Claims
- 1-29. (cancelled).
- 30. A composition comprising a three-dimensional framework, said framework coated with a naturally secreted extracellular matrix material composed of human proteins.
- 31. The composition according to claim 30, wherein the framework is composed of a biodegradable material.
- 32. The composition according to claim 31, wherein the biodegradable material is cotton, polyglycolic acid, cat gut sutures, cellulose, gelatin, or dextran.
- 33. The composition according to claim 30, wherein the framework is composed of a non-biodegradable material.
- 34. The composition according to claim 33, wherein the nonbiodegradable material is a polyamide, a polyester, a polystyrene, a polypropylene, a polyacrylate, a polyvinyl, a polycarbonate, a polytetrafluorethylene, or a nitrocellulose compound.
- 35. The composition according to claim 30, wherein the three-dimensional framework has pore spaces of about 150 μm to about 220 μm.
- 36. The composition according to claim 30, wherein the extracellular matrix is secreted by human stromal cells.
- 37. The composition according to claim 36, wherein the stromal cells are fibroblasts.
- 38. The composition according to claim 36, wherein the stromal cells are found in loose connective tissue or bone marrow.
- 39. The composition according to claim 38, wherein the stromal cells are endothelial cells, pericytes, macrophages, monocytes, leukocytes, plasma cells, mast cells or adipocytes.
- 40. An injectable formulation for the treatment of a skin or tissue defect, comprising a cell-free, injectable formulation of naturally secreted human extracellular matrix components synthesized by cells in vitro and a pharmaceutically acceptable carrier formulated for in vivo administration by injection via a syringe.
- 41. The injectable formulation according to claim 40, in which the matrix is produced by a method comprising:
(a) providing a living stromal tissue prepared in vitro comprising human stromal cells and connective tissue proteins naturally secreted by the stromal cells attached to and substantially enveloping a framework, said framework composed of a biocompatible, non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells; (b) killing the cells in the living stromal tissue; (c) removing the killed cells and any cellular contents from the framework; (d) collecting the connective tissue proteins naturally secreted by the stromal cells attached to the framework; and (e) processing the collected connective tissue proteins of step (d) with a pharmaceutically acceptable carrier into a formulation that is suitable for in vivo administration by injection via a syringe.
- 42. The injectable formulation according to claim 41, in which the collected connective tissue proteins of step (d) are processed by homogenizing, cross-linking, or suspending the collected connective tissue proteins in a physiological acceptable carrier prior to step (e).
- 43. The injectable formulation according to claim 41 in which the collected connective tissue proteins of step (d) are processed by adjusting ratios of collagen types I-V, respective to each other, prior to step (e).
- 44. The injectable formulation according to claim 41, in which the stromal cells of the living stromal tissue are fibroblasts.
- 45. The injectable formulation according to claim 41 in which the stromal cells of the living stromal tissue are cells found in loose connective tissue or bone marrow.
- 46. The injectable formulation according to claim 45 in which the stromal cells of the living stromal tissue are endothelial cells, pericytes, macrophages, monocytes, leukocytes, plasma cells, mast cells, chondrocytes or adipocytes.
- 47. The injectable formulation according to claim 41, in which the framework is composed of a biodegradable material.
- 48. The injectable formulation according to claim 47, in which the biodegradable material is cotton, polyglycolic acid, cat gut sutures, cellulose, gelatin, or dextran.
- 49. The injectable formulation according to claim 41, in which the framework is composed of a non-biodegradable material.
- 50. The injectable formulation according to claim 49, in which the non-biodegradable material is a polyamide, a polyester, a polystyrene, a polypropylene, a polyacrylate, a polyvinyl, a polycarbonate, a polytetrafluorethylene, or a nitrocellulose compound.
- 51. The injectable formulation according to claim 41, in which the framework is a mesh
- 52. The injectable formulation according to claim 51 in which the mesh has pore spaces of about 150 μm to about 220 μm.
- 53. The injectable formulation according to claim 41, in which the pharmaceutically acceptable carrier contains an anesthetic agent, a lubricating agent, a tissue growth factor or combinations thereof.
- 54. The injectable formulation according to claim 40 produced by a method comprising:
(a) providing a living stromal tissue prepared in vitro comprising human stromal cells and connective tissue proteins naturally secreted by the stromal cells attached to and substantially enveloping a framework, said framework composed of a biocompatible, non-living biodegradable material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells; (b) killing the cells in the living stromal tissue; (c) removing the killed cells and any cellular contents from the framework; and (d) processing the connective tissue proteins naturally secreted by the stromal cells attached to the framework and the biodegradable framework with a pharmaceutically acceptable carrier into a formulation suitable for in vivo administration by injection via a syringe.
- 55. The injectable formulation according to claim 41, in which the stromal cells recombinantly express a gene product.
- 56. The injectable formulation according to claim 55, in which expression of the gene product is under the control of an inducible promoter.
- 57. The injectable formulation according to claim 41, in which steps (b) and (c) are carried out concurrently.
- 58. The injectable formulation according to claim 54, in which steps (b) and (c) are carried out concurrently.
- 59. The injectable formulation according to claim 30 in which the cells are grown in vitro on a three-dimensional framework.
Parent Case Info
[0001] This application is a continuation-in-part application of U.S. patent application Ser. No. 08/470,101 filed Jun. 6, 1995, which is incorporated by reference herein in its entirety.
Continuations (3)
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Number |
Date |
Country |
Parent |
10805774 |
Mar 2004 |
US |
Child |
10851773 |
May 2004 |
US |
Parent |
09948379 |
Sep 2001 |
US |
Child |
10805774 |
Mar 2004 |
US |
Parent |
08660787 |
Jun 1996 |
US |
Child |
09948379 |
Sep 2001 |
US |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
08470101 |
Jun 1995 |
US |
Child |
08660787 |
Jun 1996 |
US |