Transplantable artificial tissue

• US 4,902,295 A
• Filed: 11/06/1987
• Issued: 02/20/1990
• Est. Priority Date: 08/26/1985
• Status: Expired due to Fees

• Current Assignee: Somatix Therapy Corp. (ANI Pharmaceuticals, Inc.)
• Original Assignee: HANA Biologics Incorporated
• Inventors: Voss, Houston F., Walthall, Bennie J., McHugh, Yvonne E.
• Primary Examiner(s): NOT, DEFINED
• Application Number:
  US07/118,280
• Time in Patent Office: 837 Days
• Field of Search: 435/178, 435/180, 435/182, 424/94.21, 424/95, 623/11, 623/66, 623/12
• US Class Current: 623/23.72
• CPC Class Codes: A61K 35/39 Pancreas; Islets of Langerhans Langerhans cells of epidermis A61K35/36
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/1658 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61L 27/22 Polypeptides or derivatives thereof , e.g. degradation products
• CPC Class Codes: A61L 27/60 Materials for use in artificial skin

Abstract

A transplantable artificial tissue matrix structure containing viable cells which is suitable for insertion into the body is made by polymerizing precursors in an aqueous solution to form a shape retaining solid matrix comprising viable cells, matrix polymer and reversible gel polymer. The solution contains a matrix polymer precursor, a reversible gel polymer precursor, and viable cells. The reversible gel polymer is dissolved and removed to yield an insoluble, porous matrix containing viable cells. The conditions and reagents are selected to maintain the viability of the cells. The invention is particularly suitable for artificial transplant matrix tissue containing pancreatic islet cells.

Claims

1. A matrix composition comprising viable cells incorporated throughout a porous matrix of non-toxic biocompatible polymer substantially free from fibroblasts, said biocompatible polymer consisting essentially of the product of the polymerizations of a matrix polymer precursor and a reversible gel polymer, the matrix having a particle size of from 0.02 to 3 mm;

a pore structure and size permitting cell movement throughout the matrix, movement of host cells into the matrix, diffusion of nutrients and macromolecules into and out of the matrix;

wherein the composition is free from encapsulation in a semi-permeable membrane.

2. The matrix composition of claim 1 wherein the matrix is a product of the polymerization of a matrix polymer precursor selected from the group consisting of plasma, fibrinogen, casein, fibrin, limulus lysate, milk protein and collagen and mixtures thereof.

3. The matrix composition of claim 1 wherein the viable cells are pancreatic islet cells.

4. The matrix composition of claim 1 produced by

(a) polymerizing polymer precursors in an aqueous solution containing a matrix polymer precursor, a reversible gel polymer precursor, and viable cells to form a shape retaining solid matrix comprising viable cells, matrix polymer and reversible gel polymer,

(b) dissolving gel polymer and removing gel polymer dissolution products from the matrix, and

(c) recovering an insoluble, porous, unencapsulated matrix containing viable cells,

wherein the conditions and reagents are selected to not significantly impair the viability of the cells.

5. The matrix composition of claim 4 wherein the viable cells are pancreatic islet cells.

6. The matrix composition of claim 1 produced by

(a) polymerizing polymers precursors in an aqueous solution containing a matrix polymer precursor, a reversible gel polymer precursor, and viable cells to form a shape retaining solid matrix comprising viable cells, matrix polymer and reversible gel polymer,

(i) wherein the matrix polymer precursor is selected from the group consisting of plasma, fibrinogen, casein, fibrin, limulus lysate, milk protein, collagen, and mixtures thereof, and

(ii) the reversible gel polymer precursor is a member selected from the group consisting of agarose, carrageenan, agar, alginate, guar gum, gum arabic, pectin, tragacanth gum, xanthan gum, and mixtures thereof,

(b) dissolving gel polymer and removing gel polymer dissolution products from the matrix, and

(c) recovering an insoluble, porous, unencapsulated matrix containing viable cells,

wherein the conditions and reagents are selected to not significantly impair the viability of the cells.

7. The matrix composition of claim 1 wherein the aqueous solution from which the matrix composition is formed contained fibronectin and laminin.