Methods and devices for promoting endothelial morphogenesis

Abstract

In one aspect, the present invention provides methods for promoting endothelial morphogenesis. The methods of this aspect of the invention include the step of providing to one or more endothelial cells an amount of an osteoprotegerin sufficient to promote endothelial morphogenesis. The methods of this aspect of the invention can be practiced in vivo or in vitro. In another aspect, the present invention provides implantable medical devices that each include: (a) a device body; and (b) a layer attached to a surface of the device body, the layer comprising a molecule selected from the group consisting of osteoprotegerin and a nucleic acid molecule encoding osteoprotegerin, wherein the device is adapted to be completely or partially implanted into an animal body. The implanted medical device thus promotes the growth of blood vessels in the surrounding tissue, thereby reducing or preventing the formation of a collagenous capsule around the implanted medical device.

1 . An implantable medical device comprising:
 (a) a device body; and   (b) a layer attached to a surface of the device body, said layer comprising a molecule selected from the group consisting of osteoprotegerin and a nucleic acid molecule encoding osteoprotegerin, wherein said device is adapted to be completely or partially implanted into an animal body.   
     
     
         2 . The implantable medical device of  claim 1 , wherein said implantable medical device is selected from the group consisting of a vascular graft, a stent, an artificial blood vessel, an artificial bone joint, a biosensor, a catheter, and artificial skin. 
     
     
         3 . The implantable medical device of  claim 2 , wherein the biosensor is a glucose sensor. 
     
     
         4 . The implantable medical device of  claim 1 , wherein said medical device is a cardiovascular device. 
     
     
         5 . The implantable medical device of  claim 1 , wherein said device comprises a scaffold that supports tissue growth. 
     
     
         6 . The implantable medical device of  claim 5 , wherein said tissue growth forms an anatomical structure. 
     
     
         7 . The implantable medical device of  claim 1 , wherein said layer completely covers said surface of said device. 
     
     
         8 . The implantable medical device of  claim 1 , wherein said layer partially covers said surface of said device. 
     
     
         9 . The implantable medical device of  claim 1 , wherein said layer comprises osteoprotegerin. 
     
     
         10 . The implantable medical device of  claim 1 , wherein the osteoprotegerin is at least 80% identical to the osteoprotegerin consisting of the amino acid sequence set forth in SEQ ID NO: 2. 
     
     
         11 . The implantable medical device of  claim 1 , wherein the osteoprotegerin is covalently attached to said layer. 
     
     
         12 . The implantable medical device of  claim 1 , wherein the osteoprotegerin is non-covalently attached to said layer. 
     
     
         13 . The implantable medical device of  claim 1 , wherein said layer comprises a nucleic acid molecule encoding osteoprotegerin, said nucleic acid molecule hybridizing to the complement of the nucleic acid molecule set forth in SEQ ID NO: 1 under conditions of 5×SSC at 60° C. for 30 minutes. 
     
     
         14 . The implantable medical device of  claim 1 , wherein said layer comprises a porous matrix. 
     
     
         15 . The implantable medical device of  claim 1 , wherein said layer comprises genetically engineered tissue expressing osteoprotegerin.