Prosthetic tubular article

Abstract: The invention involves the use of absorbable or absorb­ able/nonabsorbable components to fabricate textile vascular grafts of all sizes and specifically for repair of the peripheral vascular system and for coronary bypass use. The bioab­ sorbable components of the graft fosters increased tissue ingrowth into the graft as compared to conventional 100% nonabsorbable grafts. Increased tissue ingrowth leads to greater patency through formation of a vascularized neointi­ ma and less tendency to be aneurysmal through formation of a suitable adventitia.

Description: This invention relates to a tubular article and specifically to a vascular graft containing an absorbable/nonabsorbable biomaterial. The use of the vascular graft is for repair of the peripheral vascular system and for coronary bypass. The absorbable material fosters increased tissue ingrowth into the graft as compared to nonabsorbable grafts. Increased tissue ingrowth leads to greater patency through formation of a vascularized neointima and less tendency to be aneurysmal through formation of a suitable adventitia. The absorbable material can vary and includes polyglycolic acid (hereafter PGA), and a copolymer comprising glycolic acid ester and trimethylene carbonate linkages, e.g. the copolymer in the MAXON™ (American Cyanamid Company, Wayne, N.J. 07470 U.S.A.) suture. Prosthetic devices manufactured from polyglycolic acids and fabric structures of an intermixture of PGA and non-absorbable material are described in US-A-3 463 158. EP-A-0 159 502 describes an absorbable or non-absorbable surgical repair mesh made from absorbable or partially absorbable fibers. The absorbable fibers are manufactured from a polymer having a glycolic acid ester linkage. The nonabsorbable material (which is used as the backbone) can be proprietary materials, e.g. a Hytrel™ (E.I. du Pont and Co., Wilmington, Delaware, U.S.A.) polymer, such as the polymer in the NOVAFIL™ (American Cyanamid Company, Wayne N.J.) suture. Alternatively, the nonabsorbable material can be more conventional polymers including a polyester, polyamide or polypropylene. There has been a long felt need in the vascular graft art to develop a small diameter graft which will be generally acceptable to essentially all of the surgical community. The reasons for this long felt need are many and relate both to the biological requirements for a small diameter graft and to the limitations of the biomaterials generally used for these applications. Consequently, prior art small diameter vascular grafts, e.g. at or less than 8 mm diameter to even smaller diameter grafts, e.g. at or less than 4 mm diameter, have not been universally accepted by the surgical community. To solve this long felt need, critical questions about vascular graft construction and use have to be considered, including, but not limited to, the following: a. What is the porosity of the vascular graft? b. What is the compliance of the vascular graft? c. What are the optimum textile and biological factors for manufacturing a graft, having a double tube configuration specifically, a nonabsorbable outer tube and an absorbable inner tube structure? d. What are the optimum textile and biological factors for manufacturing a vascular graft having an external support structure? A knitted vascular graft as defined in claim 1 has now been invented which solves this long felt need. The vascular graft has a plurality of fibers which are manufactured from an absorbable copolymer. The copolymer comprises up to 50% by weight of trimethylene carbonate linkages. The copolymer in the MAXON™ (American Cyanamid Company, New Jersey, U.S.A.) suture contains a copolymer having trimethylene carbonate linkages. MAXON™, which is a poly(glycolide- co-trimethylene carbonate), has superior and unexpected properties when contrasted to other absorbable fibers. It is long-lasting. A portion of its original strength is retained out to 56 days; 50% of the strength remains through 28 days. The absorption rate of MAXON™ is approximately equal to PGA. A MAXON™ fiber is more compliant than polyglycolic acid (herein PGA). A graft containing 75% MAXON™ in combination with Dacron™ has a measured compliance of 3.03. A similarly constructed PGA/Dacron™ graft has a compliance