Synthetic Platelet Microgels Containing Fibrin Knob B Mimetic Motifs Enhance Clotting Responses

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.

Automated summary

Native platelets play a crucial role in wound healing by promoting clotting at injury sites through GPIIb/IIIa receptor binding fibrin. Synthetic platelet-like particles have been developed to aid clotting in cases of poor platelet activity, and fibrin-binding peptides are explored as cost-effective alternatives to antibodies. Soft microgels decorated with fibrin-affine peptide are found to enhance clotting yield in vitro and decrease bleeding in vivo.