FIELD OF INVENTION

This invention relates to a method of covering a stent with biomaterial. In particular, this invention relates to a method of covering a stent with acellular matrix.

BACKGROUND OF INVENTION

Stents, consisting of an "open" metal scaffolding, are now widely used for

supporting narrowed or stenotic blood vessels that have been opened or expanded by balloon angioplasty. The stent is deployed to its target location within a vessel by

threading the stent-carrying catheter through the vessel from an incision or percutaneous

puncture some distance away. The stent is then expanded either on its own accord or by

ballooning the catheter for supportive engagement with the interior of the vessel wall to

maintain vessel enlargement.

Balloon expandable stents are typically metal mesh that are mounted on balloon

catheters and delivered to the target location. When the balloon is expanded, the stent

expands to the desired diameter to support the interior of the vessel. Examples of such

stents are described in United States Patent Nos. : 5,059,211; 5,282,824; 5,306,286; and

5,334,201.

Self-expanding stents are made of an alloy having a "memory" that expand to the desired size after being placed at the target site of the vessel. Examples of such stents are

described in United States Patent Nos. : 4,800,882; 5,282,824; and 5,342,387.

In United States Patent No. 5,342,387, Summers, a wire double helix stent design

is illustrated. The double helix is advantageous because by narrowing and widening the gaps between the parallel struts, it can be contracted and expanded in diameter without

changing its length.

Although balloon expandable stents of the prior art have been very successful in

treating narrowed or occluded blood vessels, these stents still suffer from a serious

drawback.

All intravascular stents consist of an open metal scaffolding. The ratio of open

space to stent material varies from 80/20 to about 90/10. When the vessel is stretched by

balloon angioplasty and a stent is expanded in place across a now dilated lesion, a healing

response is triggered. The healing response is a proliferation of smooth muscles cells from

the area of vessel wall which has been injured by the procedure. Although the scaffolding

effect of the stent serves to restrict the build up of scar tissue (smooth muscle cell

proliferation) and subsequent renarrowing, the gaps in the metal provide an opportunity for ensuing smooth muscle cell proliferation to grow through the open spaces of the stent.

As a result, about 30% of patients will experience restenosis of the vessel. The stent and

the expansion of the vessel initiates a reaction which causes tissue ingrowth (intimal

hyperplasia) which eventually leads to renarrowing or restenosis, which may necessitate a revascularization procedure to reopen the narrowed area inside the stent. This additional

intervention is costly and, more importantly, exposes the patient to further risk.

Attempts have been made to mmimize these complications. In United States Patent

No. 5,282,824, Gianturco, a stent assembly is disclosed which has a flexible nylon sleeve

attached to the outside circumferential surface of a stent. On implantation of the stent, the

sleeved stent is allowed to expand, pressing the flexible sleeve against the walls of the

blood vessel. The sleeve is intended to prevent tissue growth between the gaps defined by

the stent. However, nylon and other synthetic materials probably will not provide a long

term solution as such materials can cause massive inflammatory or thrombogenic reactions.

Recently, investigators have developed materials which are not associated with

thrombosis or inflammatory reactions. Acellular matrix is a biomaterial derived from

tissue extracted from mammalians which is processed to remove all cells and soluble

proteins. This biomaterial has been shown to be non-thrombogenic and non-mflammatory. Acellular matrix comprises a framework of largely insoluble collagen and elastin, which

are very stable proteins. Experimental studies with this matrix have been successful in a

variety of cardiovascular applications. (Courtman et al.: "Development of Pericardial

Acellular Matrix Biomaterial: Biochemical and Mechanical Effects of Cell Extraction"

Journal of Biomedical Materials Research, Vol. 28, 655-666 (1994), and Wilson et al.

"Acellular Matrix Allograft Small Caliber Vascular Protheses", Vol. XXXVI Trans. AM. Soc. Artif. Intern Organs, (1990), and see also United States Patent nos. 4,776,853 and

4,801 ,299)

Heretofore, acellular matrices have been surgically implanted during experimental

studies. Acellular matrix prothesis have not been incorporated as an integral part of stents. In addition, investigations have also been undertaken into the effects of endothelial seeding on damaged vascular surfaces after angioplasty has exposed the subendothelial

layer and caused intimal dissection of the vessel. Furthermore, animal studies have

demonstrated that rapid restoration of an endothelial cell monolayer significantly reduces

subsequent platelet deposition and may reduce the rate of actute arterial reocclusion.

