TIB
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KAIST develops biocompatible adhesive applicable to hair transplants
Aside from being used as a new medical adhesive, the new material can be applied to developing a new method of hair transplants, which cannot be repeated multiple times using current method of implanting the wholly intact follicles into the skin.
Medical adhesives are materials that can be applied to various uses such as wound healing, hemostasis, vascular anastomosis, and tissue engineering, and is expected to contribute greatly to the development of minimally invasive surgery and organ transplants. However, adhesives with high adhesion, low toxicity, and capable of decomposing in the body are rare. Adhesives based on natural proteins, such as fibrin and collagen, have high biocompatibility but insufficient adhesive strength. Synthetic polymer adhesives based on urethane or acrylic have greater adhesion but do not decompose well and may cause an inflammatory reaction in the body.
A joint research team led by Professor Myungeun Seo and Professor Haeshin Lee from the KAIST Department of Chemistry developed a bio-friendly adhesive from biocompatible polymers using tannic acid, the source of astringency in wine.
The research team focused on tannic acid, a natural polyphenolic product. Tannic acid is a polyphenol present in large amounts in fruit peels, nuts, and cacao. It has a high affinity and coating ability on other substances, and we sense the astringent taste in wine when tannic acid sticks to the surface of our tongue. When tannic acid is mixed with hydrophilic polymers, they form coacervates, or small droplets of jelly-like fluids that sink. If the polymers used are biocompatible, the mixture can be applied as a medical adhesive with low toxicity. However, coacervates are fundamentally fluid-like and cannot withstand large forces, which limits their adhesive capabilities. Thus, while research to utilize it as an adhesive has been actively discussed, a biodegradable material exhibiting strong adhesion due to its high shear strength has not yet been developed.
The research team figured out a way to enhance adhesion by mixing two biocompatible FDA-approved polymers, polyethylene glycol (PEG) and polylactic acid (PLA). While PEG, which is used widely in eyedrops and cream, is hydrophilic, PLA, a well-known bioplastic derived from lactic acid, is insoluble in water. The team combined the two into a block copolymer, which forms hydrophilic PLA aggregates in water with PEG blocks surrounding them. A coacervate created by mixing the micelles and tannic acid would behave like a solid due to the hard PLA components, and show an elastic modulus improved by a thousand times compared to PEG, enabling it to withstand much greater force as an adhesive.
Figure 1. (Above) Principle of biodegradable adhesive made by mixing poly(ethylene glycol)-poly(lactic acid) diblock copolymer and tannic acid in water. Yellow coacervate is precipitated through hydrogen bonding between the block copolymer micelles and tannic acid, and exhibits adhesion. After heat treatment, hydrogen bonds are rearranged to further improve adhesion. (Bottom) Adhesion comparison. Compared to using poly(ethylene glycol) polymer (d), it can support 10 times more weight when using block copolymer (e) and 60 times more weight after heat treatment (f). The indicated G' values represent the elastic modulus of the material.
Furthermore, the research team observed that the material’s mechanical properties can be improved by over a hundred times through a heating and cooling process that is used to heat-treat metals. They also discovered that this is due to the enforced interactions between micelle and tannic acid arrays.
The research team used the fact that the material shows minimal irritation to the skin and decomposes well in the body to demonstrate its possible application as an adhesive for hair transplantation through an animal experiment. Professor Haeshin Lee, who has pioneered various application fields including medical adhesives, hemostatic agents, and browning shampoo, focused on the adhesive capacities and low toxicity of polyphenols like tannic acid, and now looks forward to it improving the limitations of current hair transplant methods, which still involve follicle transfer and are difficult to be repeated multiple times.
Figure 2. (a) Overview of a hair transplantation method using a biodegradable adhesive (right) compared to a conventional hair transplantation method (left) that transplants hair containing hair follicles. After applying an adhesive to the tip of the hair, it is fixed to the skin by implanting it through a subcutaneous injection, and repeated treatment is possible. (b) Initial animal test results. One day after 15 hair transplantation, 12 strands of hair remain. If you pull the 3 strands of hair, you can see that the whole body is pulled up, indicating that it is firmly implanted into the skin. All strands of hair applied without the new adhesive material fell off, and in the case of adhesive without heat treatment, the efficiency was 1/7.
