Endovascular graft coatings

Abstract

An endovascular graft, e.g., having both an expandable stent portion and a stent cover portion positioned within and/or surrounding the expandable portion, the graft itself and/or a stent cover portion being coated with a bioactive agent adapted to promote initial thrombus formation, preferably followed by long term fibrous tissue ingrowth. The endovascular graft addresses concerns regarding endoleaking by permitting the graft to be deployed and used in a manner that promotes a short term hemostatic effect in the perigraft region. This short term effect can, in turn, be used to promote or permit long term fibrous tissue ingrowth. Particularly where the stent cover portion is prepared from a porous material selected from PET and ePTFE, the bioactive agent can include a thrombogenic agent such as collagen covalently attached in the form of a thin, conformal coating on at least the outer surface of the stent cover. An optimal coating of this type is formed by the activation of photoreactive groups provided by either the cover material itself, by the bioactive agent itself, and/or by a linking agent.

1 . An endovascular graft comprising an expandable stent portion and a stent cover portion, wherein the stent cover portion comprises a porous, fibrous material having both an outer perigraft surface and an inner luminal surface, and is coated on at least the outer surface with a hemostatic bioactive agent covalently attached by the activation of photoreactive groups provided by the stent cover portion, by the bioactive agent itself, and/or by a linking agent, wherein the coating comprises the bioactive agent attached to the fibers of the material without occluding its pores.  
   
   
       2 - 5 . (canceled)  
   
   
       6 . A graft according to  claim 1  wherein the agent is selected from the group consisting of proteins having a specific hemostatic effect, and positively charged compounds having a nonspecific effect.  
   
   
       7 . (canceled)  
   
   
       8 . A graft according to  claim 6  wherein the agent is (a) a positively charged polymeric molecule selected from the group consisting of chitosan, polylysine, poly(ethyleneimine) and acrylic polymers incorporating positively-charged groups in the form of primary, secondary, or tertiary amines or quaternary salts, or (b) a positively charged non-polymeric molecule selected from the group consisting of alkyldimethylbenzylammonium chloride and tridodecylmethylammonium chloride.  
   
   
       9 - 10 . (canceled)  
   
   
       11 . A method of preparing an endovascular graft comprising an expandable stent portion and a stent cover portion, comprising the step of coating at least the outer surface of the stent cover portion with a hemostatic bioactive agent that is covalently attached by the activation of photoreactive groups provided by the stent cover portion, by the bioactive agent, and/or by a linking agent.  
   
   
       12 - 15 . (canceled)  
   
   
       16 . A method according to  claim 11  wherein the agent is selected from the group consisting of proteins having specific hemostatic effect, and positively charged compounds having a nonspecific hemostatic effect.  
   
   
       17 . (canceled)  
   
   
       18 . A method according to  claim 16  wherein the agent is (a) a positively charged polymeric molecule selected from the group consisting of chitosan, polylysine, poly(ethyleneimine) and acrylic polymers incorporating positively-charged groups in the form of primary, secondary, or tertiary amines or quaternary salts, or (b) a positively charged non-polymeric molecule selected from the group consisting of alkyldimethylbenzylammonium chloride and tridodecylmethylammonium chloride  
   
   
       19 - 20 . (canceled)  
   
   
       21 . A method of preventing endoleaking in the course of deploying and using an endovascular graft that comprises an expandable stent portion and a stent cover, the method comprising the step of first coating the stent cover by a method that comprises the step of coating at least the outer surface of the stent cover portion with a hemostatic bioactive agent that is covalently attached by the activation of photoreactive groups provided by the stent cover portion, by the bioactive agent, and/or by a linking agent.  
   
   
       22 . A method according to  claim 21  wherein the stent cover portion is prepared from a porous material selected from PET and ePTFE.  
   
   
       23 . A method according to  claim 21  wherein the agent is selected from the group consisting of proteins having a specific hemostatic effect, and positively charged compounds having a nonspecific hemostatic effect.  
   
   
       24 - 25 . (canceled)  
   
   
       26 . A method according to  claim 21  wherein the coating is provided on the perigraft, as opposed to luminal, surface of the stent cover.  
   
   
       27 . A method according to  claim 21  wherein the coating adds about 5%, or less, to the original thickness of the material used as the stent cover portion.  
   
   
       28 . A method according to  claim 21  wherein the bioactive agent used to coat the surface is itself photoderivatized.  
   
   
       29 - 30 . (canceled)  
   
   
       31 . A method of preventing endoleaking in the course of deploying and using an endovascular graft, the method comprising the steps of: 
 a) providing an endovascular graft comprising an expandable stent portion and a stent cover portion, wherein the stent cover portion comprises a porous, fibrous material having both an outer perigraft surface and an inner luminal surface, the cover portion having a hemostatic bioactive agent on at least the outer surface in the form of a coating covalently attached to the fibers of the material without occluding its pores, by the activation of photoreactive groups provided by the stent cover portion, by the bioactive agent, and/or by a linking agent, and    b) implanting the stent in the vessel in a manner that avoids endoleaking.    
   
   
       32 . A method according to  claim 31  wherein the stent cover portion is prepared from a porous material selected from PET and ePTFE.  
   
   
       33 . A method according to  claim 31  wherein the agent is selected from the group consisting of proteins having a specific hemostatic effect, and positively charged compounds having a nonspecific hemostatic effect.  
   
   
       34 - 35 . (canceled)  
   
   
       36 . A method according to  claim 31  wherein the coating is provided on the perigraft, as opposed to luminal, surface of the stent cover.  
   
   
       37 . A method according to  claim 31  wherein the coating adds about 5%, or less, to the original thickness of the material used as the stent cover portion.  
   
   
       38 . A method according to  claim 31  wherein the bioactive agent used to coat the surface is itself photoderivatized.  
   
   
       39 - 40 . (canceled)  
   
   
       41 . A method according to  claim 31  wherein the agent is immobilized in an amount between about 0.05 μg/cm 2  to about 10 μg/cm 2 .  
   
   
       42 . A method according to  claim 31  wherein the endovascular graft is provided in the form of a collapsed small diameter tube of on the order of two mm or less overall diameter, and can be expanded to form a larger diameter tube in situ of between about six mm and about thirty mm.  
   
   
       43 . A method according to claim  39  wherein the bioactive agent used to coat the surface is itself photoderivatized, and is immobilized in an amount between about 0.05 μg/cm 2  to about 10 μg/cm 2 , and wherein the endovascular graft is provided in the form of a collapsed small diameter tube of on the order of two mm or less overall diameter, and can be expanded to form a larger diameter tube in situ of between about six mm and about thirty mm.  
   
   
       44 . A graft according to  claim 1  wherein the bioactive agent is attached to the surface in the form of a thin, conformal coating.  
   
   
       45 . A graft according to  claim 1  wherein the coating adds no more than 25% to the original thickness of the material used as the stent cover portion.  
   
   
       46 . A graft according to  claim 1  wherein the stent cover portion is prepared from a porous material selected from PET and ePFTE.  
   
   
       47 . A graft according to  claim 1  wherein the bioactive agent is immobilized in a range of about 0.01 μg/cm 2  to about 50 μg/cm 2 .  
   
   
       48 . A graft according to  claim 1  wherein the photoreactive group is provided on the bioactive agent itself.  
   
   
       49 . A graft according to  claim 1  wherein the photoreactive group is provided on at least the outer surface of the stent cover portion.  
   
   
       50 . A graft according to  claim 1  wherein the coating is provided in a manner sufficient to prevent endoleaking.