Abstract:
A method of impregnating an implantable device, such as a vasclar graft or a covering adapted to be disposed over a prosthesis, is provided. The substances may be impregnated within the implantable device as a passive coating or as a delivery matrix for a matrix for a therapeutic substance. Also provided is an implantable device having such substances impregnated therein.

Description:
CROSS REFERENCE 
     This is a divisional application of U.S. Ser. No. 09/608,444, which was filed on Jun. 29, 2000 now U.S. Pat. No. 6,585,765. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates generally to implantable devices, such as synthetic vascular grafts and covered stents. More particularly, the present invention is directed to a method of impregnating an implantable device with substances as well as to an implantable device that has been so impregnated. 
     2. Description of the Related Art 
     Occlusion of blood vessels reduces or blocks blood flow. During the course of atherosclerosis, for example, growths called plaques develop on the inner walls of the arteries and narrow the bore of the vessels. An embolus, or a moving clot, is more likely to become trapped in a vessel that has been narrowed by plaques. Further, plaques are common sites of thrombus fonnation. Together, these events increase the risk of heart attacks and strokes. 
     Traditionally, critically stenosed atherosclerotic vessels have been treated with bypass surgery in which veins removed from the legs, or small arteries removed from the thoracic cavity, are implanted in the affected area to provide alternate routes of blood circulation. More recently, implantable devices, such as synthetic vascular grafts and stents, have been used to treat diseased blood vessels. 
     Synthetic vascular grafts are macro-porous vessel-like configurations typically made of expanded polytetrafluoroethylene (ePTFE), polyethylene terephthalate (PET), polyurethane (PU), or an absorbable polymer. Grafts made of ePTFE or PET are very non-wetting materials when introduced into an aqueous environment, causing difficulty in impregnating the materials. In addition, grafts made of ePTFE or PET are permanently implanted in the body, while grafts made of an absorbable polymer bioabsorb over time. A graft may be positioned into the host blood vessel as a replacement for a diseased or occluded segment that has been removed. Alternatively, a graft may be sutured to the host vessel at each end so as to form a bypass conduit around a diseased or occluded segment of the host vessel. 
     Intravascular stents may be permanently or temporarily implanted in narrowing blood vessels. Typically, a vascular catheter, or similar transluminal device, is utilized to carry the stent to the treatment site. The stent is expanded to support, and if desired expand, the diseased portion of the arterial wall. The insertion of a stent into a vessel in which plaque has become brittle over time, however, may cause complications if the stent causes the brittle plaque to break off from the vessel wall and embolize the lumen. A covered stent, in which a graft-like covering is slip-fit onto the stent, may therefore be employed to isolate the brittle plaque from direct contact with the stent, which is rigid. 
     To treat such damaged vasculature tissue and to help prevent thrombosis and restenosis, there is a need for administering therapeutic substances to the treatment site. To provide an efficacious concentration to the treatment site, systemic administration of the therapeutic substance often produces adverse or toxic side effects for the patient. Local delivery is a highly suitable method of treatment, in that smaller levels of therapeutic substances, as compared to systemic dosages, are concentrated at a specific site. Local delivery produces fewer side effects and achieves more effective results. 
     One technique for the local delivery of therapeutic substances is through the use of medicated coatings on implantable devices. In addition to providing local delivery capabilities, such a coating protects vessel tissue from injury and helps prevent excessive foreign body reaction that may occur when such a device is implanted. 
     SUMMARY OF THE INVENTION 
     The present invention provides a method by which implantable devices, including those made of very non-wetting materials, may be impregnated with passive as well as therapeutic substances. An implantable device that has been impregnated with such substances is also provided. 
     In accordance with one embodiment of the present invention, a method of impregnating an implantable device, such as a vascular graft or a covering adapted to be disposed over a prosthesis, is provided. The method includes an act of providing a substrate having a body and interstices throughout the body, an act of applying a composition containing a first substance and a first fluid to the substrate such that the composition penetrates into the interstices of the body of the substrate, and an act of removing essentially all of the first fluid from the composition within the body of the substrate. The first substance remains within the body of the substrate. An implantable device having a first substance deposited therein in accordance with the above-described method is also provided. 
     In some embodiments of the method described herein, the first substance is a pre-polymer. In such embodiments, the method further includes the act of causing the pre-polymer to crosslink to form a hydrogel within the body of the substrate. In addition, an implantable device having a hydrogel formed therein in accordance with the method is provided. 
     In other embodiments of the above-described method, the body of the substrate has a first end, an opposing second end, and a hollow bore extending longitudinally through the body from the first end to the second end. In such embodiments, the method may further include the act of providing a prosthesis and the act of inserting the prosthesis at least partially within the hollow bore of the body of the substrate. In some embodiments, the prosthesis has a plurality of depots formed therein. In such embodiments, the act of providing a prosthesis may further include the act of forming the plurality of depots within the prosthesis. The act of providing a prosthesis may also include the act of depositing a second substance within the plurality of depots. The deposited material may be selected from therapeutic substances, polymeric materials, and radiopaque materials, among other possibilities. 
     In other embodiments of the above-described method, prior to applying the composition, the method additionally includes an act of applying a second fluid to the substrate. In other embodiments, subsequent to applying the second fluid and prior to applying the composition, the method additionally includes an act of applying a third fluid to the substrate. In still other embodiments, the method additionally includes an act of applying a bridging fluid to the substrate between the otherwise consecutive application of immiscible fluids. 
     In other embodiments of the above-described method, the composition additionally includes a therapeutic substance. The therapeutic substance is selected from a group of antineoplastic, antimitotic, antiplatelet, anticoagulant, fibrinolytic, thrombin inhibitor, antiinflammatory and antiproliferative, antioxidant, and antiallergic substances, and mixtures thereof. 
     Also disclosed is an implantable device. The device includes a substrate having a body and interstices within the body. The body has a first end, an opposing second end, and a hollow bore extending longitudinally through the body from the first end to the second end. The device also includes a first substance impregnated within the interstices of the body of the substrate and a prosthesis inserted at least partially within the hollow bore of the body of the substrate. The prosthesis has a plurality of depots formed therein. In some embodiments of the implantable device, the plurality of depots contain a second substance. 
