WO2003082156A1

WO2003082156A1 - Vascular biomaterial devices and methods

Info

Publication number: WO2003082156A1
Application number: PCT/US2003/008691
Authority: WO
Inventors: Naren R. Vyavahare; John J. Marigliano
Original assignee: Clemson University
Priority date: 2002-03-22
Filing date: 2003-03-21
Publication date: 2003-10-09
Also published as: AU2003220442A1; US6837903B2; US20030181976A1

Abstract

Vascular biomaterial structures may be coated with a plasma-induced layer on their surface. Vascular biomaterial structures may include cardiovascular devices such as heart valves, stents, vascular graphs, and the like. Devices coated with a plasma polymerized coating may show reduced amounts of undesirable coagulation of blood at the surface of the device. A reduced amount of thrombosis may be observed for such plasma coated medical devices.

Description

VASCULAR BIOMATERIAL DEVICES AND METHODS Field of the Invention

The invention is directed to vascular biomaterials which include a plasma-induced coating upon their surface. In particular, the invention may be directed to apparatus and methods for increasing biological compatibility of synthetic cardiovascular biomaterial by application of a plasma coating process.

Background of the Invention Thrombosis is a primary method of failure for artificial or mechanical cardiovascular biomaterials, such as heart valves. Thrombosis refers to the undesirable coagulation of blood at or near the surface of such a structure. Current mechanical heart valves have demonstrated improved mechanical properties and durability. However, the constant contact of mechanical heart valves with blood sometimes leads to the formation of blood clots following undesirable thrombosis. Thus, thrombosis and blood clotting is a major concern in mechanical biomaterial design, including particularly heart valve design.

To prevent thrombosis, it is common to place patients upon long- term anticoagulation therapy. However, such therapy is expensive, and may pose other risks or side effects. Thus, anticoagulation therapy is not

an ideal solution. Every year, it is estimated that over 150,000 heart valve replacement surgeries are performed, with more than half occurring in the United States alone. When a natural heart valve becomes diseased

and is no longer able to function properly, valve replacement therapy

may be necessary. The most commonly replaced valves are the aortic and mitral. Success rates for valve replacement surgeries have risen,

and surgeons currently are likely to employ replacement as a treatment for damaged natural valves

What is needed in the industry and in the medical community is an

improved biomaterial that is less prone to undesirable thrombosis. Also,

a method of constructing a suitable biomaterial which lessens the

incidence of undesirable blood clotting would be very desirable. In particular, a mechanical heart valve that reduces the incidence of

thrombosis when surgically implanted is needed.

Summary of the Invention

In one aspect of the invention, a vascular biomaterial is provided comprising a metallic support structure and a plasma polymerized

coating which is adhered to the support structure. In some applications, the vascular biomaterial comprises a valve. In other applications, the

vascular biomaterial may include a stent, a vascular graft, or another structure adapted for implantation, which could be in contact with blood

tissue. The support structure in one aspect of the invention may include carbon, such as pyrolytic carbon. In other aspects of the invention, it

may be possible to provide a method of coating a vascular biomaterial

using plasma deposition techniques. In the method, a monomer is

polymerized upon a reactive surface of the support structure, using plasma deposition techniques. The monomer may contain a hydroxyl, carboxyl, sulfonate, or amine group.

Brief Description of the Drawings

A full and enabling disclosure of this invention, including the best mode shown to one of ordinary skill in the art, is set forth in this

specification. The following Figures illustrate the invention:

Figure 1 is a perspective view of a typical bileaflet mechanical

heart valve;

Figure 2 shows a diagram of a typical barrel reactor that may be

used to provide a plasma coating;

Figure 3 shows plasma reactions causing radical formation on the

substrate;

Figure 4 illustrates one set of monomer structures that may be

employed in coatings as applied in the invention; and Figure 5 shows data comparing the relative thrombogenicity of untreated pvrolitic carbon surfaces and plasma induced surface-modified pyrolytic carbon substrates. Detailed Description of the Invention

Reference now will be made to the embodiments of the invention, one or more examples of which are set forth below. Each example is provided by way of explanation of the invention, not as a limitation of the

invention. In fact, it will be apparent to those skilled in the art that

various modifications and variations can be made in this invention

without departing from the scope or spirit of the invention.

