Ultrasoft microgels displaying emergent platelet-like behaviours

• Type of Material: Article
• Authors: Ashley C. Brown, Georgia Institute of Technology; Sarah E. Stabenfeldt, Arizona State University; Byungwook Ahn, Georgia Institute of Technology; Riley T. Hannan, Georgia Institute of Technology; Kabir S. Dhada, Georgia Institute of Technology; Emily S. Herman, Georgia Institute of Technology; Victoria Stefanelli, Georgia Institute of Technology; Nina Guzzetta, Emory University; Alexander Alexeev, Georgia Institute of Technology; Wilbur Lam, Emory University; L. Andrew Lyon, Georgia Institute of Technology; Thomas H. Barker, Georgia Institute of Technology
• Language: English
• Date: 2014-12-01
• Publisher: Nature Publishing Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Macmillan Publishers Limited.
• Final Published Version (URL): http://dx.doi.org/10.1038/NMAT4066
• Title of Journal or Parent Work: Nature Materials
• ISSN: 1476-1122
• Volume: 13
• Issue: 12
• Start Page: 1108
• End Page: 1114
• Grant/Funding Information: 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: Technology; ANTIBODY; MACROMOLECULES; Materials Science, Multidisciplinary; DISSIPATIVE PARTICLE DYNAMICS; Physics, Applied; Materials Science; PHAGE DISPLAY; Physics; Chemistry; Physical Sciences; Chemistry, Physical; THROMBUS FORMATION; Physics, Condensed Matter; FIBRIN
• Research Categories: Engineering, Materials Science; Health Sciences, General; Engineering, Biomedical

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.