Fibrin based glue with functionalized hydrophilic polymer protein binding agent

Abstract

The present invention provides a non-liquid biomaterial that may be used as a surgical sealant, a suture support, a blood flow controller, an adhesion reducing agent, an adhesion preventing agent, a tissue support, a tissue filler, a wound dressing or a combination thereof. The non-liquid biomaterial may comprise a blood derived material such as plasma, platelet poor plasma, platelet rich plasma or a material derived from blood containing tissue aspirate, such as bone marrow aspirate, a protein binding agent and a polymerizing agent. Methods for making and using the non-liquid biomaterial are also provided.

1 . A non-liquid biomaterial comprising:
 a blood product solution comprising blood derived material selected from plasma, platelet rich plasma and platelet poor plasma, the blood derived material having an anticoagulant and a hydrophilic polymer, the hydrophilic polymer having a protein binding functionality of at least two;   a hemostatic agent including thrombin selected from at least one of autologous thrombin, xenogenic thrombin and recombinant thrombin, the thrombin being present in an amount of from about 10 U/ml to about 1000 U/ml with respect to the blood product solution; and   wherein upon mixing the blood product solution and the hemostatic agent the non-liquid biomaterial is formed, and wherein the anticoagulant prevents the blood product solution from forming the non-liquid biomaterial prior to being mixed with the hemostatic agent.   
     
     
         2 . The non-liquid biomaterial of  claim 1 , wherein the plasma, platelet rich plasma or platelet poor plasma is concentrated from about 1-fold to about 8-fold. 
     
     
         3 . The non-liquid biomaterial of  claim 1 , wherein the hydrophilic polymer is poly(ethylene glycol), poly(ethylene oxide), poly(vinyl alcohol), poly(vinylpyrrolidine), poly(ethyloxazoline), poly(ethylene glycol)-co-poly(propylene glycol) block polymers and copolymers or combinations thereof. 
     
     
         4 . The non-liquid biomaterial of  claim 1 , wherein the hydrophilic polymer has a concentration of from about 0.25 mg/ml to about 10 mg/ml with respect to the blood product solution and has a protein binding functionality of from 2 to about 8. 
     
     
         5 . The non-liquid biomaterial of  claim 1 , wherein a functional group of the hydrophilic polymer comprises an ester or an aldehyde. 
     
     
         6 . The non-liquid biomaterial of  claim 5 , wherein the ester is an active ester of N-hydroxy succinimide. 
     
     
         7 . The non-liquid biomaterial of  claim 1 , wherein the hemostatic agent is configured to at least one of convert fibrinogen in the blood derived material to fibrin and to activate platelets. 
     
     
         8 . The non-liquid biomaterial of  claim 1 , wherein at least one of the blood product solution and the hemostatic agent comprises Ca 2+ . 
     
     
         9 . The non-liquid biomaterial of  claim 1 , wherein the non-liquid biomaterial is formed within one minute after mixing the blood product solution and the hemostatic agent. 
     
     
         10 . The non-liquid biomaterial of  claim 1 , wherein the non-liquid biomaterial is a surgical sealant, a suture support, a blood flow controller, an adhesion reducing agent, an adhesion preventing agent, a tissue support, a tissue filler, a tissue or cell scaffold, a wound dressing or a combination thereof. 
     
     
         11 . The non-liquid biomaterial of  claim 1 , wherein the non-liquid biomaterial further comprises one or more of a pharmacological agent, a biological agent and tissue regenerative cells, the tissue regenerative sells being selected from at least one of chondrocytes, osteoprogenitor cells, endothelial cells, endothelial progenitor cells, epithelial cells, cardiomyocytes, dermatocytes and smooth muscle cells. 
     
     
         12 . The non-liquid biomaterial of  claim 1 , further comprising cells derived from tissue aspirate, stem cells, osteoblasts, fibroblasts, erythrocytes, leukocytes, adipocytes or combinations thereof. 
     
     
         13 . The non-liquid biomaterial of  claim 1 , wherein the non-liquid material is integrated with at least a portion of a porous scaffold, the scaffold comprising at least one of calcium, a biocompatible resorbable or semi-resorbable polymer, collagen, processed bone and a biocompatible metal. 
     
     
         14 . A non-liquid biomaterial comprising:
 a plasma solution comprising a plasma product selected from platelet poor plasma and platelet rich plasma and a hydrophilic polymer having a functionality of at least two;   a hemostatic agent; and   wherein the non-liquid biomaterial is formed upon mixing the plasma solution and the hemostatic agent.   
     
     
         15 . The non-liquid biomaterial of  claim 14 , wherein the plasma product is at least one of an autologous plasma product and a concentrated plasma product concentrated from about 1.5-fold to about 4-fold. 
     
     
         16 . The non-liquid biomaterial of  claim 14 , further comprising cells derived from at least one of tissue aspirate, stem cells, osteoblasts, fibroblasts, erythrocytes, leukocytes, adipocytes, chondrocytes, osteoprogenitor cells, endothelial cells, endothelial progenitor cells, epithelial cells, cardiomyocytes, dermatocytes and smooth muscle cells. 
     
     
         17 . The non-liquid biomaterial of  claim 14 , further comprising a pharmacological agent or biological agent. 
     
     
         18 . The non-liquid biomaterial of  claim 14 , wherein the hydrophilic polymer has a concentration of from about 1 mg/ml to about 5 mg/ml with respect to the plasma solution. 
     
     
         19 . The non-liquid biomaterial of  claim 14 , wherein the hydrophilic polymer is poly(ethylene glycol) or poly(ethylene oxide). 
     
     
         20 . The non-liquid biomaterial of  claim 14 , wherein the hemostatic agent is thrombin having a concentration of from about 50 U/ml to about 200 U/ml with respect to the plasma solution.