CA1169346A - Implantable material - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
Porous polymeric material, which, in tubular form, is suitable for use as a vascular graft, is made by a procedure wherein polymeric fibres are wound on a mandrel while overlying fibres are simultaneously bonded together.
In one preferred embodiment, a viscous solution of a biocompatible polymer is extruded from a spinnaret to form a plurality of filaments which are wound on a rotating mandrel as the spinnaret reciprocates relative to the mandrel. The filaments are wet as they contact each other, so that on evaporation of the solvent the fibres become bonded to each other.

Description

I ~ 6~3~6 The vascular graft which may be forme~ by the pro-cedure of the invention is porous and flexible, is bio-compatible and biocompliable, and exhibits high suturing strength and high toughness to resist cyclic fatigue.
Anisotropic properties may be obtained by varying the manner of winding of the fibres.
In accordance with another aspect o~ the present invention, there is provided a flexible biocompatible and biocompliable tubular product useful as a vascular graft having an inside diameter of about 1 to about 50 mm, a wall thickness of about 0.1 to about 2 mm and a porosity of about 50 to about 80 vol.%, comprising polymeric material fibres of diameter from about 10 to about 30 microns which intersect and overlie one another at an angle of about 60 to about 70 to the axis of the product and are joined together at each such intersection.
The porous nature of the graft and the relatively small pore size therein induces endothelialization of the inner surface of the graft and tissue ingrowth into the outer surface. The phenomenon of endothelialization of porous vascular graft surfaces is described in Canadian Patent No. 1,092,303 in the name of David C. MacGregor.
As set forth in that patent, nucleated cells in the bloodstream colonize onto the porous surface and sub-sequently differentiate into other cell types. The tissue coating organizes over about a one to three month pexiod, does not appe~r to increase significantly in thickness there-after and includes flattended endothelial-like cells at the surface thexeof.
Vascular grafts of the invention may vary in dimen-sions over wide ranges, depending on the size and type of the blood vessel that they are to replace. The inside diameter may vary widely from about 1 mm to about 50 mm, typically 3 to about 25 mm, and is dictated by the diameter of the mandrel on which the graft is formed. The wall thickness may vary from about 0.1 to about 2 mm, typically about 0.5 to about .
.
: . : . . .
,. : . . . . :
, 1 :~ 6 ~
2a 1 mm and is controlled by the number of :ayers of windings formed on the mandrel.
The pore size of the porous structure of the graft may be varied by varying the thickness of the fibres and angle of winding. The pore size is considered the shortest distance between twv fibres located in th~ same plane and usually is, in the longer dimension, about 5 to about lO00 microns, typically about lO to about 100 microns.
The porosity of the graft is largely dependant on the angle of winding. In addition, compression of the graft prior to drying and removal from the mandrel serves to alter the porosity, so that variation of the porosity over a wide range may be achieved by a con~ination of these procedures.
The porosity may va~y from 5 to about 85 vol~%, typically about 50 to about 80 vol.~.
The graft is required to have a minimum strength in use consistent with the requirements that the graft may be sutured readily without tearing and that the graft have sufficient strength to prevent structural breakdown at the anastomosis and along the length of the graft. Such characteristics are provided by the vascular graft of this invention.
The actual minimum strength requirements will vary depending on the intended use of the graft, the strength requirements for venous grafts being very much less than those for arterial grafts because of the lower venous blood pressures. The grafts provided for venous use should ' ~ 3 6~

be a~le to withstand venous ~lood pressure of no~ less than 25 mm Hg for prolonged periods, generally greater than one year, pre~era~ly greater than 5 years, in a physiological _ . _ , . . .
- environment. An arterial gra~t should ~e able to withs~and pulsatile arterial ~lood pressure of greater than about 300 mm Hg, prefera~ly greater than a~out 500 mm Hg, for a prolonged period of tlme, generally greatex than five years, preferably g-reater than ten~years-, in a physiological environment. ~~-The non-woven struc~ure which is formed on the mandrel utilizing the procedure of ~his invention may be utilized for a variety of bio-medical applications other than as a .. . ... . ..
vascular graft and for a variety of non-medical applications.
The tu~ular structure may ~e cut to form a flat sheet, or may be otherwise shaped, for utilization in A-V shunts, sewing rings for heart valves, sewing pa*ches for heart wall and ~lood vessels, artificial ~lood pump diaphragms, and many other implant and bio-medical applications in dental, ortho-paedic and plastic surgery areas, and additionally in many 20 non-medical applications.
In one embodiment of the present invention, a biocompatible polymeric material from which the ~ubular material is to be constructed, for example, a biocompatible . ~ . , . . :

