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 6,372,244 B1
• Filed: 08/25/2000
• Issued: 04/16/2002
• Est. Priority Date: 10/13/1995
• Status: Expired due to Fees

• Current Assignee: Islet Sheet Medical LLC
• Original Assignee: Islet Sheet Medical LLC
• Inventors: Dorian, Randel, Antanavich, Richard D
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Ware, Todd D
• Application Number:
  US09/648,050
• Time in Patent Office: 599 Days
• Field of Search: 424/422, 424/423, 424/424, 424/425, 623/11.11
• US Class Current: 424/423
• 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 process for making a biocompatible implant, comprising the steps of:

combining living tissue or cells to be implanted with a solution of an alginate, the concentration of alginate being sufficient to form a gel in the presence of a crosslinking agent;

contacting the resulting mixture with a solution of crosslinking agent in a concentration sufficient to gel said alginate; and

optionally, forming a coat layer thereon, said coat layer comprising a biocompatable alginate gel.

2. The process of claim 1, wherein said coat layer is formed by contacting said gelled alginate with a liquid alginate containing sufficient chelating agent to liquify at least part of said gel.

3. A method of making a physiologically active and biocompatible cellular implant for implantation into a host body, said method comprising steps of:

(a) forming first and second films of first and second substantially uncross-linked polymer solutions,

(b) forming a sandwich of a cell suspension layer of physiologically active cells in a substantially uncross-linked third polymer solution between said first and second films, and

(c) diffusing cross-linking agent through said first and second films to the cell suspension layer until the first and second polymer solutions of said first and second films, respectively, and said cell suspension layer are cross-linked to form a gelled cellular implant.