title: Ultrasoft microgels displaying emergent platelet-like behaviours.
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.
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta GA 30332.|School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: Ashley C
authors.initials: AC
authors.lastname: Brown
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona 85287.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Stabenfeldt
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta GA 30332.|Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Byungwook
authors.initials: B
authors.lastname: Ahn
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta GA 30332.
authors.forename: Riley T
authors.initials: RT
authors.lastname: Hannan
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: Kabir S
authors.initials: KS
authors.lastname: Dhada
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Herman
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta GA 30332.
authors.forename: Victoria
authors.initials: V
authors.lastname: Stefanelli
authors.affiliation: Department of Pediatrics, Division of Pediatric Cardiology, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Guzzetta
authors.affiliation: The George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: Alexander
authors.initials: A
authors.lastname: Alexeev
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta GA 30332.|Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA.|The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: Wilbur A
authors.initials: WA
authors.lastname: Lam
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332.|The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: L Andrew
authors.initials: LA
authors.lastname: Lyon
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta GA 30332.|The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Barker
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D001777:Blood Coagulation / Q000502:physiology*; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D005337:Fibrin / Q000737:chemistry* / Q000378:metabolism; D005782:Gels / Q000737:chemistry*; D006489:Hemostatic Techniques; D018613:Microscopy, Confocal; D008954:Models, Biological; D054730:Protein Interaction Domains and Motifs; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D005782:Gels; D005337:Fibrin