of 2.45. Compliance is measured as a percentage of diametral change per 133 mbar (100 mm Hg) internal pressure change. Finally, the bending modulus of MAXON™ is approximately 2239,25 N/mm² (325,000 p.s.i.), indicating that MAXON™ is a much more flexible fiber than other absorbable fibers. In one embodiment, the copolymer comprises 50% by weight of glycolic acid ester linkages. In another embodiment, the copolymer consists of at least one glycolic or lactic acid ester linkage. Another embodiment is a graft which is manufactured on a warp knitting machine. The absorbable polymer comprises more than 50% by weight of the article. The remainder, comprises a plurality of fibers manufactured from a nonabsorbable polymer. In a specific embodiment, the graft is manufactured on a Raschel knitting machine. In another specific embodiment, the plurality of nonabsorbable polymer fibers of the graft comprises 20 to 35% by weight of the graft. In a more specific embodiment, the plurality of absorbable and nonabsorbable fibers are separately texturized by either a false twist or a knit/deknit process. In a most specific embodiment, the nonabsorbable polymer is Hytrel®. Another most specific embodiment is wherein the nonabsorbable polymer is polyethylene terephthalate. Hytrel™ is a trademark of E.I. DuPont de Nemours & Co., Wilmington, Del. U.S.A. for a class of prior art polymers having the generic name of a polyether-ester. A specific embodiment of Hytrel® which is useful in this invention is a grade of Hytrel® having a 72 durometer D hardness. The polymer in the Novafil™ , (American Cyanamid Company, New Jersey, U.S.A.) suture contains Hytrel®. Novafil™, which is a polybutester, has superior and unexpected properties when contrasted to other nonabsorbable fibers. It is more flexible than other conventional-type, graft fibers, e.g. Dacron™. Novafil™ has a bending modulus of approximately 1584,7 N/mm² (230,000 p..s.i.). Also, the compliance of a Novafil™ containing graft measures 4.20 in combination with MAXON™. A similar graft manufactured from Dacron™ and Maxon™ has a compliance of 3.03. Compliance is measured as a percentage of diametral change per 133 mbar (100 mm Hg) internal pressure change. A concentric knit relationship, wherein PGA comprises the inner tube, Maxon™ comprises the middle tube, and either Dacron™ or Novafil™ comprises the outer tube, has the following synergistic advantages: (1) Dacron™ is known from the prior art to incite a thrombogenic reaction. (2) Dacron™ or Novafil™ fibers can be shielded from blood by inner layers of PGA and MAXON™, thereby minimizing the tendency to thrombose and occlude the graft. (3) As PGA and then MAXON™ degrade and are absorbed, the inner capsule becomes larger and, hence, has a higher probability of remaining patent in small diameter applications. (4) Based upon animal studies, a PGA- and MAXON™ containing graft tends to have greater patency than a commercial graft material. The concentric relationship can be a plurality of single tubes attached together by sewing, gluing, or merely held together by frictional contact between the layers. The MAXON™ and/or PGA absorbable components of the graft become absorbed and are replaced by natural tissue. This leaves skeletal structure of nonabsorbable Dacron™ or Novafil™ fiber which is encapsulated in healthy collagenous tissue. The inside wall or neointima of the skeletal structure develops into an endothelial-like growth. The outside wall has been shown to be comprised of a matrix of mature, highly vascularized granulation tissue. The materials are constructed into vascular grafts as concentric tubes. The graft structures can be either straight or bifurcated (branched) tubes. A knitted tube can be manufactured on a Raschel knitting machine. The number of needles per 2.54 cm (inch) can be about 25 to 35. The gauge (which is twice the number of needles per 2.54 cm (inch) can therefore be about 50 to 70. Prior art Raschel knitting machines are commercially available in a 56, 60 or 64 gauge. DESCRIPTION OF THE PREFERRED EMBODIMENT The following steps are followed when preparing knit vascular grafts starting from the appropriate yarns. The proper denier yarns for the specific construction have to be knit. If the denier to be used can only be obtained by using