Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix

Mikaël M. Martino, Priscilla S. Briquez, Adrian Ranga, Matthias P. Lutolf, Jeffrey A. Hubbell

Research output: Contribution to journalArticlepeer-review

260 Scopus citations

Abstract

By binding growth factors (GFs), the ECM tightly regulates their activity. We recently reported that the heparin-binding domain II of fibronectin acts as a promiscuous high-affinity GF-binding domain. Here we hypothesized that fibrin, the provisional ECMduring tissue repair, also could be highly promiscuous in its GF-binding capacity. Usingmultiple affinity-based assays, wefound that fibrin(ogen) and its heparin-binding domain bind several GFs from the PDGF/VEGF and FGF families and some GFs from the TGF-β and neurotrophin families. Overall, we identified 15 unique binding interactions. The GF binding ability of fibrinogen caused prolonged retention ofmany of the identified GFs within fibrin. Thus, based on the promiscuous and high-affinity interactions in fibrin, GF binding may be one of fibrin's main physiological functions, and these interactions may potentially play an important and ubiquitous role duringtissue repair. To prove this role in a gain-of-function model, we incorporated the heparin-binding domain of fibrin into a synthetic fibrin-mimetic matrix. In vivo, themultifunctional syntheticmatrix could fullymimic the effect of fibrin in a diabeticmousemodel of impairedwound healing, demonstrating the benefits of generating a hybrid biomaterial consisting of a synthetic polymeric scaffold and recombinant bioactive ECM domains. The reproduction ofGF-ECMinteractions with a fibrinmimetic matrix could be clinically useful, and has the significant benefit of a more straightforward regulatory path associated with chemical synthesis rather than human sourcing.

Original languageEnglish (US)
Pages (from-to)4563-4568
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number12
DOIs
StatePublished - Mar 19 2013

Keywords

  • Angiogenesis
  • Hydrogel
  • Regenerative medicine

ASJC Scopus subject areas

  • General

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