Artificial platelets to buy trauma victims vital time

Around 1.5 million people die from catastrophic bleeding. A large number of these people have been involved in accidents and - because infusing blood - and specifically blood clotting products - outside of a medical setting is very difficult - they often die before they reach hospital. But now, scientists at North Carolina State University have developed a particle based on an artificial gel decorated like a christmas tree with proteins that give it the right functions to mimic the actions of platelets. These cells fragments in our blood are responsible for kick starting the clotting process; these artificial ones could buy people the time they need to get to urgent care. Ashley Brown is an author on the study...

Ashley - When someone receives platelets, such as after injury or when someone's having surgery or if they have chemotherapy, for example, patients will receive platelets that come from donors. However, platelets are in really short supply because they have to come from adult or human donors. They are always going to be limited in supply. They also have a really short shelf life. So platelets can be stored anywhere from seven days to a couple of weeks, but that's a really short shelf life. And so by making a synthetic platelet, we can get around some of those challenges of normal platelet donations. Additionally, by making a synthetic platelet, we have the ability to get around blood type matching as well as limitations in platelet transport and any potential issues that might come from infection.

Chris - When you say artificial platelets or sort of platelet mimics, are we talking about growing things in dishes that then turn into platelets or starting completely in a different direction, with artificial molecules that just do the same job as a platelet but are not natural tissue.

Ashley - We are not growing cells in a dish. We start out with a biomaterial. So this is what is known as a polymer, which we use to make a hydrogel network. We create a hydrogel that is the size of a nanoparticle and then we decorate it with what's known as an antibody fragment. And this allows us to mimic certain features of natural platelets such as the size, the shape, and the ability of natural platelets to target wound sites.

Chris - When you inject these, do they actually work like platelets, although they've got all those other features which are very attractive, will they actually promote blood coagulation where they should?

Ashley - Absolutely. So as you mentioned, the way that these work is that we inject them into the bloodstream and they are able to go straight to sites of injury. The way that they do that is because they're decorated with an antibody that specifically will interact with certain proteins that are at the wound site. And so what that means is when we inject our particles, they will just circulate in your bloodstream until they come into contact with an area where you have active bleeding and active clot formation. The particles then bind specifically to that area and begin to accumulate. They then work with the body's natural clotting system to enhance and speed up the clotting process.

Chris - Is there not a danger though, if you're putting something which has got this kind of power into the circulation, that it could tip the balance towards developing blood clots where you don't want them, things like your coronary arteries to cause a heart attack or your cerebral vessels and cause a stroke?

Ashley - Because of the way in which we've designed these particles, they go straight to those injury sites. We have, however, looked very extensively to look for that off-target clotting. And in the models that we've used so far, we have not seen any evidence of off-target clotting.

Chris - And when you put them in, if you've got you say a model, things like mice and rats and bigger animals and so on. If you put them into an animal and it has an injury akin to the kind of injury a human would expect to receive, platelets to treat, does it work? Does it actually save lives and prevent haemorrhage in those animals?

Ashley - Absolutely. So we've looked in multiple models and in mice, rats and large animal pore signs or pig models, we've seen that the particles are able to stop bleeding very rapidly and essentially yes, save the life of the animal and enhance healing over a period of several days. The specifics of those bleeding dynamics depend on the injury. The models that we have looked at have been with what's known as a traumatic liver injury. So this is a very major type of injury. In mice, we see that the bleeding stops within minutes in the porcine models, we also see bleeding stop on the order of minutes to tens of minutes, which is significantly better than what we see in saline only treatment groups. I'd also like to point out that we've compared these particles to natural platelets and we see that our particles actually perform even better than normal platelets, if we do a platelet to particle matching.

Chris - Obviously the problem doesn't stop as soon as you stop the blood clotting. You've then got a blood thrombus, a clot at the site of the injury, which naturally would break down over time as the tissue healed. So what happens to your particles in the long term? Do they break down as well?

Ashley - So they don't break down specifically. However, we have seen that they are safely tolerated by the body and any particles that don't go to the wound site are able to come out through the urine. And we've seen that after delivery of the particles. There's no adverse effects that we've observed to this point, even at really high doses of the particles. So they're well tolerated and they're able to be excreted through normal mechanisms.

Chris - What are the implications and the next steps then now you've got this proof of concept? Is the next step to go to clinical trials and try this in people?

Ashley - Absolutely. So currently we're working towards a few additional preclinical toxicology studies, which are required before moving into clinical trials. But then the next step after that would be moving into human clinical trials.