6~6 polyurethane, is dissolved in a sui~able solvent to form a viscous solution from which a continuous fibre may be drawn.
The solution is extruded through an opening and a continuous filament of desired thickness is drawn ~rom the extruded material, typically less than about 100 microns, preferably to a filament thic~ness of about 10 to about 30 microns. Usually, ~he opening through which the solution is extruded is preferably about 4 to 5 times the diameter of the filament drawn from the extruded material.
In order to increase the speed of formation of the tubular material, it is preferred to wind a plurality of filaments on the mandrel simultaneously, by housing the polymer solution in a spinnaret having a plurality of extrusion openings and drawing a fibre from each extrusion opening.
The drawn fibre is placed in contact with a rotating mandrel. me diameter of the mandrel determines the inside diameter of the tube which is formed. The spinnaret from which the filaments are extruded then reciprocates from one axial end of the fixed position mandrel to the other and parallel thereto at a speed which results in the filaments subtending any desired angle to the~mandrel, preferably about 60 to 70 to the axis of the mandrel, so that the filaments laid in one traverse of the mandrel in one direction and the filaments laid in the previous traverse of the mandrel in ~he opposite direction criss-cross each other, to form a porous structure. The reciprocation of the spin-naret with respect to the mandrel is continued until the desired thickness of overlayed filaments is obtained. Usually the mandrel~is mounted extending horizontally while the spinnaret is vertically spaced from the mandre] to recipro-cate alon~ an axis parallel to the axis of the mandrel.
The solution form of the polymer at the time of formation of the filaments means that the filaments are "wet" when they are laid on the mandrel and this results in firm secure bonding of the filaments to each other ' .

: . , . ' .
- . ~

'' - ,- , ~ ' - 1 1 6~3~;
_ 5 through integral joining at their overlapping-points upo~
evaporation of the solvent, to form a stable non-woven structure without any further processing. Evaporation of the solvent may be enhanced by the application o~ heat during the winding of the filaments on the mandrel, and subsequent to completion o~ the winding operation, if required.
Exposing the tube to infra-red radiation has been found to be a suitable manner of achieving the application of heat.
When the desired thickness of tubular product has been achieved, the porous structure is washed free from residual solvent and removed from the mandrel. As mentioned above, the tubuIar product may be compressed prior to removal from the mandrel to alter the porosity and pore size. The washed product then is dried.
The thickness of the individual fibres in the non-woven structure which resuIts from the above-described procedure may be controlled by the ratio of the 10w rate of polymer solution and the speed of rotation of the mandrel.
The size and shape of the openings or ~ores defined by the fibres in the non-woven structure may be controlled by the angle subtended by the fibres to the mandrel and the fibre diameter.
The procedure just described is suitable for use with polymeric materials which form viscous solutions in volatile solvents from which continuous fibres may be drdwn. The procedure of the invention may be used in rnodified form with other polymeric materials, such as, polyethylene.
In such a modified procedure, extruded fibres are provided in a tacky fusible substantially solvent-free form in the overlaid condition followin~ winding of the fibres on a mandrel so that fibre-to-fibre bonding occurs and the non-woven structure is provided as the - 35 fibres solidify. The tacky fusible form o~the fibres may be provided in any convenient manner, such as, by hot e~truding the fibres from a melt of the polymer and forming the overlying layers while the ~ibres are still hot and fusibLe. Alternatively, the mandrel may be heated ' 3 ~ G

