JP2729625B2 - Method for producing an implantable artificial blood vessel - Google Patents

Description

The present invention generally relates to a vascular prosthesis having an outer surface having a porous structure, wherein the vascular prosthesis is of a non-braided and non-woven type; It has an outer surface porosity that provides an environment that assists tissue ingrowth into the pores of the porous surface.
The vascular graft is made of a fiber-forming polymer extruded into fibers, which are wound or spun onto a mandrel while being subjected to intermittent electrostatic conditions. Typically, a break occurs in the formed fiber during spinning, and the cut fiber is easily reconnected at or near its cut point with the aid of electrostatic conditions. Such electrostatic conditions have good inter-fiber bonding and tightly controlled pore size, especially by providing an exceptionally smooth and optionally low porosity or substantially non-porous inner surface. Help provide artificial blood vessels.

The vascular graft is extruded to provide a desired degree of porosity to the graft that can be implanted, particularly in order to provide an ingrowth environment that is particularly suitable for promoting tissue ingrowth at the implantation site. It is known to be made by a process that involves winding the material over a mandrel. One such approach is described in U.S. Patent No. 4,475,972, the description of which is incorporated herein by reference. This patent is made by extruding a polyurethane solution under pressure through an opening and then pulling the extruded material while winding it on a mandrel.

Several problems are encountered when implementing a method such as that of this patent. It is not always possible to control the extruded fibers properly to obtain both a small pore size and good adhesion between the connecting spun fibers. It is particularly difficult to obtain a proper joint of the first few layers of the vascular prosthesis, which later contributes to its tearing during mandrel removal, both of which allow the torn fibers to enter the lumen of the vascular prosthesis. This leads to the manufacture of a vascular prosthesis having an extended uneven jagged inner surface. It is highly desirable that the vascular prosthesis have a substantially smooth and minimally obstructive inner surface, thereby typically providing a pass-through condition that is substantially optimal for the internal diameter of the prosthesis.

When producing these types of wound spun fiber artificial blood vessels, the fibers are particularly usually preferred during the spinning operation,
Freshly extruded and still only partially cured filaments are often cut when a force is applied in a manner that tends to cut the filaments, and the spun fibers are pulled longitudinally during spinning. These situations or any other situations (such as inertial effects, foam in polymer etc.)
When such a fiber cut occurs, the relative movement between the extruder and the mandrel is typically stopped, and the broken fiber end is manually reconnected to the rest of the fiber on the mandrel or to the mandrel itself It is necessary to.

In addition to labor intensive, time consuming, and leading to downtime, this need for manual reconnection often leads to poor fiber adhesion at the reconnection plane, which can lead to vascular prosthesis detachment. . Fiber cutting, reconnected by previously known methods, involves reconnecting the fiber at the end of the vascular prosthesis, cutting off the end and discarding. The operation of manually reconnecting one fiber without cutting the other fiber involves drying the underlying fiber layer,
It takes a long period of time not to bond well with the next layer. The uniformity of the spun strand is thus coated, leading to potential weaknesses or unsightly sections of the finished vascular graft. This is particularly important for vascular prostheses intended for arterial applications, as the prosthesis must be able to withstand pulsating arterial blood pressure of at least 300 mmHg, preferably 500 mmHg or more, for prolonged periods on the order of 10 years or more. is there.

For the purpose of providing a vascular prosthesis having a porous surface, after implanting such a vascular prosthesis, the surface of the porous surface can be removed from adjacent biological tissue to provide a junction between the biological tissue host and the porous vascular prosthesis. Promoting metastatic growth and tissue ingrowth into the depth. Typically, living tissue in-growth is combined with promoting tissue growth from nucleated blood flow cells into a porous surface. Such porous surfaces provide a porous depth that achieves a means of anchoring to host tissue by soft tissue in-growth into the porous depth of the surface, and they provide a colony on the blood-contacting surface of the vascular graft. It is caused by formation and tissue formation. Provides a blood compatible tissue-graft interface. Tissue ingrowth is desired on the outer surface. Desirable on the inner surface is endothelial cell ingrowth provided by nucleated blood cells. It is therefore important that such vascular grafts have a porosity and that the parameters of such porosity are strictly controlled during the production of the vascular graft in order to obtain the desired degree of post-implantation in-growth.

