A new bioabsorbable wound dressing builds on the proven blood-flow-stanching properties of chitosan.
The new work harnesses the combined power of organic nanomaterials-based chemistry and chitosan, a natural product found in crustacean exoskeletons, to help bring emergency medicine one step closer to a viable solution for mitigating blood loss.
Hemorrhage is a leading cause of death in traumatic injuries, ranking fourth in the United States at a total cost of $671 billion in 2013.
The researchers successfully encapsulated highly entangled nanofibers of chitosan within a sugar-based hydrogel that dissolves in as little as seven days, leaving behind a significantly larger available wound-healing surface while eliminating the need for subsequent physical removal.
“Bioabsorbable wound dressings that can be applied and left in the injury site are desirable for a variety of blood loss scenarios—for example, to control bleeding in traumatic injuries and to save lives on both civilian and military fronts,” says first author Eric Leonhardt, a PhD student in chemistry at Texas A&M University.
“The composite materials we’ve developed are malleable and could be easily administered to wound sites. They have also performed significantly better in terms of reducing the amount of blood loss and the time required to achieve hemostasis against commercially available bioabsorbable wound dressing in several animal models.”
CLUMPY CHITOSAN
Mahmoud Elsabahy, assistant director of the Laboratory for Synthetic-Biologic Interactions, recognized that although chitosan is a desirable option in such dressings, it also has a tendency to clump, rendering it difficult to incorporate into a bioabsorbable material.
The team overcame that obstacle by loading chitosan into a nanostructured template scaffold to better disperse it and increase its interaction with blood components, thereby speeding up both absorption and healing.
As a first step in their breakthrough discovery process, the researchers developed hydrogels from cyclodextrins—a type of saccharide with hydrolytically degradable linkages—designed with sites that were capable of ionically interacting with and binding to chitosan molecules.
After freeze-drying the resulting composite material, they exposed it to a solution that removed the template scaffold. They then used scanning electron microscopy to further analyze the chitosan, which they determined had assembled into mats of highly entangled nanofibers measuring about 10-to-20 nanometers in diameter.
“Not only are these fibers considerably smaller than what has been previously reported for chitosan, they also are highly desirable, given that the corresponding increase in surface area is expected to greatly enhance hemostatic effect,” says Elsabahy, director of the Assiut Clinical Center of Nanomedicine at Al-Rajhy Liver Hospital.
“We believe this work will enhance the scope of chitosan as a hemostatic technology through the demonstration of its fabrication and use as a bioabsorbable wound dressing.”
To date, the team has applied their composite wound dressings to liver injuries in rats, rabbits, and pigs, measuring the amount of blood loss, time to hemostasis and mean arterial pressure in each case to gauge effectiveness. They also implanted dressings in the liver and imaged after seven days to evaluate the biodegradation of the composite materials. The researchers could not observe any residues in any of the settings.
WOUND DRESSINGS COULD SAVE LIVES
“Hemorrhage is responsible for more than 35 percent of pre-hospital deaths and more than 40 percent of deaths within the first 24 hours of injury,” Leonhardt says.
“Hemostatic dressings have the potential to reduce morbidity and mortality through the early control of hemorrhage. These dressings can be included in first aid kits and carried by soldiers to save lives in the battlefield, and they can be also utilized to control bleeding in various injury scenarios and surgical procedures in hospitals.
“Absorbable hemostatic dressing can be left in the injury site and eliminate the necessity for carrier removal, which reduces the risk of re-bleeding—in case of carrier removal of non-absorbabledressings—and decreases the duration required for the surgical interventions.”
NEXT STEPS
Karen Wooley, a chemist who led the research team, intends to extend this initial work to the evaluation of the materials in studies that simulate lethal hemorrhage scenarios, followed by clinical trials. In addition, she would like to conduct future fundamental studies to further explore the mechanism of chitosan nanofiber formation within the template scaffolds, with the aim of ultimately achieving control over the assembly to enable tuning and optimization of the resulting morphology of the wound dressings.
The results appear in Nature Communications. Additional researchers are from Assiut University in Egypt and Texas A&M. Support for the work came from the NASA and the Welch Foundation.
Source: Shana Hutchins for Texas A&M University
Original Study DOI: 10.1038/s41467-019-10290-1
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