Treatment of metallic surfaces using radiofrequency plasma deposition and chemical attachment of bioactive agents

A treatment for metallic surfaces and devices having metallic surfaces is described. A film of heptafluorobutylmethacrylate (HFBMA) is applied to a surface by radiofrequency (RF) plasma deposition and subsequently treated with a biologically active agent. A water vapor RF plasma treatment of the HFBMA coating provides reactive groups thereon which can covalently bond to the biologically active agent. Alternatively, a spacer group can be bonded to the activated HFBMA and the biologically active agent can then be bonded to the spacer group. Devices coated according to the invention possess enhanced biocompatibility and the HFBMA coatings are durable even under severe crimping and expansion conditions.

BACKGROUND AND BRIEF DESCRIPTION OF THE INVENTION 
The present invention generally relates to the treatment of metallic 
surfaces to enhance their biocompatibility and to medical devices and the 
like which include such biocompatible surfaces. More specifically, the 
invention relates to depositing a film of heptafluorobutylmethacrylate 
("HFBMA") on a metallic surface using radiofrequency plasma deposition and 
subsequently functionalizing the deposited HFBMA by a water vapor 
radiofrequency plasma treatment. Biologically active agents are bound to 
the HFBMA coated surface so that medical devices which include such 
surfaces possess an improved biocompatibility. 
Those skilled in the art will appreciate the importance of certain medical 
devices having surfaces of an enhanced biocompatibility. Medical devices 
made from polymeric materials as well as from metallic materials generally 
benefit from having enhanced biocompatibility especially where such 
devices are intended for subcutaneous implantation where they can 
experience in vivo environments depending on the nature of the particular 
device. The biocompatibility of such medical devices is generally enhanced 
by attempting to secure certain agents to the surface of those devices. 
For example, anti-thrombogenic agents are often secured to the surfaces of 
medical devices having blood contacting surfaces. It would be particularly 
undesirable to have the anti-thrombogenic agent leach away in wet 
environments such as those encountered by medical devices that engage 
blood or other body fluids. 
Attempts have been made and approaches have been suggested for activating 
the surface of a medical device with a radiofrequency ("RF") plasma. The 
activated surface reacts with heparin or other biologically active agents 
to provide a biocompatible surface having specific characteristics such as 
Anti-thrombogenicity, endothelial growth promoters, and the like. The 
treatment of surfaces with a radiofrequency plasma has been described in 
various patents. Included are patents incorporating plasma discharge 
treatment with a gaseous environment including a variety of gases such as 
inert and organic gases. Patents in this regard include U.S. Pat. Nos. 
4,613,517, 4,656,083 and 4,948,628, which mention a variety of plasma 
media including those generated from hydrogen, helium, ammonia, nitrogen, 
oxygen, neon, argon, krypton, xenon, ethylenic monomers and other 
hydrocarbons, halohydrocarbons, halocarbons and silanes. Certain of these 
plasma media are relatively expensive and can be hazardous to use within a 
manufacturing environment and/or to dispose of as waste. Certain plasma 
media are more suitable for treatment of specific substances. 
Other surface treatments have been proposed specifically for metal surfaces 
intended to contact bodily fluids and the like during implantation. One 
such treatment involves the chemical oxidation of the metallic surface, 
such as a tantalum surface, until enough of a metal oxide layer is 
provided for bonding with a bioactive agent. Many other approaches in this 
area have concentrated on utilizing polymeric surfaces as the surface 
which encounters the body fluids and then treating those polymeric 
surfaces according to a variety of procedures. Polymeric surfaces and 
metallic surfaces each pose different problems which must be overcome to 
provide a polymeric or metallic surface that is suitable for implantation 
and/or extended-time residence within the body. U.S. Pat. Nos. 3,549,409 
and 3,639,141 describe treatments of particular polymeric surfaces by 
swelling the polymeric surface, bonding an agent thereto and noncovalently 
coupling heparin to that agent. The latter of these patents mentions 
contacting the polymeric surface with an amino alkyl trialkoxysilane 
dissolved in an organic solvent to swell the polymeric material. Another 
approach involving a chemical treatment is exemplified by U.S. Pat. Nos. 
