e.g. bile or pancreatic ducts), genito-urinary (e.g. ureter or urethra) or the respiratory systems (lung airways). Thus, the invention extends to 10 the manufacture of graft tubing for body fluids other than blood, either for carrying the fluid directly or for placement around natural (intact or grafted) flow conduits. Some preferred embodiments of the invention will now be described by way of example and with reference to the accompanying drawings, in which: Figure 1 shows a mandrel to be positioned inside a tubular wall; 15 Figure 2 shows a tubular wall with the mandrel of Figure 1 inserted therein; Figure 3 shows the tubular wall supported by the mandrel and with an elongate member applied thereto; Figure 4 shows a graft after removal from the mandrel of Figure 1; Figure 5 shows another graft made with the mandrel of Figure 1; 20 Figure 6 shows a mandrel round which a tubular wall is to be wound; Figure 7 shows the mandrel of Figure 6 with the tubular wall in place; Figure 8 shows the mandrel and the tubular wall of Figure 7 and an elongate member applied to the tubular wall; and Figure 9 shows a graft after removal from the mandrel of Figure 6. 25 Figure 1 shows a tool in the form of a mandrel 10. The mandrel is a stainless steel rod having a helical shape. In this embodiment, the mandrel has been fabricated from a cylindrical stainless steel rod, using a ball nosed cutter in a CNC milling machine. The co-ordinates are drawn up on a CAD/CAM system to provide a desired helical pitch and amplitude. The mandrel is designed to be inserted inside 30 a tubular wall 6, so as to modify the longitudinal cavity of the tube to conform to the shape of the helical mandrel. This is seen in Figure 2.

WO 2006/136861 PCT/GB2006/002354 -12 Figure 3 shows a later stage when an elongate member in the form of a strip 8 has been applied to the tube 6, to extend longitudinally therealong with a helix angle and pitch the same as that of the tube. Figure 4 shows a graft after removal from the mandrel of Figure 1. 5 Figure 5 shows a another graft after removal from the mandrel of Figure 1. This graft has an external helical support tape 20. Figure 6 shows a tool in the form of a mandrel 2 formed with a helical groove 4 extending along its length. In this particular embodiment, the mandrel has been fabricated from a cylindrical stainless steel rod, using a ball nosed slot drill 10 milling cutter in a CNC milling machine. The co-ordinates are drawn up on a CAD/CAM system to provide a desired helical pitch and amplitude. The amplitude is determined by the cutting depth. The groove has a diameter suitable to receive a tubular wall or tube 6, as seen in Figure 7. In this case the tube is of a type conventionally used as a graft, in 15 its normal cylindrical form, made of ePTFE. It is then shaped from its usual linear shape to a shape following the helical groove 4 of the mandrel 2. In Figure 8 an elongate member in the form of a strip 8 has been applied to the tube 6. The strip 8 extends longitudinally along the tube in a helix having the same pitch as the helical groove (and the tube as shaped by the groove). 20 Figure 9 shows a graft 12 consisting of the tubular wall with a helical shape and the strip 8 externally bonded to the tubular wall. The graft has a longitudinally extending cavity 14 with a centre line following a helical path. The graft tends to resist axial extension, whether during deployment e.g. by a surgeon or during operation in a human or animal body, by virtue of the longitudinally extending strip 25 8. Example 1 A tube made of ePTFE of a conventional cylindrical type available for use as vascular prosthesis was used. The tube had an internal diameter of approximately 6 30 mm and an external diameter of approximately 7 mm. The mandrel of Figure 1 was inserted in the tube. The mandrel had an external diameter of 5.8 mm. The tube internal diameter of 6 mm was such as to ensure a close fit to the mandrel. The WO 2006/136861 PCT/GB2006/002354 - 13 initially cylindrical tube was deformed to adopt a helical shape, as seen in Figure 2. An ePTFE filament which had been flattened into strip form was then wound around the tube on the mandrel, with the pitch of the strip winding being the same as that of the mandrel. The strip was secured to the mandrel at one end and subjected to 5 longitudinal tension. Because the strip was wound around a curved surface, such longitudinal tension caused the strip to exert a normal (or pressure) force, ensuring close apposition of the strip and graft. The whole assembly was then placed in an oven at 330'C for 10 minutes. This softened the ePTFE of the tube and strip sufficiently for them to bond to each 10 other. Thereafter the assembly was allowed to cool at room temperature. A graft as shown in Figure 8 was produced. It was found that with this process there is firm adherence of the strip to the exterior of the tube. There is moreover no detectable ridging or grooving of the interior of the graft. The graft becomes, as a result of the procedure, essentially 15 inextensible. The graft is nevertheless able to be bent, say into a U-tube, with a curvature (tube radius/radius of curvature) of about 1/3. Puncturing of the adherent strip with a needle (as may occur when the graft is used for vascular access in renal dialysis patients) did not reduce the inextensibility of the graft. Even repeated puncturing across the width of the strip, 20 such that it was effectively severed, was found to have only a localised effect and the graft as a whole remained satisfactorily inextensible. The manufacture of a helically reinforced graft in a single heating step, as described above, was achieved. 25 Example 2 The mandrel of Figure 1 was inserted in the same type of tube as described in Example 1. The tube diameter was such as to ensure a close fit to the mandrel. The initially cylindrical tube was deformed to adopt a helical shape, as seen in Figure 2. In this case, a strip was not wound around the tube. The assembly was 30 placed in an oven at 330'C for 10 minutes, and then allowed to cool. The mandrel was removed from the tube, which had become helical.