This research was conducted by first co-authors Dr. Jongmin Park (currently a senior researcher at the Korea Research Institute of Chemical Technology) from Professor Myeongeun Seo’s team and Dr. Eunsook Park from Professor Haeshin Lee’s team in the KAIST Department of Chemistry, and through joint research with the teams led by Professor Hyungjun Kim from the KAIST Department of Chemistry and Professor Siyoung Choi from the Department of Chemical and Biomolecular Engineering. The research was published online on August 22 in the international journal Au (JACS Au) under the title Biodegradable Block Copolymer-Tannic Acid Glue.
This study was funded by the Support Research Under Protection Project of the National Research Foundation (NRF), Leading Research Center Support Project (Research Center for Multiscale Chiral Structure), Biodegradable Plastics Commercialization and Demonstration Project by the Ministry of Trade and Industry, and institutional funding from the Korea Research Institute of Chemical Technology.
2022.10.07 View 7677 -
Scientist of October, Professor Haeshin Lee
(Professor Haeshin Lee from the Department of Chemistry)
Professor Haeshin Lee from the Department of Chemistry received the ‘Science and Technology Award of October’ from the Ministry of Science and ICT and the National Research Foundation of Korea for his contribution to developing an antibleeding injection needle. This novel outcome will fundamentally prevent the problem of secondary infections of AIDS, Ebola and Hepatitis viruses transmitting from patients to medical teams.
This needle’s surface is coated with hemostatic materials. Its concept is simple and the key to this technology is to make materials that are firmly coated on the needle so that they can endure frictional force when being injected into skin and blood vessels. Moreover, the materials should be adhesive to skin and the interior of blood vessels, but harmless to humans.
Professor Lee found a solution from natural polymer ingredients. Catecholamine can be found in mussels. Professor Lee conjugated catechol groups on the chitosan backbone. He applied this mussel-inspired adhesive polymer Chitosan-catechol, which immediately forms an adhesive layer with blood, as a bioadhesion for the antibleeding injection needle.
Professor Lee said, “Chitosan-catechol, which copies the adhesive mechanism of mussels, shows high solubility in physiological saline as well as great mucoadhesion. Hence, it is perfectly suitable for coating the injection needle. Combining it with proteins allows for efficient drug delivery to the heart, which is a challenging injection location, so it will be also useful for treating incurable heart disease.”
2018.10.05 View 8472 -
Distinguished Professor Lee Named International Fellow of the CAS
Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering at KAIST was awarded the title of distinguished professor and international fellow from the Chinese Academy of Sciences (CAS), and honorary professor from its affiliated organization the Tianjin Institute of Industrial Biotechnology (TIB).
The CAS recognized Distinguished Professor Lee for his significant contributions to biotechnology. He has made significant pioneering academic achievements in the area of systems metabolic engineering, which produces useful chemicals from microorganisms. Not only did he develop the first and best source technology in that field, but also came out with processes for the production of biofuel and environmentally-friendly chemicals.”
As a global leader in systems metabolic engineering, Distinguished Professor Lee has also been appointed as an honorary professor at Jiangnan University in Wuxi, China.
Distinguished Professor Lee was listed in the ‘Top 20 Translational Researchers of 2014’ selected by the renowned international journal Nature Biotechnology. Moreover, he was the first Asian recipient of the James E. Bailey Award in 2016 and Marvin J. Johnson Award in 2012, which are given to scholars in the field of biotechnology.
He is also one of 13 global scientists who are foreign members of the renowned academic societies the National Academy of Engineering and the National Academy of Sciences in the US. Furthermore, he received the ‘2017 Korea Best Scientist Award’ from the president of Korea in July. Finally, his founding field, systems metabolic engineering, was chosen as one of the ‘Top 10 Emerging Technologies of 2016’ by the World Economic Forum.
The Chinese Academy of Sciences, established in November 1949, is an academic organization that carries out research on basic sciences and natural sciences in China. It defined its science and technology system to include the fields of basic sciences, natural sciences, and high technology. While having a base in Beijing, its branch academies are located in 12 main cities along with 117 affiliates and 100 national key labs.
