WO1998000075A1

WO1998000075A1 - Bio compatible material and method

Info

Publication number: WO1998000075A1
Application number: PCT/AU1997/000410
Authority: WO
Inventors: John Campbell Woodard
Original assignee: Cortronix Pty. Ltd.
Priority date: 1996-06-28
Filing date: 1997-06-27
Publication date: 1998-01-08
Also published as: AUPO071896A0

Abstract

A bio compatible material (10) including a surface (11) from which a contoured structure extends, particularly in the form of fibrils (12). The bio compatible material (10) is formed by a moulding method involving use of a master negative mould (15), the method allowing independent control over the characteristics of the base material on the one hand and the fibrils (12) which extend from the base on the other hand. A particular form of the method involves use of a laser source (17) operating through a mask (19) to form the master negative mould (15).

Description

BIO COMPATIBLE MATERIAL AND METHOD

The present invention relates to a bio compatible material and method, more particularly, to such a material and method adapted for use as a blood-contacting structure or such structure incorporating a blood-contacting surface.

Background

No artificial material is able to fully mimic the non- thro bogenic properties of the endothelial cells which line the blood-contacting structures of the body. Thromboembolic complications have therefore been a more or less serious problem with intermediate to long-term use of devices that are in contact with flowing blood such as left ventricular assist devices (LVAD) and total artificial hearts. These thromboembolic complications involve the deposition of proteinaceous and cellular components of the blood on the artificial surface. Aggregations of this haematogenous material may then become detached from the artificial surface and be carried by the flowing blood until they embolize (block a nutrient artery to) end organs such as the brain, causing serious organ damage or death.

Four distinct approaches have been employed in the past 30 years to attempt to reduce the level of thromboembolic complications associated with artificial blood pumping devices: a) ultra-smooth surface

A highly biocompatible, microscopically smooth polymeric surface has been employed to ensure minimal cell adhesion (as used in the Novacor left ventricular assist system) . However, such surfaces are extremely expensive to produce with the low level of surface defects required. When such a smooth surface is implanted, defects develop due to chemical and mechanical degradation and calcification can be deposited on the surface in areas of high strain.

These defects can then contribute to eventual formation of thrombi. In addition, crevices and voids at the inevitable seams and junctions between smooth- surfaced blood pumping circuits will also serve as a nidus for thrombus formation. b) "Biolized" surface

An alternative smooth surface is a blood contacting surface coated with a biological material such as 5% glutaraldehyde cross-linked dehydrated gelatin. Baylor College of Medicine has been developing a totally implantable ventricular assist system utilising this approach. c) "Seeded" surface

To reproduce nature's own biocompatible lining by pre- seeding biopolymers, smooth or textured, with an autologous endothelial cell layer. This could result in a completely endothelialised neointima with all the desirable non-thrombogenic properties of the cells expressed. d) Textured surface

Instead of trying to combat the deposition of a layer of haematogenous material forming on the artificial surface, one approach has been to encourage this layer, to form but to ensure that its thickness is maintained within narrow limits and that the deposited material is not shed from the surface. The Thermo Cardiosystems Inc. pneumatic VAD features such textured blood contacting surfaces. Sintered titanium micro spheres are used on the rigid metallic components and integrally textured polyurethane is used on the flexible pusher plate diaphragm. The integrally-textured polyurethane surface is made by means of the replamineform process.

Similar concerns apply in the field of cardiovascular grafts, blood vessel patches and the like. Efforts to provide appropriate surfaces for blood contact are described in US4, 657,544 (Pinchuk) , US5, 104,400 (Berguer) and also see Surgery, 79:02,1976 Feb, 229-32 (White R A et al) which describes use of the Replamineform process to produce a vascular prosthesis.

It is an object of the present invention to provide an alternative and/or improved blood contacting surface of the textured surface type. Broad Statement of Invention

Accordingly, in one broad form of the invention, there is provided a method of producing a textured surface on a biologically compatible material. Preferably said textured surface is a blood contacting surface.

Preferably said surface is textured with features which tend to trap haematogenous material.

Preferably said textured surface is smooth with fibrils extending from it.

Preferably said fibrils have a pitch (p) , a length (1) and a diameter at base (d) where 10 < p < 150, 10 < 1 < 350 and 5 < d < 60, all dimensions in micro metres.

Preferably said p is approximately 100, 1 is approximately 250 and d is approximately 30 micro metres. Preferably said p = 100, 1 = 250 and d = 30 micro metres.