     These and other aspects of the present invention may be better appreciated in view of the detailed description and drawings of the exemplary embodiments. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1A  illustrates a perspective view of an implantable device with a central hollow bore; 
         FIG. 1B  illustrates a cross-section taken along line  1 B- 1 B of  FIG. 1A ; 
         FIG. 1C  illustrates a cross-section taken along line  1 C- 1 C of  FIG. 1B ; 
         FIG. 2A  illustrates a perspective view of the implantable device of  FIG. 1 , wherein a stent is within the central hollow bore of the implantable device; 
         FIG. 2B  illustrates a cross-section taken along line  2 B- 2 B of  FIG. 2A ; 
         FIG. 2C  illustrates a cross-section taken along line  2 C- 2 C of  FIG. 2B ; 
         FIG. 3A  is a side view of a conventional intraluminal prosthesis, the body of the prosthesis being defined by thread elements engaged to one another by connecting elements; 
         FIG. 3B  is an enlarged view of section  3 B of  FIG. 3A , illustrating a portion of the thread elements and connecting elements and having depots formed therein; 
         FIG. 3C  is a cross-sectional view of the thread element, taken in the direction of the arrows and along the plane of line  3 C- 3 C of  FIG. 3B , illustrating a depot formed in the prosthesis in accordance with the various disclosed embodiments; 
         FIG. 3D  illustrates the thread element of  FIG. 3C  in which a material has been deposited into the depot; 
         FIG. 4A  illustrates the application of a fluid to an implantable device in accordance with the various disclosed embodiments; 
         FIG. 4B  illustrates a cross-sectional view of the implantable device of  FIG. 4A  as a fluid penetrates into interstices thereof in accordance with the various disclosed embodiments; 
         FIG. 5A  illustrates a fluid on a solid substrate having a contact angle Φ 1 ; 
         FIG. 5B  illustrates a fluid on a solid substrate having a contact angle Φ 2 ; and 
         FIG. 6  illustrates the chemical structure of PEG diacrylate end-capped with lactide. 
     
    
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
     The following definitions apply hereinthroughout unless a contrary intention is expressly indicated:
         “Crosslink” means to attach a polymer chain to another polymer chain or to a monomer by lateral bonds with or without the assistance of crosslinking agents and/or energy in the form of electromagnetic radiation and/or heat;   “Miscible” means that two liquids are capable of being mixed in at least some proportions, and is inclusive of fully miscible systems that are capable of being mixed in all proportions without phase separation, as well as partially miscible systems that are capable of being mixed in some, but not all, proportions;   “Polymer,” “poly,” and “polymeric” mean the product of a polymerization reaction and are inclusive of homopolymers, copolymers, terpolymers etc., whether natural or synthetic, including random, alternating, block, graft, crosslinked, blends, compositions of blends and variations thereof, and   “Pre-polymer” means a reactive polymer that has not yet been crosslinked.       

     Referring now to the drawings, wherein similar parts are identified by like reference numerals, FIGS.  1 A and  1 B- 1 C illustrate prospective and cross-sectional views, respectively, of an implantable device  10 . Implantable device  10  includes a body  12  having a first end  14  and an opposing second end  16 . A central hollow bore  18  extends longitudinally through body  12  from first end  14  to second end  16 , giving body  12  a thickness t 1 . Implantable device  10  can have any suitable length  1 . The values of length  1   1  and thickness t 1  depend, for example, on the procedure for which implantable device  10  is used. 
     Implantable device  10  contains a plurality of interstices  20 , which cause body  12  to have a generally permeable characteristic. Body  12  can be made from any suitable material including, but not limited to, highly open-pored materials such as polymers of expanded polytetrafluoroethylene (ePTFE) and polyethylene terephthalate (PET). 
     In an alternative embodiment, body  12  is made from a less porous material, such as, but not limited to, polyurethanes, absorbable polymers, and combinations or variations thereof. Polyurethanes from which implantable device  10  may be made include, but are not limited to, Biomer, Biospan, and Elastion. Absorbable polymers from which implantable device  10  may be made include, but are not limited to, polycaprolactone (PCL), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), polyanhydrides, polyorthoesters, polyphosphazenes, and components of extracellular matrix (ECM). In such an embodiment, additional interstices  20  can be formed in body  12  by any conventional methods known to one of ordinary skill in the art, including exposure of body  12  to a laser discharge to form a network of pores. 
     In one embodiment of the present invention, implantable device  10  of  FIGS. 1A ,  1 B, and  1 C is a vascular graft. In an alternative embodiment, illustrated in  FIGS. 2A ,  2 B, and  2 C, implantable device  10  is a covering for a prosthesis  22 , which may be, for example, a self-expandable stent or a balloon-expandable stent. In such an embodiment, implantable device  10  is placed over all or part of the longitudinal outer surface of prosthesis  22  such that prosthesis  22  is at least partially within central hollow bore  18  of implantable device  10 . The thickness t 2  of the implantable device  10  of  FIG. 2A  for such an embodiment should not hinder the functionality of prosthesis  22 , for example, the ability of prosthesis  22  to be radially expanded to a significantly rigid structure to maintain the patency of a vessel. Thickness t 2  can be, for example, in the range of about 50 microns to about 500 microns, depending on the application. Additionally, the material from which implantable device  10  is made should have enough elasticity so as to allow prosthesis  22  to be expanded from a collapsed configuration to an expanded configuration. Body  12  of  FIG. 2A  can have any suitable length  12 , depending on the application. 
     Prosthesis  22  may be any prosthesis so long as prosthesis  22  is capable of securely receiving the covering. The underlying structure of prosthesis  22  can be virtually of any design. For example, prosthesis  22  may be an expandable stent having a plurality of thread elements  24  that are interconnected by connecting elements  26  that are disposed between adjacent thread elements  24 , as shown in  FIG. 3A . Although thread elements  24  are illustratively shown in the form of cylinders or rings connected axially-displaced in parallel, other configurations, such as helices, coils, or braids, and other connections may be utilized. 
     Prosthesis  22  can be made of a metallic material or an alloy such as, but not limited to, stainless steel, “MP35N,” “MP20N,” elastinite (Nitinol), tantalum, nickel-titanium alloy, platinum-iridium alloy, gold, magnesium, or combinations thereof. “MP35N” and “MP20N” are trade names for alloys of cobalt, nickel, chromium and molybdenum available from standard Press Steel Co., Jenkintown, Pa. “MP35N” consists of 35% cobalt, 35% nickel, 20% chromium, and 10% molybdenum. “MP20N” consists of 50% cobalt, 20% nickel, 20% chromium, and 10% molybdenum. Prosthesis  22  also may be made from bioabsorbable or biostable polymers. 
