US2008038352A1PendingUtilityA1

Electroprocessed Collagen and Tissue Engineering

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Assignee: UNIV VIRGINIA COMMONWEALTHPriority: Feb 25, 1999Filed: Aug 21, 2007Published: Feb 14, 2008
Est. expiryFeb 25, 2019(expired)· nominal 20-yr term from priority
Inventors:David SimpsonGary BowlinGary WnekPeter J. StevensMarcus CarrJamil A. MatthewsSaravanamoorthy Rajendran
A61L 15/32Y10T442/60A61K 38/00A61L 27/3839Y10T442/614A61L 27/507A61K 2035/126B29C 67/0007Y10T442/2525Y10T428/298A61P 41/00D01D 5/0038A61L 27/18D01F 4/00B29C 41/006C12N 2533/40C07K 14/78C12N 5/0068C12N 5/0012A61L 31/041A61L 27/3804A61L 27/24D01F 1/10A61L 27/34A61L 27/3895C12N 2533/54A61F 2/08A61L 2430/30A61L 27/26
60
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Claims

Abstract

The invention is directed to formation and use of electroprocessed collagen, including use as an extracellular matrix and, together with cells, its use in forming engineered tissue. The engineered tissue can include the synthetic manufacture of specific organs or tissues which may be implanted into a recipient. The electroprocessed collagen may also be combined with other molecules in order to deliver substances to the site of application or implantation of the electroprocessed collagen. The collagen or collagen/cell suspension is electrodeposited onto a substrate to form tissues and organs.

Claims

exact text as granted — not AI-modified
1 - 17 . (canceled)  
     
     
         18 . An engineered mat-like matrix, comprising electrospun isolated collagen fibers, wherein the electrospun isolated collagen fibers are cross-linked.  
     
     
         19 . The matrix of  claim 18 , wherein the diameter of the collagen fibers range from 10 nanometers to 100 μm.  
     
     
         20 . The matrix of  claim 18 , further comprising cells.  
     
     
         21 . The matrix of  claim 20 , wherein the cells are selected from the group consisting of osteoblasts, myoblasts, neuroblasts, fibroblasts, glioblasts, germ cells, hepatocytes, chondrocytes, keratinocytes, smooth muscle cells, cardiac muscle cells, connective tissue cells, glial cells, epithelial cells, endothelial cells, hormone-secreting cells, cells of the immune system, stem cells and neurons.  
     
     
         22 . The matrix of  claim 18 , wherein the electrospun isolated collagen fibers are selected from the group consisting of collagen type I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, and XIX, and a combination thereof.  
     
     
         23 . The matrix of  claim 18 , further comprising one or more substances.  
     
     
         24 . The matrix of  claim 23 , the one or more substances is selected from the group consisting of elastin fibrin, elastin, laminin, fibronectin, integrin, hyaluronic acid, chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, heparin sulfate, heparin, and keratan sulfate, proteoglycans, and a combination thereof.  
     
     
         25 . The matrix of  claim 18 , wherein the collagen fibers have been crosslinked using a cross-linking agent selected from the group consisting of: 1-ethyl-3(3 dimethyl aminopropyl)carbodiimide hydrochloride, n-hydroxysuccinimide, osmium tetroxide, ammonia, Factor XIIIa, glutaraldehyde, fibronectin, heparin sulfate, lysyl oxidase or UV light.  
     
     
         26 . The matrix of  claim 18 , further comprising DNA.  
     
     
         27 . The matrix of  claim 18 , further comprising addition of a growth factor.  
     
     
         28 . The matrix of  claim 18 , wherein the matrix has a thickness of about 520 μm.  
     
     
         29 . The matrix of  claim 18 , further comprising a drug.  
     
     
         30 . The matrix of  claim 18 , wherein the matrix further comprises pores having an average diameter of 10 μm or less.  
     
     
         31 . The matrix of  claim 18 , wherein the matrix comprises pores having an average area of between about 0.1 square μm and 100 square μm.  
     
