Controlling the Multiscale Structure of Nanofibrous Fibrinogen Scaffolds for Wound Healing

Nano Lett. 2019 Sep 11;19(9):6554-6563. doi: 10.1021/acs.nanolett.9b02798. Epub 2019 Aug 23.

Abstract

As a key player in blood coagulation and tissue repair, fibrinogen has gained increasing attention to develop nanofibrous biomaterial scaffolds for wound healing. Current techniques to prepare protein nanofibers, like electrospinning or extrusion, are known to induce lasting changes in the protein conformation. Often, such secondary changes are associated with amyloid transitions, which can evoke unwanted disease mechanisms. Starting from our recently introduced technique to self-assemble fibrinogen scaffolds in physiological salt buffers, we here investigated the morphology and secondary structure of our novel fibrinogen nanofibers. Aiming at optimum self-assembly conditions for wound healing scaffolds, we studied the influence of fibrinogen concentration and pH on the protein conformation. Using circular dichroism and Fourier-transform infrared spectroscopy, we observed partial transitions from α-helical structures to β-strands upon fiber formation. Interestingly, a staining with thioflavin T revealed that this conformational transition was not associated with any amyloid formation. Toward novel scaffolds for wound healing, which are stable in aqueous environment, we also introduced cross-linking of fibrinogen scaffolds in formaldehyde vapor. This treatment allowed us to maintain the nanofibrous morphology while the conformation of fibrinogen nanofibers was redeveloped toward a more native state after rehydration. Altogether, self-assembled fibrinogen scaffolds are excellent candidates for novel wound healing systems since their multiscale structures can be well controlled without inducing any pathogenic amyloid transitions.

Keywords: FTIR; Self-assembly; fibers; fibrinogen; secondary structure; solid-state CD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fibrinogen / chemistry*
  • Fibrinogen / pharmacology
  • Humans
  • Nanofibers / chemistry*
  • Nanofibers / therapeutic use
  • Wound Healing*

Substances

  • Fibrinogen