     In some embodiments, prosthesis  22  may include a single depot, or a plurality of depots, formed in an outer surface thereof. The depots may be filled, fully or partially, with a material as discussed below. 
       FIGS. 3B ,  3 C, and  3 D illustrate a portion of thread elements  24  and connecting elements  26  of an exemplary prosthesis  22  having depots  28  formed in an outer surface thereof. Depots  28  can be formed in virtually any prosthesis  22  structure. Depots  28  are formed by a manufacturer at any preselected location and have any preselected depth, size, and geometrical configuration. The location of depot  28  within prosthesis  22  varies according to intended usage and application. The depth and size of depot  28  typically depend on the material and dimensions of prosthesis  22  and the type and amount of materials deposited within depot  28  as well as on the clinical purpose and usage of prosthesis  22 . The depth and size of the individual depots  28  formed on a single prosthesis  22  can vary relative to one another. Depots  28  may be formed in a variety of selected geometrical shapes including, but not limited to, generally cylindrical shapes, generally conical shapes, and elongated trenches. 
     Depot  28 , which may also be referred to as a pore or a cavity, may be formed as a laser trench on prosthesis  22  by exposing the surface to an energy discharge from a laser, such as an excimer laser. Alternative methods of forming such depots  28  include, but are not limited to, physical and chemical etching techniques. Techniques of laser fabrication or etching to form depots are well-known to one of ordinary skill in the art. 
     In some embodiments, depots  28  contain a material  30 , as depicted in  FIG. 3D . Depots  28  may contain a material that is the same, or different than the material impregnated in the covering as described below. 
     In some examples, the deposited material  30  is a therapeutic substance or agent such as, but not limited to, antineoplastic, antimitotic, antiinflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antiproliferative, antibiotic, antioxidant, and antiallergic substances as well as combinations thereof. Examples of such antineoplastics and/or antimitotics include paclitaxel (e.g., TAXOL® by Bristol-Myers Squibb Co., Stamford, Conn), docetaxel (e.g., Taxotere® from Aventis S.A., Frankfurt, Germany), methotrexate, azathioprine, vincristine, vinbiastine, fluorouracil, doxorubicin hydrochloride (e.g., Adriamycin® from Pharmacia &amp; Upjohn, Peapack N.J.), and mitomycin (e.g., Mutamycin from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of such antiplatelets, anticoagulants, antifibrin, and antithrombins include sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein lIb/IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, and thrombin inhibitors such as Angiomax™ (Biogen, Inc., Cambridge, Mass.). Examples of such cytostatic or antiproliferative agents include angiopeptin, angiotensin converting enzyme inhibitors such as captopril (e.g., Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.), cilazapril or lisinopril (e.g., Prinivil® and Prinzide® from Merck &amp; Co., Inc., Whitehouse Station, NJ), calcium channel blockers (such as nifedipine), colchicine, fibroblast growth factor (FGF) antagonists, fish oil (omega  3 -fatty acid), histamine antagonists, lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand name Mevacor from Merck &amp; Co., Inc., Whitehouse Station, NJ), monoclonal antibodies (such as those specific for Platelet-Derived Growth Factor (PDGF) receptors), nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitors, suramin, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), and nitric oxide. An example of an antiallergic agent is permirolast potassium. Other therapeutic substances or agents that may be used include alpha-interferon, genetically engineered epithelial cells, and dexamethasone. While the preventative and treatment properties of the foregoing therapeutic substances or agents are well-known to those of ordinary skill in the art, the substances or agents are provided by way of example and are not meant to be limiting. Other therapeutic substances are equally applicable for use with the disclosed methods and compositions. 
     In other examples, the therapeutic substance in depots  28  is a radioactive isotope for prosthesis usage in radiotherapeutic procedures. Examples of radioactive isotopes include, but are not limited to, phosphoric acid (H 3 P 32 O 4 ), palladium (Pd 103 ), cesium (Cs 131 ), and iodine (I 125 ). 
     In still other examples, material  30  is a radiopaque substance, such as gold, that is deposited into depots  28 . 
     In other examples, deposited material  30  is a polymeric material. The polymeric material may be impregnated with a therapeutic substance. The polymeric material is most suitably biocompatible, including polymers that are non-toxic, non-inflammatory, chemically inert, and substantially non-immunogenic in the applied amounts. The polymer is typically either bioabsorbable or biostable. A bioabsorbable polymer breaks down in the body and is not present sufficiently long after implantation to cause an adverse local response. Bioabsorbable polymers are gradually absorbed or eliminated by the body by hydrolysis, metabolic process, bulk, or surface erosion. Examples of bioabsorbable materials include but are not limited to polycaprolactone (PCL), poly-D, L-lactic acid (DL-PLA), poly-L-lactic acid (L-PLA), poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polydioxanone, polyorthoester, polyanhydride, poly(glycolic acid), poly(glycolic acid-cotrimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly (amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), copoly(ether-esters), polyalkylene oxalates, polyphosphazenes, polyiminocarbonates, and aliphatic polycarbonates. Biomolecules such as heparin, fibrin, fibrinogen, cellulose, starch, and collagen are typically also suitable. Examples of biostable polymers include Parylene®, Parylast®, polyurethane (for example, segmented polyurethanes such as Biospan®), polyethylene, polyethlyene teraphthalate, ethylene vinyl acetate, silicone and polyethylene oxide. 
     Material  30  may be deposited into depots  28  using any suitable method. In an exemplary method of depositing material  30  into depots  28 , material  30  is added to a first solvent. Material  30  is dispersed throughout the first solvent so that material  30  is in a true solution, saturated or supersaturated with the first solvent or suspended in fine particles in the first solvent. The first solvent can be virtually any solvent that is compatible with material  30 . A high capillary permeation and a viscosity not greater than about ten centipoise allows the first solvent to penetrate into depots  28  more quickly, eliminating a requirement to apply the first solvent to prosthesis  22  for a prolonged period of time. Examples of suitable first solvents include, but are not limited to, acetone, ethanol, methanol, isopropanol, tetrahydrofuran, and ethyl acetate. The first solvent containing material  30  is applied to prosthesis  22 , for example by immersing or spraying the solvent using procedures that are well-known to one having ordinary skill in the art. The first solvent containing material  30  is applied for a predetermined period of time, the specific time depending on the capillary permeation and viscosity of the first solvent, the volume of depots  28 , and the amount of material  30  to be deposited. 