Preferably said fibrils are tapered from a base located on said surface to an apex extended from said surface.

In a further broad form there is provided a method of forming a textured surface comprising the steps of producing a master negative mould of the design texture and reproducing this texture by casting against said master negative mould.

Preferably said master mould is micro machined by use of an excimer laser. Preferably said excimer laser is operated in imaging mode.

Preferably said excimer laser is diverged so as to provide a broad laser beam which is directed at a mask having an array of apertures there through in a pattern corresponding to the texture pattern desired in said master negative mould.

Preferably the laser light which passes through said apertures passes through a demagnifying optical stage before striking the surface of said master negative mould. Preferably said laser and the degree of exposure of said master negative mould to the laser light are controlled so as to control the extent and depth of ablation of mould material. Preferably an array of blind, tapered holes of pitch (p) , length (1) and base diameter (d) are produced in said master negative mould.

Preferably said master negative mould is made from a minimum energy of ablation material. Preferably said minimum energy material comprises a polymer.

Preferably said method further includes the step of solution casting a bio compatible polyurethane onto said master negative mould, allowing said bio compatible polyurethane to cure and then separating said cured polyurethane material from said master negative mould, said cured polyurethane material thereby removed comprising a textured biological surface. In a further broad form there is provided a textured surface produced by the above method.

The method allows a textured surface to be customised to particular applications. In a further broad form there is provided a biologically compatible material having a textured surface manufactured according to the above method and further including fibrils that are flexible and long enough to form an interlocking mat so as to retain haematogenous deposits. In a further broad form there is provided a method of producing a textured surface on a biologically compatible material comprising, in combination, the use of excimer laser micro machining to form a castable mould and the step of producing a cast from said mould.

Brief Description of Drawings

One embodiment of the invention will now be described with reference to the accompanying drawings where: Fig. 1 illustrates a mould and resulting bio compatible material produced therefrom according to a first embodiment of the invention,

Fig. 2 illustrates the steps of utilisation of the mould of Fig. 1

Fig. 3 is a perspective, diagrammatic view of a laser apparatus adapted to produce the mould of Fig. 1 Fig. 4 is a perspective view of one example of a textured surface on a bio compatible material producible by the method illustrated in Fig. 2, and Fig. 5 illustrates alternative fibril shapes in accordance with alternative embodiments of the invention.

Detailed Description of Preferred Embodiment

With reference to Fig. 1 there is shown a bio compatible material 10 which includes a surface 11 from which extend a plurality of fibrils 12.

As shown in the inset each fibril 12 is substantially in the form of a tapered cone having a base of diameter d, a height of 1 and an inter-fibril spacing (centre to centre) of p. In one particular form 10 < p < 150 microns,

10 < 1 < 350 microns and 5 < d < 60 microns (or micrometres) . More particularly p is approximately 100 microns, 1 is approximately 250 microns and d is approximately 30 microns (or micrometres) . It will be observed that the fibrils 12 taper from a base 13 to an apex 14.

The fine level of detail incorporated in the surface

11 of bio compatible material 10 is achieved by micro machining a master negative mould 15. As will be observed in Fig. 1 the master negative mould 15 includes a plurality of tapered holes 16 which correspond to the fibrils 12 of the bio compatible material 10 produced when the master negative mould 15 is used in a moulding operation to produce the bio compatible material 10. With reference to Fig. 2 the moulding operation comprises firstly the production of the master negative mould 15 by a micro machining process to be described below. In a second step the mould 15 then receives a bio compatible material such as a bio compatible polyurethane onto the mould. The material is cured and then, in a third step, the cured bio compatible material 10 is separated from the mould 15.

The polyurethane used in this example is a polycarbonate urethane elastomer, Corethane 80A (Corvita Corporation, Miami, FL, USA) . The polyurethane was solved in Dimethylacetamied (DMAC) . The viscosity of the polyurethane solution needs to be so reduced that the solution infiltrates down into the tips of holes. The concentration of the polyurethane in DMAC was reduced down to 10% when cast under vacuum. The solvent was removed by heating the polyurethane solution in an oven at 50-60 degrees Celsius for 4 days, then was further dried at 40-50 degrees Celsius under vacuum.

Heating duration and temperature need to be selected according to both the amount of solution to be cast and the solution concentration in DMAC. Finally, the cured polyurethane forming the bio compatible material 10 is gradually peeled off the mould 15.