(Thompson et al.: "Platelet deposition after angioplasty is abolished by restoration of the

endothelial cell monolayer" Journal of Vascular Surgery, Vol. 19. No. 3 (1994); Beam

et al. : "Prosthetic Graft Seeding: Breathing New Life into Old Grafts" J.R. Cell Surg.

Edinb 39, February, 1994)

Summary of the Invention

The disadvantages of the prior art may be overcome by providing a stent with a

biomaterial covering for implantation, wherein the stent is prepared by inserting

biomaterial through the stent when the stent. The combined biomaterial and stent is

capable of being transluminally or surgically inserted to a target site.

It is desirable to provide an acellular matrix or other biomaterial covering for a

stent, wherein the covering is non-thrombogenic and inhibits tissue ingrowth when

deployed inside a blood vessel, duct, or conduit.

It is further desirable to provide a stent with an acellular matrix or other biomaterial

covering, wherein the biomaterial is seeded with endothelial cells.

It is desirable to provide an acellular matrix or other biomaterial covering which can form a barrier between an implanted stent and the wall of the host blood vessel, duct,

or conduit.

It is further desirable to provide an acellular matrix or other biomaterial covering

which provides a smooth inner surface through which fluid flows.

It is further desirable to provide an acellular matrix or other biomaterial covering

to encourage organized growth from the anastomosis sites inward.

It is further desirable to provide a plurality of stents covered with an acellular

matrix or other biomaterial on a single catheter for multiple deployment of the stents. It is still further desirable to provide a stent covered with an acellular matrix or

other biomaterial for use as a vascular graft for bypassing stenotic or occluded blood

vessels.

It is still further desirable to provide a stent covered with acellular matrix or other

biomaterial for use as a stent or graft for other ducts or conduits within a living body.

It is still further desirable to provide a stent lined with acellular matrix or other

biomaterial that restricts tissue ingrowth for congenital vascular defects such as pulmonary

artery stenosis, portacaval shunts, arterio-venous shunts, deterioration of saphenous vein

grafts for coronary artery by-pass grafts and peripheral arteries and endoluminal grafting.

According to one aspect of the invention, a method of preparing a stent for

implantation is provided wherein an open ended tube of biomaterial is placed relatively

inside the stent.

According to another aspect of the invention, the use of a stent with biomaterial for

treating occlusion and stenosis of a blood vessel is provided, wherein the use comprises

the steps of: providing a catheter having a distal end; mounting acellular matrix or other

biomaterial on the distal end of the catheter; sliding a stent over the biomaterial; attaching

the biomaterial to the stent; delivering the stent and biomaterial to a target site; expanding

the stent; and withdrawing the catheter. The biomaterial is attached to the stent by

suturing, surgically stapling, taping, gluing or other suitable means.

In another aspect of the invention, the distal and proximal ends of the biomaterial

are rolled back over the ends of the stent and the tube ends are attached to the tube itself

or the ends are attached together. The biomaterial is attached to itself by suturing, surgically stapling, taping, gluing or other suitable means.

In another aspect of the invention, the acellular matrix or other biomaterial is

seeded with endothelial cells. The biomaterial may be seeded before or after it is placed

on the stent. Alternatively, the biomaterial may be seeded in situ once the stent and biomaterial are implanted.

In another aspect of the invention, the stent and biomaterial is covered by a protective sheath and delivered to a target site and expanded by removing the protective

sheath.

According to another aspect of the invention, the use of a stent with biomaterial for

treating occlusion and stenosis of a blood vessel is provided. The use comprises the steps

of: providing a catheter having a distal end and an internal release wire; mounting a

tubular acellular matrix on the distal end of the catheter; sliding a self-expanding stent over

the matrix, the self-expanding stent having a protective sheath; extending the distal and

proximal ends of the stent through the acellular matrix to engage the release wire, contracting the stent into an implantable condition; withdrawing the sheath; rolling,

respectively, the distal and proximal ends of the tubular acellular matrix over the distal and proximal ends of the stent; attaching the distal and proximal ends of the tubular acellular

matrix to the matrix, inserting the catheter distal end into the blood vessel; guiding the

catheter distal end to a targeted portion of the blood vessel; withdrawing the release wire,

allowing the stent to expand; and withdrawing the catheter from the blood vessel. The

distal and proximal ends of the tubular acellular matrix may be attached together.