to provide the heat required for fusion of ~he overlayed f ibres as they are wound on the: mandrel . q~he latter procedure may: be enhanced by using fibres which are still h~t from the extrusion.
The procedure of the inven~ion, therefoxe, enables non-woven porous tu~ular products to be formed directly from extruded filaments withou~ the necessity of post-treatment to form an integrated strcture. The porous tubuIar products may be used as such, for example, as vascular grafts, may be used in modifiea form in various bio-medical applications, or m~y be used as such or in modified form in non-medical applications.
The invention is ii.luskrated by the followlng Examples:
Example 1:
A 45% w/w solution o a hydrophilic segmented polyether-polyurethane urea block copolymer in dimethyl formamide was placed in a 5 cc syringe having a 23 G-l needle.
A glass rod of 3 mm in diameter was rotated at 700 rpm.
~he polymer solution was squeezed out from the syringe through the needle. A fibre was drawn from the needle and was initially wound on the rotating rod at a dis-tance of about 5 to 6 inches, after which the rotating glass rod pulled out the fibre continuously without breaking. The syringe was movad back and forth along the longitudinal axis of the rod so as to lay the fibres at an angle of about 45 to the rod axis. Solvent evaporation and fibre drying were assisted by the utiliza~ion of an I.R. lamp.
The drawn fibres were not completely dry as they were laid on each other and bonded together on contact with each other to form a non-woven fabric tube. Once the tube had dried under the I.R. lamp, it was soaked in water and slid from the rod. The tube exhibited elasticit~ and flex-ibility. Scanning electron microscopic (SEM) examination 35 showed a fibre diameter of about 12 microns and pores having maximum dimensions in the range of 50 to 150 microns.
Example 2 The procedure of Example 1 was repeated using ~ ~ .

3 ~ 6~

a 40% solution of a polyurethane (Pellethane 2363 75DX) dis~
solved in dimethyl formamide to form non-woven mater~al tubes on a 6 mm diameter mandrelr with the excep~ion that a housing with six orifices was used to contain the polymer solution, six fibres were simuItaneously wound on the mandrel, and the housing was reciprocably driven relative to the mandrelO
The effect of variation of winding angle on the physical properties of the resulting product were determined. The results are reproduced in the following Table I:

:

1 ~ ~;93 ~ U~
a)a) O o o N
U~ o o~
O U~ O
~ ~_ Z;
U~
~n C) ~_ L~
~1 X ~ U~
o o o o E~
~ ~ ~ .

X ~ C) . . . .
~ ~ o O

_ ~ ~ ~
~ ,~ O ~

~1 ~ dP . , , . U~ 0 5~
H'~ Z O LO ~ ~ o ~ ~i 1:~3 Ui `- Ql O ~ ~

~ CD ~ D'a ~ 3 O ~1 r-l , , ,~ . ..
U~ 1` ~ 1 O 1~ 0~
P~
a,) _ ~r o R -l ~ ~ o ~r1 1:} ~'~1 ~ ~I r_l ~4 a rl ~
t~ O O O O
s: ~ L~ In o o '~ ~

i :
.
' ' ~ ~ ~;93~

As may be.seen from thé xesu~*s of Table I, the porosity and pore size of the product decline as the winding angle is increased. FurtherJ the stiffness and minimum kink~
ing diameter declined significantly as the winding angle increased. These variations enable a balance of ~he properties of pore size, porosity, stiffness and minimum kinking diameter to be achieved by varying the winding angle.
In summary of this disclos.ure, porous t.ubular products, suitable for use in implantable.bio-medical 10 devices and havin~ other non medical uses,:are formed by a unique procedure. Modifications.are poss.ible within the scope of this invention.

:

:

.

1 69~6 ., SUPPLEMENTARY DISC~..OSUÆ
In the parent application, there is descri~ed a method of forming a porous tubular product, which comprises winding an extruded material on a mandrel while simultaneously providing fibre-to-fibre bonding between overlying fibres.
The angle of winding of the fibres with respect to the axis may vary widely and, in accordance with one aspect of this Supplementary Disclosure, generally is from 10 to 80, preferably about 45 to 80. As the angle of winding is decreased, the pore size and the porosity of the graft also decrease, while the shape of the pores also changes.
In accordance with another aspect of this supple-mentary Disclosure, there is provided a flexible bio-compatible and biocompliable tubular product useful as a vascula~ graft having an inside diameter of about l to about 50 mm, a wall thickness of about O.l.to about 2 mm and a porosity of about 50 to about 80 vol. ~, comprising polymeric material fibres of diameter from about lO to about 30 microns which intersect and overlie one another at an angle of about 20 10 to about 80 to the axis of product and are joined to-~` gether at each such intersection.
`; The invention is illustrated by the.accompanying ~: drawings, wherein:
. Figure l is a schematic representation of an apparatus used to effect the present invention;
Figure 2 is a photograph of a medium caliber vas-_ular graft provided in accordance with one embodiment of the invention;
Figure 3 is scanning electron micrograph of the surface of~the graft of Figure l at 20x magnification;
Figure 4 is a scanning electron micrograph of an :~ edge of the vascular gxaft of Figure 2 at lO00 times magni-fication; : : :
Figures 5 to 8 are scanning electron micrographs at 150 x magnification of the inside surface of four vascular grafts consisting of fibres of nom1nal diamèters 13, 16, 20 :
i~'~ '` ` ' .
'~`"~ ~
.... . . . . . , . . ~