WO 2006/136861 PCT/GB2006/002354 -14 Example 3 In this case a tube made of ePTFE having an internal diameter of 6 mm was used. The tube was cylindrical and was provided with an external helical support wrap or tape 20 wound at a helix angle of approximately 80 degrees. The mandrel of Figure 5 1 was inserted into the tube. The initially cylindrical tube was deformed to adopt a helical shape, as seen in Figure 2. A strip 8 (as used in Example 1) was not wound around the tube. The assembly was placed in an oven at 360*C for 20 minutes, and then allowed to cool. The mandrel was removed from the tube, which had become helical. The resulting helical graft is shown in Figure 5. The graft was found to 10 show satisfactory resistance to axial extension when a tensile load was applied thereto. Example 4 The mandrel of Figure 1 was inserted in the same type of tube as described in 15 Example 1. The tube diameter was such as to ensure a close fit to the mandrel. The initially cylindrical tube was deformed to adopt a helical shape, as seen in Figure 2. The tube and mandrel were placed in an oven at 275*C for 1 hour and then removed so as to cool in air at room temperature. A strip of the same type as described in Example 1, made of ePTFE, was applied to the tube at the same helix angle as the 20 tube. This was done by winding the strip onto the tube with a small tension to ensure intimate contact and then securing the two ends of the strip by clamps in order to maintain its position. The combination of mandrel, tube and strip was heated to about 350 to 360'C for 30 minutes. This softened the ePTFE of the tube and strip sufficiently for them to bond to each other. A graft similar to that shown in 25 Figure 9 was produced. Example 5 A tube made of the same type as described in Example 1 was used, namely a tube made of ePTFE of a conventional cylindrical type available for use as vascular 30 prosthesis, with an internal diameter of approximately 6 mm and an external diameter of approximately 7 mm. The tube was wound round a mandrel as shown in Figure 7, following the helical groove 4 which had a width of approximately 8 mm.

WO 2006/136861 PCT/GB2006/002354 - 15 It was placed in an oven at 275'C for 1 hour and then removed so as to cool in air at room temperature. This heating step was a thermosetting step, whereby the shape of the tube was set in a generally helical shape determined by the shape of the helical grove. 5 A strip made of ePTFE was applied to the tube whilst it was still on the mandrel. The strip was wound onto the tube whilst applying a small amount of tension to the strip so as to minimise distortion of the cross-section of the tube whilst ensuring intimate contact therewith. The strip was laid approximately centrally of the groove, on the radially outermost surface of the tube, so that it adopted the same 10 helix angle as the tube. The ends of the strip were secured by clamps so that it stayed in place. The combination of mandrel, tube and strip was then placed in an oven at about 350 to 360*C for 30 minutes. This softened the ePTFE tube and strip and allowed them to bond to each other. They were allowed to cool in air at room temperature and then removed from the mandrel. The graft so formed is shown in 15 Figure 9. The strip 8 had a width of approximately 1.3 mm and a thickness of approximately 0.3 mm. In a control experiment, it was found that using the above ePTFE tube it was difficult to apply the strip before the tube had been thermoset, because of the deformability of the tube making it problematic to obtain the desired uniform strip to 20 tube contact. In Example 5, however, after the thermosetting step the tube was less easily deformed as the strip was applied to its surface, so facilitating placement of the strip in intimate contact with the tube. This resulted in a good strip to tube bond in the second heating step. It was found that it was unnecessary to insert a support inside the tube either during the shaping step or the step of applying the strip. 25

