More than two million platelet units are needed in the United States every year. However, natural platelets aren’t always available or portable, have a high risk of contamination, and have a limited shelf life of 5 to 7 days, prompting research over the last several decades into synthetic alternatives.
For that reason, alternatives have been sought through the design of synthetic platelets. These could help save lives by rapidly stabilizing clots to reduce blood loss from traumatic injuries. A new effort has engineered platelet-mimicking procoagulant nanoparticles (PPNs) that help generate a protein mesh that acts as a natural netting to stabilize blood clots and help stop bleeding in an injury-responsive manner. Studies in rodents demonstrated that PPNs provided hemostatic efficacy in animal models of hemorrhage. If proven safe and efficient in clinical trials, the technology would bolster the scientists’ advances in a decade-long effort to develop and optimize what they call synthetic platelet surrogates.
This work is published in Science Translational Medicine, in the paper, “Platelet-mimicking procoagulant nanoparticles augment hemostasis in animal models of bleeding.”
“This is the next step in artificial-platelet technology and it’s truly a critical advance,” said Anirban Sen Gupta, PhD, professor of biomedical engineering at Case Western Reserve. “We have not only been able to form a plug to reduce bleeding from a traumatic injury, but to also help format fibrin, a protein mesh that secures the plug, further stabilizing the clot.”
Sen Gupta and his team have, for the last decade, pioneered research in artificial platelet systems, working on therapeutic technologies with applications in hemostasis (stopping bleeding), thrombolysis (breaking harmful blood clots), and inflammation (numerous blood cell-related pathologies).
They reported that the PPNs helped the clot form faster and stop bleeding in animal models, even when natural platelets were significantly depleted. These promising results suggest that this new nanoparticle design could further enhance the performance of artificial platelet technologies that Sen Gupta and his research team have been working to develop over the last decade.
That team’s first-generation design has proven to mimic two functions of natural platelets, Sen Gupta said. The first is a type of “homing” mechanism that helps platelets sense and then stick to a bleeding injury. The second is the ability of platelets to pile up on each other to form a plug, like stacking sandbags as a barrier that stops a flood—in this case bleeding.
“But to ensure that the sandbags stay put under the force of flood, you would need netting to secure them and then peg the netting down so it wouldn’t move,” Sen Gupta said. “Fibrin is this netting, and we have shown that the PPNs can amplify formation of fibrin even when natural platelets are depleted.”
First, the team tested PPNs in vitro using human plasma. They write that, doing this, they could show “plasmin-triggered exposure of phosphatidylserine and the resultant assembly of coagulation factors on the PPN surface.” In addition, they showed that this phosphatidylserine exposed on the PPN surface “could restore and enhance thrombin generation and fibrin formation in human plasma depleted of platelets.” The PPNs also improved fibrin stability and clot robustness in a fibrinolytic environment.
Using a mouse model of thrombocytopenia, the PPNs reduced blood loss in a similar manner to platelets. And, in rodent models of traumatic hemorrhage, PPNs substantially reduced bleeding and improved survival.
The results suggest that PPNs can be used as a viable platelet surrogate to stop bleeding when natural platelet transfusion products are limited.