With reference to Fig. 3 the step of micro machining to produce the master negative mould 15 is performed by laser. As illustrated in Fig. 3 the apparatus comprises an excimer laser source 17 operating in "imaging mode". The beam 18 is diverged to provide a broad beam that illuminates a mask 19. Holes in the mask 19 permit the laser light to pass through and thence through a demagnifying optical stage 20 after which the laser light strikes and ablates material in the target mould 21.

In this arrangement the laser causes blind, tapered holes to form in the target material of the target mould 21 in correspondence to the apertures in the mask 19. The pitch p and diameter at base d of the tapered holes are controllable by changing the diameter and pitch of the holes or apertures in the mask 19 and the demagnification factor of the beam occurring in the demagnifying optical stage 20. The length 1 is controlled by the amount of laser energy applied to forming the holes.

In this example the target mould is made from a polymer whereby laser energy required is minimised whilst the flexible characteristic of the polymer permits undercuts in the resulting bio compatible material formed by the mould to be relatively easily pulled from the mould. In this instance the target material 21 of the master negative mould 15 comprises a two component Silastic rubber (Silastic J RTV, Dow Corning Corporation, Midland USA) . This material has been found to facilitate the separation of the cured polyurethane material forming the bio compatible material from the mould 15. The Silastic material also has the capacity to withstand repeated use, for example at least 30 demouldings. In this example the tapered nature of the holes 16 in the master negative mould 15 is the result of a reduction of incident laser beam energy with increasing depth of penetration. Furthermore, the combination of the tapered fibrils 12 of the dimensions and density (pitch) indicated earlier together with the high degree of smoothness reflected in the micro machining process of which the bio compatible material 10 is a facsimile provide a bio compatible material whose surface is suited for contact with blood and which is adapted to retain haematogenous deposits.

In one form the height 1 of the fibrils together with their composition is such that they are long enough and flexible enough to form an interlocking mat so as to facilitate the retention of haematogenous deposits.

This particular arrangement is illustrated in Fig. 4 wherein it will be observed that a mat 22 of interlocking fibrils 12 can be produced by the method of the invention. The above describes only one embodiment of the invention and modifications, obvious to those skilled in the art can be made thereto without departing from the scope and spirit of the present invention.

For example, with reference to Fig. 5A, there is shown fibrils 23 having a square base, although otherwise tapered as previously.

Fig. 5B illustrates fibrils 24 of circular cross section throughout.

Fig. 5C illustrates fibrils 25 having a circular cross section which increases along the length of the fibril in the form of an inverted taper. This arrangement is possible by appropriate selection of structure and mould material. The method of the invention permits independent control of the base from which the fibrils extend on the one hand and the structure of the fibrils which form the textured surface on the other. So, for example, the base structure including its thickness can be selected to match the elastic modulus of the artery or vein to which the material is to be attached and/or selection of appropriate strength to provide a good hold for sutures.

The structure of the fibrils including their length, contours and density can be selected to provide an appropriate shear force gradient with respect to blood flow near the surface of the bio compatible material.

Industrial Applicability

The bio compatible material and its method of manufacture are particularly suited for construction of surfaces which contact the blood including, for example, vascular grafts and vascular patches.

Claims

1. A method of producing a textured surface on a biologically compatible material.

2. The method of Claim 1 wherein said textured surface is a blood contacting surface.

3. The method of Claim 1 or Claim 2 wherein said surface is textured with features which tend to trap haematogenous material.

4. The method of Claim 3 wherein said textured surface is smooth with fibrils extending from it.

5. The method of Claim 4 wherein said fibrils have a pitch (p) , a length (1) and a diameter at base (d) where 5 < p < 150, 10 < 1 < 350 and 5 < d < 60, all dimensions in micro metres. 6. The method of Claim 4 wherein p is approximately 100,

1 is approximately 250 and d is approximately 30 micro metres. 7. The method of Claim 6 wherein p = 100, 1 = 250 and d =

30 micro metres. 8. The method of Claim 4 wherein said fibrils are tapered from a base located on said surface to an apex extended from said surface. 9. A method of forming a textured surface comprising the steps of producing a master negative mould of the design texture and reproducing this texture by casting against said master negative mould.

