title: A totally recombinant human fibrin sealant.
abstract: BACKGROUND
  Applications of plasma-derived human fibrin sealants (pdhFS) have been limited because of cost, limited supply of pathogen-screened plasma, the need for bioengineering improvements, and regulatory issues associated with federal approval. We describe a totally recombinant human fibrin sealant (rhFS), which may engender an abundant, safe, and cost-effective supply of efficacious fibrin sealant.
  
  
  METHODS
  A first-generation rhFS made from recombinant human fibrinogen (rhFI; produced in the milk of transgenic cows), activated recombinant human factor XIII (rhFXIIIa; produced in yeast), and recombinant human thrombin (rhFIIa; purchased, made in animal cell culture) was formulated using thromboelastography (TEG). The hemostatic efficacy of rhFS versus commercial pdhFS was compared in a nonlethal porcine hepatic wedge excision model.
  
  
  RESULTS
  The maximal clot strength of rhFS measured in vitro by TEG was not statistically different than that of pdhFS. TEG analysis also showed that the rhFS gained strength more quickly as reflected by a steeper α angle; however, the rhFS achieved this clot strength with a 5-fold lower factor I content than the pdhFS. When these fibrin sealants were studied in a porcine hepatic wedge excision model, the hemostatic scores of the rhFS were equivalent or better than that of the pdhFS.
  
  
  CONCLUSIONS
  The bioengineered rhFS had equivalent or better hemostatic efficacy than the pdhFS in a nonlethal hemorrhage model, despite the factor I concentration in the rhFS being about one-fifth that in the pdhFS. Because the rhFS is amenable to large-scale production, the rhFS has the potential to be more economical and abundant than the pdhFS, while having a decreased risk of blood-borne pathogen transmission.
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska; Department of Surgery, VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska. Electronic address: macarlso@unmc.edu.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Carlson
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Calcaterra
authors.affiliation: Department of Vascular Surgery, University of Nebraska Medical Center, Omaha, Nebraska; Department of Surgery, VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Johanning
authors.affiliation: Department of Vascular Surgery, University of Nebraska Medical Center, Omaha, Nebraska; Department of Surgery, VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska.
authors.forename: Iraklis I
authors.initials: II
authors.lastname: Pipinos
authors.affiliation: Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Crystal M
authors.initials: CM
authors.lastname: Cordes
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska.
authors.forename: William H
authors.initials: WH
authors.lastname: Velander
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002417:Cattle; D002478:Cells, Cultured; D004195:Disease Models, Animal; D026122:Factor XIIIa / Q000235:genetics / Q000494:pharmacology; D015718:Fibrin Tissue Adhesive / Q000494:pharmacology*; D005340:Fibrinogen / Q000235:genetics / Q000494:pharmacology; D006470:Hemorrhage / Q000188:drug therapy*; D006487:Hemostasis; D006801:Humans; D022125:Lacerations / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects / Q000293:injuries*; D008297:Male; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology*; D034421:Sus scrofa; D013916:Thrombelastography; D013917:Thrombin / Q000235:genetics / Q000494:pharmacology; D015003:Yeasts
chemical_list: D015718:Fibrin Tissue Adhesive; D011994:Recombinant Proteins; D005340:Fibrinogen; D026122:Factor XIIIa; D013917:Thrombin; C513462:recombinant human thrombin
keywords: Factor XIII; Fibrin sealant; Fibrinogen; Hemorrhage; Hemostasis; Human; Recombinant; Swine; Thrombin