Patent Publication Number: US-8119151-B2

Title: Spread coating a medical device

Description:
CROSS REFERENCE TO RELATED APPLICATION 
     The present application claims priority to U.S. provisional application Ser. No. 60/912,939, filed Apr. 20, 2007, the disclosure of which is incorporated herein by reference in its entirety. 
    
    
     TECHNICAL FIELD 
     The present invention generally relates to methods for selectively coating medical devices. More specifically, the present invention relates to medical devices, such as expandable stents, self-expanding stents, and vena-cava filters, and methods for coating these devices, wherein a coating is applied to the medical device and then spread on one or more accessible surfaces of the device. 
     BACKGROUND 
     Coating medical devices is an often repeated procedure in contemporary manufacturing. Medical devices may be coated by methods that include spray coating, dip coating and roll coating. During each of these procedures coating is applied to the medical device and is then allowed to dry or cure prior to the medical device being used for an intended purpose. 
     When the medical device is formed partially or completely out of lattice struts or some other open framework, each of the faces of these struts or framework may be exposed to coating during the coating methods listed above. 
     In some cases, when the medical device being coated is a stent, all faces of the struts that comprise the stent may be coated when using the coating systems identified above. For example, when dip coating is used, each face of the stent struts will be exposed to the coating and thereby coated. This coating will remain when the stent is removed from the dip and will dry on surfaces of the struts without further intervention. Coating may even remain in the spaces between the struts after the coating has been applied to the workpiece. This phenomenon is sometimes called “webbing.” Here, not only are the individual struts covered, but some or all of the spaces between the struts are spanned by the coating as well. 
     BRIEF DESCRIPTION 
     The present invention is directed to methods, systems, devices, and kits, wherein a coating is applied to an accessible surface of a medical device and then subsequently spread. The coating may be spread to other areas of the medical device not in contact with the coating when it is first applied. The coating may also be spread to reduce the thickness of the coating on the medical device and to change its coverage area. The coating may be spread for other reasons. The coating may be applied by various applicators and it may be spread by various spreaders as well. The applicators employed may include hand-held devices and computer controlled devices. Likewise, the spreaders may themselves be hand-operated and may also be more automated. The coating being applied may include a therapeutic agent and it may be applied directly to the medical device as well to a coating already present on a medical device. Portions of the coating may be dried during the coating process while other portions remain wet or not dried. 
     The invention may be embodied through numerous devices, systems, methods, and kits. The following detailed description, which, when taken in conjunction with the annexed drawings, discloses examples of the invention. Other embodiments, which incorporate some or all of the features as taught herein, mixing and drawing from the various descriptions, are also possible. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Referring to the drawings, which form a part of this disclosure: 
         FIG. 1   a  shows an applicator coating a strut of a medical device as may be employed in accord with the present invention; 
         FIG. 1   b  shows a spreader positioned above the coated strut of  FIG. 1   a  in accord with the present invention; 
         FIG. 1   c  shows the spreader of  FIG. 1   b  in contact with coating on the strut; 
         FIG. 1   d  shows the spreader of  FIG. 1   b  in contact with coating on the strut and also applying additional coating; 
         FIG. 2  shows a medical device positioned on a machine tool applicator as may be employed in accord with the present invention; 
         FIG. 3   a  is a cross-sectional view of a portion of a coated strut from a medical device that has been coated in accord with the present invention; 
         FIG. 3   b  is a cross-sectional view showing the coated strut of  FIG. 3   a  after a second coating has been applied as may be employed in accord with the present invention; 
         FIG. 3   c  is a side-view of a stent, which is a medical device that may be coated in accord with the present invention; 
         FIG. 4  shows a medical device positioned on a mandrel which may be employed in accord with the present invention; 
         FIG. 5  shows a side-view of a dryer which may be used to dry the medical device during the coating process in accord with the present invention; 
         FIG. 6   a  shows a ball-point applicator which may be used in accord with the present invention; 
         FIG. 6   b  shows a felt-tip applicator which may be used in accord with the present invention; 
         FIG. 6   c  shows a paint gun which may be used in accord with the present invention; 
         FIG. 7   a  shows a blade which may be used in accord with the present invention positioned prior to contacting the coating on a strut; 
         FIG. 7   b  shows a blade which may be used in accord with the present invention; 
         FIG. 8   a  is a front-view of a plate having a reducing orifice as may be employed in accord with the present invention. 