three or more ends, the yarn must be ply-twisted together. For example, if the construction is a 330-denier PGA and 100-denier textured Dacron™, and the only available PGA is 110-denier, it is necessary to twist three ends of 110-denier PGA and the one end of 100-denier Dacron™. Other variations can be used, depending on the type of construction called for. After ply-twisting onto a king spool, the twisted yarn is transferred to a model 50 cone, using a coning machine. It is preferred that any material that is not twisted and is to be used for knitting be transferred to a cone, or to a similar type package from which the yarn may easily be removed. The yarn is then set up on the knitting machine. The knitting machine can be commercially available. It can be a floor-type self-contained unit, completely assembled, with exception of the yarn tension or stop-motion assembly. A direct V-belt drive from a fractional horsepower motor to the knitting head allows for a quiet knitting speed up to about 1100 rpm. A variable speed take-down assures minimum breakdowns and absolute quality stitch control. Operating speeds can vary depending on cylinder size and also the type of yarn or fibers used. The proper density of the graft construction is obtained by changing the stitch cam and take-down settings. The stitch cam controls the length of the stitch, and the take-down controls the tension of the tubular fabric being knit. After knitting, the graft material is scoured in xylene under ultrasonic agitation for two ten-minute baths. The material is allowed to dry in a fume hood until no xylene odors can be detected. The graft material is then cut to appropriate lengths (e.g. 4 mm x 60 mm; and/or 8 mm x 80 mm) and then reversed. Reversing involves turning the graft inside out to have a smooth inner surface, and a rougher outer surface to promote ingrowth. Any graft containing PGA is then post-treated on stainless steel mandrels at temperatures of about 115°C to 150°C, under a vacuum approximately equal to 1.33 mbar (1 torr) or lower. The post-treatment process seems to increase the tensile strength retention for the absorbable component, up to about 60 days after implant. A graft that does not contain PGA may not undergo the post-treatment process. The ends of the graft may then be heat-sealed on a hot surface to prevent unravelling. During heat-sealing, the ends of the graft are melted only slightly. Following scouring in xylene or another medically approved nonaqueous solvent and drying, the graft is then packaged in a polycarbonate folding container, which is then placed in a foil inner pouch. The graft is then sent through an absorbable device EtO-sterilization cycle. After sterilization, the graft is repacked in a 2-web TYVEK® (a spun bonded polyolefin manufactured by E. I. DuPont & Co., Wilmington, Del., U.S.A.)/Mylar™ (a polyethylene terephthalate also manufactured by E. I. DuPont & Co.) pouch, sealed and EtO-sterilized a second time. A series of in vivo studies with woven vascular grafts in several configurations was completed. The following materials, although not exclusive, were included: a) PGA/Dacron™ 80/20 low and high porosity, 4 and 6 mm in diameter b) PGA/copolymer having glycolic acid ester, and trimethylene carbonate linkages, 4 mm c) Woven non-crimped Dacron™, 4 and 6 mm; and d) Gore-Tex (a Trademark of Wil-Gore & Associates, Inc. U.S.A.) 4, 8 and 10 mm. The overall patency rate for PGA containing grafts was substantially higher than controls: 58% vs. 41%. Bi- and tri-component vascular grafts made of biodegradable and non-degradable fibers have been studied in the beagle. Observations carried out from ∼ 30 days to ∼ 7 months showed that as the absorbable component left the graft structure, organized and oriented tissue invaded the graft approximating the location of the degraded material. The tissue ingrowth appeared to mobilize as a neointima with the lumenal surface covered by cells strongly resembling endothelium. The non-degradable component exhibited dispersed fibers within a matrix of mature, highly vascularized granulation tissue. This rich blood supply persisted for the period of maximum observation. The graft structures were provided in two diameters: 4 and 8 mm ID. The former were studied as interpositional grafts in