Ultrasoft microgels displaying emergent, platelet-like, behaviors

Details

• Alternative Title:
  Nat Mater
• Personal Author:
  Brown, Ashley C. ; Stabenfeldt, Sarah E. ; Ahn, Byungwook ; Hannan, Riley T. ; Dhada, Kabir S. ; Herman, Emily S. ; Stefanelli, Victoria ; Guzzetta, Nina ; Alexeev, Alexander ; Lam, Wilbur A. ; Lyon, L. Andrew ; Barker, Thomas H.
• Description:
  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.
• Subjects:
  Biocompatible Materials Blood Coagulation Blood Platelets Endothelium, Vascular Fibrin Gels Hemostatic Techniques Microscopy, Confocal Models, Biological Protein Interaction Domains And Motifs Surface Properties

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• Source:
  Nat Mater. 13(12):1108-1114
• Pubmed ID:
  25194701
• Pubmed Central ID:
  PMC4239187
• Document Type:
  Journal Article
• Funding:
  R01HL121264/HL/NHLBI NIH HHSUnited States/ ; R01 EB011566/EB/NIBIB NIH HHSUnited States/ ; U54 HL11230/HL/NHLBI NIH HHSUnited States/ ; R21EB013743/EB/NIBIB NIH HHSUnited States/ ; R21 EB013743/EB/NIBIB NIH HHSUnited States/ ; R01 HL121264/HL/NHLBI NIH HHSUnited States/ ; R01EB011566/EB/NIBIB NIH HHSUnited States/ ; R21 EB019068/EB/NIBIB NIH HHSUnited States/ ; K08 HL093360/HL/NHLBI NIH HHSUnited States/
• Volume:
  13
• Issue:
  12
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:5fb5515f185c63e7531f85ed47a89734dee1458b08df70eb14c27024b257e824
• Download URL:
  https://stacks.cdc.gov/view/cdc/149747/cdc_149747_DS1.pdf
• File Type:
  [PDF - 855.13 KB ]