Year: 2024
Type: article
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.
Source: Science Translational Medicine
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Science Foundation, U.S. Department of Defense, U.S. Department of Veterans Affairs, American Heart Association, North Carolina State University, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, Division of Materials Research, Congressionally Directed Medical Research Programs
Awards: Development of Platelet-Like Particles for Augmentation of Hemostasis in Congenital Heart Defect Patients at High Risk for Bleeding during Cardiac Surgery, G2800195642, DEVELOPMENT OF PLATELET-LIKE PARTICLES FOR AUGMENTATION OF HEMOSTASIS IN CONGENITAL HEART DEFECT PATIENTS AT HIGH RISK FOR BLEEDING DURING CARDIAC SU, G2866282304, G4119534169, G4245701555, Targeted treatment of thrombotic occlusions using a dual-delivery microgel therapeutic, Platelet-like particles for augmenting hemostasis, G5850682332, CAREER: Dynamic Microgels that Mimic Platelet Behavior to Promote Healing, Comparative Medicine and Translational Research Training Program, NC State Molecular Biotechnology Training Program (MBTP), Fibrin-Based Nanoparticles as a Novel Sealant for Vascular Anastomosis, Anti-microbial platelet-like-particles to treat internal bleeding and augment subsequent healing
OpenAlex ID: W4394674610