According to another aspect of the invention, a stent with a covering of acellular

matrix or other biomaterial is provided. The acellular matrix or other biomaterial is

attached to the stent by suturing, surgical stapling, gluing, taping or other suitable means for attaching the biomaterial to the stent. The biomaterial may be seeded with endothelial

cells.

According to another aspect of the invention, a stent with an inner tubular lining

of acellular matrix or other biomaterial is provided. The inner lining has open ends for

rolling about ends of the stent. The open ends of the inner tubular lining are attached to the tube or to each other. The acellular matrix may be seeded with endothelial cells.

Description of the Drawings

In drawings which illustrate embodiments of the invention:

Figure 1 is a perspective view of an embodiment of the stent and biomaterial

covering of the present invention in an unwrapped condition and

mounted on a dual release wire catheter;

Figure 2 is a side sectional view of the self-expanding stent and acellular

matrix mounted on a single release wire catheter;

Figure 3 is a sectional view of the self-expanding stent of Figure 2 partially

covered with an acellular matrix; Figure 4 is a sectional view of the self-expanding stent of Figure 2 fully

covered with an acellular matrix; and

Figure 5 is a perspective view of another self-expanding stent which can be

incorporated into the present invention.

Figure 6 is a sectional view of another embodiment of the stent and biomaterial covering of the present invention mounted on a catheter.

Detailed Description of the Invention

A stent to be used with the present invention is illustrated in Figure 1. Stent 12 is

more particularly described in United States Patent no. 5,342,387, the contents of which

are incorporated herein by reference. In this embodiment, stent 12 is self-expanding.

However, the present invention also contemplates utilizing any self-expandable or balloon expandable stent. Figures 1 and 6 are illustrations of self-expandable stents.

Referring to Figure 2, the stent 12 is illustrated mounted on a catheter 14. Acellular matrix 16 is mounted between the catheter 14 and the stent 12, presenting an inner lining for the stent 12.

Acellular matrix 16 of the preferred embodiments is derived from mammalian,

preferably a human vessel, including blood vessels, namely arteries and veins, ducts, or

conduits, and are therefore, tubular in shape having open ends. The size of the vessel to

be harvested is dictated by the size and type of stent to be implanted in the patient.

Preferably, acellular matrix 16 is extracted from human sources. However, bovine,

porcine, canine or similar mammalian sources may also be suitable. Further, cryo- preserved human veins or other ducts or conduits are contemplated as being a suitable

source for the biomaterial.

The method of extracting and preparing the matrix 16 is fully described in Courtman et al.: "Development of Pericardial Acellular Matrix Biomaterial: Biochemical

and Mechanical Effects of Cell Extraction" Journal of Biomedical Materials Research, Vol.

28, 655-666 (1994), and Wilson et al. "Acellular Matrix Allograft Small Caliber Vascular

Protheses", Vol. XXXVI Trans. AM. Soc. Artif. Intern Organs, (1990), and United States Patent nos. 4,776,853 and 4,801,299, all of which are incorporated herein by reference.

The acellular matrix material may be seeded by placing it in a high density culture

medium of endothelial cells that are either from the host or some other mammalian source. The acellular matrix material may be seeded with endothelial cells before or after the

acellular matrix is placed inside the stent by placing it in a high density culture medium.

Alternatively, the seeding may be done in situ. Methods of endothelial seeding are known

in the art. (Thompson et al. : "Effect of Seeding Time and Density on Endothelial Cell

Attachment to Damaged Vascular Surfaces" Br. J. Surg. 1993, Vol. 80). (Combe et al. :

"Endothelial Seeding of Vascular Prosthesis: A Technique of In Situ Enzymatic Retrieval

of Endothelial Cells without Vein Sacrifice" Annals of Vascular Surgery 1993, Vol. 7, No.

5). The endothelial cells may be seeded in a monolayer or layers on the acellular

matrix.