When a heart valve must be replaced with a prosthetic valve, there currently are several options available. The choice of a particular

type of prosthesis (i.e., artificial valve) depends on factors such as the

location of the valve, the age and other specifics of the patient, and the

surgeon's experiences and preferences. Available prostheses include three categories of valves or materials: mechanical valves, tissue valves, and aortic homograft valves. Mechanical valves include caged ball valves (such as Starr-

Edwards brand valves), bileaflet valves (such as St: Jude type valves),

and tilting disk valves (such as Medtronic-Hall or Omniscience valves).

Caged ball valves usually are made with a ball made of a silicone rubber inside a titanium cage, while bileaflet and tilting disk valves are made of

various combinations of pyrolytic carbon and titanium. All of these valves are attached to a cloth sewing ring so that the valve prosthesis

may be sutured to the patient's native tissue to hold the artificial valve in

place postoperatively. All of these mechanical valves can be used to replace any of the four heart valves. Valve function may be related to

platelet activation, as further discussed below.

Blood platelets are non-nucleated, disc shaped cells with a diameter of approximately 3-4 μm. The basic function of platelets is to assist in the clotting of blood by forming platelet plugs and catalyzing coagulation reactions leading to the formation of fibrin networks.

Platelets are very sensitive cells, and upon activation, their shape

becomes more irregular and spread out as the contents of their granules are released into the extracellular matrix. The release of these platelet

products stimulates surrounding platelets, causing irreversible platelet aggregation leading to a thrombus formation.

It has been shown that flow dynamics play an important role in the

localization of platelet aggregation on bileaflet mechanical heart valves, initiating thrombus formations. Localized jets, steep velocity gradients, and vortex recirculation have been observed in vitro near leaflet

surfaces. In vivo flow patterns promote recirculation of blood toward the

pivot points, and leakage through gaps created at the pivot-leaflet

junction is believed to be a major factor responsible for platelet damage. As a result, it has been demonstrated that platelet aggregation is concentrated at the leaflet edges and pivot points.

Modern implantable prosthetic mechanical heart valves are

typically formed of an annular valve seat in a relatively rigid valve body

and one or more occluding spheres, disks or leaflets that are movable between a closed, seated position in the annular valve seat and an open position in a prescribed range of motion. Such mechanical heart valves may be formed of blood compatible, non-thrombogenic materials.

Pyrolytic carbon and titanium may be used, with hinge mechanisms or

pivoting guides prescribing the range of motion of the disk or leaflets.

Typical rotatable suturing rings for asymmetric mechanical valves

are shown in U.S. Pat. Nos. 3,727,240, 3,763,548, 3,781,969, 3,800,403,

3,835,475, 4,197,593, 5,766,240 and Re. 30,507; and are incorporated

by reference. Prosthetic vascular grafts are also known. Examples of

vascular prostheses are described in U.S. Patent No. 5,500,014.

Furthermore, grafts or blood vessels prepared from artificial materials are

disclosed in U.S. Patent Nos. 4,086,665, issued to Poirier on May 2,

1978; U.S. Pat. No 4,118,806, issued to Poirier on Oct. 10, 1978; and U.S. Pat. No. 4,670,286, issued to Nyilas et al on Jun. 2, 1987. The invention of this application could employ plasma induced surface modification techniques upon vascular grafting materials.

Vascular grafts may be prepared from synthetic structures. Grafts are

prepared by chemically treating segments of biografts. Examples of

these various grafts are disclosed in U.S. Pat. No. 4,671 ,797, issued to Vrandecic Pedero on Jun. 9, 1987 and U.S. Pat. No. 4,466,139, issued to Kefharanathan on Aug. 21 , 1984. The invention may be directed to

providing a plasma polymerized coating upon a synthetic graft support structure. The invention may include grafting olefinic monomers or polymers upon a metallic support structure of a mechanical heart valve.

The invention of this application could be applied to stents as well.

Stents are disclosed in U.S. Patent No. 5,496,277. Furthermore, U.S.

Pat. No. 4,699,611 (Bowden) is directed to stents which hold arteries, veins, and the like in an open position when inserted.

Mechanical heart valves made from pyrolytic carbon (PyC) may

be used to replace diseased or damaged native valves, as they offer

good durability and mechanical strength. Furthermore, other composite

or metallic materials could be employed as a support material or support structure in the invention.

