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Biomedical researchers headed by a team at the Lampe Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill/North Carolina State University, have developed an injectable microgel to help reduce bleeding in infants who require surgical care. Tests in an animal model showed that the hemostatic microgels, known as B-knob-triggered microgels (BK-TriGs), reduced bleeding by at least 50%.
Research lead Ashley Brown, PhD, who is the Lampe Distinguished Professor of Biomedical Engineering, is co-corresponding author of the team’s published paper in Science Advances, titled “Hemostatic B-knob-triggered microgels (BK-TriGs) to address bleeding in neonates.” In their paper the team concluded “This study highlights the potential of BK-TriGs, designed for neonatal-specific clotting mechanisms, to address the heightened bleeding and thrombosis risks in neonates, who face 4.4 times higher postsurgery mortality … Our findings support BK-TriGs as a promising approach for improving hemostasis in neonates, offering a tailored, effective solution for this vulnerable patient population.”
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, neonatal patients normally receive blood from adult donors to compensate for blood lost during the operation. “Current treatments rely on transfusing adult blood products, which may cause complications resulting from structural and functional differences between neonatal and adult fibrinogen,” the authors wrote. “… these transfusions pose serious safety concerns by increasing morbidity, prolonging intensive care unit stays, and elevating posttransfusion thrombosis risks in neonates.”
Brown noted, “… if you give adult blood to an infant, the difference in adult hemostasis versus infant hemostasis can lead to too much clotting. 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.”
The scientists have now reported on their development of 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. “Functionalized with a fibrin hole b–specific peptide, BK-TriGs enhance clot density and resistance to degradation,” the team noted.
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. “In vitro studies using neonatal platelet-poor plasma (PPP) showed that at an optimal concentration, BK-TriGs increased clot density by more than 100% and improved stability by reducing fibrinolysis,” they wrote in summary. “Under flow conditions BK-TriGs promoted robust clot formation compared to plasma-only controls.” Brown noted, “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.”
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. “This innovative model enabled the evaluation of BK-TriGs in a setting that replicates key aspects of neonatal fibrinogen polymerization and fibrinolytic sensitivity, providing preliminary insights into their potential clinical utility.”
Brown added, “We found that the BK-TriGs outperformed any of the other options we tested at reducing blood loss. Specifically, the BK-TriGs reduced blood loss by 50-60% compared to the control group.”
The authors further stated, “The findings highlight the potential of BK-TriGs as a promising synthetic platelet-mimetic approach for enhancing clot density and stability, particularly in neonatal plasma where traditional blood products may pose risks … A fibrin-targeted approach like BK-TriGs, which enhances clot formation without introducing systemic thrombotic risk, may offer a safer alternative to adult fibrinogen transfusions.”
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,” Brown, acknowledged. “We need to make sure there are no unforeseen risks associated with blood clotting.” The team also commented, “Expanding this research to include different clinical bleeding scenarios will be essential to advancing these materials toward therapeutic applications.”
“This is particularly relevant in neonates, where the most severe bleeding complications often arise in critical sites such as the gastrointestinal tract and the brain,” Brown continued, “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.”