     
         32 . The matrix of  claim 18 , wherein the matrix has an elastic modulus of between about 0.5 MPa and about 10 MPa when hydrated.  
     
     
         33 . An engineered mat-like matrix, comprising cross-linked electroaerosolized collagen droplets.  
     
     
         34 . An engineered mat-like matrix of  claim 33 , additionally comprising chemically cross-linked electrospun collagen fibers.  
     
     
         35 . The matrix of  claim 34 , wherein the diameter of the collagen fibers range between about 10 nanometers to 100 μm.  
     
     
         36 . The matrix of  claim 34 , further comprising cells.  
     
     
         37 . The matrix of  claim 36 , wherein the cells are selected from the group consisting of osteoblasts, myoblasts, neuroblasts, fibroblasts, glioblasts, germ cells, hepatocytes, chondrocytes, keratinocytes, smooth muscle cells, cardiac muscle cells, connective tissue cells, glial cells, epithelial cells, endothelial cells, hormone-secreting cells, cells of the immune system, stem cells and neurons.  
     
     
         38 . The matrix of  claim 33 , wherein the collagen is selected from the group consisting of collagen type I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, and XIX, and a combination thereof.  
     
     
         39 . The matrix of  claim 34 , wherein the collagen fibers have been crosslinked using a cross-linking agent selected from the group consisting of: 1-ethyl-3(3 dimethyl aminopropyl)carbodiimide hydrochloride, n-hydroxysuccinimide, osmium tetroxide, ammonia, Factor XIIIa, glutaraldehyde, fibronectin, heparin sulfate, lysyl oxidase or UV light.  
     
     
         40 . The matrix of  claim 33 , further comprising DNA.  
     
     
         41 . The matrix of  claim 33 , further comprising addition of a growth factor.  
     
     
         42 . The matrix of  claim 34 , wherein said matrix has a thickness of about 520 μm.  
     
     
         43 . The matrix of  claim 33 , further comprising a drug.  
     
     
         44 . The matrix of  claim 34 , wherein the matrix further comprises pores having an average diameter of 10 μm or less.  
     
     
         45 . The matrix of  claim 34 , wherein the matrix comprises pores having an average area of between about 0.1 square μm and 100 square μm.  
     
     
         46 . The matrix of  claim 34 , further comprising one or more substances.  
     
     
         47 . The matrix of  claim 46 , the one or more substances is selected from the group consisting of elastin fibrin, elastin, laminin, fibronectin, integrin, hyaluronic acid, chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, heparin sulfate, heparin, and keratan sulfate, proteoglycans, and a combination thereof.  
     
     
         48 . The matrix of  claim 34 , wherein the matrix has an elastic modulus of between about 0.5 MPa and about 10 MPa when hydrated.  
     
     
         49 . An engineered mat-like matrix, comprising electrospun isolated collagen fibers, wherein the electrospun isolated collagen fibers are chemically cross-linked.  
     
     
         50 . The matrix of  claim 49 , wherein the chemical cross-linking is achieved with a chemical cross-linking agent selected from the group consisting of glutaraldehyde, 1-ethyl-3(3 dimethyl aminopropyl)carbodiimide hydrochloride, osmium tetroxide, n-hydroxysuccinimide and ammonia.  
     
     
         51 . The matrix of  claim 49 , wherein the diameter of the collagen fibers range between about 10 nanometers to 100 μm.  
     
     
         52 . The matrix of  claim 49 , further comprising cells.  
     
     
         53 . The matrix of  claim 52 , wherein the cells are selected from the group consisting of osteoblasts, myoblasts, neuroblasts, fibroblasts, glioblasts, germ cells, hepatocytes, chondrocytes, keratinocytes, smooth muscle cells, cardiac muscle cells, connective tissue cells, glial cells, epithelial cells, endothelial cells, hormone-secreting cells, cells of the immune system, stem cells and neurons.  
     
