Document Type
Article
Publication Date
4-10-2024
Abstract
Uncontrolled bleeding after trauma represents a substantial clinical problem. The current standard of care to treat bleeding after trauma is transfusion of blood products including platelets; however, donated platelets have a short shelf life, are in limited supply, and carry immunogenicity and contamination risks. Consequently, there is a critical need to develop hemostatic platelet alternatives. To this end, we developed synthetic platelet-like particles (PLPs), formulated by functionalizing highly deformable microgel particles composed of ultralow cross-linked poly (N-isopropylacrylamide) with fibrin-binding ligands. The fibrin-binding ligand was designed to target to wound sites, and the cross-linking of fibrin polymers was designed to enhance clot formation. The ultralow cross-linking of the microgels allows the particles to undergo large shape changes that mimic platelet shape change after activation; when coupled to fibrin-binding ligands, this shape change facilitates clot retraction, which in turn can enhance clot stability and contribute to healing. Given these features, we hypothesized that synthetic PLPs could enhance clotting in trauma models and promote healing after clotting. We first assessed PLP activity in vitro and found that PLPs selectively bound fibrin and enhanced clot formation. In murine and porcine models of traumatic injury, PLPs reduced bleeding and facilitated healing of injured tissue in both prophylactic and immediate treatment settings. We determined through biodistribution experiments that PLPs were renally cleared, possibly enabled by ultrasoft particle properties. The performance of synthetic PLPs in the preclinical studies shown here supports future translational investigation of these hemostatic therapeutics in a trauma setting.
Recommended Citation
Kimberly Nellenbach et al., Ultrasoft platelet-like particles stop bleeding in rodent and porcine models of trauma. Sci. Transl. Med. 16, eadi4490 (2024). https://doi.org/10.1126/scitranslmed.adi4490
Copyright
American Association for the Advancement of Science
Included in
Medicinal-Pharmaceutical Chemistry Commons, Other Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons
Comments
This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Science Translational Medicine, volume 16, in 2024 following peer review. This article may not exactly replicate the final published version. The definitive publisher-authenticated version is available online at https://doi.org/10.1126/scitranslmed.adi4490.