-, I 1 6 ~
lOa and 30 microns respectively, Figures 9 and 10 are scanning electron micrographs at 150 times magnification of the inside surface of two - vascular grafts formed at winding angles of 30 and 80 respectively; and Figures 11 to 14 are micrographs of the graft of Figure 2 after being interposed in the abdominal aorta of : a dog for three months, with Figure 11 being a light micrograph of the gross appearance of the graft showing the uniform, smooth, glistening neo-intima with a complete absence of gross thrombi, Figure 12 being a scanning electron micrograph at 70 x magnification of the distal `:
:~ .
:`

:

~ :
:.; ~ :

...... . ~ ~. ..
.

.., . - ~ , .. I .1 ~'13 anastomosis, Figure 13. being a scanning elec~ron micrograph, at 500x magnl~i.cation of the mid-portion, and Flgure 14 being a light micrograph at 40x magnification o~,a cros.s~
section of the graft showing the neointima on the inner surface, transmural growth of fibrovascuLar tissue and outer tissue encapsul'at}on.__ _ _ _ Referring to Figure 1, alcohol is pumped from a tank lO.by a volumetric pump 12 into a high pressure cylinder 14 containing a polymer solution 16 which is separated fr,om the alcohol.by a plunger 18. This arrangement is used to avoid pumping h-gh viscosity polymer solution through.a precision pump.
- The plunger 18-is pushed.by the alcohol and the plunger 18, in turn, pushes the polymer solution through:
a distributor 20 into six orifices 22. The polymer solution is extruded through:the orifices to form.fibres 24 which are wound onto a rotating mandrel 26. The mandrel 26 is rotated.by motor 28. A high circumferential speed of the mandrel 26 resuTts in stretching of the fibres 24.
The distributor 20 reciprocates along the length of the mandrel 26 until the desired thickness of tube has been formed. For example, approximately 800 to-and-fro .
passes of the distr.ibutor 20 are needed to produce a 6 mm I.D. tube having 500 micron thick walls.
The invention is illustrated by the following addl~
tional Examples:
Exam~le 3 ' A woven vascular graft was prepared using the apparatus which is schematically depicted in.Figur.e 1.
A 45~ w/w solution of a h~drophilic segmented polyether-polyurethane urea block copolymer in dimethyl formamide was extruded from a housing having six orifices at a flow rate of 0.1 cc/min. Six fi~res wer~ simultaneously wound on the mandrel..which.:ro.tated at.a speed of 900.:rpm and had.a diameter of lO.'mm while the housing was.reciprocally driven.relative to the man.drel to provide:an:angle of winding of,45. A:su~ficient number of-passes were made to provide.a wall thic~ness of tube of:,about 850 microns.

. ~

:

