Platelets crucially facilitate wound healing but can become depleted in traumatic injury or chronic wounds. Previously, our group developed injectable platelet‐like particles (PLPs) comprised of highly deformable, ultralow crosslinked pNIPAm microgels (ULCs) coupled to fibrin binding antibodies to treat post‐trauma bleeding. PLP fibrin‐binding facilitates homing to sites of injury, promotes clot formation, and, due to high particle deformability, induces clot retraction. Clot retraction augments healing by increasing clot stability, enhancing clot stiffness, and promoting cell migration into the wound bed. Because post‐traumatic healing is often complicated by infection, the objective of these studies was to develop antimicrobial nanosilver microgel composite PLPs to augment hemostasis, fight infection, and promote healing post‐trauma. A key goal was to maintain particle deformability following silver incorporation to preserve PLP‐mediated clot retraction. Clot retraction, antimicrobial activity, hemostasis after trauma, and healing after injury were evaluated via confocal microscopy, colony‐forming unit assays, a murine liver trauma model, and a murine full‐thickness injury model in the absence or presence of infection, respectively. We found that nanosilver incorporation does not affect base PLP performance while bestowing significant antimicrobial activity and enhancing infected wound healing outcomes. Therefore, Ag‐PLPs have great promise for treating hemorrhage and improving healing following trauma.
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.
more » « less- Award ID(s):
- 1847488
- NSF-PAR ID:
- 10453706
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Therapeutics
- Volume:
- 4
- Issue:
- 5
- ISSN:
- 2366-3987
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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