4,526,714 and 4,634,762 which indicate that a surface can be rendered 
biocompatible by coating it with a conjugate of heparinous material and a 
protein, with the conjugate being formed by coupling carried out in the 
presence of 1-ethyl-3-dimethyl-aminopropyl carbodiimide (known as EDC) and 
the like as a coupling agent. The conjugate is attached to the substrate 
surface at the sites where the surface free functional groups suitable for 
bonding to the conjugate are present. In order to effect the coupling 
needed to form this conjugate, these free functional groups on the 
substrate surface are provided as free amino groups. 
Another treatment procedure involves treatment of a surface with heparin 
benzalkonium chloride (HBAC). A quaternary amine structure is involved. 
The result is an ionic linkage, and subsequent ionic exchange occurs quite 
readily. For example, HBAC is easily leached from the treated surfaces to 
the extent that substantially all of the heparin is removed within about 
three days under leaching conditions. In addition, 4M guanidine, which is 
used to demonstrate the ionic nature of bonds by an ionic exchange 
mechanism, quickly removes the heparin in a one hour, non-physiological 
ionic release test. Furthermore, because benzalkonium chloride is in 
essence a surfactant, an HBAC conjugated surface is a cytotoxic material 
as well as a hemolytic material, causing a breakdown of red blood cells. 
Other quaternary amine alternatives are believed to be non-hemolytic such 
as tetradodecylammonium chloride (TDAMC), for example. These types of 
materials are typically applied from a hydrocarbon solvent system, also 
providing ionic bonding and ionic exchange can and does occur quite 
readily. Because of its molecular structure, heparin and materials having 
similar functions do not escape quite as readily from TDAMC as from HBAC, 
but leaching is still very apparent. When attachment to a surface is by 
means of ionic bonding of TDAMC and the like, most of the heparin or 
bioactive agent is leached away after three hours of contact with blood 
plasma or after about 24 hours within a phosphate buffered saline solution 
under physiological conditions. The ionically attached material is 
substantially completely removed with guanidine within about one hour 
during non-physiological testing. 
Many of the above-discussed attempts to improve the biocompatibility of 
various medical devices do not fare well under in vivo or biological 
conditions, and they fall short of fulfilling desirable attributes such as 
having the coating remain functional for a length of time adequate to 
provide maximum thrombus prevention. Another important consideration is 
whether the coating interferes with endothelialization. For metallic 
medical devices which undergo movements, such as bending of a portion 
thereof during implantation and/or use, the mechanical properties of the 
treatment coating should be able to withstand flexure during bending, 
expansion and the like of the coated member. For example, metallic 
radially expandable generally tubularly shaped endoprostheses which are 
generally known as stents, must be able to withstand such flexure. An 
exemplary stent is described in U.S. Pat. No. 5,019,090, the subject 
matter thereof being incorporated by reference hereinto. Such stents are 
made of a very fine gauge metallic wire, typically tantalum or stainless 
steel wire. During implantation, these stents are mounted onto the balloon 
of an angioplasty catheter or the like until a partially occluded location 
within the blood vessel is reached, at which time the balloon and the 
stent are radially and circumferentially expanded for purposes of opening 
the occlusion and supporting the vessel at that location. This necessarily 
involves rather extensive bending of the tantalum wire. Many previously 
available coatings do not have the flexibility and/or adherence properties 
needed to avoid cracking and/or loss of the coating when subjected to this 
type of flexure. 
It would be desirable to design and utilize a system which meets the 
objectives of imparting biocompatibility to a metallic substrate to 
thereby substantially prevent thrombus formation on the metallic surface. 
Such a system should not crack or otherwise deteriorate due to mechanical 
movement of the treated metallic member and the system should not allow 
substantial leaching of the biologically active material and should not 
substantially interfere with endothelialization after in vivo 
implantation. 
