Produced by: Science Popularization China Author: Yang Wen Producer: China Science Expo I don’t know if you remember a text called "The Invention of Super Glue" in the elementary school textbook. The protagonist Congcong imagined that he would invent a super glue that could immediately stick to bleeding wounds. Even if one’s legs and arms were broken, they could be restored by sticking them together with this "super glue". We have also seen a lot of glue in our daily lives, such as 502 glue, instant glue and glass glue. Although these glues can quickly and tenaciously bond broken glass and other items, these glues will lose their adhesion ability or have very low adhesion ability on the interface with water (such as human blood and body fluids), and they are toxic, so they cannot be used on the human body. So, does "universal glue" that is suitable for the human body exist? What kind of "glue" can be used as medical tissue adhesive? An ideal medical tissue adhesive should meet some principles: 1. It has high adhesion strength with the wet interface of tissues or organs to prevent it from falling off after adhering to the wound; 2. Non-toxic and harmless to the human body, i.e. good biocompatibility; 3. It can effectively stop bleeding, because most wounds are accompanied by bleeding; 4. Appropriate mechanical and physical properties, such as appropriate tensile, shear and rupture strength, to accommodate the extrusion of surrounding tissues after adhesion; 5. Able to cope with the contours and sizes of complex or irregular wounds. Existing clinical tissue adhesives have many shortcomings, including weak adhesion to wet tissue surfaces, poor sealing effects, unsatisfactory hemostasis effects, cytotoxicity, and slow wound healing in cases of bleeding and body fluid environments. It is still a huge challenge to develop an integrated medical tissue adhesive that meets clinical application requirements, achieves rapid hemostasis of damaged tissues, seamless sealing, and accelerates wound healing. Overcome difficulties, magical creatures are here to help! Recently, the research team of Dai Jianwu/Chen Yanyan from the Suzhou Institute of Nanotechnology, Chinese Academy of Sciences, inspired by the natural adhesives secreted by mussels, ivy and oysters, developed an injectable strong tissue adhesive that can be used for emergency hemostasis, wound sealing and accelerated wound healing according to clinical needs. At this point you may ask: I have seen these creatures, can I use them to make "universal glue"? Then let’s take a look at what is so “magical” about them. Mussels can attach to various surfaces underwater, mainly because they can secrete byssus proteins, which contain a large number of dopamine groups and positively charged amino acids. Positively charged amino acids can repel interfacial water, and a large number of dopamine groups can interact physically and chemically with the adherends at the interface. mussels (Photo source: Veer Gallery) Ivy can grow vertically on the wall because the mucus it secretes contains a large amount of arabinogalactose and globular glycoprotein, and the mucus can penetrate the wall and then quickly solidify under the action of calcium ions, allowing the ivy to adhere firmly to the wall. ivy (Photo source: Veer Gallery) Oysters can produce a "glue" that is a composite of organic and inorganic substances. The organic component is mainly protein, and the main inorganic component is calcium carbonate. After the glue solidifies, it firmly adheres the oysters to the reef like cement. This phenomenon is also called biomineralization. Oyster (Photo source: Veer Gallery) Combining the key elements of strong wet surface adhesion, the research team simulated the adhesion mechanisms of these three animals and plants, and simulated the three key processes of wet surface adhesion, namely drainage, molecular chain penetration and anchor cross-linking, and designed and synthesized for the first time a collagen-based medical tissue adhesive with the characteristics of rapid removal of interfacial water, multiple dynamic reversible permeation cross-linking and enhanced biomineralization curing. This adhesive has the characteristics of strong wet surface tissue adhesion, high sealing performance, fast self-healing, injectability, excellent shape adaptability and high biocompatibility, solving the problems of existing commercial adhesives. Look, these three seemingly ordinary creatures come in handy at critical moments! Don't know how to imitate bionics? Scientists: No problem, I'll do it! Collagen and starch are two naturally derived bio-based polymers that have been approved by the Food and Drug Administration for use in the human body. In this study, researchers introduced dopamine groups on the collagen molecular chains to simulate the adhesion mechanism of mussel-secreted proteins. On the one hand, calcium ions interact with the hydrogel network, and on the other hand, collagen and starch are good composite templates for biomineralization. The dopamine group helps accelerate biomineralization, simulating the formation of an enhanced network of oyster particles and strengthening the adhesive network. The researchers named this synthetic bionic glue CoSt. In addition, the researchers confirmed through a number of in vivo and in vitro results that CoSt tissue adhesive has the characteristics of high tensile properties, moderate modulus, self-healing properties and injectability. These excellent properties enhance the connection between CoSt tissue adhesive and surrounding tissues. Schematic diagram of the synthesis (a) and adhesion mechanism (b) of CoSt tissue adhesive (Image source: author) The researchers also evaluated the hemostatic ability of CoSt tissue adhesive and applied it to various bleeding models, including rat tail amputation, liver incision, severe liver defect, abdominal aorta incision and complete transection spinal cord bleeding models, to verify its in vivo hemostatic performance in different bleeding environments. The results showed that CoSt tissue adhesive can achieve rapid hemostasis within 60 seconds, whether it is large-volume bleeding under major liver defects or incompressible bleeding due to nerve transection. The researchers confirmed that the main reason is that CoSt tissue adhesive has excellent wound sealing performance, excellent red blood cell blocking ability and synergistic effect of activating hemostatic barrier membrane. In addition, skin incision/defect injury animal model studies further confirmed that CoSt tissue adhesive can accelerate wound healing and functional recovery. The wounds of rats treated with CoSt tissue adhesive showed almost no scar formation, and the regeneration of new epidermis and hair was also improved. This study cleverly combined the adhesion mechanisms of several marine organisms and plants, and innovatively used these three adhesion mechanisms to develop a new type of tissue adhesive. It shows unique advantages in application scenarios such as emergency treatment and hemostasis of incompressible tissue trauma. It is a medical tissue adhesive with broad application prospects. summary There are all kinds of wonders in nature. Nature will always be the most precious book in front of us. By learning from nature, researchers will be able to develop bionic glue with stronger adhesion, greater intelligence and more integrated functions. Editor: Sun Chenyu References: https://onlinelibrary.wiley.com/doi/10.1002/adfm.202211340 |
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