Journal
SCIENCE ADVANCES
Volume 3, Issue 11, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aaq0723
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)
- Cooperative Research Project of Research Center for Biomedical Engineering (MEXT)
- Japan Science and Technology Agency (Start-ups from Advanced Research and Technology program)
- Japan Science and Technology Agency (Center of Innovation stream)
- Japan Agency for Medical Research and Development (Acceleration Transformative Research for Medical Innovation program)
- Canon Foundation
- Secom Science and Technology Foundation
- Terumo Foundation for Life Sciences and Arts
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Kanagawa Institute of Industrial Science and Technology
- Grants-in-Aid for Scientific Research [15K09423, 16H05171] Funding Source: KAKEN
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Although previous studies have attempted to create electronics-free insulin delivery systemsusing glucose oxidase and sugar-binding lectins as a glucose-sensingmechanism, no successful clinical translation has hitherto been made. These protein-based materials are intolerant of long-term use and storage because of their denaturing and/or cytotoxic properties. We provide a solution by designing a protein-free and totally synthetic material-based approach. Capitalizing on the sugar-responsive properties of boronic acid, we have established a synthetic polymer gel-based insulin delivery device confined within a single catheter, which exhibits an artificial pancreas-like function in vivo. Subcutaneous implantation of the device in healthy and diabetic mice establishes a closed-loop system composed of continuous glucose sensing and skin layer-regulated insulin release. As a result, glucose metabolism was controlled in response to interstitial glucose fluctuation under both insulin-deficient and insulin-resistant conditions with at least 3-week durability. Our smart gel technology could offer a user-friendly and remarkably economic (disposable) alternative to the current state of the art, thereby facilitating availability of effective insulin treatment not only to diabetic patients in developing countries but also to those patients who otherwise may not be strongly motivated, such as the elderly, infants, and patients in need of nursing care.
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