Miniature Bleeding Model May Help Research into Wound Healing, Blood Disorders

Researchers at Emory University School of Medicine have developed a small-scale model system to study bleeding and clotting of wounds. The miniature model also accurately reproduces the alterations observed in hemophilia A patients.

Their work, “A microengineered vascularized bleeding model that integrates the principal components of hemostasis”, was published in Nature Communications.

Hemostasis is the body’s way of stopping injured blood vessels from bleeding. In case of an injury and consequent bleed, the body slows blood flow and forms a blood clot to prevent severe blood loss.

Besides blood flow control, this process involves three major biological mechanisms, including narrowing (constriction) of blood vessels, activity of cell-like blood particles (platelets) that help in blood clotting, and activity of proteins found in blood (clotting factors) that work with platelets to help the blood clot.

However, “current methods to study blood clotting require isolation of each of these components, which prevents us from seeing the big picture of what’s going with the patient’s blood clotting system,”Wilbur Lam, MD, PhD, said in a press release. Lam is assistant professor in the Department of Pediatrics at Emory University School of Medicine and in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, and lead author of this study.

Scientific progress has enabled the manipulation of fluids in channels with dimensions of tens of micrometers — microfluidics — as a distinct new field. Microfluidics has the potential to influence subject areas from chemical synthesis to biological analysis.

Now, and for the first time, scientists used this technology to create a lab-made bleeding model that biologically mimics what happens in a scenario of a mechanical injury in a small blood vessel.

The team used donated human blood to develop this model system. A layer of human endothelial cells (blood vessels’ lining) were cultured on top of a micro-engineered pneumatic valve that, when opened, created an open wound (around 130 micrometers across) and caused bleeding.

Using fluorescently labeled antibodies, or cellular dyes, scientists tracked the entire hemostatic process via microscopy at single-cell resolution.

Results showed that an anti-platelet drug, Integrilin (eptifibatide),  pescribed to prevent blood clot formation, did not affect bleeding time (about eight minutes in a “healthy situation”), but lowered platelet density within the clot, showing the system responds to drugs.

Concerning bleeding time, similar findings had been reported previously in preclinical and clinical studies. Nonetheless, the system helped scientists gain insight into the effects of a well-established drug, as Inteligrin’s effect on clot make-up was never described previously.

In addition, supplying the microsystem with hemophilia A patients’ blood increased bleeding time and resulted in abnormal blood clot formation.

“The vascularized microfluidic bleeding model presented here recapitulates a true mechanical injury and enables the use of human (and therefore patient) blood samples, while the experiments themselves are relatively inexpensive and simple to conduct,” the team wrote.

Despite the novel insights this system provided, it only physically models the microvasculature and does not reproduce aspects of larger blood vessels.