Recombinant human fibrinogen that produces thick fibrin fibers with increased wound adhesion and clot density

Jennifer Calcaterra, Kevin Van Cott, Stephen P. Butler, Geun Cheol Gil, Marta Germano, Harrie A. Van Veen, Kay Nelson, Erik J. Forsberg, Mark Alan Carlson, William H Velander

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 predominately 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.

Original languageEnglish (US)
Pages (from-to)169-178
Number of pages10
JournalBiomacromolecules
Volume14
Issue number1
DOIs
StatePublished - Jan 14 2013

Fingerprint

Fibrin
Fibrinogen
Adhesion
Plasmas
Fibers
Thrombin
Dairies
Factor XIIIa
Sealants
Factor XIII
Carbohydrates
Tissue engineering
Biomaterials
Liver
Electron microscopy
Biocompatible Materials
Tissue
Polymers

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Recombinant human fibrinogen that produces thick fibrin fibers with increased wound adhesion and clot density. / Calcaterra, Jennifer; Van Cott, Kevin; Butler, Stephen P.; Gil, Geun Cheol; Germano, Marta; Van Veen, Harrie A.; Nelson, Kay; Forsberg, Erik J.; Carlson, Mark Alan; Velander, William H.

In: Biomacromolecules, Vol. 14, No. 1, 14.01.2013, p. 169-178.

Research output: Contribution to journalArticle

Calcaterra, Jennifer ; Van Cott, Kevin ; Butler, Stephen P. ; Gil, Geun Cheol ; Germano, Marta ; Van Veen, Harrie A. ; Nelson, Kay ; Forsberg, Erik J. ; Carlson, Mark Alan ; Velander, William H. / Recombinant human fibrinogen that produces thick fibrin fibers with increased wound adhesion and clot density. In: Biomacromolecules. 2013 ; Vol. 14, No. 1. pp. 169-178.
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AU - Germano, Marta

AU - Van Veen, Harrie A.

AU - Nelson, Kay

AU - Forsberg, Erik J.

AU - Carlson, Mark Alan

AU - Velander, William H

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