Seeding implantable medical devices with cells

Abstract

The invention is directed to apparatus and methods for seeding an implantable medical device, such as a vascular prosthesis, with cells, such as endothelial cells. The invention supports techniques for seeding a luminal surface of the device with axial centrifugation. Cells are introduced in suspension into the lumen of the device, and the device is subjected to centrifugation around a longitudinal axis defined by the lumen. Axial centrifugation causes the cells to concentrate toward the luminal surface. Shortly after axial centrifugation, the seeded device can be presented for implantation in a patient.

1 . A method for seeding cells comprising: 
 introducing cells into a lumen of an implantable medical device adapted to be implanted in a living body, wherein the lumen comprises a luminal surface comprising expanded polytetrafluoroethylene and wherein the lumen defines a longitudinal axis; and    applying centrifugation to the implantable medical device to rotate the implantable medical device around the axis.    
     
     
         2 . The method of  claim 1 , further comprising placing the implantable medical device in a protective sleeve prior to introducing the cells.  
     
     
         3 . The method of  claim 1 , further comprising delivering the implantable medical device for implantation in the living body after centrifugation.  
     
     
         4 . The method of  claim 3 , further comprising incubating the implantable medical device after centrifugation and before delivering the implantable medical device for implantation in the living body.  
     
     
         5 . The method of  claim 4 , wherein the incubating occurs for about five minutes to about two hours.  
     
     
         6 . The method of  claim 1 , further comprising: 
 wetting the luminal surface with a wetting agent;    placing a growth medium on the luminal surface, the growth medium supplanting the wetting agent; and    introducing the cells after the growth medium is placed on the luminal surface.    
     
     
         7 . The method of  claim 1 , wherein applying centrifugation to the implantable medical device comprises applying centrifugation for about 250 g to about 500 g to the luminal surface for about one to about ten minutes.  
     
     
         8 . The method of  claim 1 , wherein applying centrifugation to the implantable medical device comprises applying between about 1 g and about 10,000 g.  
     
     
         9 . The method of  claim 1 , wherein the cells are endothelial cells.  
     
     
         10 . The method of  claim 1 , further comprising: 
 placing the implantable medical device in a tube prior to introducing the cells, the tube comprising at least one open end;    introducing the cells into the lumen through the open end of the tube; and    sealing the open end of the tube with a plug.    
     
     
         11 . The method of  claim 10 , further comprising loading the sealed tube into a centrifuge.  
     
     
         12 . The method of  claim 1 , wherein the implantable medical device comprises a vascular prosthesis.  
     
     
         13 . The method of  claim 1 , wherein the implantable medical device comprises a mechanical heart valve, a bioprosthetic heart valve, a coronary stent, a stent graft or an AAA graft.  
     
     
         14 . The method of  claim 1 , wherein the surface comprising expanded polytetrafluoroethylene comprises nodes formed of polytetrafluoroethylene, and wherein the surface includes recesses defined by nodes lifted from the surface.  
     
     
         15 . A method for seeding cells comprising: 
 introducing cells into a lumen of an implantable medical device adapted to be implanted in a living body, wherein the lumen includes a luminal surface having recesses defined by nodes lifted from the surface, and wherein the lumen defines a longitudinal axis; and    applying centrifugation to the implantable medical device to rotate the implantable medical device around the axis.    
     
     
         16 . The method of  claim 15 , wherein the luminal surface comprises expanded polytetrafluoroethylene.  
     
     
         17 . The method of  claim 16 , wherein the surface comprising expanded polytetrafluoroethylene comprises nodes formed of polytetrafluoroethylene, and wherein the surface includes recesses defined by nodes lifted from the surface.  
     
     
         18 . The method of  claim 15 , further comprising placing the implantable medical device in a protective sleeve prior to introducing the cells.  
     
     
         19 . The method of  claim 15 , wherein applying centrifugation to the implantable medical device comprises applying centrifugation for about 250 g to about 500 g to the luminal surface for about one to about ten minutes.  
     
     
         20 . The method of  claim 15 , wherein applying centrifugation to the implantable medical device comprises applying centrifugation for about 1 g to about 10,000 g.  
     
     
         21 . The method of  claim 15 , further comprising: 
 incubating the implantable medical device after centrifugation; and    delivering the implantable medical device for implantation in the living body.    
     
     
         22 . The method of  claim 15 , wherein the implantable medical device comprises a vascular prosthesis.  
     
     
         23 . The method of  claim 15 , wherein the implantable medical device comprises a mechanical heart valve, a bioprosthetic heart valve, a coronary stent, a stent graft or an AAA graft.  
     
     
         24 . An apparatus to apply centrifugation to an implantable medical device comprising: 
 an adapter configured to mate with a rotor of a centrifuge proximate to an axis of rotation of the rotor, the adapter comprising a chamber that extends in the direction of the axis;    a tube configured to receive the implantable medical device, and further configured to be received in the chamber, the tube including an open end; and    a plug configured to seal the open end of the tube.    
     
     
         25 . The apparatus of  claim 24 , further comprising a cap configured to mate removably with the adapter to seal the tube in the chamber.  
     
     
         26 . The apparatus of  claim 25 , wherein the cap is configured to bear against the plug when the tube is in the chamber, the plug sealing the tube and the cap sealing the chamber.  
     
     
         27 . The apparatus of  claim 24 , further comprising a fixation mechanism configured to secure the adapter to the rotor.  
     
     
         28 . The apparatus of  claim 24 , wherein the tube is configured to receive a vascular prosthesis.  
     
     
         29 . The apparatus of  claim 24 , wherein the tube is configured to receive a mechanical heart valve, a bioprosthetic heart valve, a coronary stent, a stent graft or an AAA graft.  
     
     
         30 . The apparatus of  claim 24 , wherein the chamber defines a height that extends in the direction of the axis, and wherein the height is less than about 22 cm.  
     
     
         31 . An apparatus to apply centrifugation to an implantable medical device comprising: 
 an adapter means configured to mate with a rotor of a centrifuge proximate to an axis of rotation of the rotor, the adapter comprising a chamber; and    a container means configured to receive the implantable medical device, and further configured to be received in the chamber.    
     
     
         32 . The apparatus of  claim 31 , further comprising a sealing means configured to seal the implantable medical device inside the container means.