A disadvantage of the type discussed so far is that the present invention provides a vascular prosthesis that is formed under tightly controlled conditions so that the porosity can be changed from layer to layer, while at the same time accurately and consistently formed. Has been virtually eliminated by the advancement. For example, the present invention achieves fiber cut reconnection while minimizing the chance of forming unwanted delamination sites. The present invention also facilitates the formation of a vascular prosthesis having a low porosity or substantially non-porous, substantially smooth inner surface. Also, an electrostatic field is used to provide a well-bonded layer to the outside of the vascular prosthesis to prevent handling of the spiny prosthesis during implantation. A single pass outside the vascular graft provides a hairnet effect without affecting the pore size.

In summary, the present invention extrudes a fiber-forming polymer,
Includes artificial blood vessels created by intermittently applying an electrostatic charge between the extruder and mandrel to simultaneously mandrel wrap it and simultaneously accelerate the movement of the fiber-forming polymer strand toward the mandrel . Typically, an electrostatic charge is applied during the first or innermost spinning extrusion and winding to provide a vascular graft having a low porosity inner layer as a substantially smooth inner surface. You. The application of an electrostatic charge during fiber cutting during any part of the spinning operation extrudes the cut fibers at or near the cutting location and before the cut ends are hardened to a point where smooth reconnection is no longer possible. Accelerate from the machine onto the mandrel.

Accordingly, it is a general object of the present invention to provide an improved non-woven vascular prosthesis.

Another object of the present invention is an improved artificial tissue having an outer surface therein for promoting tissue ingrowth and having a reduced porosity inner surface which permits cell ingrowth when compared to the outer surface. To provide blood vessels.

Another object of the present invention is to provide an improved vascular prosthesis, including extrusion and wrapping of a fiber forming polymer onto a mandrel while applying an electrostatic charge to accelerate the forming fiber onto the mandrel at a selected time. To provide.

It is another object of the present invention to provide an improved vascular prosthesis and process for producing the same, comprising a process comprising intermittent application of electrostatic energy between a mandrel and an extruder for a fiber-forming polymer. .

It is another object of the present invention to provide an improved method for producing an artificial blood vessel, which involves strictly controlling the porosity of the various layers of the artificial blood vessel.

Another object of the present invention is to produce a non-woven vascular graft,
It is an object of the present invention to provide an improved method that includes repairing a cut electrostatically in a fiber-forming polymer extrusion.

These and other objects, features, and benefits of the present invention will be more clearly understood upon consideration of the following detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS In the course of this description, reference will be made to the accompanying drawings.

FIG. 1 is a generally schematic sketch illustrating the steps of manufacturing a vascular prosthesis according to the present invention.

 FIG. 2 is a sectional view taken along line 2-2 of FIG.

 FIG. 3 is a sectional view taken along line 3-3 in FIG.

FIG. 4 is a cross-sectional view illustrating a vascular graft manufactured according to a process that employs electrostatic repair, but does not apply a large electrostatic charge when the inner layer is wound.

FIG. 5 is a cross-sectional view similar to FIG. 4 and generally illustrating the results obtained by electrostatic acceleration of the fiber-forming polymer extrudate during inner wrapping.

FIG. 6 is an enlarged sketch of the outer surface of a vascular prosthesis manufactured in accordance with the present invention, magnified on the order of about 150 times.

FIG. 7 is a cross-sectional sketch of a vascular prosthesis according to the present invention, magnified about 1000 times.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS The apparatus shown in FIG. 1 suitable for performing the method according to the present invention, which typically forms polymer fibers 22 in combination with fiber formation by extrusion techniques from a fiber-forming polymer solution. Distributor 21 to achieve
Contains. Before such fibers are completely set, they are typically wound onto a rotating mandrel 23 in a suitable jaw 24. In the device shown, the distributor 21 reciprocates generally in the plane between the jaws 24 while the mandrel is rotated by suitable means, such as the motor 25 shown. Instead the distributor is a mandrel
It can take the form of a spinneret rotating around 23. Whatever mechanism or technique is used, combined rotational and reciprocal relative movement between the polymer fibers 22 and the mandrel 23 will be obtained. The desired number of layers of polymer fibers 22 are overlaid on the mandrel 23.