It has been determined that a system providing covalent linkages between a 
bioactive agent and a functionalized HFBMA coated metal surface meets 
these objectives, providing an enhanced metallic surface with permanently 
improved biocompatibility. Such a system includes treating a metallic 
surface of the medical device with an RF plasma to deposit a film of HFBMA 
and subsequently functionalizing the deposited film by water vapor plasma 
treatment, thus providing available carboxy and hydroxy groups on the 
HFBMA coating to facilitate bonding with bioactive agents. The bioactive 
agents can be bound to the HFBMA surface using different reaction schemes 
and reagents including without limitation carbodiimide chemistry, 
organosilane chemistry, Woodwards K reagent and glutaraldehyde 
cross-linking. Various anti-thrombogenic agents, endothelial growth 
promoters, smooth muscle cell anti-proliferative agents, platelet growth 
factor antagonists, vasoconstrictors and vasodialators and cellular 
adhesion promoters can all be applied alone or in combination with spacers 
such as albumin, polyethylene oxide, various diacid chlorides, 
polyethyleneimine, N-(2-aminoethyl-3-aminopropyl) trimethoxysilane and the 
like. 
The activated HFBMA-modified metallic surface may be treated with either a 
spacer or the bioactive agent using carbodiimide chemistry utilizing a 
water soluble carbodiimide. The molecule attached to the surface (either 
the HFBMA or the spacer) must have a primary or secondary amine and for a 
spacer there must be at least two primary or secondary amines. 
Endovascular stents can be made using these HFBMA coated metallic 
surfaces. There is evidence to show that a completely and quickly 
endothelialized object, such as a stent, does not promote smooth muscle 
cell proliferation and therefore could prevent restenosis. 
It is accordingly a general object of the present invention to provide an 
improved biocompatible metallic surface, a method of preparing such a 
surface and a method of implanting a device having such a surface. 
Another object of the present invention is to provide an improved stent or 
other medical device having a HFBMA coating which is capable of covalently 
bonding to bioactive agents and is able to withstand flexure and 
interaction with fluids. 
Another object of this invention is to provide a method for depositing a 
film of HFBMA by radiofrequency plasma deposition and binding a bioactive 
agent thereto to provide an enhanced metallic surface with permanently 
improved biocompatibility. 
Another object of the present invention is to provide an improved metallic 
surface which is particularly compatible and exhibits advantageous 
properties conducive to long-term placement within a body. 
Another object of the present invention is to provide a treatment for 
metallic surfaces without detrimentally affecting the mechanical 
properties of the metal. 
These and other objects, features and advantages of the present invention 
will be clearly understood by those skilled in the art through a 
consideration of the remainder of the disclosure, including the drawings 
and the detailed description of the preferred embodiments.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
The present invention provides an improved biocompatible metallic surface 
for medical devices and the like by RF plasma deposition of HFBMA over the 
metallic surface followed by a suitable treatment with a biologically 
active agent. The resulting surface and/or device shows a permanently 
improved biocompatibility for in vivo use such as for endovascular stents 
and the like. 
A metallic surface to be treated in accordance with the principles of the 
present invention is first coated with a film of HFBMA by RF plasma 
deposition and subsequently functionalized by water vapor RF plasma 
treatment to provide reactive carboxy and hydroxy groups to facilitate the 
subsequent bonding of the biologically active agent thereto. The modified 
HFBMA surface may be treated with either a spacer or bioactive agent 
having a primary or secondary amine and for a spacer molecule there should 
be at least two primary or secondary amines to form a covalent bond 
between the carboxy group of the activated HFBMA and the amine on the 
spacer or bioactive molecule. The reaction between the HFBMA and the 
bioactive agent typically proceeds by a condensation reaction or peptide 
bond formation using a carbodiimide coupling agent to form a covalent bond 
between the carboxy group of the activated HFBMA and the amine of the 
bioactive agent. 