         FIG. 8   b  shows the plate of  FIG. 8   a  moving over a medical device to reduce a coating thickness; and 
         FIG. 9  shows a flow-chart illustrating method steps that may be employed with embodiments of the present invention. 
     
    
    
     DETAILED DESCRIPTION 
     The present invention regards coating one or more accessible surfaces of a medical device while not coating other surfaces of the medical device. In some embodiments this may include coating the outside or side surfaces of the medical device while not coating the inside surfaces of the medical device. In some instances this may include coating the inside surfaces of the device. By selectively coating in this fashion the amount of coating resident on the medical device may be reduced. This can be useful when the amount of coating is metered or otherwise is of interest. For example, if the medical device is a stent and the coating contains therapeutic agent a reduction in coating may allow the therapeutic agent, to be delivered in a more targeted fashion after the stent is implanted at a target site. The controlled application of therapeutic may also improve the efficiency of the process and reduce the amount of lost or wasted therapeutic. 
     The selective coating of a medical device may be accomplished with an applicator and spreader. An applicator may apply a layer of coating onto an accessible surface of a strut of a lattice portion of a stent. During or after the coating is the applied, a spreader, such as a roller, may be used to spread the coating on the accessible surfaces of the stent. The spreader may remove coating during this process and may also be in communication with a coating reservoir to deliver additional coating if desired. Each of the medical device, the applicator, and the spreader may be movable relative to each other to facilitate the coating of one or more surfaces of the work piece. 
     A system for coating an accessible outer surface  104  of a strut  102  of a lattice portion of a stent in accord with the present invention is shown in  FIGS. 1   a - d . There, a coating system is shown having an applicator  106  and a spreader  108 . The applicator  106  visible in  FIG. 1   a  is a micro-scale dispenser, however, any suitable applicator  106  may be used including, but not limited to ball point applicators, felt-tip applicators, and paint guns, which are shown in  FIGS. 6   a - 6   c . In  FIG. 1   a , the micro-scale dispenser  106  may be a fluid dispensing system which is configured to place coating  110  onto the strut  102 . For example, the micro-scale dispenser  106  may be coordinated with the movement of the strut  102  to dispense coating  110  on a unique external pattern of the work piece, in this instance a stent, within precise dimensions. 
     Although in the preceding examples, the applicators  106  are shown connected to a machine tool  114  component, the applicators  106  may also be hand-held. 
     The spreader  108  shown in  FIG. 1   b  is a roller, however, any suitable spreader device  108  for regulating coating may be used including, but not limited to rods, pins, straight edges, serrated edges, coils, which are not shown, and blades which are shown  FIG. 7   a - 7   b . In the example, the roller is about the same size as the width of the outer surface  104  of the strut  102 . In some instances, the spreader  108  may be hand-held, and in other instances, the spreader  108  may be connected to a machine tool  114 . For example, in  FIGS. 1   b - 1   d , the roller is connected to a conventional machine tool  114  configured to move the roller in the x, y, and z planes. 
     As seen in  FIG. 1   a , the applicator  106  may apply a layer of coating  110 , such as a bead, having a thickness. In this example, a bead of coating  110  is applied to accessible outer surface  104  of a strut  102  of a lattice portion of the medical device. Then, as shown in  FIGS. 1   b - c , once the coating  110  is applied, the spreader may be positioned in contact with the coating  110  to apply pressure to spread the coating  110  over a larger surface area of the outer surface  104  of the stent. In so doing the original thickness of the bead of coating  110  dispensed from the applicator  106  may be reduced through the application of pressure by the spreader. The spreader shown in the figures may be moved along any desired axis or in any direction. 
       FIG. 1   d  shows another step that may be used in accord with embodiments of the present invention. In this example, the spreader illustrated may, in addition to being able to apply pressure to reduce coating thickness, also be in fluid communication  116  with a coating reservoir (not shown) to apply additional coating  112  during the pressing step. The sequence of  FIGS. 1   a - 1   d  may be reordered, added, removed, or combined in accord with the teachings of the invention. The sequence may also be modified in other ways, such as by repeating the steps in continuous fashion. 
