Chitosan

The porous material, derived from shellfish, optimizes absorption while activating a previously overlooked blood-clotting mechanism, stemming bleeding within minutes. More than 11 million people in the United States take anticoagulation or antiplatelet medications, such as heparin or aspirin, to treat serious conditions like heart attack and stroke. However, these medications also put patients at risk of life-threatening bleeding in the case of injury or during surgery. To improve strategies for reducing blood loss, a team led by investigators from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, developed a porous material that maximizes blood absorption and effectively activates clotting mechanisms, even in patients on anticoagulation or antiplatelet medication. Findings, published in PNAS, show that the bleed-stopping material, or "hemostat," halted bleeding within an average of about five minutes in patients on anticoagulants who underwent cardiac catheterization, a dramatic reduction from traditional compression methods that can take over two hours. "This is a next-generation hemostat that effectively stops bleeding, even in patients who take anticoagulation or antiplatelet medications," said corresponding author Hae Lin Jang, Ph.D., of the Center for Engineered Therapeutics. "We used an exciting, interdisciplinary approach that combines engineering principles, materials science, and understandings of molecular biology to overcome the limitations of existing therapies and address a real clinical need." Over 5 million people globally die each year due to trauma, with over a third of these deaths attributed to uncontrolled bleeding. The researchers used what is known as a "rational engineering" approach to develop a more effective hemostat. They began by simulating blood flow through pores to determine what microscopic design would optimize absorption. They drew inspiration from the architecture of the human lungs, which contain spherical "air sacs" called alveoli that enable a high interaction rate with blood within a short time. Alveoli have a large surface area based on their tortuous porous structure, which led the researchers to engineer a highly interconnected, spherical microporous structure in their material to rapidly absorb blood and accumulate clotting components like platelets in a highly concentrated manner, which facilitate blood clotting. The researchers developed the alveoli-like structure using chitosan, which can be extracted from shellfish. Chitosan is already used in some hemostats: its positively charged surface is known to strongly attract negatively charged platelets and fibrinogen, the two major components of a blood clot. However, contrary to previous assumptions, the researchers discovered that chitosan also directly stimulates blood clotting by activating the TLR-2 clotting pathway, making it a viable mechanism for increasing blood clotting even in patients on anticoagulants. The researchers demonstrated the efficacy of the material in 70 patients who underwent cardiovascular catheterization procedures while on the anticoagulant heparin, with bleeding observed to stop after a mean time of about five minutes for patients on low-dose heparin and in under about nine minutes in patients on heparin doses of up to 12,500 IU. Other advantages of the hemostatic material included its easy application and removal. The chitosan pad eliminated the need for strong and prolonged compression, which can take several hours and requires extensive nursing. Furthermore, gauze removal can cause severe pain to patients and is frequently associated with a reoccurrence of bleeding; in contrast, the more absorptive chitosan hemostat was removed relatively cleanly from wounds and received high patient comfort scores. The researchers are continuing to study the wound-healing process after application of the chitosan hemostat. Moreover, they are investigating other next-generation wound dressings, which may be able to deliver drugs or improve the cleanliness of the wound environment, thus reducing the need for frequent changes. "This hemostat can save valuable time in emergency situations," said first author Vivian K. Lee, Ph.D., of the Center for Engineered Therapeutics. "In emergencies, it can be extremely challenging to screen the prescription information of a patient to provide appropriate anticoagulation reversal therapy to patients on anticoagulants. If a hemostat can bypass a medication's anticoagulating mechanisms, it can be used in a wide range of patients, saving time, and potentially saving lives."

Crustacean and seaweed materials combined in a unique way could provide a sustainable alternative to plastic films. Materials with enhanced structure derived from crustaceans and seaweed could be part of a next-generation answer to the challenge of replacing petroleum-based plastic films, according to new research from North Carolina State University. Combining chitosan, a biopolymer that makes crab shells hard, with agarose, a biopolymer extracted from seaweed that is used to make gels, creates unique biopolymer composite films with enhanced strength. The films are also biodegradable, have antibacterial properties, repel water and are transparent. The findings could eventually lead to sustainable packaging films for food and consumer goods. "How do we find sustainable replacements for synthetic polymers?" asked Orlin Velev, S. Frank and Doris Culberson Distinguished Professor of Chemical and Biomolecular Engineering at NC State and corresponding author of a paper describing the research. "Synthetic polymers make very good films, but we want to replace them with natural biopolymers. The question becomes how do we adjust the joint structure of these natural polymers -- in our case, agarose and chitosan -- so we can have all the desirable properties of synthetic polymers inside a sustainable, biodegradable film?" It may not be enough to simply mix chitosan and agarose together. Velev says previous efforts to produce such mixtures reported improvements in properties, but when dried created gritty films that may lack the right strength. Instead, Velev and his collaborators took a different approach, reinforcing the agarose films with fibrillated colloidal scale material -- called soft dendritic colloids -- made from chitosan. The strong chitosan micro- and nanoscale fibrils are hierarchically branched to provide strength and stability to the agarose film where they are embedded. "It is challenging to modify natural polymers chemically, but we can alter their morphology and use them as composites," said Yosra Kotb, an NC State Ph.D. graduate and first author of the paper. "We use chitosan dendritic particles to reinforce the agarose matrix because of the compatibility of both materials leading to good mechanical properties; chitosan particles also have an opposite charge to agarose. When mixed, these charges are neutralized so the resulting materials also become more resistant to water." The biopolymer composites are about four times stronger than agarose films alone, the research shows, and also resist E.coli, a commonly studied bacterium. The paper also showed that a sheet made from biopolymer composite films greatly degraded after a month underground, while, for comparison, a common plastic sandwich baggie remained completely intact after the same period underground. "Interestingly, our composite is initially strongly antibacterial," Velev said, "but because it is made from natural materials, after some time bacteria will still colonize it -- so after a month underground it will biodegrade readily." Velev added that his lab will continue working to make improvements in the structure of the biopolymer composite films with the goal of eventually matching the properties of synthetic polymer ones. "If you package food, you want the package to be impermeable to oxygen and water," he said. "But natural materials are permeable, so we will continue to work to make our films more impermeable to water and oxygen." Increasing the scalability of the material production process is also one of the future goals. "How do you make the polymer substitute film in a continuous process that is rapid enough to make it in large enough amounts -- like papermaking?" Velev said. The findings appear in Cell Reports Physical Science. NC State has filed a patent application on the new biopolymer composite films and the process for creating them. The research has been supported by the National Science Foundation under grant CMMI-2233399, and partially by EFMA-2029327, CMMI-1825476 and CMMI-2134664.