Although carbodiimide chemistry is one mechanism by which the HFBMA and the 
bioactive agent are covalently bonded, different reaction schemes and 
reagents will also produce the desired result. Such schemes and reagents 
include without limitation organosilane chemistry, Woodwards K reagent as 
well as glutaraldehyde cross-linking. Numerous bioactive agents can be 
used in practicing the invention including anti-thrombogenic agents such 
as heparins, hirudin, hyaluronic acid and PK 
(D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone); endothelial 
growth promotors such as vascular endothelial growth factor, gelatin, 
fibronectin, collagen, laminin, matrigel, and victronectin; smooth muscle 
cell anti-proliferative agents such as anti-.beta.-FGF, meulinolin, 
enoxaparin and 5-fluorouracil; platelet growth factor antagonist; 
vasoconstrictors and vasodilators; and cellular adhesion promoters. 
While the bioactive agents may be applied directly to the HFMBA coating, it 
may be desirable to first attach a spacer group prior to treating the 
surface with the bioactive agent. Suitable spacer groups include albumin, 
polyethyleneimine and N-(2-aminoethyl--3-aminopropyl) trimethoxysilane. 
Where the bioactive molecule is bound through an organosilane spacer 
molecule, the reaction is a condensation reaction between the hydroxy 
groups on the HFBMA coating and the silane functionality on the 
organosilane. The bioactive molecule is subsequently bound to the amine of 
the silane by carbodiimide chemistry. 
While virtually any metallic surface can experience an enhanced 
biocompatibility by a treatment of the surface in accordance with the 
principles disclosed herein, for convenience and simplicity the disclosure 
frequently discusses the application of the invention in the context of 
treating endovascular stents such as the stent 10 of FIG. 1. Those skilled 
in the art will understand that the broader teachings of the invention 
apply to any metallic surface where an enhanced biocompatability is 
desired. 
In coating a metallic surface of a stent or the like with HFBMA, an RF 
plasma deposition technique is used and the HFBMA coating is subsequently 
activated using water plasma treatment. In preparing stents by plasma 
polymerization, stents are mounted on a metal mount and loaded into a one 
inch diameter, twelve inch long glass reactor tube. The reactor is RF 
coupled capacitively by external electrodes and the system is pumped down 
to remove air. Water and oxygen are introduced into the reactor in a 
three-to-one ratio and the pressure is adjusted to 100 mtorr. Fifty watts 
of RF is applied to pretreat the stents with a water/oxygen plasma. After 
pretreatment, the system is pumped down to remove water and oxygen. 
Nitrogen and HFBMA are next introduced into the reactor while pressure is 
maintained at 250 mtorr using a pressure controller system. RF power at 20 
watts is then applied for 3.5 minutes to obtain a HFBMA coating. The 
system is again pumped down to remove the residual HFBMA monomer and 
nitrogen. Water vapor is introduced into the reactor while pressure is 
controlled at 400 mtorr and RF power at 20 watts is applied to create a 
water vapor plasma for 45 seconds to modify the polymer coating obtained 
in the HFBMA treatment step. 
Once the HFBMA coating has been deposited and subsequently activated, the 
activated surface can be treated with either a bioactive agent or a spacer 
molecule, as discussed herein. Typically, an aqueous solution of the 
spacer or bioactive agent is applied to the activated HFBMA coating with 
an amount of a carbodiimide compound to facilitate a condensation or 
peptide bond formation using the carbodiimide as a coupling agent. As a 
coupling agent, the carbodiimide will covalently bond to both the carboxy 
group on the HFBMA and the amine on the spacer molecule or the bioactive 
agent. An aqueous solution of 
N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) is a 
suitable coupling agent. Preferably, the EDC concentration on a weight per 
volume basis is approximately equal and up to twice the concentration of 
the spacer or the bioactive agent and is typically between about 4.0 mg/ml 
and about 8.0 mg/ml. Most typically, where heparin is employed as the 
bioactive agent, a 1:1 ratio of heparin:EDC is desired. A carbodiimide is 
not required with an organosilane spacer group since a condensation 
reaction will occur between the hydroxy groups of the activated HFBMA 
surface and the hydroxy groups of the silane functionality. 