- During the ~ormation of the .gr~ft, solvent evaporation~
and f,ibre drying were:assisted:by the utili.zation of an I.R. lamp.
The drawn f.ibres were not completely dry as they were laid on each.other.and.bonded together on contact with each other to form a non-woven fabric t.ube. Once the tube had dried under the I~R. lamp, it was soaked in water to remove residual solvent and then sLid rom the rod. The t.ube exh.ibited elasticity and flexibility, The structure of the graft which.was formed is shawn in the.accompanyi.ng Figures 2 to 4. Figure 2 is a a photograph.of,the overall.appearance of the graft while Figur.e 3 is:an SEM'of the outer surface of,the ' graft.at 20 x magnification.and.Figure 4 is an SEM of an edge of the graft at 1000 x-magn.ification, clearly showing thff fused nature of the overlying.f.ibres.
_ .... _ .. .. . .
Example 4 Following the procedure of Example 2, grafts were produced from fibres of varying diameters of 13, 16, 20 and 30 microns. Scanning electron micrographs of:the inside surface of the grafts appear as Figures~5 to ,8 respectively.
The physical appearance.of grafts produced at angles ~: of winding of 30 and 80 appears in Figures 9 and 10 .~ respecti'vely.: As may be seen therein, altering the angle 25~ of winding from 30~ to 80 decreases the porosity by over . 10% and the pore si~ze from about 45 to about 21 microns.
Example 5 Two pro,totype vascular grafts produced by the procedure of Example 4~were tested in vivo. One graft .was.a medium~caliber graft havlng an internal d:iameter of l0..mm and a~wal1 thic~ness of 858:microns whi~e the other graft was a.small caliber graft of intsrnal:diameter `~ of 4 mm and a: wall th-ic~ess of,822~ microns.
. 5:cm length o~ the::medium and.~small caliber grafts were;;interposed~between. segments of~the abdomina~
aorta and left carotid:artery of two dogs,~respect~vely.
'Both dogs were.sacrified three:months after implantation and thè graf.ts examined grossly and~by~llght and.scanning electron microscopy. ~ ~ ~
:

..
.:
.

I 1 6 ~

The medium caliber aortic yrat was found to be widely patent and lined by a uniform,.smooth,: glistening .. . . . . . _ _ ., _ .... .. . .
neo-intima completely devoid of gross thrombi. Light microscopy of the graft (Figure 11) shawed the uniform, smooth,: glistening neo~intima with a complete abs~nce of gross emboli. -Scanning electron microscopy showed completeendotheliali.zation of the.anastomotic sites (Figure 123 and patchy endothel.ialization o~.the mid-portion of the graft with.the intervening areas:being covered.by.branching collagen.bundles to which.platelets: and-strands of.f:~brin were:adhering.~Fïg.ure 13). Light~microscopy of a cross-section Qf the graft (Figure 14) confirmed the presence of a neo-antimal lining with transmural growth of fibro-v vascular tissue and outer tissue encapsulation.
The small caliber carotid graft was also widely patent with a similar uniform,. smooth, glistening neo-intima.
The appearance of the neo-intima on scanning electron and light microscopy was similar to that formed on the medium caliber graft.

.

'`-~

Claims (18)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A method of forming a porous tubular product, which comprises:
extruding an extrudable polymeric material, drawing a continuous fibre from said extruded material, winding said continuous fibre on a mandrel while simultaneously providing fibre-to-fibre bonding between overlying fibre to form a porous tubular product on the mandrel, and rotating said mandrel on its axis at sufficient speed during said winding to effect the drawing of said continuous fibre from said extruded polymeric material.

2. The method of claim 1 wherein said extrudable polymeric material takes the form of a polymeric material from which a fibre may be drawn, and said fibre-to-fibre bonding is achieved by removal of said solvent from said overlying fibres.

3. The method of claim 2 wherein said mandrel is heated to assist in evaporation of solvent from said overlying fibres to achieve said fibre-to-fibre bonding.

4. The method of claim l wherein said extrudable poly-meric material takes the form of a molten polymeric thermo-plastic material, and said fibre-to-fibre bonding is achieved by fusion of overlying fibres and solidification of the fused fibres.

5. A method of forming a porous tubular product, which comprises:
extruding an extrudable polymeric material through a plurality of openings in a spinnaret containing said polymeric material, drawing a plurality of individual continuous fibres from the extruded polymeric material, wincing said plurality of fibres onto a mandrel by rotating said mandrel on its axis at sufficient speed to effect drawing of said plurality of fibres from said spinnaret while simultaneously providing fibre-to-fibre bonding overlying fibres, and reciprocating said spinnaret relative to said mandrel as said mandrel rotates on its axis to form a porous tubular product on said mandrel.

6. The method of claim 5 wherein said spinnaret is reciprocated parallel to the axis of said mandrel as said mandrel rotates on a substantially horizontal axis to wind the fibres on the mandrel.

