User:Mingchang Zhang/sandbox

Not to be confused with Adhesive.

Further information: Wyss Institute for Biologically Inspired Engineering

Scientists in the Harvard University has published a new study which was focusing on a new hemostatic material--Tough Adhesive in the Science magazine on July 28, 2017. This material was inspired by the slugs and was able to instantly stop wound bleeding in a wet condition as well as performed good compatibility with blood. Although Tough Adhesives was an immature product since it had insufficient clinical experimental data at present, it was undeniable that it made the non-invasive hemostasis technology in surgical operations possible.

Application introduction

The design of Tough Adhesives has potential applications in many fields. Because of the good compatibility and high stretchability with blood contact, it can be used in tissue repairing and adhesion. In addition, Tough Adhesives can also be used in biomedical devices for scientists to fix an executor supporting cardiac function on the myocardial surface. The Tough Adhesives can also be used as a dressing for skin wounds which has been successfully tested on mouse epidermis, it adhered to the epidermis of mice and was easy to adapt to the dynamic movement of the tissue of the living mouse. However, the application of Tough Adhesives in these fields was only the assumption based on experimental data. As an emerging hemostatic material, Tough Adhesives is still in the experimental stage and needs a lot of clinical tests to truly benefit human beings.

The development courses

Arion subfuscus: The Arion subfuscus was secreting a special slime which could tightly adhere itself to the rock surface in wet situation.

The development of surgery is largely limited by the development of postoperative hemostasis techniques. At present, some hemostasis methods such as traditional suturing, electrocoagulation, ultrasonic knife will inevitable bring damage to the body such as physical damages, electrical damages and thermal damages which may cause more serious damages than the surgery itself. Therefore, existence of the problem which was how to overcome the secondary injury caused by hemostasis made the development of surgical technology reach a bottleneck in the recent decades. Scientists have tried using traditional adhesives such as fibrin glue and 502 glue (cyanoacrylate polymer) as hemostatic adhesives, but the results of these traditional adhesives were not satisfactory, especially in the toxicity test and stickiness test in physiological conditions. Then scientists started to look at biological mucus in nature. Although mussels, geckos, snails and other creatures produce mucus, their mucus were not suitable for using in the surgical purposes. Though prolong studies, scientists found out that a slug called Arion subfuscus was suitable in the surgical situation as they would secretes a special slime which could binds it to the rock and soil surface when they were under threats. This mucus is so viscous that it is almost impossible for predators to separate the slugs from the rock surface. In addition, another reason the scientists chose the slug was that the entire adhesion process of slugs took place in a wet environment which is similar to the physiological environment in the human body. The WYSS institute in the Harvard University has developed a new type of bilayer hydrogel based on the mucus from Arion subfuscus. The hydrogel not only extracts and simulates the extended structure of the bilayer alginate-polyacrylamide matrix in slugs, but also incorporates electrostatic interaction, covalent bonding, physical osmosis and other parameters.

Unique advantages

Two most common adhesives used in surgery today are the fibrin glue and the 502 glue. However, both adhesives have serious flaws. Cyanoacrylate polymers which was one of the components in 502 glue would gradually decompose in the wet environment containing water. This not only would reduce its viscosity, but also produce formaldehyde and other toxic substances. This feature largely limits the application range of cyanoacrylate polymer adhesives which can only be applied to the adhesion of the skin surface. On the other hand, fibrin glue is also commonly used to stop bleeding after surgery. The adhesive uses fibrinogen, which is separated from the plasma and thrombin, which converts it into fibrinogen will eventually form a clot. The clots are sticky and harmless, but the adhesive does not form a strong bond and will break down within 48 hours. This characteristic poses a great risk for postoperative recovery. In contrast to the two Adhesives, Tough Adhesives contains the extended structure of the slug bilayer alginate-polyacrylamide substrate, which is highly viscous, and the adhesion process is carried out in a wet environment without degradation in the human body over time. In addition, Tough Adhesives has good histocompatibility, and only mild inflammatory reaction in animal organ experiments. Moreover, the Adhesives are easy to operate, and after more clinical trials in the future, it is likely to make a breakthrough in non-invasive hemostasis technology in surgery.

Experimental application cases

Scientists had used Tough Adhesives as a sealant to close a major defect in pig hearts. Experimental results showed that Tough Adhesives was conformed to the geometric structure of myocardium. When the heart is inflated, the sealant expands with the deformation of the heart and no leakage is observed at 100% strain. After tens of thousands of cycles of inflation and deflation, Tough Adhesives has remained intact, clinging to the defect of the heart surface without leakage. In addition, the experimental results also show that the bursting pressure of Tough Adhesives sealant without plastic backing and the bursting pressure of Tough Adhesives sealant with plastic backing are 206 mmHg and 367 mmHg respectively. This had exceeded the normal human arterial blood pressure (80 to 120 mmHg). In theory, Tough Adhesives has the ability to surpass the performance of commercially available surgical sealants.

The scientists also evaluated the performance of Tough Adhesives as a hemostatic dressing in the rat liver and the compatibility of Tough Adhesives in rat blood. Rat livers which suffered from severe hemorrhage in ring laceration of the left lobe were prepared in the experiment. Rat livers were treated immediately with Tough Adhesives and a commercial hemostatic agent [SURGIFLO (Ethicon)] was recorded as positive controls. Untreated rat livers were recorded as negative controls. Compared with the negative control, the performance of Tough Adhesives was similar to the use of SURGIFLO which could significantly reduce blood loss. All animals in positive control group survived without secondary hemorrhage. However, two weeks later, the lesion site treated with SURGIFLO had substantial adhesion in rat liver which did not present in the liver of rats treated with Tough Adhesives.