4.8 Article

Ultrasoft microgels displaying emergent platelet-like behaviours

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NATURE MATERIALS
卷 13, 期 12, 页码 1108-1114

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NATURE PUBLISHING GROUP
DOI: 10.1038/NMAT4066

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资金

  1. NIH [HHSN268201000043C, R21EB013743, R01EB011566, R01HL121264, U54 HL11230]
  2. John and Mary Brock Discovery Research Fund
  3. DoD [W81XWH1110306]
  4. American Heart Association Postdoctoral Fellowship
  5. NSF GRF
  6. NSF CAREER Award [DMR-1255288, 1150235]
  7. U.S. Department of Defense (DOD) [W81XWH1110306] Funding Source: U.S. Department of Defense (DOD)
  8. Direct For Mathematical & Physical Scien
  9. Division Of Materials Research [1255288] Funding Source: National Science Foundation

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Efforts to create platelet-like structures for the augmentation of haemostasis have focused solely on recapitulating aspects of platelet adhesion(1); more complex platelet behaviours such as clot contraction(2) 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 affnity 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.

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