KU-SMART: tackling medical challenges collaboratively

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Traditionally, joint replacements have been made from inert metals which have a limited lifetime and place additional wear on the remaining bone. Biocompatible polymers offer an attractive alternative, being customisable, lightweight and even offering options for cartridge replacement. Professor Yuichi Ohya at Kansai University is looking for new ways to address medical challenges like this, through the design of new functional materials. Alongside 12 other researchers at Kansai University, he is part of the new KU-SMART programme, with the goal of taking new polymers right from the lab to medical devices.

Polymers are an incredibly diverse family of molecules found in all aspects of our lives. Probably the most well-known polymers are polyethylene and polypropylene, which are commonly used plastics, but even our DNA is an example of a natural polymer. What these molecules have in common is they are made of repeating chemical structure motifs that are joined together to make polymer chains. The length of these chains and the way they are joined then gives rise to the unique properties of each polymer, such as how hard or flexible a particular plastic is.

The Functional Polymer Laboratory where Professor Ohya works on his research. Kansai University is one of the top universities in polymer research.

The KU-SMART team are keen to see a greater amount of collaboration between academic research and frontline medicine.

The ability to tune the macroscopic properties of polymers is what has made them so commonly used in manufacturing. While different kinds of polyethylene are based on the same repeating chemical motif (known as a monomer subunit), by varying the overall structure of the chain from a single, uninterrupted monomer chain to a chain with many branching points on it, you can create low-density or high-density polyethylene. The former is so soft and pliable it can be used for plastic wrapping, whereas the latter is strong and rigid enough to form parts of an artificial hip joint.

Photographs of the mixed solutions of Polymer A (tri-PCG-COOH) and Polymer C (tri-PCG-NH2) at various A/C ratios under various pHs at 37 ºC: the gel-forming pH region can be controlled by changing A/C ratio.

One field that is taking advantage of the highly customisable nature of polymers is biomedicine. Researchers such as Professor Yuichi Ohya at Kansai University are interested in a range of applications for these materials not just for rigid structures such as joint replacements, but also as drug delivery systems that could help deliver therapies safely to the exact site where they are needed.

Ex vivo fluorescence images of tails of ICR mice 75 hours after the intravenous injection of Cy5-PEP·Na and Cy5-Az.

The huge scope and potential of functional polymers to solve a whole variety of medical problems is what has inspired Professor Ohya to found the Kansai University Smart Materials for Advanced and Reliable Therapeutics Project (KU-SMART). Involving a team of 13 researchers at Kansai University, the KU-SMART team of material chemists, mechanical engineers, and medical doctors (Osaka Medical College) aim to not just develop new polymers for medical applications in the laboratory, but to start incorporating them into functional, medical devices that can be used in a healthcare setting. The medical doctors help identify the needs and issues of patients that are currently unaddressed, then the material chemists provide novel materials to the engineers, who transform them into the useable, medical device.

Injectable polymers
Within the KU-SMART project, there are several research themes aimed at designing devices to meet current healthcare needs, such as new minimally-invasive therapeutics or scaffolds to help regenerate cartilage. Within these projects, Professor Ohya is using his expertise on biodegradable polymers to design new, injectable polymers.

Kansai University has a great environment and equipment to undertake the KU-SMART project. Using a confocal laser scanning microscope (CLMS), tomographic pictures of tissues or cells can be obtained.

Many of the injectable polymers that Professor Ohya creates form gels under certain temperature or pH conditions, which can be variably designed. This means they can be injected as a liquid solution but once they are inside the body, they form a hydrogel, which is a lot like edible jelly. The polymer can contain drugs or living cells, so as the gel naturally biodegrades these are gradually released from the gel into the body or to regenerate natural tissues.

Injectable hydrogel containing fibroblast cells: the cells can proliferate in the hydrogel.

There are several advantages to Professor Ohya’s temperature- and pH-sensitive polymers. While gels that are just temperature-sensitive will form gels on injection anywhere in the body, the addition of variable pH sensitivity allows for site-specific gel formation as different organs, like the stomach and liver, have different pH levels, as do tumours. This could allow better, targeted drug delivery systems.

These injectable polymers are not just restricted to acting as carriers for other molecular species but could also be used as a way of improving surgical outcomes. By incorporating anti-adhesives into the injectable polymer, these could be used during laparoscopic (key-hole) surgical procedures. Key-hole surgical approaches, that involve performing surgery via a catheter, are often preferred as they have vastly improved recovery times and reduced risks of complications over more conventional open surgery techniques. However, one of the most common complications of key-hole surgery, post-surgical adhesions, could be improved by the use of these anti-adhesive polymers during the surgical process. As part of KU-SMART, Professor Ohya and his colleagues will be looking to find ways to further improve these injectable polymers for exactly this medical need.

Prof Kotani (right) and a colleague test the new lightweight goggles which could revolutionise glaucoma screening programmes.