     Various dispensing process parameters may also be controlled to extend control over the thickness and position of the coating  110  placed on the medical device. For example, coating solution viscosity and the amount of pressure the spreader applies can each be varied to adjust the resulting thickness and position of coating  110 ,  112  resident on the medical device after it has been applied and spread. 
       FIG. 2  shows a machine tool  216  that may be employed in accord with embodiments of the present invention. In the example, a lathe is shown, however, any suitable machine tool  216  for holding, positioning, and rotating medical devices may be used. The applicator  206  may be fixed to a moveable mounting referred to as a tool post  218 . The tool post  218  is operated by lead screws  220  which together can accurately position the applicator  206  in a variety of planes (i.e., x, y, and z planes). The tool post  218  may be driven manually and may be driven automatically in coordination with a computer  222 . 
     As is evident in  FIG. 2 , the medical device  224  may be rotatably supported between a pair of points called centers. One centre is located on a head stock  226 . The head stock  226  includes a chuck for mounting one end of the medical device  224 . The other centre is mounted on a tail stock  228 . The tail stock  228  is slidable towards and away from the head stock  226  along a lathe bed  230 . Once rotatably mounted, the tool post  218  may be advanced along the lathe bed  230  so that the applicator  206  can apply coating, such as to the exposed surface of the strut of the lattice portion of a stent. The head and tail stocks  226 ,  228  allow for rotational movement of the medical device  224 . Likewise, as noted above, the tool post  218  allows the applicator  206  to move back and forth along the medical device  224  in the x, y, and z planes. Consequently, the entire surface of the medical device  224  is accessible. 
     Although the previous example shows a lathe, any suitable machine tool  216  may be used. A machine tool  216  may include any powered mechanical device used to fabricate or assemble components, such as metal stock. For example, a milling machine may also be used. 
     In accord with the embodiments of the invention, the machine tool  216  may be operated by computer numerical control (CNC). CNC refers to a computer  222  controller system which reads G-code instructions which drive the machine tool. The controller system is programmable with instructions or other retained data which may be unique to each medical device  224  to be coated and may account for the unique external pattern and precise dimensions of each medical device  224  to be coated. The controller system may also hold unique instruction sets for many different medical devices  224 . 
     A medical device  224 , such as stent in this embodiment, may be rotated by the machine tool  216  to expose different sides of the medical device  224  to the applicator  206 . As described herein, the applicator  206  may also be moved in the x, y, and z directions. Consequently, through the coordinated movement of the medical device  224  and/or the applicator  206 , in conjunction with the displacement of coating, all target portions of the medical device  224  may be exposed to and coated by the applicator  206 . 
       FIG. 3   a  is a side sectional view of a strut  302  of a stent which may be coated in accord with the present invention. The strut  302  in  FIG. 3   a  has an inner surface  313 , an outer surface  304 , and two cut faces  311 . Also shown on the strut  302  is a coating  310 . As can be seen, the coating  310 , covers only one face of the strut  302 . 
       FIG. 3   b  shows another example of how a coating  310  may be applied in accord with the invention. In  FIG. 3   b , a first coating  310  and a second coating  312  have been applied to the strut  302 . As can be seen, the first coating  310  is in contact with the strut  302  while the second coating  312  is in contact with the first coating  310  and further covers the outer surface  304  of the strut  302 . This second coating  312  may be applied in accord with the processes and methods of the present invention. It may also be applied with different methods and processes. In this example, as well as with the others described herein, if a second coating is employed this coating may comprise the same materials as the first coating and it may differ from the materials used for the first coating. In still other examples the coating may be applied in other patterns as well. For example, it may be applied to opposing cut faces and not the outer surface, likewise it may be applied to both cut faces and the outer surface. In an exemplary embodiment, the outer surface is coated and the two cut faces as well as the inner surface are not. 