2017.10.26 View 9607 -
Immune Evasion Mechanism of Hepatitis C Virus Revealed
Professor Ui-Cheol Shin
Inhibiting major histocompatibility complex [MHC] class I protein expression, T cell immune response is evaded.
The research will be a great help to the development of C hepatitis vaccine.
Roughly 1-2% of the population in Korea is known to be infected with Hepatitis C. Most Hepatitis C Virus (HCV) infections progress to a chronic disease and can cause liver cirrhosis or liver cancer, which may lead to death.
Unlike Hepatitis type A or B, there is no vaccine for Hepatitis C Virus and therefore avoiding exposure to the virus is the best known method of prevention. However, a team of researchers at KAIST has produced research results, which may contribute significantly to the vaccine development.
KAIST Graduate School of Medical Sciences & Engineering’ Professor Ui-Cheol Shin and his team have successfully identified why Hepatitis C Virus does not cause an immune response within the human body. The research results were published in the May edition of The Journal of Gastroenterology, a world-renowned journal in the field of gastroenterology.
The immune response occurs to eliminate the virus that has invaded our body. During this process, a major histocompatibility complex [MHC] class I plays a key role in inducing T cell response, which is needed for the elimination of virus-infected cells.
When a cell is infected by a virus, a substance called interferon causes the increased expression of major histocompatibility complex class I. T cell recognizes the increased MHC class I and therefore finds the virus-infected cells.
However, the effect that Hepatitis C Virus has on major histocompatibility complex class I has not been clearly identified until now.
The research team has revealed, using a cell culture for infection systems, that the Hepatitis C Virus suppresses the expression of major histocompatibility complex class I. Also, the mechanism to prove that HCV activates a protein called PKR within the cell to inhibit MHC class I protein expression was identified at a molecular level.
In this study, researchers established the hypothesis that regulating PKR protein in the cell can enhance the T cell immune response, which was then proved through experiments.
Professor Ui-Cheol Shin said, “There are a lot of new drugs to treat Hepatitis C Virus, while its vaccine has not been developed yet. Revealing the HCV immune evasion mechanism will help stimulate momentum for the HCV vaccine development.”
The first author of the journal, Dr. Won-Seok Kang is a graduate from Yonsei College of Medicine. After earning his medical degree, he has continued his training as a ‘doctor-scientist’ at KAIST Graduate School of Medical Sciences & Engineering to study Hepatitis C Virus immune evasion mechanism in this research.
Hepatitis C Virus activates PKR-eIF2a pathway, which inhibits the major histocompatibility complex class I, and therefore weakens the T cell activation to the viral activity.
2014.05.19 View 10461 -
Creation of Synthetic Antibodies: Professor Hak Seong Kim
Synthetics antibodies which can replace antibodies from humans used as ingredients of medicines have been developed. It can increase the costs to 1/100 of the current costs and is much easier to develop. It is expected that the development period will be shortened from 10 years to 5.
Prof. Hak Seong Kim from the Biology department of KAIST conducted a joint research with Prof. Dong Seob Kim to reconstruct proteins and has succeeded.
The synthetic antibody displays much strength in terms of its productivity, structural formation, and bonding capability, and is thus regarded as an ideal protein. It can replace the antigens that are currently in use. It is expected that Korea will therefore be able to lead the world market for protein medicines which is a 192trillion won industry.
The original antibody has been used for not only treating diseases, but also for various other applications in the fields of medical sciences and biology. However, it is produced through a very complex process involving the incubation of animal cells, and is therefore very expensive. Also, most antibodies are already patented by more developed countries, so a high royalty fee must be paid.
Because of this, many countries including Korea has been concentrating on developing biosimilars copying the antibody medicines for which the patents have already expired. This causes Korea to be behind in the development of antibody protein pharmaceuticals.
Prof. Kim’s research team has focused on the face that the protein existing in some eels are not antibodies but functions as one, and has been successful in developing a synthetic antibody.
The synthetic antibody can be mass produced from the colon bacillus, which allows it to be produced at 1/100 the original cost. It is in a module structure which allows the structuring of the antibody into the desired structure, enabling it to be developed into a protein-based medicine within 5 years.
