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Author Notes:

Corresponding Authors: Thomas H. Barker, Ph.D. Address: The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, 313 Ferst Drive, Suite 2108, Atlanta, GA 30332-0535 (404) 385-5039 – phone; (404) 894-4243 – fax; thomas.barker@bme.gatech.edu L. Andrew Lyon, Ph.D. Address: Georgia Institute of Technology, School of Chemistry and Biochemistry, 901 Atlantic Dr. NW, Atlanta, GA 30332-0400 (404) 894-4090 – phone; (404) 894-7452 – fax; lyon@gatech.edu.

For author contributions and acknowledgements, see the full article.

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Research Funding:

Funding sources: NIH (HHSN268201000043C, R21EB013743 and R01EB011566), John and Mary Brock Discovery Research Fund, and DoD (W81XWH1110306) to THB; NIH (R21EB013743) and DoD (W81XWH1110306) to LAL; American Heart Association Postdoctoral Fellowship to ACB; NSF GRF to VS; NSF CAREER Award (DMR-1255288) to AA; NIH (R01HL121264, U54 HL11230 and NSF CAREER Award (1150235) to WL.

Keywords:

  • Physical Sciences
  • Technology
  • Chemistry, Physical
  • Materials Science, Multidisciplinary
  • Physics, Applied
  • Physics, Condensed Matter
  • Chemistry
  • Materials Science
  • Physics
  • DISSIPATIVE PARTICLE DYNAMICS
  • THROMBUS FORMATION
  • PHAGE DISPLAY
  • FIBRIN
  • MACROMOLECULES
  • ANTIBODY

Ultrasoft microgels displaying emergent platelet-like behaviours

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Journal Title:

Nature Materials

Volume:

Volume 13, Number 12

Publisher:

, Pages 1108-1114

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2014 Macmillan Publishers Limited.

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