An electrostatic charge generator is included between the distributor 21 and the mandrel 23 to generate an electrostatic charge. Preferably, the mandrel 23 is grounded or negatively charged, while the distributor 21 is positively charged when the switch 26 or the like is closed. Alternatively, the distributor can be grounded and the mandrel can be positively charged. In the presence of this static charge, the polymer fibers 22 are accelerated from the distributor 21 to the mandrel 23 to a speed higher than that obtained during spinning and drawing in the absence of an electrostatic field. Also, when this electrostatic field is applied, adjacent polymer fibers 22 having respective similar electrifications will tend to bow away from one another as generally shown in FIG. Distributor 21 is the first
As shown in FIGS. 2 and 3, any number of individual extrusion orifices or hypodermic syringes 27 may be included.

When solidified, the polymer fibers 22 form a generally cylindrical elongated vascular prosthesis 28, as shown in FIG. 4, having an inner diameter substantially equal to the outer diameter of the mandrel 23. Individual fibers
The 22 are generally interconnected in most if not substantially all of the places where the fibers cross or otherwise contact each other. This fiber-to-fiber bonding occurs when the fibers containing solvent and only partially hardened fibers engage each other during winding, which typically causes the extruded fibers to overlie the underlying fibers. This is facilitated by stretching. This is suitably achieved by selecting an appropriate speed of relative movement between the mandrel 23 and the distributor 21 that pulls the fiber 22 at a speed faster than it is extruded from the distributor 21.

Such windings, and especially the tensioning of the fibers 22, and the internal effects of acceleration or deceleration upon reversal of the shuttle carried by the distributor 21, often tend to cause fiber breakage. The fiber cut applies an electrostatic charge as soon as the cut occurs, thereby accelerating the cut strand far from the syringe barrel 27, the free end of which is connected to the reconnection portion 29.
Is repaired by substantially contacting and adhering to the forming vascular prosthesis 28 to form The formation of the reconnection portion is based on the fact that the rapid acceleration generated by the electrostatic forces directs the fibers to the mandrel, and the polymer fibers are hardened before they set, i.e., the highly extruded polymer material typically promotes fiber adhesion. This is facilitated by the fact that it enhances the ability of the cut end to reach the forming vascular prosthesis 28 while still containing sufficient unevaporated solvent to remain tacky. In this regard, without the application of an electrostatic field, the free ends hanging from the distributor 21 will be swung into other fibers and will cause additional fiber breaks.

In the embodiment illustrated in FIGS. 5, 6 and 7, the vascular prosthesis 28a is extruded in the presence of an electrostatic field and is thus substantially composed of the polymer fibers 22 accelerated onto the mandrel 23 in a highly tacky state. An upper smooth inner surface 31 is included. The fibers are accelerated onto the mandrel at a high speed and draw ratio, and they impinge on the mandrel 23 before significant solvent evaporation occurs. Such conditions can be achieved by formulating the polymer such that it has a particularly high solvent concentration or a less volatile solvent. Fiber acceleration often results in flattening, at least on the mandrel side of the fiber. Subsequent electrostatically accelerated fiber layers are forced into the interstices between the underlying fibers, forming an inner surface 31 that is generally smooth, has a substantially prickly surface, and has a very small pore size. . Polymers formulated to have exceptionally high solvent contents can be accelerated onto the mandrel so that the inner surface is no longer porous.

For example, the progress of fiber drawing in an electrostatic field is a small diameter,
For example, fibers of about 1 to 10 microns are obtained. Typical pore sizes in this regard are in the range of 1 to 30 microns.
If electrospinning is continued for too long, the fibers bond very well to the underlying fibers, thereby reducing their relative movement, and the resulting vascular graft is too rigid,
And has poor suture properties. When extruding a polymer such as 75D polyurethane (Upjohn), a maximum of about 20 passages through a 20 orifice spinneret is acceptable before the vascular graft becomes too rigid. If electrospun fibers were also used to form the outer portion of the vascular prosthesis, the porosity typically formed would be too small to promote good tissue ingrowth after implantation . Thus, a large portion of the outer layer of polymer fibers 22 typically forms a substantially porous outer surface 32, except for occasional and intermittent electrostatic charging, typically to achieve fiber reconnection upon cutting. Wound on inner surface fiber in absence. Porous surface 32 includes a porous portion having the desired and necessary thickness to promote tissue ingrowth therein when the vascular graft is implanted.