       FIG. 3   c  is a side view of an implantable stent  324  including a lattice portion  325  that may be coated in accord with the invention. The stent  324  may be porous or have portions thereof that are porous. The struts  302  shown in  FIGS. 3   a  and  3   b  are struts  302  that may comprise and make up this stent  324 . While the medical device shown in these initial figures is a stent  324 , many other medical devices may be coated in accord with the invention. For example, other medical devices that may be coated include filters (e.g., vena cava filters), stent grafts, vascular grafts, intraluminal paving systems, implants and other devices used in connection with drug-loaded coatings and treatments. Likewise, the medical device may not be an implantable medical device but may, instead, be another medical device that needs to be coated only on certain pre-selected surfaces. In some instances these medical devices may be made from conductive materials and in other instances they may not be. For example, they may be made from polymers or ceramics. 
     The medical implants themselves may be self-expanding, mechanically expandable, or hybrid implants which may have both self-expanding and mechanically expandable characteristics. Mechanical or expandable medical devices may aid in traversing the narrower peripheral arteries and allow for expansion to the appropriate size/geometry when the targeted vessel lumen is reached. 
       FIG. 4  shows another method step which may be used in accord with embodiments of the present invention. In  FIG. 4 , a medical device  424  is positioned on a mandrel  432 . The mandrel  432  may be any suitable device such as a inflatable balloon or sheathing comprised of masking material to prevent non-target surfaces of the medical device from coating. In the example, the medical device  424  is positioned over the mandrel  432 . Therefore, the inner surfaces and at least portions of the cut faces of the medical device  424  are prevented from being coated by the applicator during the coating process. Additionally, the ends of the mandrel  432  may also be provided with rigid support elements  434 , for example, to rotatably support the device within the head and tail stocks of the machine tool described herein. In other examples, which are not shown, the medical device may be connected to machine tools and work holders in a variety of different ways. For example, the medical device may be configured for direct mounting with the machine tool. 
     Another step in a method embodying the invention may include drying the medical device during the coating process or after the coating process is complete. For example, as shown in  FIG. 5 , the coated medical device  524  may be positioned proximate to a heating element  536  to partially dry the medical device  524  after the applicator delivers coating. In this example, the heating element  536  is an infrared heating lamp, however, any suitable heating element  536  may be used. In other instances, such as after the metering device is used or after the coating process is complete, heat may be applied to the medical device  524  to dry coating located thereon. 
       FIGS. 6   a - 6   c  show embodiments of the applicator of  FIGS. 1   a  and  2 .  FIG. 6   a  shows an example of a hand held ball point applicator  602  that may be employed in accord with the embodiments of the present invention. The ball point applicator  602  may be similar in size and shape to a pen or pencil. The ball point applicator  602  has an internal chamber filled with coating which may be dispensed at the tip during use by the rolling action of a suitable metal or plastic sphere. 
       FIG. 6   b  illustrates an example in which a marker type applicator  603  is used. The marker type applicator  603  has its own coating source and the tip is made of porous material, which in the instant case is felt. 
     In the example of  FIG. 6   c  a paint gun type applicator  605  is shown. In this instance, the single action of depressing the trigger releases a fixed ratio of coating to the air. Through proper positioning of the nozzle of the paint gun, coating may be directed towards the target surface of the work piece. 
     In all of the embodiments described, the applicators may be positioned on or with respect to any suitable machine tool, and, may also be hand held. Furthermore, although the preceding examples illustrate various applicators, the embodiments of the present invention are not limited thereto and alternative applicators may also fall within the scope of the invention. 
       FIGS. 7   a - b  and  8   a - 8   b  show embodiments of the spreader of  FIGS. 1   b - d .  FIG. 7   a  shows a bead of coating  710  which may be dispensed from the applicator and transferred to an exposed outer surface  704  of the strut  702  of a lattice portion of the stent. The coating  710  may then be smoothed, squeegeed, or otherwise spread over the target surface by the blade  706 . The blade  706  may be moved in any desired direction or directions and may be attached to machine tool component  712 . For example, in  FIG. 7   a  the blade  706  is moving downward to put pressure on the coating  710 . Consequently, the coating  710  spreads out. Accordingly, the blade  706  may then be moved longitudinally to remove coating  710 . The amount of coating  710  remaining on the medical device may depend upon the depth and movement of the blade  706 . The blade  706  may be adjusted to control the resulting film thickness as desired. 