     After applying the first solvent containing material  30  for a selected duration, the first solvent is removed from the prosthesis using conventional techniques, such as evaporation in ambient pressure, room temperature and anhydrous atmosphere and/or by exposure to mild heat (e.g., 60° C.) under vacuum condition. Prosthesis  22  typically has a clustered or gross formation of material  30  gathered on the body surface. The cluster is generally removed by immersing prosthesis  22  in a non-solvent and agitating prosthesis  22  via mechanical perturbation techniques, such as vortexing or vigorous shaking. The non-solvent can have a low capillary permeation or a contact angle greater than about 90° and a viscosity not less than about 0.5 centipoise so that the second fluid is not capable of significantly penetrating into depots  28  during the process of agitation. Examples of a suitable non-solvent include, but are not limited to, saturated hydrocarbons or alkanes, such as hexane, heptane, and octane. 
     Prosthesis  22  is rinsed in a second solvent to facilitate dissolution of material  30 . The second solvent generally has a low capillary permeation and a viscosity of not less than about 1.0 centipoise and is therefore incapable of significantly penetrating into depots  28  during the rinsing stage. The rinsing is conducted rapidly for example in a range from 1 second to about 15 seconds, the exact duration depending on the solubility of material  30  in the second solvent. Extended duration of exposure of prosthesis  22  to the second solvent may lead to the penetration of the second solvent into depots  28 . The rinsing step is repeated, if desired, until all traces of material  30  are removed from the surface of prosthesis  22 . The second solvent removes excess material  30  from the surface of the prosthesis body. Useful examples of second solvents include, but are not limited to, dimethylsulfoxide (DMSO), water, DMSO in an aqueous solution, glyme, and glycerol. The second solvent is removed from the prosthesis body using conventional techniques. The first and second solvents as well as the non-solvent are selected to not adversely affect the characteristics and composition of material  30 . Although one method of depositing material  30  into depots  28  has been described here, depots  28  may be filled using any suitable method. 
     Below, methods are disclosed that allow substances, such as solids or hydrogels, to be deposited or formed, respectively, within the above-described implantable device  10 . The methods may be used in applications where implantable device  10  is a vascular graft or a covering for a prosthesis  22 , among other possibilities. 
     Deposition of a Solid 
     In preparation for the application of a solid within implantable device  10 , a blockage  32  is caused at second end  16  of implantable device  10  such that fluid cannot significantly pass through second end  16  of implantable device  10 , as illustrated in  FIG. 4A . Blockage  32  may be created by physically blocking second end  16  of implantable device  10 , for example, by clamping second end  16  with a clamp  34  or some other device, such as a paper clip or tweezers. In embodiments in which implantable device  10  is a covering that is disposed over prosthesis  22 , second end  16  of the covering should extend beyond prosthesis  22  to allow a user to clamp second end  16  of the covering without also clamping prosthesis  22 . It is contemplated that other methods of blocking second end  16  can be employed, and the application of the embodiments of the invention is not limited to the type of blocking means employed. 
     Using a syringe or similar instrument, a composition may be introduced into bore  18  of implantable device  10  at first end  14  in a direction d. The composition should be delivered in a controlled manner and at a controlled pressure to allow the composition to penetrate into and pass through interstices  20 . The pressure can be any suitable pressure necessary to achieve a flow rate in the range of about 0.1 mL/min to about 2 mL/min so long as the pressure does not exceed the burst pressure of the material of body  12 . The pressure at which the composition is introduced into bore  18  should not adversely affect the structure of body  12  so as to cause defects, such as cavities or crests, in the inner or outer surfaces of body  12 . Additionally, the pressure at which the composition is introduced should not disrupt blockage  32  at second end  16 . Unable to pass through blockage  32  at second end  16  of implantable device  10 , the composition is forced through body  12 , as depicted in  FIG. 4B , thereby penetrating into interstices  20 . Once the composition has completely filled interstices  20 , any excess composition may seep out through the surface of implantable device  10 , interstices  20  remaining filled with the composition. 
     The composition includes a solid and a first fluid. The solid should be in true solution, saturated, super-saturated, or suspended as fine particles in the first fluid. In some embodiments, the solid may be a hydrophobic, bioerodable polymer, organic-soluble heparin, or organic-soluble phosphorylcholine. Exemplary hydrophobic, bioerodable polymers include, but are not limited to, polycaprolactone (PCL), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), polyanhydrides, polyorthoesters, and polyphosphazenes. 
     In such embodiments, the first fluid can have a viscosity from about 0.2 to about 10 centipoise, or more particularly, from about 0.4 to about 0.6 centipoise, such that the first fluid may readily penetrate into interstices  20 . In addition, the first fluid should have a high capillary permeation. Capillary permeation, or wetting, is the movement of fluid on a solid substrate driven by interfacial energetics. Capillary permeation is quantitated by a contact angle, which is defined as the angle at the tangent of the first solvent droplet in fluid phase that has taken an equilibrium shape on a solid surface.  FIG. 5A  illustrates a fluid droplet  36  on a solid substrate  38 . Fluid droplet  36  has a contact angle Φ 1 , which is less than 90°. In contrast,  FIG. 5B  illustrates a fluid droplet  36 ′ having a contact angle Φ 2 , which is greater than 90°. A low contact angle, as depicted in  FIG. 5A , indicates a higher wetting liquid; a high contact angle, as depicted in  FIG. 5B , indicates a lower wetting liquid. Since wetting of the material of which implantable device  10  is made is an essential part of the present invention, higher wetting liquids are preferred. Thus, in the embodiments described above, a first fluid should have a contact angle not more than 90°. 
     Exemplary first fluids include, but are not limited to, tetrahydrofuran (THF), dimethylformamide (DMF), dimethyl sulfoxide (DMSO), acetone, freon, hexafluoroisopropanol (HFIP), chloroform, 1,1,2-trichloroethane, and combinations thereof. The particular first fluid selected depends on the particular solid applied to implantable device  10  as well as on the material of which implantable device  10  is made. For example, if implantable device  10  is made of an absorbable polymer, caution should be exercised in the selection of all fluids since some absorbable polymers of which an implantable device  10  can be made dissolve in fluids that are otherwise suitable for usage in the present invention. 