Preferably, the electrostatic field is applied during the last few (eg, three) winding passes on the outer surface of the vascular prosthesis to prevent the outer surface from becoming spiny when handling it.
However, excessive electrostatically assisted passage over the outer surface results in stiffening of the vascular graft and reduced pore size.

The polymeric material from which the fibers 22 are extruded must be a fiber-forming type of polymer. That is, the polymer must be capable of forming into fibers when extruded through fine orifices and into the air. Regenerated cellulosic products such as polyamides such as nylon and rayon are fiber-forming. However, many currently available fiber-forming polymers are unsuitable for implantable applications and do not have the properties required for flexible vascular grafts, such as reasonable flexibility, elasticity and biocompatibility. Such a polymeric material must also form a viscous solution in a volatile solvent from which continuous fibers can be drawn. As a general class of polymers, polyurethanes tend to have desirable physical properties for the production of vascular prostheses. However, as a class, segmented polyurethanes are not typically considered to be fiber-forming in air, and when extruded they tend to exhibit excessive cutting. However, polyurethanes of the fiber-forming type are generally preferred.

The vascular prosthesis 28 manufactured according to the present invention can be varied in size as desired. The inner diameter depends on the dimensions of the mandrel, a typical range is as fine as 0.00254 cm, the practical upper limit is on the order of 2 inches or more, and large sized vascular grafts are for example gauze type products, shunts, sac, Suitable for cutting or otherwise shaping into flat sheets for the manufacture of suture rings and patches, membranes and the like. More common inner diameters range from about 1 mm to about 50 mm. The size and shape of the holes formed by the fibers from layer to layer of the fibers can be controlled by the angle formed by the fibers with respect to the mandrel and the thickness of the fibers.

The wall thickness of the graft 28 can also vary as desired, and is determined by the number of wound layers formed on the mandrel and the thickness of the individual wound fibers. The thickness of the vascular prosthesis is also controlled by the adhesion between subsequent fiber layers. If a fiber is squeezed, the next fiber to be laid down sinks into the squeezed fiber and requires more fiber passage to reach the desired diameter. The electrostatic field sinks the fiber into the underlying fiber due to the force created by the acceleration of the fiber toward the mandrel. The thickness of each fiber wound layer is controlled by the ratio of the flow rate of the polymer solution to the relative speed of movement between the distributor 21 and the mandrel 23, and by the degree to which the electrostatic charge is applied.

For example, a vascular prosthesis having an inner diameter of 6 mm manufactured to have a structure generally in line with the strategies shown in FIGS. 5, 6 and 7 will form a wound layer with a wall thickness of about 50 microns. It will be created by applying electrostatic force during spinning. Such a layer minimizes the spininess of the lumen or surface 31 and reduces its pore size. The remainder of the winding is applied until the desired thickness and porosity is obtained, during which time an electrostatic field is generated only when necessary to reconnect the fiber forming polymer cut. Typically, the electrostatic field generated and utilized according to the present invention is about 1
To about 40 kilovolts, preferably about 20 kilovolts (microamps current).

In another example, a vascular graft having an inner diameter of about 4 mm
Its inner smooth surface or lumen with multiple turns providing a wall thickness of 1 to 500 microns to form a very thin (less than 1 micron) blood-shedding surface or a smooth inner surface that supports the drug Have layers. This includes a substantially non-porous inner surface formed from a particularly dilute polymer solution that splatters substantially against the mandrel during spinning to substantially eliminate gaps at its innermost surface.

It will be understood that the described embodiments of the invention are illustrative of some of the applications of the principles of the present invention. Numerous modifications can be made by those skilled in the art without departing from the true spirit and scope of the invention.

