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

Patent metadata

Field	Value
Publication number	US-11065366-B2
Application number	US-201615740247-A
Country	US
Kind code	B2
Filing date	Jul 7, 2016
Priority date	Jul 9, 2015
Publication date	Jul 20, 2021
Grant date	Jul 20, 2021

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. Method for producing a fibrin-based bioartificial and acellular construct, comprising the following steps:
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 surface;
pressurisation of the mixture of compositions applied to the surface at least until the fibrin formation is essentially completed; and
removal of the fibrin-based acellular bioartificial construct from the surface, wherein application of the compositions takes place in a rotating hollow body and pressurization takes place by rotation of the hollow body and wherein during the rotation, liquid is discharged via holes present in the hollow body and through a semipermeable membrane arranged on an outside surface of the hollow body.

2. Method according to claim 1 , wherein rotation of the hollow body takes place during application of the compositions and the fibrin formation takes place such that an amount of at least 600 g is present on the surface.

3. Method according to claim 1 , wherein the compositions, together or separately, are applied multiple times.

4. Method according to claim 1 , wherein a thrombin-containing composition is first applied, followed by a heparin-containing composition, as compositions forming an uppermost layer.

5. Method according to claim 1 , wherein the fibrinogen-containing composition is a composition in which the fibrinogen is obtained from plasma.

6. Method according to claim 1 , wherein the compositions applied to the surface form a layer having a thickness of at least 0.5 mm.

7. The method according to claim 6 , wherein the layer has a thickness of at least 1 mm.

8. The method according to claim 7 , wherein the layer has a thickness of at least 1.5 mm.

9. 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.

10. The method according to claim 9 , wherein the non-fibrin containing layer comprises other biological materials or synthetic materials.

11. 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.

12. The method according to claim 11 , wherein the solution contains the fibrinogen in a concentration of at most 20 mg/ml.

13. Method for producing a fibrin-based bioartificial and acellular construct, comprising the following steps:
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 surface;
pressurisation of the mixture of compositions applied to the surface at least until the fibrin formation is essentially completed; and
removal of the fibrin-based acellular bioartificial construct from the surface, wherein application of the compositions takes place in a rotating hollow body and pressurization takes place by rotation of the hollow body, wherein during the rotation, liquid is discharged via holes present in the hollow body and through a semipermeable membrane, wherein the hollow body has a collar at either end of the hollow body through which the compositions can be introduced, and wherein the collar is permeable to gases over its entire area.

Assignees

• Medizinische Hochschule Hannover

Inventors

• Aper Thomas
• Wilhelmi Mathias
• Haverich Axel

Classifications

• A61L27/225 Primary

  Fibrin; Fibrinogen · CPC title

• A61L31/046

  Fibrin; Fibrinogen · CPC title

• A61L2430/06

  for cartilage reconstruction, e.g. meniscus · CPC title

• A61L33/0011

  Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title