both carotids of the host; the latter as interpositional grafts in the thoracic aorta. The 4 mm grafts (40-60 mm in length) were examined at 1 and 2 months and showed high degrees of patency. The tissue reaction showed progressively increasing tissue incorporation although endothelization was absent at 1 month and only partially manifest at 2 months. The 8 mm grafts examined at ∼ 3-∼7 months were uniformly patent and showed uninterrupted complete endothelization of the graft lumen and complete replacement of the degradable material by the tissue elements noted above. The present invention is illustrated by the following examples which can be useful in peripheral vascular surgery, as coronary artery bypasses or in general arterial or venous grafting. Reference- Example 1 This graft is a double-walled structure consisting of a 100% PGA woven inner tube and a 100% texturized knit Dacron™ velour outer tube. The structure was designed so that the inner wall, being PGA, would become absorbed and be replaced by a smooth, well-organized tissue at least partially consisting of endothelial cells. This inner wall would become the new intima. The outer wall, being constructed of porous nonabsorbable Dacron™ material, would allow tissue and capillary ingrowth and, at the same time, add support to the newly-grown neointima to prevent aneurysms. The Dacron™ outer wall material is a Sauvage Filamentous Velour® fabric supplied by U.S.C.I., a division of C. R. Bard Co., Inc., Billerica, Ma. USA. The inner wall fabric is a woven tube having a 1 x 1 plain weave construction using 5-ply, 46-denier, 21 filament (PGA) polyglycolic acid yarn in both the warp and filling direction. The graft materials were scoured in xylene in an ultrasonic bath - 2 baths of fresh xylene for 10 minutes each - to remove fiber spin finish. The outer and inner tubes for the 4 mm I.D. grafts were cut to approximately 45 mm in length. The tubular woven PGA material was mounted on stainless steel rods, placed in a vacuum chamber and treated at 130°C for 3 hours under a vacuum of less than 1.33 mbar (1 torr) (a similar treatment was done for the 8 mm tubes, except they were cut to 80 mm length). Next, the inner and outer tubes were stitched together by placing either 3 (4 mm I.D.) or 4 (8 mm I.D.) longitudinal rows of stitches between inner and outer wall. The double tube grafts were then packaged and EtO-sterilized prior to use as implants. Following graft construction and sterilization, the 4 mm grafts were implanted in the left and right carotid arteries of thoroughbred beagle dogs. The 8 mm I.D. grafts were implanted in the thoracic aorta. The grafts were left in the animal for periods of up to 90 days, at which time the dogs were sacrificed, and the grafts were dissected and removed for subjective and histological examination. Examination of the implant sites revealed absorption of the PGA fiber and replacement with a smooth, glistening endothelial-like neointima. The Dacron™ outer wall was ingrown with tissue and small blood vessels. There was little, if any, indication of aneurysmal dilation. Exclusive of technical error during implant, grafts were patent and blood flow, as determined by Doppler recordings, was satisfactory. Example 1 A 3-ply yarn, consisting of 110-denier/50-filament PGA, 105-denier/25-filament MAXON™ (a copolymer having glycolic acid ester and trimethylene carbonate linkages), and 100-denier texturized Dacron™, was plied together at approximately 2 turns per 2.54 cm (inch) of twist and knit into (a) 4 mm and (b) 8 mm inside diameter (I.D.) tubes. The knitting machine used was a Lamb ST3A circular weft knitting machine. The needle cylinder used had 25 needles per inch of circumference. Following knitting, the tubular graft material was scoured , cut, post-treated, packaged and sterilized as described in Reference Example 1. The tricomponent structure, being comprised of both MAXON™ (glycolide-TMC) and polyglycolic acid yarns, after post-treatment attains a tighter, more pebbly velour-like appearance, due to the differential shrinkage between the two absorbable fibers in the presence of textured Dacron™. The 4 mm and 8mm grafts were implanted in beagle dogs, as described under reference- Example 1. Examination of the implant sites following sacrifice revealed