Bileaflet Valves

A very successful bileaflet valve employed in the medical

community is the St. Jude valve. Figure 1 , as further discussed below, shows the St. Jude valve. In general, the widespread acceptance and

relatively large market share of the St. Jude valve has led to a host of competing bileaflet valve designs. Many of these alternative designs

represent relatively minor variations on the hinged system of the St. Jude valve. Clearly, the invention could be applied to any artificial biomaterial structure, including for example any artificial valve, as further described

herein. Thus, the types of valve described herein are shown as mere examples of the application of the invention, and are not limiting in any

way. Some of the other valves which could be employed in the practice of the invention include the ATS bileaflet valve, manufactured by ATS,

Inc. Furthermore, the Carbomedics valve is a bileaflet tilting disk valve

made of pyrolytic carbon. The Carbomedics valve is actively implanted

in the United States. The Carbomedics valve is manufactured by Sulzer

Carbomedics, Inc. of 1300 East Anderson Lane, Austin, Texas 78752. Another valve that may be employed is the Edwards Duromedics valve. The Edwards Duromedics valve is a bileaflet valve which may be

provided for mitral or aortic concave bileaflet designs. The manufacturer

was originally Hemex Scientific, but later was manufactured by Baxter-

Edwards, Inc.

Another valve that may be employed in the practice of the

invention is the Medtronic Parallel Valve. The Medtronic Parallel Valve is

a bileaflet valve with a pivot mechanism. The pivot allows the leaflets to

open to fully parallel, in contrast to the opening of the St. Jude valve

leaflets which is only about 85 degrees in most applications. The Medtronic Parallel Valve is manufactured by Medtronic, Inc.

Another pyrolytic carbon bileaflet valve which may be employed in

the practice of the invention is On-X valve. The On-X valve is manufactured by Medical Carbon Research Institute, LLC at 8200

Cameron Road, Suite A-196, Austin, Texas 78754.

The St. Jude valve, as previously discussed, is particularly

adapted for the practice of this invention because it provides excellent durability, good hemodynamics, and is very common in the United States mechanical valve market. The St. Jude valve is manufactured by St. Jude Medical, Inc., 1 Lillehei Plaza, St. Paul, Minnesota 55117. In at least one model, the St. Jude valve comprises support structure of pyrolytic carbon, with a sewing ring of double velour knitted polyester.

Furthermore, a master series is available with an attached helical spring and two retainer rings which are rotatable. The St. Jude valve is available in sizes as follows: aortic-19mm, 25mm; mitral-25mm, 33mm, and perhaps others as well. Turning to Figure 1, a St. Jude bileaflet valve 10 is shown having a valve body 11 or support structure which supports a first leaflet 12 and a second leaflet 13. The first leaflet 12 and the second leaflet 13 are oriented generally parallel to each other across the diameter of the support structure or valve body 11. The first and second leaflets 12-13 are hingedly connected to the valve body 11 so that upon application of force they hinge open to allow maximum blood flow through the valve. In Figure 1, the bileaflet valve is shown with the first and second leaflets 12- 13 in the open position. Furthermore, a suturing ring 14 is shown around the periphery of the support structure. The suturing ring 14 is used to stitch the valve in place during surgical operations.

One application of the invention provides a nonthrombogenic surface coating for mechanical heart valves by generating a plasma induced polymeric surface treatment. Jo achieve this goal, it is possible to use almost any known polymer that is capable of polymerizing in a

plasma reaction chamber to form a surface coating upon a support structure.

For example, one particular embodiment of the invention employs

two monomers, 2-hydroxyethyl methacrylate (HEMA) and acrylic acid, of different functionalities, to form coatings upon such surfaces.

Such coatings may be applied to the St. Jude valve, which

combines the hemodynamic advancements, a tilting disc design with the enhanced biocompatibility and durability of pyrolytic carbon ("PyC").

With the exception of the suture ring 14, which is made of polyester, the entire St. Jude valve is composed of graphite coated with PyC, prior to

receiving a plasma induced outer coating according to the practice of this invention.

Pyrolytic Carbon

Pyrolytic carbon (PyC) refers to the collection of solid, carbon rich species from the heating of organic gases to temperatures exceeding

1000°C at which point the hydrocarbon decomposes into elemental

carbon, which is then deposited onto a substrate. By manipulating certain variables during this process, multiple structures of PyC can be manufactured with wide ranging applications.

The mechanical properties of PyC completely depend upon the

structure. In comparison to the more familiar structure of graphite, in.

which the layers are ordered with respect to one another so that the crystal structure is three-dimensional, PyC possesses two-dimensional

order. The layers consist of hexagonal planes of carbon, which are

primarily held together by strong covalent bonds and van der Waals interactions. However it has been shown that in its strongest form, PyC contains cross-links that form between planes.