     In one example, the composition can include organic-soluble heparin and a first fluid selected from freon, tetrahydrofuran (THF), and dimethylformamide (DMF). 
     In another example, the composition can include organic-soluble phosphorylcholine and a first fluid selected from acetone and freon. 
     In yet another example, the composition can include polycaprolactone (PCL) and acetone as the solid and first fluid, respectively In another example, the composition can include poly(lactic acid) (PLA) and a first fluid selected from hexafluoroisopropanol (HFIP), chloroform, and 1,1,2-trichloroethane. 
     In still another example, the composition can include poly(glycolic acid) (PGA) and hexafluoroisopropanol (HFIP) as the solid and first fluid, respectively. 
     In another example, the composition can include a polyanhydride and a first fluid selected from tetrahydrofuran (THF) and dimethyl sulfoxide (DMSO). 
     In yet another example, the composition can include a polyorthoester and a first fluid selected from chloroform, methylene chloride, and dioxane. 
     In still another example, the composition can include a polyphosphazene and a first fluid selected from tetrahydrofuran (THF) and dimethylformamide (DMF). 
     The application of the composition is followed by the removal of the first fluid from implantable device  10 . The first fluid may be removed from implantable device  10  using techniques such as evaporation at ambient pressure and room temperature in an anhydrous atmosphere for 48 hours, or exposure to mild heat, e.g., 60-65° C., under vacuum conditions. In examples wherein implantable device  10  is made of an absorbable polymer, the first fluid should be removed relatively quickly to avoid prolonged solvent exposure and thereby ensure the mechanical integrity of the absorbable implantable device  10 . Upon removal of essentially all of the first fluid, the solid remains within interstices  20  of implantable device  10 . 
     In alternative embodiments, another fluid or a plurality of other fluids are applied to implantable device  10  prior to, and in the same manner as, the application of the composition described above. For example, in some embodiments, a second fluid is applied to implantable device  10  prior to the application of the composition. Unable to pass through blockage  32  at second end  16  of implantable device  10 , the second fluid is forced through body  12 , as depicted in  FIG. 4B , thereby penetrating into interstices  20 . 
     In such embodiments, the second fluid should have a high capillary permeation, as defined above, and thus, the second fluid should have a contact angle not more than 90°. The second fluid can also have a viscosity from about 0.2 to about 10 centipoise, or more particularly from about 0.4 to about 0.6 centipoise, such that the second fluid may penetrate into interstices  20 . Such second fluids depend on the particular solid applied to implantable device  10  as well as on the material of which implantable device  10  is made and may include, but are not limited to, acetone, isopropanol, ethanol, freon or combinations thereof. 
     In embodiments in which the second fluid is miscible with the first fluid contained in the composition, application of the composition as described above following the application of the second fluid causes the composition to mix with the second fluid already within interstices  20 . As the composition is applied to implantable device  10 , the composition increasingly dilutes, and finally significantly replaces, the second fluid within interstices  20 . Traces or residues of the second fluid may remain in interstices  20 . 
     In other embodiments in which the second fluid is not miscible with the first fluid contained in the composition, a third fluid can be applied to implantable device  10  subsequent to the application of the second fluid and prior to the application of the composition in the manner described above. The third fluid should be miscible with both the first and second fluids. 
     In one embodiment where the second fluid is not miscible with the first fluid contained in the composition, the third fluid is miscible with both the first and second fluids. As the third fluid penetrates into interstices  20 , the third fluid mixes with the second fluid already within interstices  20 . As the third fluid is applied to implantable device  10 , the third fluid increasingly dilutes, and finally significantly replaces, the second fluid within interstices  20 . Similarly, as the composition penetrates into interstices  20 , the first fluid mixes with, increasingly dilutes, and finally significantly replaces, the third fluid within interstices  20 . 
     In one embodiment where the second fluid is not miscible with the first fluid contained in the composition, the third fluid is miscible with the first fluid but is not miscible with the second fluid. In such an embodiment, a fourth fluid which is miscible with both the second and third fluids can be applied to implantable device  10  in the manner described above. The fourth fluid can be introduced after the introduction of the second fluid and prior to the introduction of the third fluid. Alternatively, the fourth fluid can be added to and introduced simultaneously with either the second fluid or the third fluid. For example, if freon is selected as the second fluid and water is selected as the third fluid, a fourth fluid of acetone or n-propanol is a suitable bridging fluid between the immiscible second and third fluids. 
     In another embodiment where the second fluid is not miscible with the first fluid contained in the composition, the third fluid is miscible with the second fluid but is not miscible with the first fluid. In such an embodiment, a fourth fluid which is miscible with both the first and third fluids can be applied to implantable device  10  in the manner described above. The fourth fluid acts as a bridging fluid between the immiscible first and third fluids and can be introduced after the introduction of the third fluid and prior to the introduction of the composition or simultaneously with either the third fluid or the composition. 
     In still another embodiment where the second fluid is not miscible with the first fluid contained in the composition, the third fluid is not miscible with the first fluid nor with the second fluid. In such an embodiment, a more suitable third fluid should be selected. Alternatively, bridging fluids applied between the second and third fluids and between the third fluid and the composition may be applied in the manner described above. 
     In another embodiment of the present invention, second and third fluids which are miscible with one another as well as with the first fluid contained in composition  10  are successively applied to implantable device  10  prior to, and in the same manner as, the application of composition  10  described above. In such an embodiment, the second fluid is applied to implantable device  10 . After the second fluid penetrates into interstices  20 , the third fluid is applied. The third fluid mixes with, increasingly dilutes, and finally significantly replaces, the second fluid already within interstices  20 . The composition is then applied to implantable device  10 . As the composition penetrates into interstices  20 , the composition mixes with, increasingly dilutes, and finally significantly replaces, the third fluid within interstices  20 . 
