Tissue scaffold having aligned fibrils, apparatus and method for producing the same, and artificial tissue and methods of use thereof

• US 20080147199A1
• Filed: 02/25/2008
• Published: 06/19/2008
• Est. Priority Date: 06/04/2003
• Status: Abandoned Application

• Current Assignee: University of South Carolina
• Original Assignee: University of South Carolina
• Inventors: Goldsmith, Edie C., Gore, C. Michael, Goodwin, Richard L., Yost, Michael J., Terracio, Louis
• Application Number:
  US12/072,232
• Publication Number:
  US 20080147199A1
• Time in Patent Office: Days
• US Class Current: 623/23.72
• CPC Class Codes: B29C 48/09 Articles with cross-sections having partially or fully enclosed cavities, e.g. pipes or channels
• CPC Class Codes: B29C 48/33 with parts rotatable relative to each other
• CPC Class Codes: C12M 21/08 for producing artificial tissue or for ex-vivo cultivation of tissue prostheses A61F2/00, grafts A61L27/00
• CPC Class Codes: C12M 25/14 Scaffolds; Matrices in general C12N5/0068

Abstract

A tubular tissue scaffold is described which comprises a tube having a wall, wherein the wall includes biopolymer fibrils that are aligned in a helical pattern around the longitudinal axis of the tube where the pitch of the helical pattern changes with the radial position in the tube wall. The scaffold is capable of directing the morphological pattern of attached and growing cells to form a helical pattern around the tube walls. Additionally, an apparatus for producing such a tubular tissue scaffold is disclosed, the apparatus comprising a biopolymer gel dispersion feed pump that is operably connected to a tube-forming device having an exit port, where the tube-forming device is capable of producing a tube from the gel dispersion while providing an angular shear force across the wall of the tube, and a liquid bath located to receive the tubular tissue scaffold from the tube-forming device. A method for producing the tubular tissue scaffolds is also disclosed. Also, artificial tissue comprising living cells attached to a tubular tissue scaffold as described herein is disclosed. Methods for using the artificial tissue are also disclosed.

Claims

1. A method for preconditioning a tubular artificial tissue scaffold comprising seeding a tubular artificial tissue scaffold having aligned biofibrils with living cells and culturing the cells in the presence of media containing at least one growth factor and under conditions where the tubular artificial tissue scaffold is subjected to stretch and pressure pulse of controlled frequency and amplitude.

2. A preconditioned artificial tissue comprising living cells that are attached to a tubular artificial tissue scaffold having aligned biofibrils, wherein the cells have been cultured in the presence of media containing at least one growth factor and under conditions where the tubular artificial tissue scaffold is subjected to stretch and pressure pulse of controlled frequency and amplitude.

3. A method of treatment comprising implanting in the body of a subject artificial tissue comprising living cells attached to a tubular tissue scaffold comprising a tube having a wall, wherein the wall includes biopolymer fibrils that are aligned in a helical pattern around the longitudinal axis of the tube where the pitch of the helical pattern changes with the radial position in the tube wall.

4. The method according to claim 3, wherein the biopolymer is selected from the group consisting of collagen, fibronectin, laminin, elastin, fibrin, proteoglycans, hyaluronan, and combinations thereof.

5. The method according to claim 4, wherein the collagen is selected from the group consisting of type I collagen, type II collagen, type III collagen, type V collagen, type XI collagen, and combinations thereof.

6. The method according to claim 3, wherein the living cells are introduced to the luminal and outer surfaces of the substrate.

7. The method according to claim 3, wherein the living cells align along the helical pattern of the biopolymer fibrils.

8. The method according to claim 3, wherein the living cells are selected from the group consisting of myocyte precursor cells, cardiac myocytes, skeletal myocytes, satellite cells, fibroblasts, cardiac fibroblasts, chondrocytes, osteoblasts, endothelial cells, epithelial cells, embryonic stem cells, hematopoetic stem cells, neuronal cells, mesenchymal stem cells, anchorage-dependent cell precursors, and combinations thereof.

9. The method according to claim 8, wherein the living cells originate from the subject receiving treatment.

10. The method according to claim 3, wherein the living cells are cultured in vitro for a period of time necessary for the cells to degrade the original scaffold biopolymer and regenerate a matrix of secreted extracellular matrix proteins.

11. The method according to claim 3, wherein the living cells establish intercellular and extracellular connections.

12. The method according to claim 11, wherein the living cells are contractile.

13. The method according to claim 12, wherein the contractile cells are cardiac myocytes.

14. The method according to claim 13, wherein the cardiac myocytes contract synchronously along the helical pattern of the biopolymer fibrils to pump fluid through the lumen of the tubular tissue scaffold.

15. The method according to claim 12, wherein the contractile cardiac myocyte-containing artificial tissue is preconditioned by the application of mechanical stress before being implanted in the subject.

16. The method according to claim 3, wherein treatment is for an injury, disease, or disorder selected from the group consisting of congestive heart failure, dilated cardiomyopathy, hypertrophic cardiomyopathy, infiltrative cardiomyopathy, ischemic heart disease, heart attack, heart failure, coronary artery disease, atherosclerosis, hypertension, chronic renal disease, cerebrovascular disease, carotid artery disease, and peripheral vascular disease.

17. The method according to claim 12, wherein the rate of contraction is controlled by a pacing device.

18. The method according to claim 3, wherein the tubular artificial tissue is used to repair or replace a tube-shaped organ.

19. The method according to claim 18, wherein the tube-shaped organ is selected from the group consisting of blood vessels, coronary arteries, renal arteries, ureters, fallopian tubes, and nerve fiber conduits.

20. The method according to claim 3, wherein the tubular tissue scaffold is split longitudinally and opened into a sheet prior to attaching living cells to the tissue scaffold.

21. The method according to claim 20, wherein the sheet is coated with a layer of biopolymer fibrils, wherein the biopolymer fibrils polymerize and are oriented in the direction in which they are applied.

22. The method according to claim 21, wherein the living cells are selected from the group consisting of myocyte precursor cells, cardiac myocytes, skeletal myocytes, satellite cells, fibroblasts, cardiac fibroblasts, chondrocytes, osteoblasts, endothelial cells, epithelial cells, embryonic stem cells, hematopoetic stem cells, neuronal cells, mesenchymal stem cells, anchorage-dependent cell precursors, and combinations thereof.

23. The method according to claim 22, wherein the living cells are selected from the group consisting of myocyte precursor cells, cardiac myocytes, skeletal myocytes, satellite cells, fibroblasts, and combinations thereof.

24. The method according to claim 22, wherein the living cells originate from the subject receiving treatment.

25. The method according to claim 20, wherein treatment is for hernia, heart attack, congenital heart defects, skin burns, organ damage, and muscle damage.

26. A method of identifying the effects of a pharmaceutical composition on cell function comprising administering said pharmaceutical composition in vitro to artificial tissue comprising living cells attached to a tubular tissue scaffold comprising a tube having a wall, wherein the wall includes biopolymer fibrils that are aligned in a helical pattern around the longitudinal axis of the tube where the pitch of the helical pattern changes with the radial position in the tube wall.

27. The method according to claim 26, wherein the living cells are contractile cardiac myocytes.

28. The method according to claim 27, further comprising determining the effects of the pharmaceutical composition on the living cells.

29. The method according to claim 26, wherein the tubular artificial tissue has been split longitudinally and opened into a sheet.