PyC formed at relatively low temperatures (1000-1500°C), is

isotropic, and highly cross-linked. As a result of the high degree of

cross-linking between planes, so called Low Temperature Isotropic

Pyrolytic Carbon is the strongest and hardest type of PyC with a scratch

hardness near that of diamond. It has been shown that PyC deposited at higher temperatures (1900°C and above) have larger grains visible in

their microstructures, and cracks which form in these grains under

stress, can ultimately lead to fracture. High temperatures large growth features develop and may act as stress raisers causing failure under low

loads.

The type of reactor plays an important role in determining the structure of PyC. For example, a simple static reactor produces a highly

oriented, anisotropic PyC, Which is used in rocket nozzles, but not

suitable for mechanical heart valves. In order to produce the pyrolytic carbon used in mechanical heart valves, a fluidized bed reactor is

necessary. A fluidized bed consists of a large number of small particles,

which behave as a liquid when suspended in an upward flowing gas. Plasma Coating Processes

Often referred to as the fourth state of matter, plasma is simply a

gas containing a mixture of electrons, ions, radicals, and neutral species.

Plasmas can be generated through electron excitation as a result of the

application of radio frequency, microwave, or heat energy. Under the right conditions, plasmas can be used to deposit molecules onto

surfaces. Plasma may provide a thin coating without altering the bulk properties of the base support material.

The energy used to initiate the plasma causes the electrons to

oscillate, which can heat the electrons sufficiently enough to provide the required ionization. This process is known as breakdown. Following breakdown, the next state is called glow discharge, as light is emitted

from the plasma. Most of the energy used in this system is to accelerate

electrons and ions through the sheath, the area between the plasma and the substrate (See Figure 3). The energy from ion and electron bombardment is. enough to break chemical bonds on the surface of the

substrate, and it is this property of plasma deposition that promotes the creation of highly reactive species. By varying the plasma gases, it is

possible to obtain a wide variety of functional groups deposited on the surface of a support structure of a biomaterial.

One advantage of plasma technology in applying coatings to biomaterials such as heart valves is the ability to produce ultra thin

polymer surfaces. Plasma polymerization results in highly cross-linked polymeric surfaces that strongly adhere to the underlying substrate. The underlying substrate is pyrolytic carbon in the case of the St. Jude heart valve. These reactions are very complex and highly system dependent, thus they are governed by many parameters such as the monomer gas used, substrate properties, reaction conditions (power, pressure, flow rate, reaction time), the placement and orientation of the sample within the reaction chamber, and the type of reaction chamber used. Through the variation of these parameters, it is possible to create a wide variety of polymers from a single monomer. There are at least two methods in which to plasma polymerize a given surface of a biomaterial support structure. One method is to simply allow a monomer vapor into the reaction chamber and initiate a plasma. This would then lead to the creation and deposition of monomer radicals, which upon reacting with each other, results in a thin polymer layer.

A second method is to initially create a reactive surface with a non-reactive gas plasma such as oxygen or argon, and then expose this reactive surface to a monomer solution. When a surface is first treated with an oxygen plasma and then exposed to the air, reactive peroxides are generated on the surface, which initiate the polymerization reaction when the material is exposed to the monomer solution. This form of surface modification is known as plasma induced polymerization, in which plasma deposition is initially used to generated a reactive surface that will induce polymerization. Traditionally, planer reactors, which accelerate ions in one direction between charged plates, have been used for plasma deposition, however barrel reactors offer the advantage of

deposition without the possibility of etching the substrate.

A barrel reactor, shown in Figure 2, inductively couples AC power through coils that surround the reaction chamber. This allows for a

smaller sheath, which prevents electron and ionic bombardment that may lead to etching.

The advantages of plasma polymerization are numerous but are

best demonstrated in comparison to conventional surface polymerization.

In order to create a polymer coating using conventional processes the following steps would have to be taken: synthesis of the polymer, preparation of the coating solution, process the coating, dry and cure the final product. In plasma polymerization, these steps may be combined,

and polymerization usually occurs directly from the monomer. Many

coatings are simply not capable of being achieved by conventional

means.

The processing of the polymeric- coatings of the invention employs an oxygen plasma to create a reactive surface upon the support

structure of the vascular biomaterial that can induce polymerization when in contact with the liquid monomer solution.

