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EP0213908A2 Expired / Lapsed EP ⏱️ 0.0 years remaining

Transplantable artificial tissue and process

Assignee: Hana Biologics Inc
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Filing: 1986-08-22
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Granted: —
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Expires: 2006-08-22
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Abstract

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.

Inventors

  • 👤 Ben J. Walthall
  • 👤 Houston F. Voss
  • 👤 Yvonne E. Mchugh

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-10-23 16:13
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/14; A61K9/16; A61K9/1682; A61K9/1694; A61F; A61F2/00; A61F2/02; A61K35/00; A61K35/12; A61K35/37; A61K35/39; A61K9/1605; A61K9/1629; A61K9/1652; A61K9/1658; A61L; A61L27/00; A61L27/14; A61L27/22; A61L27/50; A61L27/60

Claims Analysis

Total Claims: 23
Claim 1
Independent Claim 82 words
A process for making a transplantable artificial tissue matrix comprising 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 and removing gel polymer from the matrix, and c) recovering an insoluble, porous matrix containing viable cells, wherein the condition and reagents are selected to not significantly impair the viability of the cells.
Claim 2
Dependent Claim 82 words
A process for making a transplantable artificial tissue matrix comprising 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 and removing gel polymer from the matrix, and c) recovering an insoluble, porous matrix containing viable cells, wherein the condition and reagents are selected to not significantly impair the viability of the cells.
Claim 3
Dependent Claim 23 words
A process of claim 1 wherein the matrix polymer precursor is selected from plasma, fibrinogen, casein, fibrin, limulus lysate, milk protein and collagen.
Claim 4
Dependent Claim 26 words
A process of claim 2 wherein the matrix polymer precursor is plasma, and the matrix polymer polymerization is effected by mixing the plasma with Ca+2 ions.
Claim 5
Dependent Claim 23 words
A process of claim 2 wherein the matrix polymer precursor is fibrinogen and the polymerization is effected by mixing the fibrinogen with thrombin.
Claim 6
Dependent Claim 30 words
A process of claim 2 wherein the matrix polymer precursor is casein or milk protein and the polymerization is effected by mixing the matrix polymer precursor with renin or pepsin.
Claim 7
Dependent Claim 24 words
A process of claim 2 wherein the matrix polymer precursor is fibrin and the polymerization is effected by mixing the fibrin with Factor XIIIa.
Claim 8
Dependent Claim 35 words
A process of claim 2 wherein the matrix polymer precursor is collagen and the polymerization is effected by raising the temperature of the collagen solution from 37 to 55°C while maintaining a neutral solution pH.
Claim 9
Dependent Claim 18 words
A process of any one of the preceding claims wherein the reversible gel polymer precursor is a polysaccharide.
Claim 10
Dependent Claim 39 words
A process of claim 8 wherein the reversible gel polymer precursor is an alginate or a polysaccharide gum, and the polymerization of the reversible gel polymer precursor is effected by mixing the reversible gel polymer precursor with Ca+2 ions.
Claim 11
Dependent Claim 50 words
A process of claim 9 wherein the gel polymer in the matrix is dissolved by reducing the concentration of Ca+2 ions in an aqueous solution containing the matrix by mixing the solution with a sequestering agent or cation exchange resin capable of binding Ca+2 ions, to depolymerize the gel polymer.
Claim 12
Dependent Claim 33 words
A process of claim 8 wherein the reversible gel polymer precursor is agarose, and the polymerization is effected by decreasing the temperature of the agarose solution to a level which promotes agarose polymerization.
Claim 13
Dependent Claim 33 words
A process of claim 11 wherein the reversible gel polymer in the matrix is dissolved by elevating the temperature of an aqueous solution containing the matrix to a level which promotes agarose depolymerization.
Claim 14
Dependent Claim 25 words
A process of claim 11 wherein the reversible gel polymer in the matrix is dissolved by mixing an aqueous solution containing the matrix with agarase.
Claim 15
Dependent Claim 27 words
A process of claim 8 wherein the polysaccharide is selected from agarose, carrageenan, agar, alginate, guar gum, gum arabic, pectin, tragacanth gum, xanthan gum and mixtures thereof.
Claim 16
Dependent Claim 142 words
A process for making a transplantable artificial tissue matrix comprising 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, i) wherein the matrix polymer precursor is selected from plasma, fibrinogen, casein, fibrin, limulus lysate, milk protein and collagen and mixtures thereof, and ii) the polysaccharide is selected from agarose, carrageenan, agar, alginate, guar gum, gum arabic, pectin, tragacanth gum, xanthan gum and mixtures thereof, b) dissolving and removinggel polymer from the matrix by exposing the matrix to a solution having characteristics which effect depolymerization of the gel polymer, and c) recovering an insoluble, porous matrix containing viable cells, wherein the conditions and reagents are selected to not significantly impair the viability of the cells.
Claim 17
Dependent Claim 142 words
A process for making a transplantable artificial tissue matrix comprising 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, i) wherein the matrix polymer precursor is selected from plasma, fibrinogen, casein, fibrin, limulus lysate, milk protein and collagen and mixtures thereof, and ii) the polysaccharide is selected from agarose, carrageenan, agar, alginate, guar gum, gum arabic, pectin, tragacanth gum, xanthan gum and mixtures thereof, b) dissolving and removinggel polymer from the matrix by exposing the matrix to a solution having characteristics which effect depolymerization of the gel polymer, and c) recovering an insoluble, porous matrix containing viable cells, wherein the conditions and reagents are selected to not significantly impair the viability of the cells.
Claim 18
Dependent Claim 59 words
A matrix composition comprising viable cells incorporated throughout a porous matrix of nontoxic biocompatible polymer, the matrix having a particle size of from 0.02 to 5 mm and a pore structure and size permitting cell movement within the matrix and movement of host cells into the matrix and diffusion of nutrients and macromolecules into and out of the matrix.
Claim 19
Dependent Claim 59 words
A matrix composition comprising viable cells incorporated throughout a porous matrix of nontoxic biocompatible polymer, the matrix having a particle size of from 0.02 to 5 mm and a pore structure and size permitting cell movement within the matrix and movement of host cells into the matrix and diffusion of nutrients and macromolecules into and out of the matrix.
Claim 20
Dependent Claim 35 words
A matrix composition of claim 16 wherein the matrix is a product of the polymerization of a matrix polymer precursor selected from plasma, fibrinogen, casein, fibrin, limulus lysate, milk protein and collagen and mixtures thereof.
Claim 21
Dependent Claim 17 words
A matrix composition of claim 16 or claim 17 wherein the viable cells are pancreatic islet cells.
Claim 22
Dependent Claim 15 words
A matrix composition produced by the process of any one of claims 1 to 15.
Claim 23
Dependent Claim 14 words
A matrix composition of claim 19 wherein the viable cells are pancreatic islet cells.

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