10. The method of Claim 9 wherein said master mould is micro machined by use of a laser.

11. The method of Claim 10 wherein said excimer laser is operated in imaging mode. 12. The method of Claim 10 wherein the beam from said excimer laser is diverged so as to provide a broad laser beam which is directed at a mask having an array of apertures there through in a pattern corresponding to the texture pattern desired in said master negative mould.

13. The method of Claim 12 wherein the laser light which passes through said apertures passes through a demagnifying optical stage before striking the surface of said master negative mould. 1 . The method of Claim 9 wherein the power of said laser and the degree of exposure of said master negative mould to the laser light are controlled so as to control the extent and depth of ablation of mould material. 15. The method of Claim 14 wherein an array of blind, tapered holes of pitch (p) , length (1) and base diameter (d) are produced in said master negative mould.

16. The method of Claim 9 wherein said master negative mould is made from a minimum energy of ablation material.

17. The method of Claim 16 wherein said minimum energy material comprises a polymer.

18. The method of Claim 9 wherein said method further includes the step of solution casting a bio compatible polyurethane onto said master negative mould, allowing said bio compatible polyurethane to cure and then separating said cured polyurethane material from said master negative mould, said cured polyurethane material thereby removed comprising a textured biological surface.

19. A textured surface produced by the method of any preceding claim.

20. The method of any previous claim wherein said textured surface is customised to particular applications.

21. A biologically compatible material having a textured surface manufactured according to the method of any previous claim and further including fibrils.

22. The material of Claim 21 wherein said fibrils are flexible and long enough to form an interlocking mat so as to retain haematogenous deposits.

23. A method of producing a textured surface on a biologically compatible material comprising, in combination, the use of laser micro machining to form a castable mould and the step of producing a cast from said mould.

24. The method of Claim 23 wherein said laser is an excimer laser.

25. The method of Claim 23 wherein said laser is a carbon dioxide laser.

26. A blood contacting structure comprising a base adapted for structural behaviour and having a surface texture integrally attached but independently controlled and designed for its ability to promote controlled deposition and to define a selected velocity profile of blood therethrough.

AMENDED CLAIMS

[received by the International Bureau on 28 October 1997 (28.10.97); original claim 26 amended and renumbered as claim 35; new claims 26-34 and 36-43 added; remaining claims unchanged (2 pages)]

26. A biologically compatible material having a textured surface which includes fibrils.

27. The material of claim 26 wherein said fibrils are flexible and long enough to form an interlocking mat so as to retain haematogenous deposits.

28. The material of Claim 26 wherein said textured surface is a blood contacting surface.

29. The material of Claim 26 wherein said surface is textured with features which tend to trap haematogenous material.

30. 'i'ne material of Cit-ir-i 2G wi-eft-slu --aid l-<--xture i-fε-ce is smooth with said fibrils extending from it.

31. The material of Claim 26 wherein said fibrils have a pitch (p ) , a length ( 1 ) and a diameter at base ( d ) where 10 < p < 150, 10 < 1 < 350 and 5 < d < 60, all dimensions in micro metres.

32. The material of Claim 31 wherein p is approximately 100, 1 is approximately 250 and d is approximately 30 micro metres. 33. The material of Claim 31 wherein p = 100, 1 = 250 and d = 30 micro metres. 34. The material of Claim 26 wherein said fibrils are tapered from a base located on said surface to an apex extended from said surface. 35. A blood contacting structure comprising a base selected for its structural behaviour and having a textured s iiace mtegraxiy aτtacned tnereto but independently controlled during formation and designed for its ability to promote controlled deposition and to define a selected velocity profile of blood therethrough. 36. The material of claim 35 wherein said textured surface includes fibrils which are flexible and long enough to form an interlocking mat so as to retain haematogenous deposits.

37. The material of Claim 36 wherein said textured surface is a blood contacting surface.

38. The material of Claim 36 wherein said surface is textured with features which tend to trap haematogenous material.

39. The material of Claim 36 wherein said textured surface is smooth with said fibrils extending from it.

40. The material of Claim 36 wherein said fibrils have a pitch ( p ) , a length ( 1 ) and a diameter at base ( d) where 10 < p < 150, 10 < 1 < 350 and 5 < d < 60, all dimensions in micro metres.

41. The material of Claim 40 wherein p is approximately 100, 1 is approximately 250 and d is approximately 30 micro metres. 42. The material of Claim 40 wherein p = 100, 1 = 250 and d = 30 micro metres. 43. The material of Claim 36 wherein said fibrils are tapered from a base located on said surface to an apex extended from said surface.