Retrievable bioartificial implants having dimensions allowing rapid diffusion of oxygen and rapid biological response to physiological change, processes for their manufacture, and methods for their use

• US 6,165,225 A
• Filed: 08/03/1998
• Issued: 12/26/2000
• Est. Priority Date: 10/13/1995
• Status: Expired due to Term

• Current Assignee: Islet Sheet Medical LLC
• Original Assignee: Islet Sheet Medical LLC
• Inventors: Dorian, Randel, Antanavich, Richard D.
• Primary Examiner(s): Milano, Michael J.
• Application Number:
  US09/128,188
• Time in Patent Office: 876 Days
• Field of Search: 424/422, 424/423, 424/424, 435/1, 435/177, 435/178, 435/179, 435/180, 435/182, 435/240.22, 435/240.241, 435/240.243, 623/1, 623/11, 623/12
• US Class Current: 623/23.72
• 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 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 27/20 Polysaccharides
• CPC Class Codes: A61L 27/36 containing ingredients of undetermined constitution or reaction products thereof , e.g. transplant tissue, natural bone, extracellular matrix isolated natural compounds, e.g. collagen A61L27/24
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C08L 5/04 Alginic acid; Derivatives thereof

Abstract

Bioartificial implants and methods for their manufacture and use are described, particularly bioartificial pancreases. In particular, the implants may be thin sheets which enclose cells, may be completely biocompatible over extended periods of time and may not induce fibrosis. The high-density-cell-containing thin sheets are preferably completely retrievable, and have dimensions allowing maintenance of optimal tissue viability through rapid diffusion of nutrients and oxygen and also allowing rapid changes in the secretion rate of insulin and/or other bioactive agents in response to changing physiology. Implantations of living cells, tissue, drugs, medicines and/or enzymes, contained in the bioartificial implants may be made to treat and/or prevent disease.

Claims

1. A viable, physiologically active and biocompatible cellular or tissue implant having (a) a total volume greater than 10 cubic millimeters, (b) a tissue or cell content of at least 10% by volume, and (c) dimensions permitting sufficient oxygen diffusion to sustain cell or tissue viability when the implant is implanted into a vascularized site in a patient.

2. The implant of claim 1, wherein said total volume is at least 100 cubic millimeters.

3. The implant of claim 1, wherein said total volume is at least 500 cubic millimeters.

4. The implant of claim 1, wherein said tissue or cell content is at least 20% by volume.

5. The implant of claim 2, wherein said tissue or cell content is at least 35% by volume.

6. The implant of claim 1, wherein the implant has a thin sheet configuration.

7. The implant of claim 1, wherein the implant has a thickness of less than 400 μ

m.

8. The implant of claim 1, wherein the implant is retrievable.

9. The implant of claim 1, wherein the implant comprises (a) a core of living tissue and a first gelled alginate, surrounded by (b) one or more layers of a second gelled alginate, which may be the same as or different from said first gelled alginate.

10. The implant of claim 9, wherein said core further comprises one or more trophic factors or nurse cells.

11. The implant of claim 9, wherein said core further comprises a substrate material.

12. The implant of claim 9, where said core further comprises an antioxidant material.

13. The implant of claim 9, wherein said living tissue comprises islets of Langerhans.

14. A method of treating or preventing a disease which can be treated or prevented with an active agent secreted by a cell or tissue, comprising implanting the implant of claim 1 in a patient in need thereof.

15. A method of treating or preventing a disease which can be treated or prevented by catabolism of a disease-causing agent or substance in a cell or tissue, comprising implanting the implant of claim 1 in a patient in need thereof.

16. The method of claim 14, wherein said disease is diabetes.

17. The implant of claim 9, wherein said core further comprises trophic factors and nurse cells.