Ultrasoft microgels displaying emergent platelet-like behaviours

Ashley C. Brown, Sarah Stabenfeldt, Byungwook Ahn, Riley T. Hannan, Kabir S. Dhada, Emily S. Herman, Victoria Stefanelli, Nina Guzzetta, Alexander Alexeev, Wilbur A. Lam, L. Andrew Lyon, Thomas H. Barker

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

Efforts to create platelet-like structures for the augmentation of haemostasis have focused solely on recapitulating aspects of platelet adhesion; more complex platelet behaviours such as clot contraction are assumed to be inaccessible to synthetic systems. Here, we report the creation of fully synthetic platelet-like particles (PLPs) that augment clotting in vitro under physiological flow conditions and achieve wound-triggered haemostasis and decreased bleeding times in vivo in a traumatic injury model. PLPs were synthesized by combining highly deformable microgel particles with molecular-recognition motifs identified through directed evolution. In vitro and in silico analyses demonstrate that PLPs actively collapse fibrin networks, an emergent behaviour that mimics in vivo clot contraction. Mechanistically, clot collapse is intimately linked to the unique deformability and affinity of PLPs for fibrin fibres, as evidenced by dissipative particle dynamics simulations. Our findings should inform the future design of a broader class of dynamic, biosynthetic composite materials.

Original languageEnglish (US)
Pages (from-to)1108-1114
Number of pages7
JournalNature materials
Volume13
Issue number12
DOIs
StatePublished - Dec 1 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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    Brown, A. C., Stabenfeldt, S., Ahn, B., Hannan, R. T., Dhada, K. S., Herman, E. S., Stefanelli, V., Guzzetta, N., Alexeev, A., Lam, W. A., Lyon, L. A., & Barker, T. H. (2014). Ultrasoft microgels displaying emergent platelet-like behaviours. Nature materials, 13(12), 1108-1114. https://doi.org/10.1038/nmat4066