Seeding implantable medical devices with cells

• US 20070059335A1
• Filed: 09/01/2006
• Published: 03/15/2007
• Est. Priority Date: 03/02/2005
• Status: Active Grant

• Current Assignee: Kips Bay Medical, Inc.
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Wolf, Michael, Trescony, Paul, Yunker, Laurie
• Granted Patent: US 7,759,120 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61F 2/062 Apparatus for the production of blood vessels made from natural tissue or with layers of living cells prostheses made from natural tissue or living cells A61L27/507
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/3616 Blood, e.g. platelet-rich plasma
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/3808 Endothelial cells
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: C08L 27/18 Homopolymers or copolymers or tetrafluoroethene
• CPC Class Codes: Y10S 623/915 Method or apparatus for preparing biological material
• CPC Class Codes: Y10S 623/916 Blood vessel

Abstract

Apparatus and methods for seeding an implantable medical device, such as a vascular prosthesis, with cells, such as endothelial cells, are described. 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. The introduction of the cells may occur after a blood centrifugation product, such as platelet-poor plasma, is applied to the luminal surface. After the cells are introduced, the device is then subjected to centrifugation around a longitudinal axis defined by the lumen. Axial centrifugation causes the cells to concentrate toward and adhere to the luminal surface. Shortly after axial centrifugation, the seeded device can be presented for implantation in a patient. The implantable medical device may be inserted into a protective sleeve prior to seeding the device with cells, and the sleeve may or may not be removed prior to implantation.

Claims

1. A method for seeding cells on a luminal surface of an implantable medical device, the method comprising:

applying a blood centrifugation product to the luminal surface;

introducing cells into a lumen of the implantable medical device, wherein the luminal surface defines the lumen, and the lumen defines a longitudinal axis; and

centrifuging the implantable medical device by rotating the implantable medical device substantially around the longitudinal axis.

2. The method of claim 1, wherein applying a blood centrifugation product comprises applying a platelet-poor plasma.

3. The method of claim 2, further comprising incubating the platelet-poor plasma.

4. The method of claim 1, further comprising applying a preparation media to the luminal surface, wherein the preparation media comprises calcium.

5. The method of claim 4, wherein applying the preparation media comprises applying the preparation media prior to applying the blood centrifugation product, and wherein applying the blood centrifugation product comprises applying the blood centrifugation product prior to introducing cells.

6. The method of claim 1, further comprising rubbing the luminal surface of the implantable medical device to lift nodes from the luminal surface and create recesses on the luminal surface.

7. The method of claim 1, wherein the luminal surface comprises expanded polytetrafluoroethylene.

8. The method of claim 1, further comprising inserting the implantable medical device into a protective sleeve prior to applying the blood centrifugation product.

9. The method of claim 1, wherein introducing cells comprises introducing endothelial cells.

10. The method of claim 1, wherein the implantable medical device comprises a vascular prosthesis.

11. The method of claim 1, further comprising:

injecting a blood sample into a device that separates the blood sample;

spinning the blood sample in the device in a soft spin to separate red blood cells;

spinning the blood sample in a hard spin to form a pellet of platelets, wherein the remaining solution is the blood centrifugation product.

12. A method comprising:

inserting an implantable medical device into a protective sleeve;

inserting the protective sleeve into a tube through an open end of the tube, wherein the tube defines a longitudinal axis;

sealing the open end of the tube with a septum;

delivering cells to a lumen of the implantable medical device through the septum; and

centrifuging the implantable medical device with the cells in the lumen by rotating the tube substantially around the longitudinal axis.

13. The method of claim 12, further comprising securing the septum over the open end with a tube cap.

14. The method of claim 12, further comprising:

removing the implantable medical device from the protective sleeve; and

implanting the implantable medical device after removing the implantable medical device from the protective sleeve.

15. The method of claim 12, further comprising:

implanting the implantable medical device; and

removing the implantable medical device from the protective sleeve after implanting the implantable medical device.

16. The method of claim 15, further comprising attaching the protective sleeve to a tunneling device, wherein implanting the implantable medical device comprises drawing the protective sleeve and the implantable medical device through a tunnel formed through patient tissue by the tunneling device with the sleeve attached to the tunneling device.

17. The method of claim 12, further comprising applying at least one of a preparation media that comprises calcium and a blood centrifugation product to a luminal surface of the implantable medical device after inserting an implantable medical device into the protective sleeve.

18. The method of claim 17, further comprising delivering at least one of the preparation media and the blood centrifugation product to the lumen of the implantable medical device through the septum.

19. The method of claim 12, wherein inserting the implantable medical device comprises inserting a vascular prosthesis.

20. A system for protecting a vascular prosthesis during a cell seeding procedure, the system comprising:

a protective sleeve that defines a lumen sized to receive the vascular prosthesis;

a tube sized to receive the protective sleeve via an open end, wherein the tube is adapted to be received by a centrifuge; and

a septum that seals the open end of the tube, wherein the septum is adapted to allow delivery of materials to a lumen of the vascular prosthesis through the septum when the prosthesis is within the tube.

21. The system of claim 20, wherein the septum is self-sealing after a needle puncture.

22. The system of claim 20, further comprising a tube cap attachable to the open end of the tube over the septum, wherein the cap defines a delivery hole sized to allow a needle to access the septum.

23. The system of claim 22, wherein a diameter of the delivery hole is between approximately 0.5 millimeters and approximately 20 millimeters.

24. The system of claim 20, wherein the protective sleeve comprises polytetrafluoroethylene.

25. The system of claim 20, wherein the tube comprises at least one of polycarbonate or polyvinyl chloride.

26. The system of claim 20, wherein an inner diameter of the protective sleeve is between approximately 1 millimeters and approximately 40 millimeters, and wherein an outer diameter of the protective sleeve is between approximately 1.5 millimeters and approximately 40.5 millimeters.

27. The system of claim 20, wherein an inner diameter of the tube is between approximately 1.5 millimeters and approximately 40.5 millimeters, and wherein an outer diameter of the tube is between approximately 2 millimeters and approximately 45 millimeters.

28. The system of claim 20, wherein a length of at least one of the protective sleeve or the tube is between approximately 1 centimeter and approximately 80 centimeters.