Medical Device with Coating that Promotes Endothelial Cell Adherence

Abstract

This invention provides compositions and methods for producing a medical device coated with a matrix and an antibody which reacts with an endothelial cell antigen. The matrix coating the medical device may be composed of synthetic material, such as polyurethane, poly-L-lactic acid, cellulose ester or polyethylene glycol. In another embodiment, the matrix is composed of naturally occurring materials, such as collagen, fibrin, elastin, amorphous carbon. In a third embodiment, the matrix may be composed of fillerenes. The fullerenes range from about C60 to about C100. The medical device may be a stent or a synthetic graft. The antibodies promote adherence of eadothelial cells on the medical device. The antibodies may be mixed with the matrix or covalently tethered through a linker molecule to the matrix. Following adherence to the medical device, the endothelial cells differentiate and proliferate on the medical device. The antibodies may be different types of monoclonal antibodies. Methods of preparing such composition and methods of treating a mammal with atherosclerosis or other types of vessel obstruction are disclosed. By facilitating adherence of endothelial cells to the surface of the medical device, the methods and compositions of this invention will decrease the incidence of restenosis as well as other thromboembolic complications resulting from implantation of medical devices.

1 - 51 . (canceled)  
   
   
       52 . A method for forming an endothelial cell layer in vivo, comprising administering to a patient at a site in need thereof a ligand for stem cells or progenitor cells, wherein circulating stem cells or progenitor cells are captured by the ligand.  
   
   
       53 . The method of  claim 52 , wherein the ligand is immobilized to a matrix material at the site of implantation.  
   
   
       54 . The method of  claim 52 , wherein the ligand is incorporated into a matrix material or at the site of implantation.  
   
   
       55 . The method of  claim 52 , wherein the ligand is released from genetically engineered cells at the site of implantantion.  
   
   
       56 . The method of  claim 52 , wherein the ligand specifically binds to stem cells or progenitor cells.  
   
   
       57 . The method of  claim 52 , further comprising providing molecules inducing proliferation or differentiation of stem cells or progenitor cells.  
   
   
       58 . The method of  claim 52 , wherein the matrix is formed of a natural or synthetic polymer.  
   
   
       59 . The method of  claim 53 , wherein the matrix is a fibrous mesh.  
   
   
       60 . The method of  claim 53 , wherein the ligands are tethered to the matrix.  
   
   
       61 . The method of  claim 52 , wherein the ligand is an antibody, antibody fragment or combination thereof.  
   
   
       62 . The method of  claim 61 , wherein the antibody, antibody fragment or combination thereof is selected from the group consisting of antibodies against CD45, CD34, CD31, Flk- 1 , Tie-2, and E-selectin.  
   
   
       63 . The method of  claim 60 , wherein the ligand and the matrix are part of a coating on a medical device.  
   
   
       64 . The method of  claim 63 , wherein the medical device comprises a stent or synthetic graft.  
   
   
       65 . The method of  claim 52 , wherein the circulating stem or progenitor cells are endothelial cells transfected with a mammalian expression vector.  
   
   
       66 . The method of  claim 65 , wherein the expression vector comprises one or more cloned genes encoding a protein selected from the group consisting of platelet derived growth factor (PDGF), fibroblast growth factor (FGF), and nitric oxide synthase.