partial to complete absorption of the bioabsorbable yarns, excellent patency, no noticeable aneurysmal formation and a uniform granular tissue forming the neointima and extending through the wall to the advential surface. Table 1 is a summary of the in vivo animal data for the knit grafts constructed according to Example 1. Reference- Example 2 A 4-ply yarn consisting of three ends of 105-denier MAXON™ (as described in the Background and in Example 2, above) and one end of 100-denier texturized Dacron™ was plied together at a twist level of approximately 2 turns/2.54 cm (2 turns/inch).The yarn was knit into 4 and 8 mm I.D. tubes, on separate Lamb ST3A circular weft knitting machines, using 25-needle per inch knitting cylinders. These grafts had wall thicknesses of between 650 and 850 microns. Following knitting, the graft material was scoured, cut to 45 and 80 mm lengths, heat-set at 110°C for 1 to 3 minutes on stainless steel sizing rods, helically wrapped with 2-0 monofilament MAXON™ suture material as a means of external support, packaged and sterilized. The external support material was attached to the outside surface of the vascular graft, using polymeric glycolide/trimethylene carbonate (TMC) dissolved in methylene chloride as an adhesive. Alternatively, poly-TMC dissolved in methylene chloride can be used as an adhesive. Table 2 is a summary of the in vivo animal data for the knit grafts constructed according to Reference- Example 2. Reference- Example 3 A 4-ply yarn consisting of two ends of 46-denier PGA, one end of 62-denier PGA and one end of 100-denier texturized NOVAFIL® was assembled at approximately 2 turns per 2.54 cm (inch) of twist. The texturized NOVAFIL® yarn was false-twist texturized, using the Helanca® (trademark of Heberlein Corp., Wattwil, Switzerland) process in order to provide a surface texture that would encourage maximum tissue ingrowth. The combined yarn was knit into 4 and 8 mm I.D. tubes similar to Example 3, except that the cylinder had a needle spacing of 33 needles per inch. Following knitting, the graft materials were scoured, cut to 45 and 80 mm length tubes, post-treated on stainless steel rods under vacuum of 1 .33 mbar (1 torr) at 130°C for 3 hours, cooled, helically wrapped with 3-0 MAXON™ monofilament suture material, attached to the surface of the graft using poly-TMC as an adhesive and, finally, packaged and sterilized. Reference- Example 4 In this warp knit example, 70-denier texturized Dacron™ was combined with 105-denier MAXON™ multifilament yarn on a 48-gauge Raschel knitting machine in the following construction: Front Bar 2/0 2/4 70-denier textured Dacron™ Back Bar 2/0 4/6 105-denier MAXON™ Reference- Example 5 This construction is similar to Example 5, except that the stitch construction is reversed as follows: Front Bar 2/0 4/6 105-denier MAXON™ Back Bar 2/0 2/4 70-denier textured Dacron™ Examples 5 and 6, although formed on a 48-gauge Raschel machine can be made on a 56-, 60- or 64-gauge Raschel machine, having 14 or more guide bars, positive feeds and stitch combs.

Claims: A knitted vascular graft having at least three concentric tubes, the inner and middle tube manufactured from two different absorbable polymers, wherein the inner tube comprises PGA and the middle tube comprises a MAXON™ type (polyglyconate) polymer, the polymer in the middle tube comprising at least one trimethylene carbonate linkage and said absorbable polymers comprising more than 50% by weight of the knitted vascular graft; and the outer tube manufactured from a nonabsorbable polymer of the type of DACRON™ or NOVAFIL™ (polybutester) fibers. A graft of Claim 1, wherein the middle tube is manufactured from an absorbable copolymer comprising up to about 50% by weight of trimethylene carbonate linkages. The graft of Claim 1, wherein the nonabsorbable polymer in the outer tube is selected from the group consisting of polyethylene terephthalate and polybutester. A graft of Claim 1 manufactured on a warp knitting machine. A graft of Claim 1 or 4, wherein the nonabsorbable polymer comprises 20 to 35% by weight of the graft.

Inventors: DUMICAN BARRY LEE, DUMICAN, BARRY LEE
Applicants: AMERICAN CYANAMID CO, AMERICAN CYANAMID COMPANY
Application year: 1986
Main classification: A61L27
IPC codes: A61F2, A61L27, C08G63