Process for producing a vascularized bioartificial tissue and an experimental reactor for carrying out the process

• US 20020081728A1
• Filed: 02/28/2002
• Published: 06/27/2002
• Est. Priority Date: 05/04/2000
• Status: Active Grant

• Current Assignee: Corlife Gbr
• Original Assignee: Corlife Gbr
• Inventors: Haverich, Axel, Kofidis, Theo
• Granted Patent: US 6,960,427 B2
• Time in Patent Office: Days
• US Class Current: 435/395
• 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 23/22 Transparent or translucent parts glassware for laboratory use B01L3/00
• CPC Class Codes: C12M 23/34 Internal compartments or partitions
• CPC Class Codes: C12N 2501/165 Vascular endothelial growth factor [VEGF]
• CPC Class Codes: C12N 2533/90 Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
• CPC Class Codes: C12N 5/0062 General methods for three-dimensional culture
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0657 Cardiomyocytes; Heart cells

Abstract

The invention concerns a process for producing a three-dimensional bioartificial tissue having viable cells in or on a matrix, and by which cells and matrix can be cultivated into a tissue or a precursor of a tissue, a vascularized tissue of biological materials, obtained by this process, and an experimental reactor for scientific purposes and for producing clinically usable tissues and organs.

Claims

1. Process for producing a three-dimensional bioartificial tissue having viable cells in or on a matrix and with which the cells and matrix can be cultivated to a tissue or a precursor of it, comprising the steps of:

inserting at least one vessel supplied from the outside into a tissue at the beginning of its production; and

cultivating said tissue in a manner of hereby vessels propagate into the tissue and a vascularized bioartificial tissue is obtained.

2. Process according to claim 1, wherein vessels are of natural origin selected from the group consisting of humans and animals.

3. Process according to claim 1, wherein the vessel is a synthetic vessel, produced from a biologically compatible polymer.

4. Process according to claim 1, wherein the vessel has lateral openings departing from a longitudinally extended vessel lumen.

5. Process according to claim 1, wherein the vessel is a porous vessel.

6. Process according to claim 5, further comprising the step of preparing the porous vessel punctually with a substance or means initiating a stimulus for vascular propagation.

7. Process according to one of claim 1 further comprising the step of the vessel supplying perfused with blood or a culture medium.

8. Process according to claim 7 wherein substances promoting angiogenesis, particularly growth factors, preferably VEGF (vascular endothelial cell growth factor) are added to the culture medium.

9. Process according to claim 7 wherein the perfusion is accomplished under pressure.

10. Process according to claims 7 wherein the perfusion is accomplished in pulses.

11. Process according to claims 7 wherein the vessel is held between inlet and outlet lines needed for the perfusion so that it is simultaneously positioned and fixed in relation to the tissue being cultivated.

12. Process according to claim 1 wherein cardiomyocytes are used as cells within the three-dimensional tissue to be vascularized, and the tissue obtained is a bioartificial heart tissue.

13. Process according to claim 1 wherein keratinocytes are used as the cells, and the tissue obtained is a bioartificial skin tissue.

14. Vascularized bioartificial tissue, particularly obtained according to claim 1 wherein at least one vessel passes through said tissue from which other vessels are propagated into the tissue.

15. Vascularized bioartificial tissue according to claim 14 wherein in that vessel is selected from the group consisting of a vessel of natural origin from human or animal, and a biocompatible synthetic vessel.

16. Vascularized bioartificial tissue according to claim 14 wherein the tissue is a synthetic heart tissue having cardiomyocytes in a matrix.

17. Vascularized bioartificial tissue according to claim 14 wherein the tissue is a synthetic skin tissue having keratinocytes in a matrix.

18. Experimental reactor for controlled production of a bioartificial tissue, according to claim 1, at least one tissue culture chamber;

at least one inlet and outlet for said tissue culture chamber; and

two opposite, plane, parallel and optically transparent boundary walls for said tissue culture chamber.

19. Experimental reactor according to claim 18, further comprising at least one closable inlet and outlet for each chamber;

and a closing means.

20. Experimental reactor according to claim 18 wherein said tissue culture chamber includes a means for holding a matrix or a vessel.

21. Experimental reactor according to claim 18 wherein said at least one inlet and one outlet hold a vessel.

22. Experimental reactor according to claim 18 wherein at least one of the plane optically transparent boundary walls of the chamber is designed as a lid.

23. Experimental reactor according to claim 23 further comprising additional input points above each chamber in a replaceable lid.

24. Experimental reactor according to claim 18 further comprising electrical connections and/or electrical components are provided in said at least one tissue culture chamber.