       FIG. 7   b  shows another example in which a hand held blade  706  may be used to further regulate coating located on an exposed surface outer surface  704  of the strut  702  of a lattice portion of the stent, such as the strut of  FIG. 1   c . Although, the blade  706  shown is hand held, as with previous examples, the blade  706  may also be attached to a machine tool component. 
       FIGS. 8   a  and  8   b  show a coated stent  824  and a plate  838  having a reducing orifice  840  which may be employed in accord with the embodiments of the present invention including those in  FIGS. 1   a - 1   d . The reducing orifice  840  may also be used as a spreader to assist in regulating a thickness of coating  810 . 
     In this example, the plate  838  and reducing orifice  840  may move along the stent in a longitudinal direction, however, any suitable arrangement may be used. For example, the stent  824  may be moved through a stationary reducing orifice  840 . As the reducing orifice  840  moves over the stent  824 , the thickness of the coating  810  reduces slightly. As each portion of the stent  824  exits the reducing orifice  840 , pressure is applied to the coating  810  and the coating thickness of the stent  824  may be reduced a predetermined distance. Since the target surface of the coating  810  may be held in about the same radial position relative to the reducing orifice  840 , the reducing orifice  840  may eliminate irregularities that may arise when coating the target surface of the stent  824 . For instance, variations forming on the target surface may be reduced. 
     In all of the embodiments described, the spreader may be positioned on or with respect to any suitable machine tool, and, may also be hand-held. Furthermore, although the previous examples illustrate various spreaders, the embodiments of the present invention are not limited thereto and alternative spreaders may also fall within the scope of the invention. 
       FIG. 9  shows a flow chart including method steps that may be employed with embodiments of the present invention to coat a target surface of a work piece. In the example of  FIG. 9 , step  910  may include providing a work piece, an applicator, and a spreader. Step  920  may include applying a layer of coating having a thickness to a target surface of the work piece with the applicator. Step  930  may include positioning the spreader in contact with the coating to reduce the coating thickness by spreading the coating over a larger surface area of the target surface. In embodiments, not shown, the sequence of steps may be reordered and steps may be added or removed. The steps may also be modified to include and use other devices described herein. Further, the steps may be repeated in continuous fashion. 
     While various embodiments have been described, other embodiments are plausible. It should be understood that the foregoing descriptions of various examples of the applicator and spreader are not intended to be limiting, and any number of modifications, combinations, and alternatives of the examples may be employed to facilitate the effectiveness of the coating of target surfaces of a medical device. 
     The coating, in accord with the embodiments of the present invention, may comprise a polymeric and or therapeutic agent formed, for example, by admixing a drug agent with a liquid polymer, in the absence of a solvent, to form a liquid polymer/drug agent mixture. A suitable list of drugs and/or polymer combinations is listed below. The term “therapeutic agent” as used herein includes one or more “therapeutic agents” or “drugs.” The terms “therapeutic agents” or “drugs” can be used interchangeably herein and include pharmaceutically active compounds, nucleic acids with and without carrier vectors such as lipids, compacting agents (such as histones), viruses (such as adenovirus, adenoassociated virus, retrovirus, lentivirus and α-virus), polymers, hyaluronic acid, proteins, cells and the like, with or without targeting sequences. 
