Photo Credit: Günter Valda
Scientific Frontline: Extended "At a Glance" Summary: Hemostatic B-Knob Triggered Microgels (BK-TriGs)
The Core Concept: B-knob triggered microgels (BK-TriGs) are injectable, engineered hydrogel particles designed to safely reduce bleeding in infants undergoing surgery. By mimicking the mechanical properties of natural platelets and utilizing specialized amino acid sequences, these microgels facilitate efficient blood clotting tailored specifically to neonatal biology.
Key Distinction/Mechanism: Traditional neonatal surgical care relies on adult blood transfusions, which introduce severe risks of excessive clotting and thrombosis due to fundamental differences between adult and infant hemostasis. BK-TriGs circumvent this complication by utilizing functionalized B peptides to directly target and bridge fibrinogen "hole b" sites within the infant's own plasma. This mechanism increases clot density and stabilizes the fibrin network without the risks associated with adult blood products.
Major Frameworks/Components:
- Microgel Particles (Hydrogels): Water-absorbing polymers engineered to emulate the mechanical properties of natural blood platelets.
- Fibrin and B Peptides: Fibrin is the primary clotting protein in human blood; B peptides are short amino acid sequences that link fibrin molecules together to form clots and play a critical role in neonatal hemostasis.
- Fibrinogen Hole B Sites: Specific biological binding sites targeted by the BK-TriGs to enhance the density, stability, and degradation resistance of the resulting blood clot.
Branch of Science: Biomedical Engineering, Hematology, and Neonatology.
Future Application: BK-TriGs present a scalable, inexpensive alternative to adult blood transfusions for pediatric surgical settings. Following further clinical safety trials, these microgels could be utilized as a standalone injectable hemostatic therapeutic or deployed in conjunction with existing clinical options to drastically minimize surgical blood loss in newborns.
Why It Matters: Neonatal hemostatic immaturity presents critical challenges during surgical procedures, frequently resulting in elevated bleeding and thrombosis risks. By offering a targeted, infant-specific clotting mechanism—demonstrated to reduce blood loss by 50-60% in animal models—BK-TriGs provide a significantly safer, more effective medical intervention to protect vulnerable infants during surgery.
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.”
Funding: 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.
Published in journal: Science Advances
Title: Hemostatic B-knob–triggered microgels (BK-TriGs) to address bleeding in neonates
Authors: Nooshin Zandi, Kimberly Nellenbach, Connor Moore, Julia Storch, Sara R. Abrahams, Matthew J. Flick, Michael Daniele, and Ashley Brown
Source/Credit: North Carolina State University | Matt Shipman
Reference Number: bmed040426_01
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