Bone regeneration
Professor Iwasaki is another of the polymer chemists involved in KU-SMART who is very interested in using his polymers for treating bone-related issues. He also specialises in the design of biocompatible polymers, but the main focus of Professor Iwasaki’s research concerns phosphorus-containing polymers that can be potentially used for bone regeneration.

One of his team’s recent breakthroughs is the development of a new polymer with a very high affinity for bone material which has now been tested in mice. Like Professor Ohya’s gel polymers, these phosphate polymers can be injected in conjunction with drugs and other materials, such as imaging probes, that can be used to enhance the quality and clarity of diagnostic imaging. This new polymer, that is one of the first biodegradable polymers with such bone-binding properties, could open a wealth of possibilities for new treatments of bone-related issues and disorders.

Involving a team of 13 researchers at Kansai University, the KU-SMART team consists of material chemists, mechanical engineers, and medical doctors.

Diagnosis goggles
As well as treatments, part of the KU-SMART programme is developing non-invasive diagnostic techniques. Professor Kentaro Kotani has been developing such a device for diagnosing vision disorders, including glaucoma, one of the leading causes of blindness in Japan. While early diagnosis of glaucoma can help with treatment outcomes, regular screening is only performed for ‘high risk’ individuals as screening each eye takes around 30 minutes and is often very uncomfortable for the patient. Professor Kotani’s new lightweight goggles, which track eye movements while providing darkroom-like conditions, can improve diagnosis times and are both more convenient and comfortable, paving the way to introduction of wider glaucoma screening programmes. The devices are nearly ready for mass production in collaboration with a Japanese manufacturing company and may become commonplace in eye health checks.

Collaborative design
The final goal of KU-SMART goes beyond the development of new materials and devices: the programme also aims to raise public awareness about the important role that manufacturers play in the medical sector and generate further interest from Japan’s advanced manufacturing sector in tackling challenges in the healthcare field.

In Japan, the KU-SMART team are keen to see a greater level of collaboration between academic research and frontline medicine, which is why they have created such a diverse, interdisciplinary team. The project, funded by the Japanese government, is one of few in the country with such a scope, and the researchers hope to find ways to help make the transition of technologies from the laboratory to functional devices easier nationwide. This is not just of huge benefit to patients, particularly in Japan where an ageing population means that many age-related diseases are becoming increasingly problematic, but offers numerous commercial opportunities that make use of these joint specialisms to create truly innovative devices.

How do you think KU-SMART will encourage wider collaboration between academia and industry?

Kansai University has an organisation for promoting collaboration between academia and industry called ORDIST (Organization for Research and Development of Innovative Science and Technology). It is independent from educational faculties and departments and supports each researcher to conduct industry-university collaboration and external fund acquisition. KU-SMART is also managed by ORDIST. We have exclusive coordinators and university research administrators in ORDIST, who support publicity activities and patent applications as well as collaboration studies with companies. In addition, many academic exposition events are held every year here in Japan (for example, Bio tech 2018 ). Bio- and medical companies participate in these events, and we exhibit a KU-SMART booth at such events to make our research activities public.

References

  • Iwasaki, Y. et al. (2018). Bone-targeting poly(ethylene sodium phosphate). Biomater. Sci. 6, 91–95
  • Ohya, Y. et al. (2017). Injectable and biodegradable temperature-responsive mixed polymer systems providing variable gel-forming pH regions. J. Biomater. Sci. Polym. Ed. 28, 1158–1171
  • Ohya, Y. et al. (2017). Biodegradable injectable polymer systems exhibiting a longer and controllable duration time of the gel state. Biomater. Sci. 5, 1304–1314
  • Kotani, K. et al. (2012). Visual field screening system by using overlapped fixation patterns. Electron. Commun. Japan 95, 29–40
Research Objectives
Dr Ohya’s research fields are functional polymers and biomaterials, especially biodegradable polymers and drug delivery systems. He is the project leader of Kansai University (KU) Smart Materials for Advanced and Reliable Therapeutics Project (KU-SMART Project), which aims to apply the Kansai University Medical Polymer (KUMP, a group of new polymers created in KU) as medical devices. This project involves 13 researchers from KU, who are professionals in medical polymers or medical devices.

Funding

  • Ministry of Education, Culture, Sports, Science and Technology (MEXT)
  • Japan Society for the Promotion of Science (JSPS)
  • Kansai University

Collaborators
Osaka Medical College

Bio
Dr Ohya received his MS from Kyoto University in 1989, and started his career as a researcher at Kansai University. In 1993, he received his PhD in Engineering from Kyoto University. He received The Award of Japanese Society for Biomaterials in 2017. Now he contributes to KU-SMART Project (FY 2016-2020) as researcher and also as project leader.

Contact
Dr Yuichi Ohya, Professor
Department of Chemistry and Materials Engineering,
Faculty of Chemistry, Materials and Bioengineering
Kansai University
3-3-35 Yamate, Suita, Osaka
564-8680
Japan

E: yohya@kansai-u.ac.jp
T: +81 (6) 6368 1121
W:
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