Stent 12 may have an internal protective sheath or sleeve 18. Sheath 18 has a

longitudinally extending slot 20. Slot 20 allows access for distal end 22 and proximal end

24 of the stent to be inserted into notches 26 and 28 in the catheter 14. Notches 26 and

28 receive, respectively, the distal end 22 and proximal end 24 of stent 12 to retain the stent for deployment. Proximal end 24 is first engaged with the release wire 30 and then

the distal end 22 is wound down to compact the stent 12. The distal end 22 is then looped

through with the release wire 30. Release wire 30 extends internally within the catheter

14 through loops formed in each the distal end 22 and proximal end 24 of the stent 12 to retain the stent 12 on the catheter 14 in a compacted condition.

Once the stent 12 engages the release wire 30, the protective sheath or sleeve 18

can be withdrawn by sliding it along the catheter towards the proximal end thereof. After

the protective sheath 18 is withdrawn, the distal end 32 of acellular matrix 16 is rolled

back over itself to cover the distal end of stent 22. Similarly, the proximal end 34 is rolled

over itself to cover the proximal end 24 of stent 12.

Referring to Figure 3, the distal end 32 is rolled back to cover only a portion of the

distal end region of the stent 12. Similarly, the proximal end 34 is rolled back a portion

of the length of stent 12 to cover the proximal end region thereof.

- lO ¬

The distal end 32 and the proximal end 34 are attached to the inner tubular body of the acellular matrix 16 by suturing, surgical stapling, gluing, taping, or any other method for attaching biomaterial to itself.

The stent 12 and acellular matrix 16 can now be deployed using techniques and methods well known in the art.

Although the preferred embodiment has described the acellular matrix 16 being

mounted on a catheter for covering the stent 12, it is now readily understood that similar

cylindrical apparatus could be used. The stent 12 and acellular matrix 16 of the present invention could be mounted on such cylinder and later transferred to a stent for

implantation.

Referring to Figure 4, the distal end 32 and the proximal end 34 of acellular matrix

16 are fully retracted until the ends 32 and 34 abut. A continuous suture line may be used around the circumferential seam for joining the ends 32 and 34 together. In this

embodiment, the stent 12 is fully covered, both internally and externally and may be

deployed using techniques and methods well known in the art.

It is noted that the distal end 22 and proximal end 24 of stent 12 extend through the

acellular matrix 16 when in the ready for deployment condition. Once the release wire 30

is retracted, the distal end 22 and the proximal end 24 of stent 12 will retract back through

the punctured opening in acellular matrix 16 which will close, fully covering stent 12. The stent 12 and acellular matrix 16 are also useful in grafting. The stent 12 and

acellular matrix 16 may be implanted on ends of a blood vessel which are to be joined.

The stent 12 will provide improved structural support for the vessel over conventional prior art grafts. This improved support will reduce the risk of aneurysms.

Additionally, the stent 12 and acellular matrix 16 can be made of a larger diameter

to operate as a graft for larger ducts within the human body. For example, the stent 12

and acellular matrix 16 of the present invention has applications as a prothesis for the trachea, oesophagus, alimentary canal, genitourinary or other similar bodily ducts.

Referring to Figure 5, a second embodiment of a self-expanding stent 112 which

could be covered and implanted by the present invention is illustrated.

Referring to Figure 6, another embodiment of the present invention is illustrated. The acellular matrix 16 is attached to the stent 12 when stent 12 is in the expanded state.

Stent 12 is then collapsed and mounted on the catheter 14. Guide wire 36 is inserted

through catheter 14. A protective outer sheath 38 is then placed over said stent 12.

The acellular matrix 16 may be attached to stent 12 by suturing, surgical stapling, taping, gluing or by any other suitable method for attaching the biomaterial which would

be apparent to a skilled person.

Additionally, the acellular matrix 16 may be seeded with mammalian endothelial

cells, preferably human endothelial cells. before or after it is mounted on the catheter 14 or in situ once the stent 12 is delivered to the target site.

The stent 12 and acellular matrix 16 can now be deployed to the target site by

removing the protective sheath 38 and expanding said stent 12.

The above embodiments are illustrations of the invention. It will be obvious to those skilled in the art that various modifications and changes can be made to these

embodiments without departing from the spirit and scope of the invention.