     In the above-described embodiments in which another fluid or a plurality of other fluids are applied to implantable device  10  prior to the application of the composition, exemplary solids include, but are not limited to, hydrophilic, bioerodable polymers as well as components of extracellular matrix (ECM). Examples of hydrophilic, bioerodable polymers include, but are not limited to, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), hyaluronic acid, pluronic, water-soluble chitin, polyacrylamide, polyalginate, heparin, and water-soluble phosphorylcholine. Examples of components of extracellular matrix (ECM) include, but are not limited to, collagen, elastin, laminin, and glycosaminoglycan. 
     The concentration of the solid in the composition is selected such that the solution viscosity is low enough to allow penetration into interstices  20  and high enough to allow a sufficient amount of solid to be deposited upon drying. For example, the concentration of polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), pluronic, or polyacrylamide in the composition should be about 15-30% by weight of the total weight of the composition, the concentration of water-soluble chitin in the composition should be about 10-15% by weight of the total weight of the composition, and the concentration of hyaluronic acid in the composition should be no more than about 2% by weight of the total weight of the composition. 
     In one set of examples, the solid included in the composition, and therefore applied into implantable device  10 , can be polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), hyaluronic acid, pluronic, water-soluble chitin, polyacrylamide, polyalginate, or water-soluble phosphorylcholine. In such examples, the first fluid can be water and the second fluid can be acetone, isopropanol, ethanol or freon. The third fluid can be water. However, when the solid employed is polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), or pluronic, the third fluid may alternatively be dimethyl sulfoxide (DMSO). 
     In another set of examples, the solid included in the composition, and thus applied into implantable device  10 , is heparin, the second fluid can be acetone, isopropanol, or ethanol, and both the first and third fluids can be water. 
     In still another set of examples, the solid included in the composition, and therefore applied into implantable device  10 , can be a component of extracellular matrix. Representative examples include collagen, elastin, laminin, and glycosaminoglycan. In such examples, the second fluid can be acetone, isopropanol, or ethanol, and both the first and third fluids can be water. 
     In some embodiments of the above-disclosed method, the composition contains a therapeutic substance. The therapeutic substance can make up from about 0.1% to about 20%, or more particularly from about 1% to about 10%, by weight of the total weight of the composition. After a composition containing a therapeutic substance is applied to implantable device  10  and implantable device  10  is dried, both the solid and the therapeutic substance remain within interstices  20  of implantable device  10 . 
     Therapeutic substances or agents may include, but are not limited to, antineoplastic, antiinflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic, antiproliferative, antibiotic, antioxidant, antiallergic substances, and combinations thereof. Examples of such therapeutic substances were listed above in association with the discussion of material  30  which may be deposited into depots  28  formed within prosthesis  22 , and such examples are equally applicable here. While the foregoing therapeutic substances or agents are well-known for preventative and treatment properties, the substances or agents are provided by way of example and are not meant to be limiting. Other therapeutic substances are equally applicable for use with the disclosed methods and compositions. 
     Formation of a Hydrogel 
     In preparation for the application of a hydrogel within implantable device  10 , blockage  32  is caused at second end  16  of implantable device  10 , as illustrated in  FIG. 4A  and described above. A composition is then introduced into implantable device  10  and forced through body  12 , as depicted in  FIG. 4B  and described above, thereby penetrating into interstices  20 . 
     The composition includes at least one crosslinkable pre-polymer and a first fluid in which the pre-polymer is soluble. The pre-polymer should be in true solution, saturated, or supersaturated in the first fluid. Exemplary crosslinkable pre-polymers include, but are not limited to, polyethylene glycol (PEG) diacrylate, unsaturated hyaluronic acid, and pluronic. The concentration of pre-polymer in the composition is selected such that the solution viscosity is low enough to allow penetration into interstices  20  but still high enough to ensure effective crosslinking of the pre-polymer since a solution too dilute does not form a crosslinked hydrogel. For example, the concentration of PEG diacrylate in the composition should be about 15-30% by weight. The composition may also contain a photoinitiator if the crosslinkable pre-polymer is to be crosslinked using light energy. 
     The application of the composition is followed by crosslinking the crosslinkable pre-polymer within the composition that has penetrated interstices  20 . A snug-fit mandrel is placed within bore  18  of implantable device  10 , and the pre-polymer within the composition is cured to form a hydrogel within interstices  20  of implantable device  10 . Curing may be accomplished photochemically using ultraviolet or visible irradiation and a photoinitiator, thermally, or by moisture curing at room temperature. The practice of these and other suitable curing procedures is well known to one of ordinary skill in the art. 
     In some embodiments, the crosslinkable pre-polymer is crosslinked internally upon curing. That is, a pre-polymer molecule is crosslinked with another molecule of the same pre-polymer rather than to another substance. Examples of crosslinkable pre-polymers that may be internally crosslinked include, but are not limited to, PEG diacrylate, unsaturated hyaluronic acid, pluronic and absorbable PEG diacrylate hydrogel precursors. 
     In other embodiments, the crosslinkable pre-polymer is crosslinked with another substance. For example, a crosslinkable pre-polymer, such as PEG diacrylate, may be crosslinked with an unsaturated monomer. Examples of suitable unsaturated monomers include, but are not limited to, vinyl pyrrolidone, acrylamide, phosphorylcholine, acrylic acid, dimethyl aminoethyl methacrylate (DMAMA), vinyl pyridine, trans-amidated acrylamide, methacrylic acid, and vinyl phosphonic acid. The unsaturated monomer may be selected for the particular functional group that is contained within the monomer and is donated to the hydrogel that is formed upon crosslinking the unsaturated monomer with a crosslinkable pre-polymer. 
     Following the crosslinking of the pre-polymer within the pre-polymer solution, any remaining amounts of the first fluid injected therewith may be removed from implantable device  10 . The first fluid may be removed using drying techniques described above. Upon removal of the first fluid substantially to elimination, the hydrogel remains within body  12  of implantable device  10 . 
     In alternative embodiments, another fluid or a plurality of other fluids are applied to implantable device  10  prior to the application of the composition and the subsequent crosslinking of the pre-polymer. These embodiments may employ a second fluid, a third fluid, a bridging fluid, or a combination thereof. The use of such fluids and the methods associated therewith were described above in reference to the deposition of a solid within implantable device  10 , and the above discussion is equally applicable here in reference to the formation of a hydrogel within implantable device  10 . 
