IMPLANTABLE BIOREACTOR FOR DELIVERY OF PARACRINE FACTORS

• US 20120083767A1
• Filed: 10/03/2011
• Published: 04/05/2012
• Est. Priority Date: 10/01/2010
• Status: Abandoned Application

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Gerstenblith, Gary, Hwang, Chao-Wei, Benkoski, Jason, Brinker, Jeffrey, Coles, George, Johnston, Peter, Tomaselli, Gordon, Weiss, Robert G., Schulman, Steven P.
• Application Number:
  US13/251,910
• Publication Number:
  US 20120083767A1
• Time in Patent Office: Days
• US Class Current: 604/890.1
• CPC Class Codes: A61F 2/022 Artificial gland structures using bioreactors hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 2300/30 Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 2430/20 for reconstruction of the heart, e.g. heart valves
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/28 Materials for coating prostheses
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 29/00 Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters shape or structure of catheters A61M25/00
• CPC Class Codes: A61L 29/005 Ingredients of undetermined constitution or reaction products thereof
• CPC Class Codes: A61L 29/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/16 : Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C12N 2533/30 : Synthetic polymers
• CPC Class Codes: C12N 5/0663 : Bone marrow mesenchymal stem cells (BM-MSC)

Abstract

An implantable bioreactor containing a barrier which is designed to allow the release of cell-derived biomolecules, but restricts the entry of immunologic and other cells, or the egress of the cells contained within the bioreactor. Two broad classes of implantable bioreactors are envisioned, encompassing devices for both systemic delivery of the bio-products and local delivery at the target tissue. Bioreactors of both classes can be implanted via surgery, through percutaneous techniques, or other techniques which effect implantation.

Claims

1. An implantable bioreactor comprising a housing comprising cells which can produce paracrine factors;

wherein the housing comprises a barrier that shields the enclosed cells from immunological attack and permits the transfer of paracrine factors out of the housing.

2. The implantable bioreactor of claim 1, wherein the cells are stem cells.

3. The implantable bioreactor of claim 2, wherein the stem cells are selected from the group consisting of embryonic stem cells, mesenchymal stem cells, whole bone marrow stem cells, adipose-derived stem cells, myocardial derived stem cells and endothelial progenitor stem cells.

4. The implantable bioreactor of claim 1, wherein said housing is selected from the group consisting of a pouch, a semi-permeable membrane, a polymer matrix, a matrix gel and a microfabricated cellular enclosure.

5. The implantable bioreactor of claim 1, wherein said housing is composed of cellulosic and/or synthetic materials.

6. The implantable bioreactor of claim 5, wherein said cellulosic material is cellulose acetate.

7. The implantable bioreactor of claim 5, wherein said synthetic material is selected from the group consisting of polysulfone, polyamide, polacrylonitrile, copolymers thereof, polymethylmetacrylate, polytetrafluroethylene and derivatives thereof, silicon carbide and micro-mechanical porous silicon diaphragms.

8. The implantable bioreactor of claim 1, wherein said bioreactor is a pouch-based bioreactor.

9. The implantable bioreactor of claim 8, wherein the pouch-based bioreactor is mounted on a wire, a catheter or as part of another implantable device.

10. The implantable bioreactor of claim 4, wherein the polymer matrix is selected from the group consisting of polyethylene glycol, hyaluronic acid, chitosan, dextran, collagen and self-assembling oligopeptides.

11. The implantable bioreactor of claim 4, wherein the matrix gel is a cross-linked hydrogel.

12. The implantable bioreactor of claim 11, wherein the cross-linked hydrogel is selected from the group consisting of a N-hydroxysuccinimide ester/amine conjugate, an isocyanate/amine conjugate, an epoxy/amine conjugate, an isothiocyanate/amine conjugate, an alcohol/glutamate conjugate, and a thiol/maleimide conjugate.

13. The implantable bioreactor of claim 1, wherein the bioreactor is adhered to a medical device.

14. The implantable bioreactor of claim 4, wherein the housing is a microfabricated cellular enclosure.

15. The implantable bioreactor of claim 14, wherein the microfabricated cellular enclosure comprises a silicon-permeable membrane.

16. The implantable bioreactor of claim 14, wherein the microfabricated cellular enclosure is adhered to a medical device.

17. A method of making an implantable bioreactor comprising combining a housing with cells capable of producing paracrine factors.

18. The method of claim 17, wherein the cells are selected from the group consisting of embryonic stem cells, mesenchymal stem cells, adipose-derived stem cells, whole bone marrow stem cells, myocardial derived stem cells and endothelial progenitor stem cells.

19. The method of claim 17, wherein the housing is selected from the group consisting of a pouch, a semi-permeable membrane, a polymer matrix, a matrix gel and a microfabricated cellular enclosure.

20. The method of claim 17, wherein the implantable bioreactor is adhered to a medical device.

21. A medical device comprising a bioreactor comprising a housing comprising cells which can produce paracrine factors;

wherein the housing comprises a barrier that shields the enclosed cells from immunological attack and permits the transfer of paracrine factors out of the housing.

22. The medical device of claim 21, wherein the medical device is a stent, intra-aortic balloon pump, ventricular assist device, prosthetic valve, prosthetic valve clip, prosthetic valve ring, thrombus filter, pacemaker, defibrillator, pacemaker or defibrillator wire, septal occluder, atrial appendage device, pulmonary artery catheter, venous catheter or arterial catheter.

23. The medical device of claim 22, wherein the bioreactor housing is selected from the group consisting of a pouch, a semi-permeable membrane, a polymer matrix, a matrix gel and a microfabricated cellular enclosure.

24. The medical device of claim 23, wherein the matrix gel is a cross-linked hydrogel.

25. The medical device of claim 23, wherein the medical device is a stent and the bioreactor housing is a matrix gel.

26. The medical device of claim 25 wherein the matrix gel is a cross-linked hydrogel.

27. The medical device of claim 23, wherein the medical device is a stent and the bioreactor housing is a microfabricated cellular enclosure.