Implantable medical devices comprising isolated extracellular matrix

• US 8,874,204 B2
• Filed: 12/20/2004
• Issued: 10/28/2014
• Est. Priority Date: 12/20/2004
• Status: Expired due to Fees

• Current Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Original Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Inventors: Sih, Haris J., Pastore, Joseph M.
• Primary Examiner(s): SINGH, ANOOP KUMAR
• Application Number:
  US11/017,432
• Publication Number:
  US 20060134079A1
• Time in Patent Office: 3,599 Days
• Field of Search: 607/2, 607/5, 607/9, 607/50, 607/115, 607/116, 607/119, 607/129, 424/422, 424/82.1, 424/93.21, 424/366
• US Class Current: 607/2
• CPC Class Codes: A61K 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 38/1833 Hepatocyte growth factor; Scatter factor; Tumor cytotoxic factor II
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 38/30 Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 insulin-like growth factor binding protein A61K38/1754
• CPC Class Codes: A61K 38/39 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61N 1/05 for implantation or insertion into the body, e.g. heart electrode A61N1/06 takes precedence
• CPC Class Codes: A61N 1/375 Constructional arrangements, e.g. casings
• CPC Class Codes: A61N 1/37512 Pacemakers

Abstract

Implantable devices containing extracellular matrix and methods of using the devices are provided.

Claims

1. An implantable medical device comprising:

an implantable pulse generator including a surface, the implantable pulse generator adapted to deliver a pacing therapy and control the delivery of the pacing therapy by executing a cardiac remodeling control algorithm, wherein the surface comprises a preformed delaminated sheet of isolated decellularized extracellular matrix (ECM) populated with isolated donor cells, or a preformed delaminated sheet of isolated decellularized ECM infused with one or more isolated cytokines, wherein the ECM in the preformed delaminated sheet of ECM is xenogeneic or allogeneic and has a three dimensional microstructure of native ECM, wherein the preformed delaminated ECM sheet comprises a plurality of different molecules including collagens present in native ECM, wherein the isolated donor cells are attached to and within the three dimensional microstructure of the preformed delaminated ECM sheet, wherein the preformed ECM sheet is formed as a sheet before the preformed ECM sheet is applied to the surface, and wherein the isolated donor cells are allogeneic or autologous.

2. The implantable medical device of claim 1, wherein the donor cells are stem cells.

3. The implantable medical device of claim 1, wherein the donor cells are genetically modified cells.

4. The implantable medical device of claim 1, wherein the donor cells are autologous cells.

5. The implantable medical device of claim 1, wherein one cytokine is granulocyte-colony stimulating factor (G-CSF), stem cell factor (SCF), hepatocyte growth factor (HGF) or insulin-like growth factor (IGF).

6. The implantable medical device of claim 1, wherein the isolated ECM further comprises a drug.

7. The implantable medical device of claim 6, wherein the drug is an anti-inflammatory, an anti-thrombotic or an anti-arrhythmic.

8. The implantable medical device of claim 1, wherein the ECM sheet is glued to the surface of the implantable pulse generator.

9. The implantable medical device of claim 1, wherein the implantable pulse generator comprises a pacemaker or defibrillator.

10. The implantable medical device of claim 1, comprising a left endocardial lead.

11. The implantable medical device of claim 1, comprising an epicardial lead.

18. The implantable medical device of claim 1, wherein the isolated decellularized ECM is isolated xenogeneic decellularized ECM.

19. The implantable medical device of claim 1, wherein the isolate decellularized ECM is isolated allogeneic decellularized ECM.

20. The implantable medical device of claim 1, wherein the ECM is isolated from small intestine submucosa or urinary bladder submucosa.

22. The implantable medical device of claim 1, wherein the donor cells are bone marrow-derived cells.

23. The implantable medical device of claim 1, wherein the donor cells are mesenchymal cells.

24. The implantable medical device of claim 1 wherein the ECM sheet has a thickness of approximately 50 microns to 80 microns.

25. The implantable medical device of claim 1, wherein the ECM sheet is sutured to the surface of the implantable pulse generator.

26. The implantable medical device of claim 1, wherein the pulse generator comprises multiple sheets of the isolated decellularized xenogeneic or allogeneic ECM applied thereto.

30. The implantable medical device of claim 1, wherein the ECM sheet comprises a rinsed and mechanically delaminated portion of small intestine or urinary bladder.

31. The implantable medical device of claim 1, further comprising a lead having a surface, wherein the surface has applied thereto a preformed delaminated sheet of isolated decellularized xenogeneic or allogeneic ECM, which preformed delaminated ECM sheet comprises a plurality of different molecules including collagens present in native ECM.

32. The implantable medical device of claim 1 wherein the surface of the pulse generator comprises an electrode having the preformed delaminated sheet of isolated decellularized xenogeneic or allogeneic ECM populated with isolated allogeneic or autologous donor cells, or a preformed delaminated sheet of isolated decellularized xenogeneic or allogeneic ECM infused with one or more isolated cytokines.

12. A method to prepare a coated implantable pulse generator comprising:

(i) providing an implantable pulse generator having a surface and adapted to deliver a pacing therapy and control the delivery of the pacing therapy by executing a cardiac remodeling control algorithm;

(ii) affixing ex vivo to the surface a preformed delaminated sheet of isolated decellularized xenogeneic or allogeneic ECM; and

(iii) contacting the preformed delaminated sheet ex vivo with isolated donor cells or with one or more isolated cytokines,

wherein the preformed sheet has a three dimensional microstructure of native ECM, which microstructure comprises a plurality of different molecules including collagens present in native ECM, wherein the isolated donor cells are attached to and within the preformed ECM sheet, wherein the preformed ECM sheet is formed as a sheet before the preformed ECM sheet is applied to the surface, and wherein the isolated donor cells are allogeneic or autologous.

13. The method of claim 12, wherein the isolated decellularized xenogeneic or allogeneic ECM is in an amount effective to inhibit inflammation, inhibit bacterial infection, modulate fibrosis and/or inhibit thrombosis.

14. The method of claim 12, wherein the donor cells are stem cells.

15. The method of claim 12, wherein one cytokine is G-CSF, SCF, HGF or IGF.

16. The method of claim 12, wherein the isolated decellularized xenogeneic or allogeneic ECM further comprises a drug.

17. The method of claim 12, wherein the isolated decellularized xenogeneic or allogeneic ECM is xenogeneic.

21. The method of claim 12, wherein the ECM is isolated from small intestine submucosa or urinary bladder submucosa.

27. The method of claim 12, wherein the ECM sheet has a thickness of approximately 50 microns to 80 microns.

28. The method of claim 12, wherein affixing comprises suturing the ECM sheet to the pulse generator.

29. The method of claim 12, wherein affixing comprises applying multiple sheets of the isolated decellularized xenogeneic or allogeneic ECM to the pulse generator.