TY - JOUR
T1 - Hollow fiber-combined glucose-responsive gel technology as an in vivo electronics-free insulin delivery system
AU - Matsumoto, Akira
AU - Kuwata, Hirohito
AU - Kimura, Shinichiro
AU - Matsumoto, Hiroko
AU - Ochi, Kozue
AU - Moro-oka, Yuki
AU - Watanabe, Akiko
AU - Yamada, Hironori
AU - Ishii, Hitoshi
AU - Miyazawa, Taiki
AU - Chen, Siyuan
AU - Baba, Toshiaki
AU - Yoshida, Hiroshi
AU - Nakamura, Taichi
AU - Inoue, Hiroshi
AU - Ogawa, Yoshihiro
AU - Tanaka, Miyako
AU - Miyahara, Yuji
AU - Suganami, Takayoshi
N1 - Funding Information:
We thank Y. Shimada and T. Sawamura (Nikon Systems Inc.) for technical support in mathematical modeling and analysis, Y. Kageyama (Kageyama Kogyo Inc.) for technical support in preparation of insulin reservoir and Center for Animal Research and Education (CARE), Nagoya University for support on animal experiments. This work was supported in part by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), the Cooperative Research Project of Research Center for Biomedical Engineering (MEXT), Program for Building Regional Innovation Ecosystem (MEXT), Japan Science and Technology Agency (JST) COI Grant Number JPMJCE1305, and Japan Agency for Medical Research and Development (Acceleration Transformative Research for Medical Innovation program). This work was also supported by research grants from the Secom Science and Technology Foundation, the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Japan Diabetes Foundation, Japan Diabetes Society Junior Scientist Development Grant supported by Novo Nordisk Pharma, Japan Foundation for Applied Enzymology, Ube Industries Foundation, Ichihara International Scholarship Foundation.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Accumulating evidence demonstrates that not only sustained elevation of blood glucose levels but also the glucose fluctuation represents key determinants for diabetic complications and mortality. Current closed-loop insulin therapy option is limited to the use of electronics-based systems, although it poses some technical issues with high cost. Here we demonstrate an electronics-free, synthetic boronate gel-based insulin-diffusion-control device technology that can cope with glucose fluctuations and potentially address the electronics-derived issues. The gel was combined with hemodialysis hollow fibers and scaled suitable for rats, serving as a subcutaneously implantable, insulin-diffusion-active site in a manner dependent on the subcutaneous glucose. Continuous glucose monitoring tests revealed that our device not only normalizes average glucose level of rats, but also markedly ameliorates the fluctuations over timescale of a day without inducing hypoglycemia. With inherent stability, diffusion-dependent scalability, and week-long & acute glucose-responsiveness, our technology may offer a low-cost alternative to current electronics-based approaches.
AB - Accumulating evidence demonstrates that not only sustained elevation of blood glucose levels but also the glucose fluctuation represents key determinants for diabetic complications and mortality. Current closed-loop insulin therapy option is limited to the use of electronics-based systems, although it poses some technical issues with high cost. Here we demonstrate an electronics-free, synthetic boronate gel-based insulin-diffusion-control device technology that can cope with glucose fluctuations and potentially address the electronics-derived issues. The gel was combined with hemodialysis hollow fibers and scaled suitable for rats, serving as a subcutaneously implantable, insulin-diffusion-active site in a manner dependent on the subcutaneous glucose. Continuous glucose monitoring tests revealed that our device not only normalizes average glucose level of rats, but also markedly ameliorates the fluctuations over timescale of a day without inducing hypoglycemia. With inherent stability, diffusion-dependent scalability, and week-long & acute glucose-responsiveness, our technology may offer a low-cost alternative to current electronics-based approaches.
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U2 - 10.1038/s42003-020-1026-x
DO - 10.1038/s42003-020-1026-x
M3 - Article
C2 - 32555343
AN - SCOPUS:85086584364
SN - 2399-3642
VL - 3
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 313
ER -