[Brief description of the drawings]

FIG. 1 is a schematic view showing steps of manufacturing an artificial blood vessel according to the present invention, FIG. 2 is a sectional view taken along line 2-2 of FIG.
FIG. 4 is a sectional view taken along line 3-3 of FIG. 2, FIG. 4 is a sectional view of the artificial blood vessel of the present invention, FIG. 5 is a sectional view similar to FIG.
FIG. 6 is an enlarged view of the outer surface of the artificial blood vessel, and FIG. 7 is an enlarged sectional view. 21 is a distributor, 22 is a fiber, 23 is a mandrel, 24 is a jaw, 25 is a motor, 27 is an extrusion orifice,
28 is an artificial blood vessel.

Continuation of the front page (56) References JP-A-54-151675 (JP, A) JP-A-63-119756 (JP, A) JP-A-58-157465 (JP, A)

Claims (12)

(57) [Claims] 1. Extruding a continuous fiber-forming biocompatible polymer material through an orifice to form elongated fibers, forming the elongated fibers into a non-woven cylinder having overlapping fibers where the continuous fibers contact each other. Winding on a mandrel so as to form a plurality of turns to be formed, intermittently applying an electrostatic charge between the extrusion orifice and the mandrel; A period of time carried out in the absence of an extruder, comprising accelerating the elongated fibers onto the mandrel by applying an electrostatic charge between the orifice and the mandrel, wherein the artificial fibers are implanted within the fibers after implantation. At least a portion of the winding operation performed on at least some of the outer turns of the plurality of turns to form a substantially porous outer surface that aids in growth After the period in which the winding is performed under the influence of the electrostatic charge between the extrusion orifice and the mandrel, is performed in the absence of said electrostatic, observing the cutting of the continuous fiber during said winding operation, and such cutting As soon as possible, the cut fibers are accelerated toward the mandrel, an electrostatic charge is applied to reconnect the free end to the vascular prosthesis, and if such reconnection is achieved, such A method for producing a biocompatible artificial blood vessel, comprising: stopping application of an electrostatic charge; and removing the non-woven cylinder from the mandrel to provide the biocompatible artificial blood vessel. 2. The method according to claim 1, wherein the intermittent electrostatic charge applying operation includes forming at least one of the plurality of windings to form a substantially smooth inner surface having a porosity smaller than the substantially porous outer surface. The method of claim 1 including forming a substantially smooth inner surface of the nonwoven cylinder by extruding the inner winding and applying an electrostatic charge during the winding. 3. The intermittent electrostatic charge application operation includes applying an electrostatic charge to two or more innermost turns of the plurality of turns, thereby forcing the fibers into gaps between underlying fibers. The method of claim 2. 4. The method of claim 1 wherein said winding operation comprises stretching said formed continuous fiber by applying tension in the longitudinal direction of the fiber. 5. The extruded orifice has a diameter greater than the intended diameter of the fiber drawn therefrom, and the winding operation extends the fiber drawn from the extruded orifice by applying tension in the longitudinal direction of the fiber. The method of claim 1 comprising: 6. The method of claim 1, wherein said winding operation includes forming an interfiber bond between overlapping fibers. 7. The fiber-forming, biocompatible polymer material is a viscous solution of a polymer fiber-forming material that, upon removal of the solvent, causes interfiber bonding between the overlapping fibers during the winding operation. Method 1. 8. The fiber-forming biocompatible polymeric material is a viscous solution of a polyurethane fiber-forming material from which the removal of solvent causes interfiber bonding between the overlapping fibers during the winding operation. the method of. 9. The substantially smooth inner surface is substantially porous or does not aid in tissue ingrowth after implanting the vascular prosthesis, but does assist in cell ingrowth therein. The method of claim 1 having a porosity. 10. The method of claim 9 wherein said substantially smooth inner surface has a porosity no greater than 50 microns. 11. The method of claim 2 wherein said substantially smooth inner surface includes said plurality of turns and has a wall thickness of 1 to 500 microns. 12. The method of claim 1, wherein said intermittent electrostatic charge applying step includes applying an electrostatic charge at least during an outermost turn.