     Specific examples of therapeutic agents used in conjunction with the present invention include, for example, pharmaceutically active compounds, proteins, cells, oligonucleotides, ribozymes, anti-sense oligonucleotides, DNA compacting agents, gene/vector systems (i.e., any vehicle that allows for the uptake and expression of nucleic acids), nucleic acids (including, for example, recombinant nucleic acids; naked DNA, cDNA, RNA; genomic DNA, cDNA or RNA in a non-infectious vector or in a viral vector and which further may have attached peptide targeting sequences; antisense nucleic acid (RNA or DNA); and DNA chimeras which include gene sequences and encoding for ferry proteins such as membrane translocating sequences (“MTS”) and herpes simplex virus-1 (“VP22”)), and viral, liposomes and cationic and anionic polymers and neutral polymers that are selected from a number of types depending on the desired application. Non-limiting examples of virus vectors or vectors derived from viral sources include adenoviral vectors, herpes simplex vectors, papilloma vectors, adeno-associated vectors, retroviral vectors, and the like. Non-limiting examples of biologically active solutes include anti-thrombogenic agents such as heparin, heparin derivatives, urokinase, and PPACK (dextrophenylalanine proline arginine chloromethylketone); antioxidants such as probucol and retinoic acid; angiogenic and anti-angiogenic agents and factors; anti-proliferative agents such as enoxaprin, angiopeptin, rapamycin, angiopeptin, monoclonal antibodies capable of blocking smooth muscle cell proliferation, hirudin, and acetylsalicylic acid; anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, acetyl salicylic acid, and mesalamine; calcium entry blockers such as verapamil, diltiazem and nifedipine; antineoplastic/antiproliferative/anti-mitotic agents such as paclitaxel, 5-fluorouracil, methotrexate, doxorubicin, daunorubicin, cyclosporine, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin and thymidine kinase inhibitors; antimicrobials such as triclosan, cephalosporins, aminoglycosides, and nitrofurantoin; anesthetic agents such as lidocaine, bupivacaine, and ropivacaine; nitric oxide (NO) donors such as linsidomine, molsidomine, L-arginine, NO-protein adducts, NO-carbohydrate adducts, polymeric or oligomeric NO adducts; anti-coagulants such as D-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing compound, heparin, antithrombin compounds, platelet receptor antagonists, anti-thrombin antibodies, anti-platelet receptor antibodies, enoxaparin, hirudin, Warfarin sodium, Dicumarol, aspirin, prostaglandin inhibitors, platelet inhibitors and tick antiplatelet factors; vascular cell growth promoters such as growth factors, growth factor receptor antagonists, transcriptional activators, and translational promoters; vascular cell growth inhibitors such as growth factor inhibitors, growth factor receptor antagonists, transcriptional repressors, translational repressors, replication inhibitors, inhibitory antibodies, antibodies directed against growth factors, bifunctional molecules consisting of a growth factor and a cytotoxin, bifunctional molecules consisting of an antibody and a cytotoxin; cholesterol-lowering agents; vasodilating agents; agents which interfere with endogenous vascoactive mechanisms; survival genes which protect against cell death, such as anti-apoptotic Bcl-2 family factors and Akt kinase; and combinations thereof. Cells can be of human origin (autologous or allogenic) or from an animal source (xenogeneic), genetically engineered if desired to deliver proteins of interest at the insertion site. Any modifications are routinely made by one skilled in the art. 
     Polynucleotide sequences useful in practice of the invention include DNA or RNA sequences having a therapeutic effect after being taken up by a cell. Examples of therapeutic polynucleotides include anti-sense DNA and RNA; DNA coding for an anti-sense RNA; or DNA coding for tRNA or rRNA to replace defective or deficient endogenous molecules. The polynucleotides can also code for therapeutic proteins or polypeptides. A polypeptide is understood to be any translation product of a polynucleotide regardless of size, and whether glycosylated or not. Therapeutic proteins and polypeptides include as a primary example, those proteins or polypeptides that can compensate for defective or deficient species in an animal, or those that act through toxic effects to limit or remove harmful cells from the body. In addition, the polypeptides or proteins that can be injected, or whose DNA can be incorporated, include without limitation, angiogenic factors and other molecules competent to induce angiogenesis, including acidic and basic fibroblast growth factors, vascular endothelial growth factor, hif-1, epidermal growth factor, transforming growth factor α and β, platelet-derived endothelial growth factor, platelet-derived growth factor, tumor necrosis factor α, hepatocyte growth factor and insulin like growth factor; growth factors; cell cycle inhibitors including CDK inhibitors; anti-restenosis agents, including p15, p16, p18, p19, p21, p27, p53, p57, Rb, nFkB and E2F decoys, thymidine kinase (“TK”) and combinations thereof and other agents useful for interfering with cell proliferation, including agents for treating malignancies; and combinations thereof. Still other useful factors, which can be provided as polypeptides or as DNA encoding these polypeptides, include monocyte chemoattractant protein (“MCP-1”), and the family of bone morphogenic proteins (“BMPs”). The known proteins include BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16. Currently preferred BMPs are any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 and BMP-7. These dimeric proteins can be provided as homodimers, heterodimers, or combinations thereof, alone or together with other molecules. Alternatively or, in addition, molecules capable of inducing an upstream or downstream effect of a BMP can be provided. Such molecules include any of the “hedgehog” proteins, or the DNAs encoding them. 
