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US5770417A Expired / Lapsed US ⏱️ 0.0 years remaining

Three-dimensional fibrous scaffold containing attached cells for producing vascularized tissue in vivo

Assignee: Boston Children's Hospital
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Filing: 1994-02-28
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Granted: 1998-06-23
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Expires: 2014-02-28
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Abstract

Abstract A cell-scaffold composition is prepared in vitro for implanting to produce functional organ tissue in vivo. The scaffold is three-dimensional and is composed of hollow or solid fibers of a biocompatible, synthetic polymer which is biodegradable or non-biodegradable. The fibers of the scaffold may have a branched configuration extending outwardly from a central stem. Fibers of the scaffold are spaced apart such that the maximum distance over which diffusion of nutrients and gases must occur through a mass of cells attached to the fibers is between 200 and 300 microns. The diffusion provides free exchange of nutrients, gases and waste to and from cells proliferating throughout the scaffold in an amount effective to maintain cell viability throughout the scaffold in the absence of vascularization. Cells derived from vascularized organ tissue are attached in vitro to the surface of the fibers uniformly throughout the scaffold in an amount effective to produce functional vascularized organ tissue in vivo, the cells are grown on the scaffold in a nutrient solution in vitro to form the cell-scaffold composition which is implanted in a host at a location having adequate vascularization to allow growth of blood vessels into the cell-scaffold composition. Growth factors, compounds stimulating angiogenesis and immunomodulators may be provided in the cell-scaffold composition and the fibers may have a coating to enhance cell attachment. Combinations of cell-scaffold compositions containing different cell populations may be implanted.

Inventors

  • 👤 Joseph P. Vacanti
  • 👤 Robert S. Langer

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-23 00:40
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/36; A61L27/38; A61L27/3839; A61F; A61F2/00; A61F2/02; A61F2/04; A61F2/06; A61F2/062; A61L27/3804; C; C12; C12N; C12N5/00; C12N5/0068; A61L2430/00; A61L2430/06; A61L2430/28; C12N2501/00; C12N2501/10; C12N2501/18; C12N2533/00; C12N2533/30; C12N2533/40

Claims Analysis

Total Claims: 24
Claim 1
Independent Claim 169 words
A cell-scaffold composition prepared in vitro for growing cells to produce functional vascularized organ tissue in vivo, comprising: a fibrous three-dimensional scaffold composed of fibers of a biocompatible, non-biodegradable, synthetic polymer; and cells derived from a vascularized tissue attached in vitro to the surface of the fibers of the scaffold uniformly throughout the scaffold; wherein the fibers of the scaffold provide sufficient surface area to permit attachment in vitro of an amount of the cells effective to produce the functional vascularized organ tissue in vivo; wherein the fibers of the scaffold are spaced apart such that the maximum distance over which diffusion of nutrients and gases must occur through a mass of cells attached to the fibers is between 200 and 300 microns; and wherein the diffusion provides free exchange of nutrients, gases and waste to and from the cells uniformly attached to the fibers of the scaffold and proliferating throughout the scaffold in an amount effective to maintain cell viability throughout the scaffold in the absence of vascularization.
Claim 2
Dependent Claim 169 words
A cell-scaffold composition prepared in vitro for growing cells to produce functional vascularized organ tissue in vivo, comprising: a fibrous three-dimensional scaffold composed of fibers of a biocompatible, non-biodegradable, synthetic polymer; and cells derived from a vascularized tissue attached in vitro to the surface of the fibers of the scaffold uniformly throughout the scaffold; wherein the fibers of the scaffold provide sufficient surface area to permit attachment in vitro of an amount of the cells effective to produce the functional vascularized organ tissue in vivo; wherein the fibers of the scaffold are spaced apart such that the maximum distance over which diffusion of nutrients and gases must occur through a mass of cells attached to the fibers is between 200 and 300 microns; and wherein the diffusion provides free exchange of nutrients, gases and waste to and from the cells uniformly attached to the fibers of the scaffold and proliferating throughout the scaffold in an amount effective to maintain cell viability throughout the scaffold in the absence of vascularization.
Claim 3
Dependent Claim 27 words
The cell-scaffold composition of claim 1 wherein the scaffold fibers are constructed of a material selected from the group consisting of polymethacrylate, silicon polymers, and combinations thereof.
Claim 4
Dependent Claim 30 words
The cell-scaffold composition of claim 1 further comprising a second material overlaying the polymer forming the fibers, wherein the material enhances adhesion of cells to the surface of the fibers.
Claim 5
Dependent Claim 22 words
The cell-scaffold composition of claim 3 wherein the second material is selected from the group consisting of collagen and basement membrane material.
Claim 6
Dependent Claim 12 words
The cell-scaffold composition of claim 3 wherein the polymer fibers are hollow.
Claim 7
Dependent Claim 11 words
The cell-scaffold composition of claim 3 wherein the fibers are solid.
Claim 8
Dependent Claim 11 words
The cell-scaffold composition of claim 1 further comprising protein growth factors.
Claim 9
Dependent Claim 19 words
The cell-scaffold composition of claim 1 wherein the scaffold comprises separate areas of attachment for cells of different origin.
Claim 10
Dependent Claim 21 words
The scaffold composition of claim 8 wherein the scaffold is configured such that cell growth forms tubular structures within the scaffold.
Claim 11
Dependent Claim 24 words
The cell-scaffold composition of claim 1 comprising separate areas within the scaffold which are constructed to maximize attachment and growth of different cell populations.
Claim 12
Dependent Claim 14 words
The cell-scaffold composition of claim 1 wherein the polymer fibers are overlaid with collagen.
Claim 13
Dependent Claim 23 words
The cell-scaffold composition of claim 1 comprising: normal hepatocytes, wherein the hepatocytes are attached to the surface of the fibers throughout the scaffold.
Claim 14
Dependent Claim 19 words
The cell-scaffold of claim 1 wherein the cells contain inserted DNA encoding a protein the cells are deficient in.
Claim 15
Dependent Claim 10 words
The cell-scaffold composition of claim 1 further comprising angiogenic factors.
Claim 16
Dependent Claim 14 words
The cell-scaffold composition of claim 1 wherein the matrix is a branching fiber network.
Claim 17
Dependent Claim 16 words
The cell-scaffold composition of claim 1 wherein the structure is a porous mass of interwoven fibers.
Claim 18
Dependent Claim 15 words
The cell-scaffold composition of claim 1 wherein the cells secrete molecules secreted by pancreatic cells.
Claim 19
Dependent Claim 13 words
The cell-scaffold composition of claim 1 wherein the cells secrete blood coagulation factors.
Claim 20
Dependent Claim 25 words
The cell-scaffold composition of claim 1 comprising: normal intestinal cells, wherein the intestinal cells are attached to the surface of the fibers throughout the scaffold.
Claim 21
Dependent Claim 27 words
The cell-scaffold composition of claim 1 comprising: normal cells forming bone, wherein the cells forming bone are attached to the surface of the fibers throughout the scaffold.
Claim 22
Dependent Claim 9 words
The cell-scaffold composition of claim 1 further comprising immunomodulators.
Claim 23
Dependent Claim 11 words
The cell-scaffold composition of claim 1 further comprising factors stimulating differentiation.
Claim 24
Dependent Claim 19 words
The cell-scaffold composition of claim 1 further comprising biologically active molecules stimulating lymphatic network, nerve or blood vessel ingrowth.

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 2001-06-22 2001-12-22 2002-06-23 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 2005-06-22 2005-12-22 2006-06-23 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2009-06-22 2009-12-22 2010-06-23 $7700.00 Window Closed / Lapsed

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