Tissue patch

Abstract

Tissue patches and associated systems and methods are described. Certain embodiments are related to inventive systems and methods in which tissue patches can be made quickly and robustly without the use of complicated fabrication or sterilization equipment. For example, in some embodiments, tissue patches are made by applying a compressive force to a liquid medium comprising fibrinogen (and/or fibrin) between two surfaces (e.g., within a syringe or other chamber). A filter can be placed within or near the volume in which the compressive force is applied to the liquid medium such that unwanted material (e.g., water, blood cells, and the like) is passed through the filter while desirable components (e.g., fibrin, fibrinogen, and/or other desirable components) are retained by the filter to form the patch. In this way, the concentration of fibrin (and/or fibrinogen) within the liquid medium can be increased, potentially dramatically, as the compressive force is applied to the liquid-containing composition. In addition, in some embodiments, at least a portion of the fibrinogen and/or fibrin can chemically react (e.g., the fibrinogen can polymerize to form fibrin and/or the fibrin can cross-link) during application of the compressive force. Reaction and concentration can lead to the formation of a highly-concentrated, mechanically robust patch that can be handled relatively easily and provide good structural reinforcement at a wet site, such as a bleeding wound.

What is claimed is: 
     
         1 . (canceled) 
     
     
         2 . A method of preparing a solid matrix, comprising:
 applying a compressive force, within a chamber containing a cross-linking agent, to a composition comprising a liquid and fibrin such that:
 at least a portion of the liquid is transported through a filter; 
 at least a portion of the fibrin is retained by the filter; and 
 fibrin retained by the filter is cross-linked by the cross-linking agent to form the solid matrix. 
   
     
     
         3 . The method of  claim 2 , wherein the cross-linking agent comprises calcium. 
     
     
         4 . The method of  claim 2 , wherein the fibrin is cross-linked to such a degree that, after submerging the solid matrix in a 6M aqueous solution of urea at 25° C., the solid matrix retains its structural integrity over a period of at least about 2 hours. 
     
     
         5 . The method of  claim 2 , wherein the fibrin is cross-linked to such a degree that, after submerging the solid matrix in an 8M aqueous solution of urea at 25° C., the solid matrix retains its structural integrity over a period of at least about 2 hours. 
     
     
         6 . The method of  claim 2 , wherein the fibrin is cross-linked to such a degree that the solid matrix has a tensile strength of at least about 175 kPa when measured as a true stress at break. 
     
     
         7 . The method of  claim 2 , wherein the fibrin is cross-linked to such a degree that the solid matrix has a tensile strength of at least about 175 kPa and less than or equal to 650 kPa when measured as a true stress at break. 
     
     
         8 . The method of  claim 2 , wherein at least a portion of the cross-linking occurs prior to the applying of the compressive force. 
     
     
         9 . The method of  claim 2 , wherein at least a portion of the cross-linking occurs during the applying of the compressive force. 
     
     
         10 . The method of  claim 2 , wherein the composition comprises whole blood. 
     
     
         11 . The method of  claim 2 , wherein the composition comprises a plasma component of whole blood. 
     
     
         12 . The method of  claim 2 , wherein the compressive force is applied, at least in part, by moving a wall to reduce the volume of the chamber. 
     
     
         13 . The method of  claim 2 , wherein the composition further comprises fibrinogen. 
     
     
         14 . The method of  claim 2 , wherein at least a portion of the fibrin is formed within the chamber via polymerization of fibrinogen within the composition. 
     
     
         15 . The method of  claim 2 , wherein the filter comprises pores, and at least about 50% of the total volume of the pores in the filter is made up of pores with maximum cross-sectional dimensions of between about 100 micrometers and about 10 millimeters. 
     
     
         16 . The method of  claim 2 , wherein the solid matrix has an aspect ratio of at least about 10:1. 
     
     
         17 . The method of  claim 2 , wherein the solid matrix has a Young's modulus of about 10 GPa or less after sterilization using gamma radiation at an intensity of 30 kGy. 
     
     
         18 . The method of  claim 2 , wherein the solid matrix has at least one cross-sectional dimension of at least about 10 cm. 
     
     
         19 . The method of  claim 2 , wherein the solid matrix has at least one cross-sectional dimension of at least about 50 cm. 
     
     
         20 . A kit, comprising:
 a chamber configured to receive a quantity of a liquid-containing composition comprising fibrin and/or fibrinogen;   a filter configured to separate at least a portion of fibrin and/or fibrinogen within the liquid-containing composition from at least a portion of a liquid component of the liquid-containing composition; and   a curing agent capable of activating the polymerization of fibrinogen to fibrin.   
     
     
         21 . A system for producing a tissue patch, comprising:
 a chamber configured for containing a quantity of a liquid-containing composition comprising fibrin and/or fibrinogen, and containing a curing agent capable of activating the polymerization of fibrinogen to fibrin; and   a filter configured to separate at least a portion of fibrin and/or fibrinogen within the liquid-containing composition from at least a portion of a liquid component of the liquid-containing composition, wherein the filter is contained within the chamber and/or attached to a discharge port of the chamber.