The surface modification was assessed by water droplet contact

angle determination, which shows extent of surface hydrophilicity and electron spectroscopy for chemical processes. Both contact angle and ESCA indicated significant changes in the surface characteristics of modified PyC and polystyrene as a result of such polymeric coatings. In both cases, hydrophobic materials were altered to produce highly hydrophilic surfaces with significantly increased surface oxygen content.

Polymerized samples demonstrated increases in both carbonyl and hydroxyl groups. Surface hydrophilicity and oxygen content are both accepted factors for enhanced biocompatibility and endothelial cell

growth. The results of surface modification demonstrate an increase in the growth of endothelial cells on both PyC and untreated polystyrene substrates, as these surfaces were able to produce confluent cell layers in a shorter time period. Untreated polystyrene samples do not generally promote favorable cell growth, and the increase in endothelialization can most likely be attributed to the presence of oxygen containing functional groups generated by our polymeric coating. The increase of cell growth on PyC substrates points to the creation of a more favorable surface for cell growth, arid may correspond to stronger cellular adhesion.

Examples

Preparation of Samples

Mechanical heart valves of PyC were scored and broken into approximately 1 cm² pieces. Untreated polystyrene samples were

obtained from Eagle Scientific, and used as received. All samples were sonicated in ethanol, and then rinsed in distilled water to remove surface

contaminants. Following cleaning, samples were then allowed to dry

completely in a dust free environment prior to experimentation.

PyC samples were used as substrates for both platelet and endothelial cell studies. Polystyrene samples were only used in cell studies as a negative control. Since it is a clear substrate that has been

often used in previous experiments, the data generated from polystyrene samples allows for a more direct comparison. Plasma Polymerization

The plasma glow discharge system used primarily consisted of a barrel reactor (see Figure 2) with a diameter and depth of six inches

(source: Extended Plasma Cleaner, Harrick Scientific, Ossining, NY). A

vacuum pump with an ultimate pressure of 1 mtorr and a pumping rate of 300 liters/min (Precision Scientific, P300, Winchester, VA) was attached to the reaction chamber through a liquid nitrogen cold trap to prevent contamination of the reaction chamber. An oxygen gas inlet was

connected to the opposite end of the reaction chamber (See Figure 2). The pressure was monitored by a thermocouple vacuum gauge (Hastings Vacuum Gauge, DV-6). Surface Analysis

Plasma deposition with oxygen gas was used to initiate a graft polymerization with HEMA and acrylic acid (See Figure 3). Therefore, untreated control samples, oxygen plasma deposited samples, along

with HEMA and acrylic acid polymerized samples were each analyzed for differences in chemical composition and hydrophilicity. For the

monomer structures employed in this particular Example, see Figure 4. Numerous other monomers could be employed in the practice of the invention, and the invention is not limited to any particular monomer

structure.

Electron spectroscopy for chemical analysis (ESCA) was used to

determine the chemical composition of the samples. ESCA uses X-rays to excite the electrons of a material to a point at which they are released.

These released electrons strike a detection pad, which measures the

kinetic energy of the electrons. The kinetic energy can be used to

calculate the binding energy of a particular electron. The binding energy of electrons is specific to the chemical bonds of which they originated, and can be used to distinguish different chemical bonds. With the exception of hydrogen and helium, all other elements can be detected.

A wide scan analysis was performed to determine all of the

elements present, and high resolution scans were used to determine specific functionalities. Specifically, carbon atoms in different functional groups were identified with narrow scans of the C1s region at

approximately 285 eV. The take off angle for all the scans was 90 degrees.

Contact angle measurements were taken using a goniometer for all treated and untreated samples to compare changes in hydrophilicity.

By measuring the angle a drop of wate makes with a given surface, a determination can be made as to whether a surface is hydrophilic or hydrophobic. The more spread out the drop is, the smaller the contact

angle is, and the more hydrophilic the surface is. These measurements were taken with a drop size of 10 μL using the CAM 200 digital contact

angle meter (KSV Instruments LTD).