     As stated above, coatings used with the exemplary embodiments of the present invention may comprise a polymeric material/drug agent matrix formed, for example, by admixing a drug agent with a liquid polymer, in the absence of a solvent, to form a liquid polymer/drug agent mixture. Curing of the mixture typically occurs in-situ. To facilitate curing, a cross-linking or curing agent may be added to the mixture prior to application thereof. Addition of the cross-linking or curing agent to the polymer/drug agent liquid mixture must not occur too far in advance of the application of the mixture in order to avoid over-curing of the mixture prior to application thereof. Curing may also occur in-situ by exposing the polymer/drug agent mixture, after application to the luminal surface, to radiation such as ultraviolet radiation or laser light, heat, or by contact with metabolic fluids such as water at the site where the mixture has been applied to the luminal surface. In coating systems employed in conjunction with the present invention, the polymeric material may be either bioabsorbable or biostable. Any of the polymers described herein that may be formulated as a liquid may be used to form the polymer/drug agent mixture. 
     The polymer used in the exemplary embodiments of the present invention is preferably capable of absorbing a substantial amount of drug solution. When applied as a coating on a medical device in accordance with the present invention, the dry polymer is typically on the order of from about 1 to about 50 microns thick. In the case of a balloon catheter, the thickness is preferably about 1 to 10 microns thick, and more preferably about 2 to 5 microns. Very thin polymer coatings, e.g., of about 0.2-0.3 microns and much thicker coatings, e.g., more than 10 microns, are also possible. It is also within the scope of the present invention to apply multiple layers of polymer coating onto a medical device. Such multiple layers are of the same or different polymer materials. 
     The polymer of the present invention may be hydrophilic or hydrophobic, and may be selected from the group consisting of polycarboxylic acids, cellulosic polymers, including cellulose acetate and cellulose nitrate, gelatin, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone, polyanhydrides including maleic anhydride polymers, polyamides, polyvinyl alcohols, copolymers of vinyl monomers such as EVA, polyvinyl ethers, polyvinyl aromatics, polyethylene oxides, glycosaminoglycans, polysaccharides, polyesters including polyethylene terephthalate, polyacrylamides, polyethers, polyether sulfone, polycarbonate, polyalkylenes including polypropylene, polyethylene and high molecular weight polyethylene, halogenated polyalkylenes including polytetrafluoroethylene, polyurethanes, polyorthoesters, proteins, polypeptides, silicones, siloxane polymers, polylactic acid, polyglycolic acid, polycaprolactone, polyhydroxybutyrate valerate and blends and copolymers thereof as well as other biodegradable, bioabsorbable and biostable polymers and copolymers. 
     Coatings from polymer dispersions such as polyurethane dispersions (BAYHYDROL®, etc.) and acrylic latex dispersions are also within the scope of the present invention. The polymer may be a protein polymer, fibrin, collagen and derivatives thereof, polysaccharides such as celluloses, starches, dextrans, alginates and derivatives of these polysaccharides, an extracellular matrix component, hyaluronic acid, or another biologic agent or a suitable mixture of any of these, for example. In one embodiment of the invention, the preferred polymer is polyacrylic acid, available as HYDROPLUS® (Boston Scientific Corporation, Natick, Mass.), and described in U.S. Pat. No. 5,091,205, the disclosure of which is hereby incorporated herein by reference. U.S. Pat. No. 5,091,205 describes medical devices coated with one or more polyisocyanates such that the devices become instantly lubricious when exposed to body fluids. In another preferred embodiment of the invention, the polymer is a copolymer of polylactic acid and polycaprolactone. 
     The examples described herein are merely illustrative, as numerous other embodiments may be implemented without departing from the spirit and scope of the exemplary embodiments of the present invention. Moreover, while certain features of the invention may be shown on only certain embodiments or configurations, these features may be exchanged, added, and removed from and between the various embodiments or configurations while remaining within the scope of the invention. Likewise, methods described and disclosed may also be performed in various sequences, with some or all of the disclosed steps being performed in a different order than described while still remaining within the spirit and scope of the present invention.