Biomedical researchers have designed an injectable microgel to help reduce bleeding in infants who require surgical care. In an animal model, the engineered microgel reduced bleeding by at least 50%.
When adults cut themselves, a multi-step process called hemostasis stops the bleeding from the injured blood vessel. But hemostasis in infants is different from hemostasis in adults. This difference can be problematic if infants require surgery to address significant medical problems. In surgeries, patients normally receive blood from adult donors to compensate for blood lost during the operation.
"But if you give adult blood to an infant, the difference in adult hemostasis versus infant hemostasis can lead to too much clotting," says Ashley Brown, co-corresponding author of a paper on the work. "That can increase the likelihood of thrombosis, where blood clots form in the lungs or elsewhere and put the baby at risk.
"My research team has done a lot of work on surgery-related bleeding in newborns , and we wanted to develop a therapeutic intervention that would reduce bleeding and – by extension – reduce the need for infants to receive adult blood transfusions during surgery," says Brown, who is the Lampe Distinguished Professor of Biomedical Engineering in the Lampe Joint Department of Biomedical Engineering at North Carolina State University and the University of North Carolina at Chapel Hill.
To that end, the researchers developed a material called B-knob triggered microgels (BK-TriGs).
"Fibrin is the main clotting protein in human blood," Brown explains. "There is a short amino acid sequence called a 'B peptide' that links together fibrin molecules to create blood clots where they are needed – and these B peptides play a particularly important role in hemostasis for infants. The BK-TriGs are engineered particles that are studded with those B peptides."
The particles can absorb water and become squishy hydrogels, which mimic the mechanical properties of natural platelets in a way that maximizes the ability of the B peptides to create fibrin networks and stanch bleeding.
The researchers first tested the BK-TriGs by using microfluidic devices that allowed them to conduct in vitro testing to see how the microgels affected clotting in blood plasma from human adults and infants.
"We found that BK-TriGs worked better at improving blood clotting in infant plasma than in adult plasma, which was what we expected to see," says Brown.
To further test the efficacy of the BK-TriGs, the researchers worked with lab mice that were genetically engineered to not make fibrinogen, the precursor to fibrin. This allowed the researchers to first introduce infant fibrinogen into the lab mice so that the mice exhibit a form of hemostasis similar to infants.
"We found that the BK-TriGs outperformed any of the other options we tested at reducing blood loss," says Brown. "Specifically, the BK-TriGs reduced blood loss by 50-60% compared to the control group."
Next steps for the work are to see how BK-TriGs compare to other hemostatic therapeutics that are on the market, either on their own or when used in conjunction with BK-TriGs.
"The results we're reporting here are exciting, but we are still far removed from clinical use," says Brown. "We need to make sure there are no unforeseen risks associated with blood clotting.
"But if we do find BK-TriGs are safe and effective, we're optimistic this could be a cost-effective way to make surgery safer for infants. Manufacturing the BK-TriG particles would be relatively inexpensive – certainly in comparison to blood products."
The paper, "Hemostatic B-Knob Triggered MicroGels (BK-TriGs) to Address Bleeding in Neonates," will be published April 3 in the journal Science Advances. Co-corresponding author of the paper is Michael Daniele, a professor of electrical and computer engineering and biomedical engineering at NC State. First author of the paper is Nooshin Zandi, a postdoctoral researcher in the Lampe Joint Biomedical Engineering Department. Co-authors include Kimberly Nellenbach, a former postdoc in the joint department; Connor Moore, an undergrad in the joint department; Julia Storch, a former undergraduate at NC State; and Sara Abrahams and Matthew Flick with the UNC Blood Research Center.
The work was done with support from the American Heart Association under grant 22TPA969368; the National Science Foundation under grant 2211404; and the Comparative Medicine Institute at NC State.
Brown is a co-founder of Selsym Biotech, Inc., which develops injectable materials designed to stop bleeding.