The reaction chamber was evacuated to 10 mtorr to remove contaminants, particularly moisture. The chamber was then flooded with

research grade oxygen gas (99.99%), and evacuated until a constant

pressure of 150 mtorr was established, at which point a RF plasma of

30W was applied for ten minutes. Plasma treated PyC samples were

then immersed into monomer solutions HEMA and acrylic acid for one hour to allow polymerization of the surface to react to its completion. Polystyrene samples were polymerized in the same manner, however only HEMA was used. The reaction was terminated, and excess

monomer was removed by rinsing samples in distilled water. A plasma

polymerized coating upon the support structure resulted. Testing - Platelet Activation Studies

Platelet activation in response to plasma treated and untreated

PyC was compared to reveal results. As expected, untreated PyC

samples demonstrated severe platelet activation and aggregation. Also,

untreated samples generated "thrombus-like" structures. Acrylic acid

polymerized surfaces appeared to have less adherent platelets and

thrombus-like structures than the control group. HEMA polymerized

surfaces, on the other hand, exhibited a dramatic decrease in platelet adhesion and aggregation. See Figure 5.

A comparison of the average number of adherent platelet per given area was made in order to help quantify the relative

thrombogenicity of each surface. The calculations revealed no

significant difference between the untreated PyC samples and the acrylic

acid polymerized surfaces, but a dramatic reduction was observed for

HEMA polymerized surfaces. Platelet adhesion was reduced by over

75% when comparing the HEMA plasma polymerized coating to the

untreated PyC. Figure 5 shows these results in graphic form, with the

level or degree of adherent platelets per square millimeter shown on the

bar graph, where n=5, and alpha=0.05. It is understood by one of ordinary skill in the art that the present discussion is a description of exemplary embodiments only, and is not intended as limiting the broader aspects of the present invention, which broader aspects are embodied in the exemplary constructions. The invention is shown by example in the appended claims.

Claims

What is claimed is:

1. A mechanical heart valve comprising:

(a) a carbon-based support structure, and

(b) a plasma polymerized coating adhered to the carbon-based support structure.

2. The valve of claim 1 wherein the valve comprises a bileaflet valve.

3. The valve of claim 1 wherein the carbon-based support structure of the valve is comprised of pyrolytic carbon.

4. The valve of claim 1 wherein the plasma polymerized coating comprises a film.

5. The valve of claim 1 wherein the coating is formed from a monomer selected from the group consisting of: hydroxyls; carboxyls; sulfonates; and amines.

6. The valve of claim 1 wherein the coating comprises a polymerized monomer of a methacrylate-containing species.

7. The valve of claim 1 wherein the coating comprises a polymerized monomer of a styrene-containing species.

8. A vascular biomaterial comprising a stent, wherein the stent comprises a carbon-based support structure and a plasma polymerized coating adhered to the carbon-based support structure.

9. A vascular biomaterial comprising a vascular graft, the graft comprising a carbon-based support structure and a plasma polymerized coating adhered to the carbon-based support structure.

10. A mechanical heart valve comprising:

(a) a carbon-based bileaflet valve body,

(b) a coating adhered to the valve body, the coating comprising a plasma polymerized coating, and (c) a suture ring positioned on the valve body.

11. The valve of claim 10 in which the suture ring is positioned on the outer circumferential surface of the valve body.

12. The valve of claim 10 in which the coating comprises a polymerized monomer of a methacrylate-containing species.

13. A method of coating a mechanical heart valve with a polymer using plasma deposition techniques, comprising

(a) providing a monomer,

(b) providing a mechanical heart valve having a metal support structure,

(c) creating a reactive surface upon the metal support structure,

(d) treating the reactive surface of the support structure with plasma, and

(e) polymerizing the monomer to form a plasma polymerized coating upon the metal support structure.

14. The method of claim 13 in which the heart valve comprises a bileaflet heart valve.

15. The method of claim 13 in which the monomer comprises HEMA.

16. The method of claim 13 wherein the monomer comprises acrylic acid.

17. The method of claim 13 comprising the additional step of grafting olefins upon the metallic support structure.

18. The method of claim 13 wherein the support structure is comprised of carbon.

19. The method of claim 18 wherein the carbon comprises pyrolytic carbon.

20. The method of claim 13 wherein the plasma polymerized coating comprises a film.

21. The method of claim 20 wherein the film is capable of reducing platelet activation in vitro.

22. The method of claim 13 wherein the monomer comprises a methacrylate-containing species.

23. The method of claim 13 wherein the monomer comprises a styrene-containing species.

24. A method of coating a vascular biomaterial having a metallic surface, comprising

(a) creating a reactive surface upon a metallic surface of a vascular biomaterial,

(b) exposing the reactive surface to a monomer, and

(c) plasma polymerizing the monomer upon the metallic surface of the vascular biomaterial, thereby forming a coating.

25. The method of claim 24 in which the monomer comprises an acrylic-containing monomer.