     In one particular set of examples in which a plurality of fluids are employed, the crosslinkable pre-polymer is PEG diacrylate, unsaturated hyaluronic acid, or pluronic. In such examples, the second fluid can be acetone, isopropanol, ethanol, or freon, and both the first and third fluids can be water. In examples with freon as the second fluid, a fourth fluid of either acetone or n-propanol is applied to implantable device  10  after the application of freon and prior to the application of the third fluid, e.g., water. In examples with PEG-diacrylate or unsaturated hyaluronic acid selected as the pre-polymer, the resulting hydrogel is not bioerodable. In contrast, in examples where the pre-polymer selected is pluronic, the resulting hydrogel is bioerodable. 
     In another example in which a plurality of fluids are employed, the crosslinkable pre-polymer is an absorbable PEG diacrylate hydrogel precursor, such as a PEG diacrylate that is end-capped with lactide, as shown in  FIG. 6 . The second fluid can be acetone, isopropanol, ethanol, or freon, and both the first and third fluids can be water. If the second fluid is freon, a bridging fluid of either acetone or n-propanol is employed between the immiscible second and third fluids as described above. Upon curing, the end-capped PEG diacrylate forms a transient hydrogel, since over time the hydrogel will be cleaved at the bonds  40  and  42  of  FIG. 6  and is thus wholly bioerodable. A transient hydrogel is particularly suited for incorporation into absorbable implantable devices  10 . 
     In some embodiments of the disclosed method, the composition additionally contains a therapeutic substance. The therapeutic substance can make up from about 0.1% to about 20%, or more particularly from about 1% to about 10%, by weight of the total weight of the composition. After a composition containing a therapeutic substance is applied to implantable device  10  and crosslinked, both the resulting hydrogel and the therapeutic substance remain within interstices  20  of implantable device  10 . 
     Therapeutic substances or agents may include, but are not limited to, antineoplastic, antiinflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic, antiproliferative, antibiotic, antioxidant, antiallergic substances, and combinations thereof. Examples of such therapeutic substances were listed above in association with the discussion of material  30  which may be deposited into depots  28  formed within prosthesis  22 , and such examples are equally applicable here. While the foregoing therapeutic substances or agents are well-known for preventative and treatment properties, the substances or agents are provided by way of example and are not meant to be limiting. Other therapeutic substances are equally applicable for use with the disclosed methods and compositions. 
     In one set of examples where the composition includes a therapeutic substance, an unsaturated monomer may be selected for inclusion in the composition based on electrical charge so as to control the release rate of a therapeutic substance from a hydrogel formed within implantable device  10 . In one such example, the composition includes PEG diacrylate, a positively-charged unsaturated monomer, and a negatively-charged therapeutic substance such as heparin. Representative examples of positively-charged unsaturated monomers include, but are not limited to, dimethyl aminoethyl methacrylate (DMAMA), vinyl pyridine, and trans-amidated acrylamide. PEG diacrylate is cross-linked with the positively-charged unsaturated monomer, thereby forming a positively charged hydrogel containing the negatively-charged therapeutic substance. Since the hydrogel and the therapeutic substance have opposing charges and thus are attracted to one another, the rate at which the therapeutic substance is released from the hydrogel within implantable device  10  after implantation is decreased. 
     Conversely, in an example in which PEG diacrylate is crosslinked with a negatively-charged unsaturated monomer, thereby forming a negatively-charged hydrogel, the release rate of a negatively-charged therapeutic substance from the negatively-charged hydrogel within implantable device  10  is increased, since the negative charges on both the hydro gel and the therapeutic substance repel one another. Representative examples of negatively-charged unsaturated monomers include, but are not limited to, acrylic acid, methacrylic acid and vinyl phosphonic acid. 
     Methods of Use 
     An implanted vascular graft or covered stent, having the above-described solid or hydrogel incorporated within interstices throughout, is useful for treating occluded regions of blood vessels caused by thrombosis and/or restenosis, among other possible uses. 
     Vascular grafts may be used to replace, bypass, or reinforce diseased or damaged sections of a vein or artery. The general procedure for implantation includes the step of pre-clotting, wherein the graft is immersed in the blood of the patient and allowed to stand for a period of time sufficient for clotting to ensue. After pre-clotting, hemorrhaging is less likely to occur when the graft is implanted and thus the growth of tissue is not impeded. Grafts may be placed either through invasive surgery or non-invasively through percutaneous endoluminal transport. Percutaneous delivery of a graft avoids the complications and risks of surgery. The graft may be attached to the vessel at each end of the diseased region, thus bypassing the diseased region. Alternatively, the diseased region may be removed and replaced by the graft. 
     Covered stents may be placed in a wide array of blood vessels, both arteries and veins. Briefly, an angiography is first performed to determine the appropriate positioning for stent therapy. Angiography is typically accomplished by using a catheter to inject a radiopaque contrasting agent into an artery or vein as an X-ray is taken. A guidewire is then advanced through the lesion or proposed site of treatment. Over the guidewire is passed a delivery catheter which allows a stent in its collapsed configuration to be inserted into the passageway. The delivery catheter is inserted either percutaneously or by surgery into the femoral artery, brachial artery, femoral vein, or brachial vein and advanced into the appropriate blood vessel by steering the catheter through the vascular system under fluoroscopic guidance. A stent having the above described covering may then be expanded at the desired area of treatment. A post-insertion angiogram may also be utilized to confirm appropriate positioning. 
     EXAMPLES 
     Exemplary embodiments of the invention are illustrated below. These examples are being given by way of illustration only and not by way of limitation. The parameters given, including, without limitation, percentages of pre-polymer, solid, fluids, therapeutic substance, temperature, duration of time, and other data, are exemplary, not limiting. 
     Example 1 
     A PTFE vascular graft was closed at one end with a paper clip. Organic-soluble heparin was dissolved in freon such that organic-soluble heparin constituted about 5% by weight of the total weight of the solution. The organic-soluble heparin solution was permeated through the circumferential area of the graft by flushing the inner lumen twice with the organic-soluble heparin solution using a syringe. A mandrel was selected such that it snugly fit within the bore of the graft. The mandrel was placed within the bore of the graft, and the graft was dried in a vacuum oven at 60° C. for about 12 hours. The organic-soluble heparin remained within the interstices of the graft. 
