title: Recombinant human fibrinogen that produces thick fibrin fibers with increased wound adhesion and clot density.
abstract: Human fibrinogen is a biomaterial used in surgical tissue sealants, scaffolding for tissue engineering, and wound healing. Here we report on the post-translational structure and functionality of recombinant human FI (rFI) made at commodity levels in the milk of transgenic dairy cows. Relative to plasma-derived fibrinogen (pdFI), rFI predominantly contained a simplified, neutral carbohydrate structure and >4-fold higher levels of the γ'-chain transcriptional variant that has been reported to bind thrombin and Factor XIII. In spite of these differences, rFI and pdFI were kinetically similar with respect to the thrombin-catalyzed formation of protofibrils and Factor XIIIa-mediated formation of cross-linked fibrin polymer. However, electron microscopy showed rFI produced fibrin with much thicker fibers with less branching than pdFI. In vivo studies in a swine liver transection model showed that, relative to pdFI, rFI made a denser, more strongly wound-adherent fibrin clot that more rapidly established hemostasis.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, NE 68588-0643, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Calcaterra
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Van Cott
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Butler
authors.forename: Geun Cheol
authors.initials: GC
authors.lastname: Gil
authors.forename: Marta
authors.initials: M
authors.lastname: Germano
authors.forename: Harrie A
authors.initials: HA
authors.lastname: van Veen
authors.forename: Kay
authors.initials: K
authors.lastname: Nelson
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Forsberg
authors.forename: Mark A
authors.initials: MA
authors.lastname: Carlson
authors.forename: William H
authors.initials: WH
authors.lastname: Velander
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D005337:Fibrin / Q000008:administration & dosage / Q000138:chemical synthesis*; D005340:Fibrinogen / Q000008:administration & dosage / Q000138:chemical synthesis*; D006801:Humans; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry; D013552:Swine; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
chemical_list: D011994:Recombinant Proteins; D005337:Fibrin; D005340:Fibrinogen