Where a spacer molecule is added directly to the HFBMA coating, the stent 
is typically placed in a solution of the spacer and exposed to the 
solution for several minutes. Where a spacer such as polyethylenimine 
(PEI) is used, a PEI concentration of about 1% by weight is generally 
adequate with the stent being exposed to the solution for about 5 minutes. 
Other spacers may require different exposure times depending upon the 
spacer and the concentration thereof. A stent exposed to a solution of 
albumin at a concentration of 3.33 mg/ml typically requires exposure to 
the solution for approximately 15 minutes. Following exposure to the 
spacer solution, the stent is typically rinsed and/or air dried for a 
suitable period of time and, in the case of silane spacer, the stent may 
be oven cured at an elevated temperature of between about 100.degree. C. 
and about 120.degree. C. 
The bioactive agent may be added to the spacer in an aqueous or other 
suitable solution. The addition of heparin to the spacer is typically 
accomplished by exposing the stent to an aqueous heparin solution for a 
period of time between about 20 minutes and about 90 minutes. Where 
carbodiimide chemistry is employed in bonding the heparin with the spacer 
molecule, EDC is typically added to the heparin solution to facilitate 
bonding. A heparin concentration of 6.67 mg/ml with an equal concentration 
of EDC has been suitable. Of course, other bioactive agents can be used 
such as hyaluronic acid as well as hirudin, for example. Where heparin is 
the bioactive agent, the presence of the heparin coating on a stent may be 
confirmed by known techniques such as by extraction in phosphate buffered 
saline (PBS) followed by rinsing and staining with toluidine blue. A 
change in the light refraction will indicate that the samples have picked 
up the purple color of the dye which commonly occurs in the presence of 
heparin. Staining the treated stents with berberine sulfate, a fluorescent 
stain, and an examination of the stained stents under a fluorescent 
microscope will show a yellow glow in the presence of heparin. Fluorescent 
thrombin-anti-thrombin (TAT) immunoassay is another technique available to 
determine the presence of biologically active heparin. 
Stents that have been treated according to the invention generally have 
shown improved durability over stents that have been treated by other 
techniques to improve their biocompatibility. Coatings of the invention 
are suitable for deposition on electropolished as well as non-polished 
metallic surfaces, displaying an improved durability for both surfaces. 
Non-polished stents, for example, may present at least the potential for 
irritation of blood vessel lumen due to roughness of non-polished metallic 
surfaces. The complications can be avoided since the coatings of the 
present invention will durably adhere to electropolished surfaces. Also, 
as set forth herein, flow loop analysis performed on stents made in 
accordance with the invention has demonstrated low platelet activation as 
well as low platelet adherence, suggesting a reduction in the release of 
platelet factors which trigger smooth muscle cell migration and phenotypic 
change. The lack of muscle cell migration would limit the smooth muscle 
cell proliferation which is one component of the stenosis pathway, 
suggesting that the coating of the invention may play a part in the 
prevention of restenosis. Flow loop analysis has shown the coatings of the 
invention to be generally superior to prior art coatings with no adverse 
effects on the coagulation system. FIGS. 2 and 3 are illustrative of flow 
loop data for stents coated according to the invention. The FIGS. 2 and 3 
represent SEM photographs, taken at a magnification of 1500.times. of 
stents coated with HFBMA-albumin-heparin and subjected to flow loop 
analysis. The SEM field shown in FIG. 2 reveals no adherent platelets on 
the stent surface 12, and, the field shown in FIG. 3 reveals only four 
platelets 14 on the stent surface 16. 
The following examples illustrate the inventive biocompatible coatings for 
metal surfaces and the advantageous properties thereof. 