Claims

1. A method of making artificial graft tubing, comprising providing a helical mandrel having a centre line following a substantially helical path, providing a 5 generally tubular wall having a longitudinally extending cavity, positioning the helical mandrel inside the tubular wall so that the longitudinally extending cavity has a centre line following a substantially helical path, and causing the tubular wall to retain, at least partly, the shape with the longitudinally extending helical cavity. 10

2. A method as claimed in claim 1, wherein the tubular wall is initially substantially cylindrical.

3. A method as claimed in claim 1 or 2, wherein the tubular wall is thermoset so as to retain, at least partially, the shape with the longitudinally extending cavity. 15

4. A method as claimed in claim 1, 2 or 3, wherein the tubular wall comprises a helically wound support.

5. A method as claimed in any preceding claim, comprising applying an 20 elongate member to the tubular wall so as to extend longitudinally thereof, when the tubular wall is supported by the mandrel.

6. A method as claimed in claim 5, wherein the elongate member is applied to extend both circumferentially and longitudinally of the tubular wall. 25

7. A method as claimed in claim 6, comprising securing the elongate member at one end and subjecting it to longitudinal tension whilst applying it to the tubular wall. 30

8. A method as claimed in claim 6 or 7, wherein the elongate member is applied to extend helically along the tubular wall with a pitch substantially equal to the pitch of the helical centre line. WO 2006/136861 PCT/GB2006/002354 - 17

9. A method as claimed in claim 5, 6, 7 or 8, wherein the elongate member is bonded to the tubular wall by a heating step. 5 10. A method as claimed in claim 9, wherein the heating step is a single heating step serving both to bond the elongate member to the tubular wall and to thermoset the tubular wall to retain, at least partly, the shape with the longitudinally extending cavity.

10

11. A method of making artificial graft tubing, the method comprising providing a generally tubular wall having a longitudinally extending cavity, shaping the tubular wall so that the longitudinally extending cavity has a centre line following a substantially helical path, causing the tubular wall to retain, at least partly, the shape with the longitudinally extending helical cavity, and thereafter applying to the 15 tubular wall an elongate member so as to extend longitudinally thereof.

12. A method as claimed in claim 11, wherein the elongate member is applied to extend both circumferentially and longitudinally of the tubular wall. 20

13. A method as claimed in claim 12, wherein the elongate member is applied to extend helically along the tubular wall with a pitch substantially equal to the pitch of the helical centre line.

14. A method as claimed in claim 11, 12 or 13, wherein the step of causing the 25 tubular wall to retain, at least partly, the helical shape comprises thermosetting the tubular wall

15. A method as claimed in any of claims 11 to 14, wherein the elongate member is bonded to the tubular wall by a heating step. 30

16. A method as claimed in any of claims 11 to 15, wherein the tubular wall is shaped by being wound round a mandrel. WO 2006/136861 PCT/GB2006/002354 - 18

17. A method as claimed in claim 16, wherein the mandrel has a substantially helical groove in which the tubular wall is at least partly received. 5

18. A method as claimed in any of claims 11 to 15, wherein the tubular wall is shaped by positioning a substantially helical mandrel inside the tubular wall.

19. A method as claimed in claim 16, 17 or 18, wherein the elongate member is applied to the tubular wall when it is supported by the mandrel. 10

20. A method as claimed in any of claims 11 to 19, wherein the elongate member is applied to the tubular wall externally thereof.

21. A method of making artificial graft tubing, the method comprising providing 15 a mandrel having a substantially helical groove, providing a generally tubular wall having a longitudinally extending cavity, positioning the tubular wall at least partly in the groove so that the longitudinally extending cavity has a centre line following a substantially helical path, and causing the tubular wall to retain, at least partly, the shape with the longitudinally extending helical cavity.