Investigation of platelet activation and calcium store release by a topical hemostatic xerogel dressing for improved blood clotting

Abstract

AbstractAdequate topical hemostatic dressings are required as first‐line approach for reduction of uncontrolled hemorrhage, a leading cause of mortalities. Platelets play a major role during blood clotting to prevent hemorrhage during injuries. Here, we demonstrate the mechanisms activated through protease activating receptor 1 (PAR1), a platelet membrane protein in response to a porous composite xerogel dressing incorporating SiNPs (size 122 ± 10 nm) and calcium (2.5 mM), characterized by scanning electron microscopy–energy dispersive x‐ray spectroscopy and Fourier transform infrared spectroscopy. The composite displayed 13.9‐fold improved blood clotting index in comparison to commercial dressing. The composite displayed increased platelet aggregation due to development of well‐formed pseudopodia as compared to bare xerogel, SFLLRN (a thrombin mimic), adenosine di‐phosphate (a platelet activator), and heparin (a thrombin inhibitor). Further, PAR1 gene was significantly upregulated in model A549 epithelial cell line (1.2‐fold) and human platelets (1.4‐fold). The composite enhanced calcium release and its extrusion in A549 cells. Upregulation of PAR1 on the platelet surface and calcium release are crucial for platelet shape change and aggregation. The data indicate that xerogel composite containing SiNPs and calcium enhanced blood clotting through activation of PAR1. Such dressings can provide a potential hemostatic solution to reduce blood loss, disability, and mortality during surgery and trauma care.