We are working for the development of the World-Thinnest Biomaterial "Nano Plaster", based on polymer chemistry and molecular assembly. The nanosheet shows 10s to 100s of nanometer thickness, while the surface area is tunable from micrometer to meter scale, thus showing unique physical and mechanical properties such as ultra-flexibility and physical adhesiveness to the living body. Currently, we are investigating variety of polymers as a building block of the nanosheet.
We are also strongly collaborating with medical schools as well as medical companies to translate the original technology from bench to bedside.
Polymer nanosheet, Nano plaster, Printed nanofilm
Tissue Engineering & Cell Therapy
Tissue engineering is expected to be a promising technology for future medical applications and contribute to regenerative medicine, in vitro drug-screening systems and bio-hybrid robotics. To this end, inspiration from natural tissue structure is important for designing "smart" surfaces of biomaterials for directing cellular organization (e.g., anisotropic alignment of muscle fibers).
Our group envisages the fabrication of artificial scaffolds that topographically and mechanically mimic the microstructure of extracellular matrix using microfabrication techniques. Engineered functional biological tissues will be applicable for cell transplantation as well as bio-hybrid actuators.
Integration of flexible electronics into nano-biomaterials is expected to open a new avenue for medical diagnostics and therapeutics. Such devices should be adopted to physical and mechanical environment of a living body to direct biological signals. In this regard, emerging technologies of nanosheet-based devices are introduced, namely "printed nanofilms", with the idea of combining nanosheet technology and printed electronics by printing or loading conductive materials, chemical sensors, and electronic elements.
The printed nanofilm allowed for wireless monitoring or fluorescent imaging of biological information (e.g., surface electromyogram, body temperature, pH) and also directing biofunctions by local delivery of light and heat for photodynamic therapy and optogenetics.
Electromyogram, Neural activity, Bioimaging, Wireless power feeding, Photodynamic therapy, Optogenetics
Hasebe, A., Suematsu, Y., Takeoka, S., Mazzocchi, T., Vannozzi, L., Ricotti, L., Fujie, T. Biohybrid Actuators Based on Skeletal Muscle-Powered Microgrooved Ultra-Thin Films Consisting of Poly(styreneblock-butadiene-block-styrene). ACS Biomater. Sci. Eng., in press (DOI: 10.1021/acsbiomaterials.8b01550).
Takahashi, K., Fujie, T., Teramoto, R., Takahashi, I., Sato, N., Takeoka, S., Sawada, K. Elastomer-based MEMS optical interferometric transducer for highly sensitive surface stress sensing for biomolecular detection. MRS Commun., 9, 381-389 (2019).
Kokubo, N., Arake, M., Yamagishi, K., Morimoto, Y., Takeoka, S., Ohta, H., Fujie, T. Inkjet-Printed Neural Electrodes with Mechanically Gradient Structure. ACS Appl. Bio Mater., 2, 20-26 (2019).
Someya, D., Arai, S., Takeoka, S., Fujie, T., Takeoka, S. Extracellular pH imaging of a plant leaf with a polyelectrolyte multilayered nanosheet. RSC Adv., 8, 35651-35657 (2018).
Nishiwaki, K., Aoki, S., Kinoshita, M., Kiyosawa, T., Suematsu, Y., Takeoka, S., Fujie, T. In situ Transplantation of Adipose Tissue-Derived Stem Cells Organized on Porous Polymer Nanosheets for Murine Skin Defects. J. Biomed. Mater. Res. B, in press (DOI: 10.1002/jbm.b.34228).
Yamagishi, K., Kirino, I., Takahashi, I., Amano, H., Takeoka, S., Morimoto, Y., Fujie, T. Tissue-adhesive wirelessly powered optoelectronic device for metronomic photodynamic cancer therapy. Nat. Biomed. Eng., 3, 27-36 (2019).
Tetsu, Y., Yamagishi, K., Kato, A., Matsumoto, Y., Tsukune, M., Kobayashi, Y., Fujie, M. G., Takeoka, S., Fujie, T. Ultrathin epidermal strain sensor based on an elastomer nanosheet with an inkjet-printed conductive polymer. Appl. Phys. Express., 10, 087201 (2017).
Okamoto, M., Kurotobi, M., Takeoka, S., Sugano, J., Iwase, E., Iwata, H., Fujie, T. Sandwich fixation of electronic elements using free-standing elastomeric nanosheets for low-temperature device processes. J. Mater. Chem. C, 5, 1321-1327 (2017).
Sato, N., Murata, A., Fujie, T., Takeoka, S. Stretchable, adhesive and ultra-conformable elastomer thin films. Soft Matter, 12, 9202-9209 (2016).
Miyagawa, T., Fujie, T., Ferdinandus, Vo Doan, T. T., Sato, H., Takeoka, S. Glue-free stacked luminescent nanosheets enable high resolution ratiometric temperature mapping in living small animals. ACS Appl. Mater. Interfaces, 8, 33377-33385 (2016). (Highlighted by ACS Editors' Choice).
Suzuki, S., Nishiwaki, K., Takeoka, S., Fujie, T. Large-scale fabrication of porous polymer nanosheets for engineering hierarchical cellular organization. Adv. Mater. Technol., 1(6), 1600064 (2016).
Zucca, A., Yamagishi, K., Fujie, T., Takeoka, S., Mattoli, V., Greco, F. Roll to roll processing of ultraconformable conducting polymer nanosheets. J. Mater. Chem. C, 3, 6539-6548 (2015).
Fujie, T., Shi, X., Ostrovidov, S., Liang, X., Nakajima, K., Chen, Y., Wu, H., Khademhosseini, A. Spatial coordination of cell orientation directed by unique nanoribbon sheets. Biomaterials, 53, 86-94 (2015).