7. The method of claim 5 wherein said plurality of fibres is simultaneously drawn from a spinnaret having openings which are about 4 to 5 times larger than the diameter of the drawn fibres and containing the polymeric material.

8. The method of claim 5, 6 or 7 wherein a plurality of fibres of diameter less than about 100 microns is simul-taneously drawn from the spinnaret said fibres subtend an angle to the axis of the mandrel, and said winding is effect-ed sufficient to form a porous tubular material having pore openings of about 5 to about 1000 microns and a porosity of about 5 to about 85 volume percent.

9. The method of claim 5, 6 or 7 wherein a plurality of fibres of diameter of about 10 to about 30 microns is simultaneously drawn from the spinnaret, said fibres subtend an angle of about 60° to about 70° to the axis of the mandrel, and said winding is effected to form a porous tubular material having pore openings of about 10 to about 100 microns and a porosity of about 50 to about 80 volume percent.

10. The method of claim 5, 6 or 7 wherein a plurality of fibres of biocompatible and biocompliable polymeric material of diameter less than 100 microns is simultaneously drawn from the spinnaret, said mandrel has a diameter of about 1 to about 50 mm, said fibres subtend an angle to the axis of the mandrel and said winding is effected sufficient to form a flexible porous tubular product having pore openings of about 5 to about 1000 microns and a porosity of about 5 to about 85 volume percent, and said spinnaret is reciprocated a sufficient number of times to provide a thickness of about 0.1 to about 2 mm, whereby the tubular product is suitable for use as a vascular graft.

11. The method of claim 5, 6 or 7 wherein a plurality of fibres of biocompatible and biocompliable polymeric material of diameter from about 10 to about 30 microns are simultaneously drawn from the spinnaret, said mandrel has a diameter of about 1 to about 50 mm, said fibres subtend an angle of about 60° to about 70° to the axis of the mandrel, said winding is effected to form a flexible porous tubular product having pore openings of about 10 to about 1000 microns and a porosity of about 50 to about 80 volume percent, and said spinnaret is reciprocated a sufficient number of times to provide a thickness of about 0.1 to about 2 mm, whereby the tubular product is suitable for use as a vascular graft.

12. The method of claim 1 or 5 including the further steps of removing said porous tubular material from said mandrel and cutting the same to form a planar sheet of porous material.

13. A flexible biocompatible and biocompliable tubular product useful as a vascular graft having an inside diameter of about 1 to about 50 mm, a wall thickness of about 0.1 to about 2 mm and a porosity of about 50 to about 80 vol. %, comprising polymeric material fibres of diameter from about 10 to about 30 microns which intersect and over-lie one another at an angle of about 60° to about 70° to the axis of the product and are joined together at each such intersection.

14. The product of claim 13 wherein said inside diameter is about 3 to about 25 mm and said wall thickness is about 0.5 to about 1 mm.

CLAIMS SUPPORTED BY SUPPLEMENTARY DISCLOSURE

15. The method of claim 5, 6 or 7 wherein a plurality of fibres of diameter less than about 100 microns is simul-taneously drawn from said spinnaret, said fibres subtend an angle of about 10° to about 80° to the axis of the mandrel, and said winding is effected to form a tubular product having pore openings of about 5 to about 1000 microns and a porosity of about 50 to about 80 volume percent.

16. The method of claim 5, 6 or 7 wherein a plurality of fibres of diameter less than about 100 microns is simul-taneously drawn from the spinnaret, said fibres subtend an angle of about 45° to about 80° to the axis of the mandrel, and said winding is effected to form a tubular product having pore openings of about 5 to about 1000 microns and a porosity of about 50 to about 80 volume percent.

17. A flexible biocompatible and biocompliable tubular product useful as a vascular graft having an inside diameter of about l to about 50 mm, a wall thickness of about 0.1 to about 2 mm and a porosity of about 50 to about 80 vol. %, comprising polymeric material fibres of diameter from about 10 to about 30 microns which intersect and overlie one an-other at an angle of about 10° to about 80° to the axis of product and are joined together at each such intersection.

18. The product of claim 17 wherein the angle of winding is about 45 to 80°.