     Example 2 
     A PTFE vascular graft is closed at one end with a paper clip. Acetone is permeated through the circumferential area of the graft by flushing the inner lumen with about 2 mL of acetone using a syringe. Next, deionized water is permeated through the circumferential area of the graft by flushing the inner lumen with about 2 mL of deionized water using a syringe. An aqueous solution of hyaluronic acid is made by stirring hyaluronic acid in deionized water on a hot plate at 50° C. for about 12 hours. The hyaluronic acid constitutes 0.5% by weight of the total weight of the solution. Following the deionized water flush, the hyaluronic acid solution is flushed twice through the inner lumen of the graft using a syringe. A mandrel is selected such that it snugly fits the within the bore of the graft. The mandrel is placed within the bore of the graft, and the graft is dried in a vacuum oven at 60° C. for about 12 hours. It is predicted that hyaluronic acid will remain within the interstices of the graft. 
     Example 3 
     A covered stent having a covering made of PTFE is closed at one end with a paper clip. Acetone is permeated through the circumferential area of the covering by flushing the inner lumen with about 2 mL of acetone using a syringe. A solution of PEG-di-isocyanate is made in benzene. The PEG-di-isocyanate constitutes 30% by weight of the total weight of the solution. Following the acetone flush, the PEG-di-isocyanate solution is flushed through the inner lumen of the covering using a syringe. The covering is dried under vacuum at room temperature for 2 hours. An aqueous solution of hyaluronic acid is made by stirring hyaluronic acid in deionized water on a hot plate at 50° C. for about 12 hours. The hyaluronic acid constitutes 0.5% by weight of the total weight of the solution. Following the drying step, the hyaluronic acid solution is flushed twice through the inner lumen of the covering using a syringe. A mandrel is selected such that it snugly fits within the bore of the covering. The mandrel is placed within the bore of the covering, and the covering is dried in a vacuum oven at 80° C. for about 24 hours. It is predicted that PEG-di-isocyanate and hyaluronic acid will remain within the interstices of the covering. 
     Example 4 
     A PTFE vascular graft is closed at one end with a paper clip. Acetone is permeated through the circumferential area of the graft by flushing the inner lumen with about 2 mL of acetone using a syringe. Next, deionized water is permeated through the circumferential area of the graft by flushing the inner lumen with about 2 mL of deionized water using a syringe. A three-component aqueous solution is made by dissolving hyaluronic acid, PEG-di-amine, and water soluble carbodiimide in deionized water and vortexing the solution for 2 minutes at room temperature. Hyaluronic acid constitutes 0.5% by weight of the total weight of the solution, PEG-di-amine constitutes 10% by weight of the total weight of the solution, and water soluble carbodiimide constitutes 2% by weight of the total weight of the solution. Following the deionized water flush, the solution is flushed twice through the inner lumen of the graft using a syringe. A mandrel is selected such that it snugly fits within the bore of the graft. The mandrel is placed within the bore of the graft, and the graft is dried in a vacuum oven at 30° C. for about 12 hours. It is predicted that hyaluronic acid and PEG-di-amine will remain within the interstices of the graft. 
     Example 5 
     A covered stent having a covering made of PTFE is closed at one end with a paper clip. Acetone is permeated through the circumferential area of the covering by flushing the inner lumen with about 2 mL of acetone using a syringe. A two-component aqueous solution is made by dissolving PEG-diacrylate and benzoyl peroxide in deionized water. PEG-diacrylate constitutes 40% by weight of the total weight of the solution and benzoyl peroxide constitutes 5% by weight of the total weight of the solution. Following the acetone flush, the solution is flushed twice through the inner lumen of the covering using a syringe. A mandrel is selected such that it snugly fits within the bore of the covering. The mandrel is placed within the bore of the covering, and the covering is dried in a vacuum oven at 80° C. for about 24 hours. It is predicted that PEG-diacrylate will remain within the interstices of the covering. 
     Example 6 
     A PTFE vascular graft is closed at one end with a paper clip. Acetone is permeated through the circumferential area of the graft by flushing the inner lumen with about 2 mL of acetone using a syringe. A three-component aqueous solution is made by dissolving PEG-diacrylate, hydroxy-ethyl-methacrylate (HEMA), and benzoyl peroxide in deionized water. PEG-diacrylate constitutes 40% by weight of the total weight of the solution, hydroxy-ethyl-methacrylate constitutes 10% by weight of the total weight of the solution, and benzoyl peroxide constitutes 5% by weight of the total weight of the solution. Following the acetone flush, the solution is flushed twice through the inner lumen of the graft using a syringe. A mandrel is selected such that it snugly fits within the bore of the graft. The mandrel is placed within the bore of the graft, and the graft is dried in a vacuum oven at 80° C. for about 24 hours. It is predicted that PEG-diacrylate and hydroxy-ethyl-methacrylate will form a water soluble gel with hydroxyl functionality for use in any secondary coupling application and will remain within the interstices of the graft. 
     Example 7 
     A PTFE vascular graft is closed at one end with a paper clip. Acetone is permeated through the circumferential area of the graft by flushing the inner lumen with about 2 mL of acetone using a syringe. Next, tetrahydrofuran (THF) is permeated through the circumferential area of the graft by flushing the inner lumen with about 2 mL of THF using a syringe. An ethylene vinyl alcohol (EVAL) solution is made such that ethylene vinyl alcohol constitutes 25% by weight of the total weight of the solution, dimethyl sulfoxide (DMSO) constitutes 50% by weight of the total weight of the solution, and tetrahydrofuran (THF) constitutes 25% by weight of the total weight of the solution. Following the deionized water flush, the solution is flushed twice through the inner lumen of the graft using a syringe. A mandrel is selected such that it snugly fits within the bore of the graft. The mandrel is placed within the bore of the graft, and the graft is dried in a vacuum oven at 60° C. for about 24 hours. It is predicted that EVAL will remain within the interstices of the graft. 
     While particular embodiments, applications, and examples of the present invention have been shown and described, it will be apparent to those of ordinary skill in the art that changes and modifications can be made without departing from this invention in its broader aspects. For example, fluids may be alternatively applied to implantable device  10  by successive immersion and removal of implantable device  10  from each fluid. This immersion method of application is particularly useful when implantable device  10  is a covering for a prosthesis  22 , as such a covering is thin and thus easily permeated. Therefore, the appended claims are to encompass within their scope all such changes and modifications as fall within the true spirit and scope of this invention.