Shi, X., Fujie, T., Saito, A., Takeoka, S., Hou, Y., Shu, Y., Chen, M., Wu, H., Khademhosseini, A. Periosteum-mimetic structures made from freestanding microgrooved nanosheets. Adv. Mater., 26, 3290-3296 (2014).
Fujie, T., Mori, Y., Ito, S., Nishizawa, M., Bae, H., Nagai, N., Onami, H., Abe, T., Khademhosseini, A., Kaji, H. Micropatterned polymeric nanosheets for local delivery of an engineered epithelial monolayer. Adv. Mater., 26, 1699-1705 (2014).
Fujie, T., Ahadian, S., Liu, H., Chang, H., Ostrovidov, S., Wu, H., Bae, H., Nakajima, K., Kaji, H., Khademhosseini, A. Engineered nanomembranes for directing cellular organization towards flexible biodevices. Nano Lett., 13, 3185-3192 (2013).
Fujie, T., Kawamoto, Y., Haniuda, H., Saito, A., Kabata, K., Honda, Y., Ohmori, E., Asahi, T., Takeoka, S. Selective molecular permeability induced by glass transition dynamics of semi-crystalline polymer ultra-thin films. Macromolecules, 46, 395-402 (2013).
Fujie, T., Desii, A., Ventrelli, L., Mazzolai, B., Mattoli, V. Inkjet printing of protein microarrays on freestanding polymeric nanofilms for spatio-selective cell culture environment. Biomed. Microdevices, 14, 1069-1076 (2012).
Fujie, T., Ricotti, L., Desii, A., Menciassi, A., Dario, P., Mattoli, V. Evaluation of substrata effect on cell adhesion properties using freestanding poly(L-lactic acid) nanosheets. Langmuir, 27, 13173-13182 (2011).
Fujie, T., Haniuda, H., Takeoka, S. Convenient method for surface modification by patching a freestanding anti-biofouling nanosheet. J. Mater. Chem., 21, 9112-9120 (2011).
Fujie, T., Furutate, S., Niwa, D., Takeoka, S. A nano-fibrous assembly of collagen / hyaluronic acid for controlling cell-adhesive properties. Soft Matter, 6, 4672-4676 (2010).
Fujie, T., Saito, A., Kinoshita, M., Miyazaki, H., Ohtsubo, S., Saitoh, D., Takeoka, S. Dual therapeutic action of antibiotic-loaded nanosheets for the treatment of gastrointestinal tissue defects. Biomaterials, 31, 6269-6278 (2010).
Fujie, T., Kinoshita, M., Shono, S., Saito, A., Okamura, Y., Saitoh, D., Takeoka, S. Sealing effect of a polysaccharide nanosheet for murine cecal puncture. Surgery, 148, 48-58 (2010).
Fujie, T., Park, J-Y., Murata, A., Estillore, N. C., Tria, M. C. R., Takeoka, S., Advincula, R. C. Hydrodynamic transformation of a free-standing polymer nanosheet induced by a thermoresponsive surface, ACS Appl. Mater. Interfaces, 1, 1404-1413 (2009).
Fujie, T., Matsutani, N., Kinoshita, M., Okamura, Y., Saito, A., Takeoka, S. Adhesive, flexible and robust polysaccharide nanosheet integrated for tissue-defect repair. Adv. Funct. Mater., 19, 2560-2568 (2009).; "Fit to repair", Nature Nanotech. (Research Highlights), 4, 472 (2009).
Fujie, T., Okamura, Y., Takeoka, S. Selective surface modification of free-standing polysaccharide nanosheet with micro/nano-particles utilizing structural color. Colloid Surface A, 334, 28-33 (2009).
Fujie, T., Okamura, Y., Takeoka, S. Ubiquitous transference of free-standing polysaccharide nanosheet in the development of a nano-adhesive plaster. Adv. Mater., 19, 3549-3553 (2007).
(Selected Review Papers)
Yamagishi, K., Takeoka, S., Fujie, T.. Printed Nanofilms Mechanically Conforming to Living Bodies. Biomater. Sci., 7, 520-531 (2019).
Fujie, T.. Development of free-standing polymer nanosheets for advanced medical and health-care applications. Polym. J., 48, 773-780 (2016).
Yamagishi, K., Taccola, S., Takeoka, S., Fujie, T.., Mattoli, V., Greco, F. (2018) Conductive Nanosheets for Ultra-Conformable Smart Electronics (ch. 11), in Flexible and Stretchable Medical Devices (eds Takei, K.), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany. pp.253-285.
Fujie, T.., Takeoka, S. (2014) Development of Nanosheet Technology Towards Advanced Nanomedical Engineering (ch. 6), in Nanobiotechnology (Eds. Phoenix, D.A. and Waqar, A.), One Central Press, United Kingdom. pp.68-94.
Fujie, T.., Ostrovidov, S., Ahadian, S., S. Prakash Parthiban, Khademhosseini, A., Kaji, H. (2014) Bioinspired Muscle Tissue Devices (ch. 35), in Handbook of Biomimetics and Bioinspiration: 3 Volume Set (eds Jabbari, E., Khademhosseini, A., Lee, L. P., Kim, D.-H., Ghaemmaghami, A.), World Scientific Publishing, Singapore. pp.969-984.
Fujie, T.., Okamura, Y., Takeoka, S. (2011) Fabrication, Properties, and Biomedical Applications of Nanosheets (ch. 29), in Functional Polymer Films: 2 Volume Set (eds W. Knoll and R. C. Advincula), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany. pp. 907-931.
Comment-from Associate Professor (Lecturer) Toshinori Fujie
Nexus of Nano, Bio and Electronics for Human Healthcare! We are envisaging the development of innovative therapeutics and diagnostics.