(45e) Platelet-like Nanoparticles As Synthetic Hemostats

There is significant clinical interest in synthetic hemostats that can be used in transfusion medicine for management of bleeding complications. To this end, a promising strategy is to design particulate systems with surface functionalities that allow platelet-mimetic biochemical interactions that render hemostatically important cell-cell and cell-matrix interactions. Specifically, platelets render hemostasis by marginating to the injured vascular wall from flowing blood, undergoing adhesion and activation at the injury site by binding to von Willebrand Factor (vWF) and collagen, and subsequently promoting the activation and aggregation of other neighboring platelets at this site. Inspired by these mechanisms, we have fabricated a platelet like nanoparticle (PLN) capable of performing hemostatic functions similar to their natural counterpart. Here, we will discuss the design, synthesis and applications of PLNs, fabricated via layer-by-layer (LbL) assembly, that combine both key biophysical and biochemical parameters of natural platelets on a single particle platform. PLNs were surface-functionalized with a combination of three peptides that promote platelet-mimetic hemostatic properties of vWF-adhesion, collagen-adhesion and active platelet aggregation in tandem. In vitro studies performed under physiologically relevant flow conditions in an artificially created wound environment confirmed the simultaneous adhesive and aggregatory functionalities of PLNs. In vivo studies in a mouse tail transection model demonstrated that PLNs render ~65% reduction in bleeding time and actively localize at the clot site. These results highlight the efficacy of cell-mimetic synthetic capsules in providing a platform for the biomimicry of natural cells and their applications.