Method for producing a fibrin-based bioartificial, primarily acellular construct, and the construct itself

Patent metadata

Field	Value
Publication number	US-12168083-B2
Application number	US-202117346872-A
Country	US
Kind code	B2
Filing date	Jun 14, 2021
Priority date	Jul 9, 2015
Publication date	Dec 17, 2024
Grant date	Dec 17, 2024

Abstract

The invention relates to a method for producing a bioartificial and primarily acellular fibrin-based construct, wherein a mixture of cell-free compositions containing fibrinogen and thrombin is applied to a surface and subsequently pressurised. An additional aspect of the invention is directed to such fibrin-based bioartificial acellular constructs obtained according to the invention, with improved biomechanical properties, as well as to the use of same in the field of implantology, cartilage replacement or tissue replacement.

First claim

The invention claimed is:

1. A method for producing a fibrin-based bioartificial and acellular planar construct, comprising:
provision of a fibrinogen-containing and cell-free composition;
provision of a thrombin-containing and cell-free composition;
application of the fibrinogen-containing cell-free and the thrombin-containing cell-free compositions to a mould as an applied layer of a mixture of compositions;
pressurization of the mixture of compositions applied to the mould at least until the fibrin formation is essentially completed; and
removal of the fibrin-based acellular bioartificial planar construct from the mould,

wherein pressure is applied in a planar manner to the compositions applied to the mould,
wherein the pressurization takes place at a relative pressure of at least 1 bar,
wherein the fibrin-based acellular bioartificial construct has at least a portion with a wall thickness of at least 1 mm, and
wherein the mould has through holes.

2. The method according to claim 1 , wherein the pressurization takes place at a relative pressure of at least 5 bar.

3. The method according to claim 1 , wherein the fibrinogen-containing and cell-free composition and the thrombin-containing and cell-free composition, together or separately, are applied multiple times.

4. The method according to claim 1 , wherein the thrombin-containing and cell-free composition is first applied to the mould, followed by a heparin-containing composition, wherein the thrombin-containing and cell-free composition and the heparin-containing composition form an uppermost layer.

5. The method according to claim 1 , wherein the fibrinogen-containing and cell-free composition is a composition in which the fibrinogen is obtained from plasma.

6. The method according to claim 1 , wherein the wall thickness of a least a portion of the fibrin-based acellular bioartificial construct is at least 1.5 mm.

7. The method according to claim 1 , wherein a plurality of layers is applied successively and wherein these layers can contain different proportions of the thrombin-containing composition and the fibrinogen-containing composition and/or wherein at least one fibrin-containing layer is applied and at least one non-fibrin-containing layer is applied.

8. The method according to claim 7 , wherein the at least one non-fibrin containing layer comprises other biological materials or synthetic materials.

9. The method according to claim 1 , wherein the fibrinogen-containing composition is a solution that contains the fibrinogen in a concentration of at most 60 mg/ml.

10. The method according to claim 9 , wherein the solution contains the fibrinogen in a concentration of at most 20 mg/ml.

11. The method of claim 1 wherein the through holes in the mould are sealed with a semipermeable material.

Assignees

• Medizinische Hochschule Hannover
• Univ Hannover Gottfried Wilhelm Leibniz

Inventors

• Aper Thomas
• Wilhelmi Mathias
• Haverich Axel

Classifications

• A61L2420/02

  Methods for coating medical devices · CPC title

• A61L2300/42

  Anti-thrombotic agents, anticoagulants, anti-platelet agents · CPC title

• A61L2300/418

  Agents promoting blood coagulation, blood-clotting agents, embolising agents · CPC title

• A61L2300/254

  Enzymes, proenzymes · CPC title

• A61L2300/252

  Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines · CPC title