EXAMPLE 1 
Stent samples were coated with HFMBA using plasma deposition and the HFBMA 
coating was activated by water plasma treatment. The coated and activated 
samples were then treated with an aqueous solution of polyethylenimine 
(PEI) and EDC with a PEI concentration of 1% by weight and 5 mg/ml EDC at 
an overall pH of 8. The stent samples were exposed to the PEI:EDC solution 
for five minutes and were then removed from the solution and rinsed. 
Heparin was applied from an aqueous solution having a heparin 
concentration of 6.67 mg/ml with an equal concentration of EDC at an 
overall pH of 3. The stents were exposed to the heparin for one hour and 
were then rinsed and air dried. Samples were then extracted in phosphate 
buffered saline (PBS) for three hours at physiological temperature. The 
samples were removed and rinsed and then stained with toluidine blue. The 
light refraction for the samples indicated that the stents had picked up 
the purple color of the dye, indicating the presence of heparin. 
EXAMPLE 2 
Stents samples were coated with HFBMA and activated as in Example 1 
followed by a treatment with a 2% solution of [3-(2 aminoethyl) 
aminopropyl] trimethoxysilane for five minutes after which the samples 
were removed from the solution and air dried for about one minute to 
remove excess solvent (95% ethanol). The samples were oven cured at 
110.degree. C. for ten minutes and then cooled. The stents were exposed to 
the heparin solution of Example 1 for one hour, and were then rinsed and 
air dried. The presence of heparin on the stents was confirmed using a PBS 
extraction as in Example 1. 
EXAMPLE 3 
Stent samples were treated with HFBMA and activated as in Example 1. Each 
of the samples were then treated with an aqueous albumin:EDC solution 
containing 3.33 mg/ml albumin and 6.67 mg/ml EDC. The samples were allowed 
to sit in the albumin:EDC solution for 15 minutes at a pH of about 5. 
After fifteen minutes, the samples were removed from the solution and 
rinsed completely and then placed in a heparin:EDC solution identical to 
the solution of Example 1. The samples were treated in the heparin 
solution for thirty minutes and then removed, rinsed and allowed to air 
dry. 
EXAMPLE 4 
Stent samples were treated as in Example 3 except that the albumin 
concentration was 2.5 mg/ml and the EDC concentration was 5mg/ml at an 
overall pH of about 5. The presence of heparin on the stents was confirmed 
by PBS extraction as in Example 1. Additionally, a TAT immunoassay was 
performed on the samples by first incubating the samples in human blood 
plasma and then rinsing and incubating the samples in a solution of 
fluorescently labeled anti-thrombin. The stents were examined under 
fluorescent microscope to confirm the presence of biologically active 
heparin, as indicated by a yellow glow of the sample surfaces. The 
biologically active heparin was evenly distributed on the samples. 
Finally, berberine staining was also performed by staining the stents with 
fluorescent stain berberine sulfate followed by an examination of the 
samples under a fluorescent microscope, showing a relatively even yellow 
glow indicative of the presence of heparin. 
EXAMPLE 5 
Stents samples which had been electropolished were then treated as in 
Example 2. 
EXAMPLE 6 
Stents samples which were previously electropolished were then treated as 
in Example 4 herein. 
EXAMPLE 7 
Durability (expansion) testing was conducted on stents prepared according 
to Examples 1, 2, 4, 5 and 6 to determine the durability of the coating on 
the stent after the stent had been crimped onto a balloon and then 
expanded. The analysis was done using a scanning electron microscope 
(SEM). Results of the examination indicated that although crimping caused 
some abrasions of the stent coatings, there were no breaks in any of the 
examined coatings and all of the samples showed a uniform coating covering 
the entire surface of the stent. 