Together with this, the coherence with the important antigens can be easily controlled, thus allowing for highly effective treatments, less side-effects, high security regarding heat and pH, and the immunogen levels being negligeable. This suggests a very high rate of the antibody being converted into a protein based medication.
The synthetic antibody technology has been tested as a sample for the cure for lung diseases and rheumatism and has been proven to be appropriate. Animal testing will be conducted soon.
Prof Kim said “The original antibodies had a small area allowing the bonding with antibodies, creating barriers for raising bonding strength and structuring. The newly created antibody carries only the strengths and will become a new protein based medicine purely created by Korean technology to replace the antibodies currently used in medications.”
Furthermore, he added that, “The synthesized antibody structuring and designing technology will be widely used in the areas of detecting, diagnosing, and analyzing diseases.”
At the same time, this research result has been published in the Feb 10th issue of the PNAS, and has been supported by the future promising pioneer business program held by the Ministry of Education and Technology.
2012.04.04 View 10259 -
New drug targeting method for microbial pathogens developed using in silico cell
A ripple effect is expected on the new antibacterial discovery using “in silico” cells
Featured as a journal cover paper of Molecular BioSystems
A research team of Distinguished Professor Sang Yup Lee at KAIST recently constructed an in silico cell of a microbial pathogen that is resistant to antibiotics and developed a new drug targeting method that could effectively disrupt the pathogen"s growth using the in silico cell.
Hyun Uk Kim, a graduate research assistant at the Department of Chemical and Biomolecular Engineering, KAIST, conducted this study as a part of his thesis research, and the study was featured as a journal cover paper in the February issue of Molecular BioSystems this year, published by The Royal Society of Chemistry based in Europe.
It was relatively easy to treat infectious microbes using antibiotics in the past. However, the overdose of antibiotics has caused pathogens to increase their resistance to various antibiotics, and it has become more difficult to cure infectious diseases these days.
A representative microbial pathogen is Acinetobacter baumannaii. Originally isolated from soils and water, this microorganism did not have resistance to antibiotics, and hence it was easy to eradicate them if infected. However, within a decade, this miroorganism has transformed into a dreadful super-bacterium resistant to antibiotics and caused many casualties among the U.S. and French soldiers who were injured from the recent Iraqi war and infected with Acinetobacter baumannaii.
Professor Lee’s group constructed an in silico cell of this A. baumannii by computationally collecting, integrating, and analyzing the biological information of the bacterium, scattered over various databases and literatures, in order to study this organism"s genomic features and system-wide metabolic characteristics. Furthermore, they employed this in silico cell for integrative approaches, including several network analysis and analysis of essential reactions and metabolites, to predict drug targets that effectively disrupt the pathogen"s growth. Final drug targets are the ones that selectively kill pathogens without harming human body.
Here, essential reactions refer to enzymatic reactions required for normal metabolic functioning in organisms, while essential metabolites indicate chemical compounds required in the metabolism for proper functioning, and their removal brings about the effect of simultaneously disrupting their associated enzymes that interact with them.
This study attempted to predict highly reliable drug targets by systematically scanning biological components, including metabolic genes, enzymatic reactions, that constitute an in silico cell in a short period of time.
This research achievement is highly regarded as it, for the first time, systematically scanned essential metabolites for the effective drug targets using the concept of systems biology, and paved the way for a new antibacterial discovery. This study is also expected to contribute to elucidating the infectious mechanism caused by pathogens.
"Although tons of genomic information is poured in at this moment, application research that efficiently converts this preliminary information into actually useful information is still lagged behind. In this regard, this study is meaningful in that medically useful information is generated from the genomic information of Acinetobacter baumannii," says Professor Lee. "In particular, development of this organism"s in silico cell allows generation of new knowledge regarding essential genes and enzymatic reactions under specific conditions," he added.
This study was supported by the Korean Systems Biology Project of the Ministry of Education, Science and Technology, and the patent for the development of in silico cells of microbial pathogens and drug targeting methods has been filed.
[Picture 1 Cells in silico]
[Picture 2 A process of generating drug targets without harming human body while effectively disrupting the growth of a pathogen, after predicting metabolites from in silico cells]
2010.04.05 View 14670