Method and device for producing a bioartificial tissue construct

Patent metadata

Field	Value
Publication number	US-10500306-B2
Application number	US-201214367247-A
Country	US
Kind code	B2
Filing date	Dec 20, 2012
Priority date	Dec 23, 2011
Publication date	Dec 10, 2019
Grant date	Dec 10, 2019

Abstract

The tissue construct with viable cells in an extracellular matrix made of fibrin is produced with a special method, in which a matrix material and cells are shaped into a hollow body, in particular a tubular hollow body, by means of a rotational casting method in a hollow mould (1), the method comprising the following steps: (a) introduction of cells of at least one cell type and/or a fibrinogen preparation into the rotating hollow mould (1) with the aid of an applicator (4), said applicator (4) being displaced along the rotational axis during the introduction and step (a) being performed one or more times; (b) continuation of the rotation process until the fibrinogen solidifies into a dimensionally stable matrix, obtaining a primarily solidified tissue construct; (c) removal of the tissue construct from the mould. The construct can also he obtained in a relatively short time from autologous materials.

First claim

The invention claimed is:

1. A method for producing a tissue construct containing viable cells in an extracellular matrix, in which a matrix material and cells are molded by means of a rotary casting method in a hollow mold to give a hollow body, having the following steps:
(a) introducing cells of at least one cell type together with a fibrinogen preparation in a mixture with the aid of an applicator into the rotating hollow mold, wherein the applicator during the introduction is shifted along the axis of rotation and wherein step (a) is carried out once or several times;
(b) continuing rotation of the hollow mold up to solidification of the fibrinogen to form a dimensionally stable matrix, obtaining a primary-solidified tissue construct; and
(c) demolding the tissue construct,
wherein the cells are introduced while a rotation of 100 g to 650 g is carried out.

2. The method as claimed in claim 1 , wherein a plurality of cell types are used simultaneously or sequentially.

3. The method as claimed in claim 2 , whereby successively following application steps according to step (a), fibroblasts, smooth muscle cells and endothelial cells are used, or in one or more application steps according to step (a), only adipose tissue derived stern cells (ASC), or ASC in a mixture with endothelial cells, are used.

4. The method as claimed in claim 1 , wherein the cells are applied in each case in a mixture with the fibrinogen preparation, or simultaneously with the fibrinogen preparation, or in a mixture with a component of the fibrinogen preparation.

5. The method as claimed in claim 1 , wherein the cells and the fibrinogen preparation are introduced by spraying.

6. The method as claimed in claim 1 , wherein, in the hollow mold, before the start of the introduction of cells and fibrinogen, or between a plurality of steps according to step (a), in addition a support frame is used.

7. The method as claimed in claim 1 , wherein a post-treatment of the primary-solidified tissue construct is performed in a bioreactor.

8. The method as claimed in claim 1 , wherein the hollow body is a tubular hollow body.

9. The method according to claim 2 , wherein the cell types are selected from the group of fibroblasts, fibrocytes, muscle cells, endothelial cells (EC) and cells obtained from fat tissue.

10. The method according to claim 9 , wherein the cell types used include muscle cells selected from SMC and SPC.

11. The method as claimed in claim 9 , wherein the cell types used include endothelial cells selected from EPC and EOEC.

12. The method as claimed in claim 9 , wherein the cell types used include cells obtained from fat tissue, wherein said cells obtained from fat tissue are ASC.

13. The method as claimed in claim 4 , wherein the mixture with the cells are applied in each case in a mixture with a fibrinogen cross linking agent.

14. The method as claimed in claim 5 , wherein a layer thickness of the cells and the fibrinogen preparation is ≤1 mm.

15. The method as claimed in claim 5 , wherein a layer thickness of the cells and the fibrinogen preparation is ≤0.5 mm.

16. The method as claimed in claim 6 , wherein the support frame is made of metal or plastic.

17. The method as claimed in claim 6 , wherein the support frame is in the form of a grating.

18. The method as claimed in claim 13 , wherein an inner surface of the hollow mold is coated with polytetrafluoroethylene or includes a detachable polytetrafluoroethylene insert.

19. The method as claimed in claim 1 , wherein the cells are present on a side of a layer of the matrix facing the hollow mold.

20. The method as claimed in claim 1 , further comprising the step of lining the hollow mold with a support grid or support frame prior to performing steps a)-c).

Assignees

• Medizinische Hockschule Hannover
• Medizinische Hochschule Hannover

Inventors

• Aper Thomas
• Wilhelmi Mathias
• Haverich Axel

Classifications

• A61L27/225 Primary

  Fibrin; Fibrinogen · CPC title

• A61L27/3804

  characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells · CPC title

• A61F2/90

  characterised by a net-like or mesh-like structure · CPC title

• B29C41/36

  Feeding the material on to the mould, core or other substrate · CPC title

• B29C41/38

  Moulds, cores or other substrates · CPC title