Modification of the properties of a fibrin matrix with respect to growth and ingrowth of cells

Abstract

A method for modifying the properties of a fibrin matrix relative to growth and ingrowth of cells, wherein for forming the fibrin matrix a fibrinogen is used consisting of a selected fibrinogen variant or a fibrinogen enriched or depleted in a selected fibrinogen variant. In particular, the use of high-molecular weight (HMW) fibrinogen leads to a fibrin having accelerated angiogenesis properties, while the use of low-molecular weight (LMW and/or LMW′) fibrinogen leads to fibrin having decelerated angiogenesis properties. The use of HMW fibrinogen when setting up angiogenesis tests results in that the tests require less time. Fibrin sealants on the basis of HMW fibrinogen can be used for burns, to promote wound healing or to inhibit scar tissue. Fibrin sealants on the basis of LMW or LMW′ fibrinogen are useful to inhibit adhesions and tumor growth, for instance after surgical operations.

1 - 9 . (canceled) 
     
     
         10 . A method for modifying the properties of a fibrin matrix with respect to growth and ingrowth of cells, wherein for forming the fibrin matrix a fibrinogen is used consisting of a selected fibrinogen variant or a fibrinogen enriched or depleted in a selected fibrinogen variant, wherein the fibrin matrix is formed in vitro, the fibrin matrix being formed by converting the fibrinogen by means of a suitable enzyme, such as thrombin, and optionally factor XIIIa and CaCl 2 , and wherein the fibrin matrix is used in an angiogenesis test. 
     
     
         11 - 13 . (canceled) 
     
     
         14 . A pharmaceutical composition, comprising fibrinogen and a pharmaceutically acceptable carrier, wherein the fibrinogen consists of a selected fibrinogen variant or a fibrinogen enriched or depleted in a fibrinogen variant. 
     
     
         15 . A pharmaceutical composition according to  claim 14 , wherein the fibrinogen consists of HMW fibrinogen or of a mixture of fibrinogen variants enriched in HMW fibrinogen or depleted in LMW en/of LMW′ fibrinogen. 
     
     
         16 . A pharmaceutical composition according to  claim 15 , which is suitable for promoting wound healing, inhibiting or preventing cicatrization or treating burns. 
     
     
         17 . A pharmaceutical composition according to  claim 14 , wherein the fibrinogen consists of LMW fibrinogen or of a mixture of fibrinogen variants enriched in LMW fibrinogen or depleted in HMW fibrinogen. 
     
     
         18 . A pharmaceutical composition according to  claim 14 , wherein the fibrinogen consists of LMW′ fibrinogen or of a mixture of fibrinogen variants enriched in LMW′ fibrinogen or depleted in HMW fibrinogen. 
     
     
         19 . A pharmaceutical composition according to  claim 17 , which is suitable for inhibiting or preventing tumor growth or adhesions. 
     
     
         20 . A test kit, comprising components for the formation of a fibrin matrix, including fibrinogen, wherein the fibrinogen consists of a selected fibrinogen variant or a fibrinogen enriched or depleted in a selected fibrinogen variant. 
     
     
         21 . A test kit according to  claim 20 , wherein the fibrinogen consists of HMW fibrinogen or of a mixture of fibrinogen variants enriched in HMW fibrinogen or depleted in LMW and/or LMW′ fibrinogen. 
     
     
         22 . A test kit according to  claim 20 , also comprising an enzyme suitable for forming fibrin from fibrinogen, such as thrombin, and optionally factor XIIIa and/or CaCl 2 . 
     
     
         23 . A test kit according to  claim 20 , also comprising components for effecting angiogenesis. 
     
     
         24 . A test kit according to  claim 23 , comprising as components for effecting angiogenesis one or more angiogenic growth factors, such as fibroblast growth factor-2 (FGF-2) or vascular endothelial growth factor (VEGF), and/or tumor necrosis factor alpha (TNF-α), and/or cells, such as human endothelial cells.