We are pleased to announce the use of ChitoLytic chitosan in Dr. Hyunwoo Yuk of the Massachusetts Institute of Technology (MIT) recently published study.
Dr. Yuk’s multidisciplinary research team at MIT and Mayo Clinic developed and studied a Barnacle-inspired Chitosan-based adhesive glue (‘Chitosan Glue’) that stops bleeding and seals wet dynamic tissues in less than 15 seconds independent of blood clotting rate. The bioadhesive can be a coagulation-independent hemostasis tool for wound closure and surgical repair and in wet, dynamic, and contaminated environments.
Uncontrolled bleeding is one of the leading causes of death, accounting for more than two million deaths every year. Existing topical hemostatic and sealing agents, (such as TachoSil® (Takeda), Surgiflo® and Surgicel® (Johnson & Johnson), and CoSeal (Baxter)) accelerate intrinsic blood clotting to allow hemostasis, but do not provide rapid nor sufficient control of bleeding and sealing, especially in tissues and organs that are moving and/or covered with blood or other bodily fluids.
The researchers were inspired by materials from barnacles and chitosan, both related to crustaceans. Barnacles are a marine arthropod that naturally adheres to wet and contaminated surfaces, and chitosan is made from chitin, a natural biopolymer made from the shells of crustaceans. Barnacles’ glue-like capabilities come from their adhesive proteins embedded in a lipid-rich matrix, while chitosan is inherently cationic and confers a positive charge. The researchers were inspired by barnacles’ glue-like capabilities. But rather than using actual barnacle proteins, they repurposed one of their previous chitosan-based discoveries. According to Dr. Yuk, with chitosan as the matrix, they created “a kind of chemical rubric designed as a high-pressure physical barrier”.
The team cryogenized and pulverized biocompatible adhesive sheets made of organic molecules, water, and chitosan (>90 % degree of deacetylation) to form the bioadhesive glue. Regarding the performance of the chitosan used Dr. Yuk reported, “we are excited that ChitoLytic chitosan worked out wonderfully in our applications, it worked even better than the previous chitosans we worked with”.
The Chitosan Glue also consists of a hydrophobic oil that repels blood which sort of cleans the surface of its moisture and contaminants to allow the glue to adhere to tissue. These lipid microparticles covalently interlink with each other and tissue once gentle pressure is applied, priming the glue for its hemostatic and sealing functions. “So basically, they are terraforming the target substrate,” Yuk says. The paste-like Chitosan Glue has the look and feel of a cloudy white toothpaste.
Once applied, the Chitosan Glue stops bleeding and seals tissue in 15 seconds. It then absorbs into surrounding tissue and biodegrades over the course of approximately 12 weeks. It withstood high pressures in vivo, remained resistant and resilient, and compatibly interacted with blood-covered tissues. In a comparative analysis, it outperformed current commercial hemostatic and sealing agents in sealing ex vivo bleeding porcine aortas, and cardiac tissues and bleeding liver cells in live rats and pigs. In larger animal experiments, the Mayo Clinic surgical team also tested the Chitosan Glue’s ability to work while avoiding blood’s natural coagulation mechanism. They examined three test pigs receiving the blood thinner, heparin. Three 1 centimeter wide and 1-centimeter-deep holes were cut in each of the animals’ liver. Then the nine injuries were treated with either the Chitosan Glue or a TachoSil® patch. Dr. Tiffany Sarrafian, Mayo Clinic Surgeon, says she’s never seen anything work like this Glue. “We just put the paste on, and we’re counting” for a few seconds, Sarrafian says, recalling the procedure. “You take your hand off and you’re like, hang on, there’s no blood!’ It was pretty amazing… kind of miraculous, in a way”.
Chitosan Glue in Action
(Caution: images may be disturbing)
Video description: anesthetized rats bleeding from 2-millimeter cuts in their heart chamber muscles received either the Chitosan Glue or one of two commercial alternatives: Surgicel® and CoSeal®. But only the Chitosan Glue overcame the pressures produced by the fluid-covered beating heart to form a strong seal and stop bleeding in seconds.
This development is still in the early stages as further in vivo degradation, toxicology, and tissue healing studies must be conducted before it can be made commercially available. But, this barnacle-inspired chitosan-based bioadhesive Glue offers a promising option for rapid control of severe bleeding even in the presence of coagulopathies, where current commercial hemostatic and sealing agents are known to fail. The researchers anticipate that this may become an effective tool for rapid, coagulation-independent hemostasis, wound closure, and surgical repair that saves time… and lives.
Chitosan Mucoadhesion
Mucoadhesion is a complex phenomenon that involves wetting, adsorption, and interpenetration of polymer chains. Chitosan is considered a mucopolysaccharide. It is obtained by deacetylation of chitin through chemical (e.g., sodium hydroxide) or enzymatic hydrolysis. Chitin is the principal component of crustaceans’ exoskeletons, such as crab and shrimp shells. When the N-acetyl-glucosamine units of chitin are brought to less than 50%; it becomes chitosan. The presence of primary amine at the C-2 position of the chitosan molecule enables it with a strong positive charge, which attracts and binds it to negatively charged molecules such as those on cell membrane. Chitosan’s ability to confer its positively charged primary amine groups under physiological conditions to play a major role in its bioadhesion mechanisms is well established.
Dr. Yuk’s Chitosan Glue has demonstrated to be absorbed into tissue surface via these electrostatic interactions, enabling primary amine groups to bind covalently with carboxylic acid groups from its matrix and the tissue surface. With the permeable nature of in vivo cells and tissues, the Chitosan Glue penetrates the target surface, forming physical entanglements, and chemically anchors its adhesive mechanisms.
The primary chitosan design elements of the Chitosan Glue seem to demonstrate the ability to, (i) wet negatively charged surfaces of tissues and cells and form covalent bonds across the interface while being compatible with and to wet tissues and dynamic movements in vivo, and (ii) be tough and capable of rapidly and effectively distributing its energies when the interface is stressed.
ChitoLytic Team