EXAMPLE 8 
Flow loop analysis was performed on stent samples prepared as in Examples 4 
and 6. This analysis was used to characterize the interaction of platelets 
with the stent samples. Decalcified blood was passed through a 
polymethylmethacrylate flow cell containing a stent sample for five 
minutes. Testing done on the blood both before and after the analysis 
included activated partial thrombo plastin time (APTT), hemolysis and 
total blood counts (CBC). Platelet aggregation testing was performed prior 
to beginning the experiment to determine if the platelets in the blood 
were acceptable after blood transport to the site of the experiment. 
Following flow loop analysis, samples were fixed with glutaraldehyde and 
dehydrated with an ethanol series. SEM analysis was performed to determine 
the per unit area of platelets adhering to the samples. The samples coated 
with the HFBMA:albumin:heparin coating on either an electropolished or a 
non-polished wire exhibited very few platelets adhering to the surface. In 
some fields, no platelets were observed. The average number of platelets 
per field was approximately three and platelets that did adhere were 
observed as spherical and showing little to no signs of activation (e.g. 
no spreading, cytoplasmic streaming or pseudopod formation was observed). 
Control samples showed moderate to strong platelet adhesion with the 
platelets showing signs of activation along with the presence of 
pseudopods. 
EXAMPLE 9 
A comparison was made of coated tantalum stents by comparison of flow loop 
data collected for four stents having various coatings. The data for these 
stents is presented in Table I. The coated stents included an HFBMA coated 
stent without a bioactive agent bonded thereto, and another HFBMA coated 
stent which was further treated to include an albumin spacer group and a 
heparin coating bonded thereto. A third stent was coated with an 
aminosilane coating which also included a coating of heparin. A fourth 
stent was coated with a coating known under the trademark SPI-LON.TM., of 
the Spire Corporation of Bedford, Mass., a polytetrafluoroethylene which 
is ion-beam sputtered onto the surface of the stent. The control was an 
uncoated, unpolished tantalum stent. 
The aminosilane-heparin coating showed many adherent platelets under SEM 
examination. The SPI-LON.TM. coated stent gave very low platelet counts 
and the two HFBMA-treated stents experienced no adherent platelets in the 
fields examined by SEM. Additionally, the ability to bond heparin and 
other bioactive agents to the surface of the HFBMA coating is an advantage 
over the SPI-LON.TM. coated stents, enhancing the performance of the 
device in a targeted area of the body. 
TABLE I 
______________________________________ 
Comparative Flow Loop Data 
Flow Loop (avg. no. 
Stent Coating platelets/.006 mm.sup.2) 
______________________________________ 
HFBMA 0 
HFBMA - Albumin-Heparin 
0 
Aminosilane-Heparin 
11 
SPI-LON.TM. 2 
(Control) Massive platelet aggregates 
on internal diameter of 
stent 
______________________________________ 
The above examples illustrate various features of the invention as well as 
the manner in which devices can be made hereunder. It should now be 
appreciated that devices, such as the endovascular stents discussed 
herein, are rendered more biocompatible when coated with the inventive 
HFBMA/bioactive agent coatings disclosed herein as opposed to prior art 
coatings. Generally, the coatings of the invention possess improved 
durability and/or improved biocompatability over other commonly used prior 
art coatings. For example, the hydrophilic polymer coating known under the 
trade name HYDROMER.TM. may satisfactorily endure certain durability 
testing but typically shows poor hemocompatibility. A xylene-based polymer 
coating such as ALENE C.TM. demonstrates poor hemocompatibility, 
showing no significant differences from uncoated control samples. 
Moreover, the ALENE C.TM. coating is easily disrupted during durability 
testing, experiencing plastic deformation and even slight disruption of 
the coating. Similarly, certain tetrafluoroethylene (TFE) coatings and 
coatings made from hyaluronic acid will typically experience massive 
disruption under crimping and expansion testing. The coatings of the 
present invention, however, are biocompatible while also being very 
durable. 
It will be understood that the embodiments of the present invention which 
have been described are illustrative of some of the applications of the 
principles of the present invention. Modifications may be made by those 
skilled in the art without departing from the true spirit and scope of the 
invention.