     
         54 . The matrix of  claim 49 , wherein the collagen is selected from the group consisting of: collagen type I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, and XIX, and a combination thereof.  
     
     
         55 . The matrix of  claim 49 , further comprising DNA.  
     
     
         56 . The matrix of  claim 49 , further comprising addition of a growth factor.  
     
     
         57 . The matrix of  claim 49 , wherein said matrix has a thickness of about 520 μm.  
     
     
         58 . The matrix of  claim 49 , further comprising a drug.  
     
     
         59 . The matrix of  claim 49 , wherein the matrix further comprises pores having an average diameter of 10 μm or less.  
     
     
         60 . The matrix of  claim 49 , wherein the matrix comprises pores having an average area of between about 0.1 square μm and 100 square μm.  
     
     
         61 . The matrix of  claim 49 , further comprising one or more substances.  
     
     
         62 . The matrix of  claim 61 , the one or more substances is selected from the group consisting of elastin fibrin, elastin, laminin, fibronectin, integrin, hyaluronic acid, chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, heparin sulfate, heparin, and keratan sulfate, proteoglycans, and a combination thereof.  
     
     
         63 . The matrix of  claim 49 , wherein the matrix has an elastic modulus of between about 0.5 MPa and about 10 MPa when hydrated.  
     
     
         64 . An engineered mat-like matrix, comprising electrospun isolated collagen fibers, wherein the electrospun isolated collagen fibers are cross-linked, and wherein the matrix induces differentiation of cells in vivo or in vitro.  
     
     
         65 . The matrix of  claim 64 , wherein the matrix and the cells are placed in conditions effective to allow interaction between the cross-linked electrospun isolated collagen fibers and the cells.  
     
     
         66 . The matrix of  claim 64 , wherein the diameter of the isolated collagen fibers range between about 10 nanometers to 100 μm.  
     
     
         67 . The matrix of  claim 64 , further comprising cells.  
     
     
         68 . The matrix of  claim 67 , wherein the cells are selected from a group consisting of osteoblasts, myoblasts, neuroblasts, fibroblasts, glioblasts, germ cells, hepatocytes, chondrocytes, keratinocytes, smooth muscle cells, cardiac muscle cells, connective tissue cells, glial cells, epithelial cells, endothelial cells, hormone-secreting cells, cells of the immune system, stem cells and neurons.  
     
     
         69 . The matrix of  claim 64 , wherein the collagen is selected from the group consisting of: collagen type I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, and XIX, and a combination thereof.  
     
     
         70 . The matrix of  claim 64 , wherein the collagen fibers have been crosslinked using a cross-linking agent selected from the group consisting of 1-ethyl-3(3 dimethyl aminopropyl)carbodiimide hydrochloride, n-hydroxysuccinimide, osmium tetroxide, ammonia, Factor XIIIa, glutaraldehyde, fibronectin, heparin sulfate, lysyl oxidase and UV light.  
     
     
         71 . The matrix of  claim 64 , further comprising DNA.  
     
     
         72 . The matrix of  claim 64 , further comprising addition of a growth factor.  
     
     
         73 . The matrix of  claim 64 , wherein said matrix has a thickness of about 520 μm.  
     
     
         74 . The matrix of  claim 64 , further comprising a drug.  
     
     
         75 . The matrix of  claim 64 , wherein the matrix further comprises pores having an average diameter of 10 μm or less.  
     
     
         76 . The matrix of  claim 64 , wherein the matrix comprises pores having an average area of between about 0.1 square μm and 100 square μm.  
     
     
         77 . The matrix of  claim 64 , further comprising one or more substances.  
     
     
         78 . The matrix of  claim 77 , the one or more substances is selected from the group consisting of elastin fibrin, elastin, laminin, fibronectin, integrin, hyaluronic acid, chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, heparin sulfate, heparin, and keratan sulfate, proteoglycans, and a combination thereof.  
     
     
         79 . The matrix of  claim 64 , wherein the matrix has an elastic modulus of between about 0.5 MPa and about 10 MPa when hydrated.

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