Synthetic Platelet Microgels Containing Fibrin Knob B Mimetic Motifs Enhance Clotting Responses
Abstract
Native platelets are crucial players in wound healing. Key to their role is the ability of their surface receptor GPIIb/IIIa to bind fibrin at injury sites, thereby promoting clotting. When platelet activity is impaired as a result of traumatic injury or certain diseases, uncontrolled bleeding can result. To aid clotting and tissue repair in cases of poor platelet activity, synthetic platelet‐like particles capable of promoting clotting and improving wound healing responses have been previously developed in the lab. These are constructed by functionalizing highly deformable hydrogel microparticles (microgels) with fibrin‐binding ligands including a fibrin‐specific whole antibody or a single‐domain variable fragment. To improve the translational potential of these clotting materials, the use of fibrin‐binding peptides as cost‐effective, robust, high‐specificity alternatives to antibodies are explored. Herein, the development and characterization of soft microgels decorated with the peptide AHRPYAAK that mimics fibrin knob “B” and targets fibrin hole “b” are presented. These “fibrin‐affine microgels with clotting yield” (FAMCY) are found to significantly increase clot density in vitro and decrease bleeding in a rodent trauma model in vivo. These results indicate that FAMCYs are capable of recapitulating the platelet‐mimetic properties of previous designs while utilizing a less costly, more translational design.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 18, 2021
- Source ID
- 10.1002/adtp.202100010
Entities
People
- Ashley C Brown
- Emily Mihalko
- Halston Deal
- John Schneible
- Kimberly Nellenbach
- Mario Castaneda
- Mary Harp
- Michael Daniele
- Seema Nandi
- Stefano Menegatti
- Thomas H. Barker
Organizations
- American Heart Association
- National Heart, Lung, and Blood Institute
- National Science Foundation
- North Carolina State University
- United States Department of Defense
- University of North Carolina at Chapel Hill
- University of Virginia