Activity

2025

[Papers where our lab members played a leading role]

  1. Shinji Sakai, Hiroyuki Fujiwara, Ryotaro Kazama, Riki Toita, Satoshi Fujita, Development of on-chip cell domes using Ca-alginate hydrogel shells for non-adherent cell studies, Lab on a Chip, in press. [DOI:].
    The hemispherical cell domes (semi-permeable gel film) with a diameter of about 0.5 mm containing suspended cells that are arrayed on glass plates, which have been developed in our laboratory, have been produced from a general-purpose aqueous sodium alginate solution. This is the result of joint research with the National Institute of Advanced Industrial Science and Technology (AIST).
  2. Takashi Kotani, Takehito Hananouchi, Shinji Sakai, Enhancing visible light-induced 3D bioprinting: alternating extruded support materials for bioink gelation, Biomedical Materials, 20, 035005 (2025) [DOI:10.1088/1748-605X/adc0d6].
    We proposed a method in which a support material containing SPS and a bioink containing a polymer with phenolic hydroxyl groups (HA-Ph) and a ruthenium complex ([Ru(bpy)3]²⁺) are alternately extruded, promoting gelation under visible light, and demonstrated its effectiveness. This was the result of a collaborative study with Professor Hananouchi from Hiroshima University.
  3. Ryotaro Kazama, Satoshi Fujita, Shinji Sakai, Cell Dome-Based Transfection Array for Non-adherent Suspension Cells, Biochemical Engineering Journal, 213, 109554 (2025) [DOI:10.1016/j.bej.2024.109554].
    This paper reports that our original technology, Cell Dome, enables efficient gene delivery to non-adherent cells that proliferate without attaching to the substrate. This was the result of a collaborative study with Professor Fujita from AIST (Osaka University Photonics Center).
  4. Mitsuyuki Hidaka, Shinji Sakai, Photo- and Schiff Base-Crosslinkable Chitosan/Oxidized Glucomannan Composite Hydrogel for 3D Bioprinting, Polysaccharides, 6, 19 (2025) [DOI:10.3390/polysaccharides6010019].
    This study developed a composite hydrogel of phenolic hydroxyl group-introduced chitosan and oxidized glucomannan by combining Schiff base formation and visible light-induced phenol crosslinking. The dual crosslinking improved printability, shape fidelity, antibacterial properties, and cytocompatibility, enabling the fabrication of well-defined 3D structures using low concentrations of crosslinking agents while maintaining good biocompatibility.
  5. Ryota Goto, Masahiro Terasawa, Masaru Kojima, Koichi Matsuda, Kaoru Nishiura, Shinji Sakai, Synthesis and application of phenol-grafted rhamnan sulfate for 3D bioprinting, Journal of Biomaterials Science: Polymer Edition, in press.[DOI:10.1080/09205063.2024.2427499].
    This study demonstrated that rhamnan sulfate, a sulfated polysaccharide derived from seaweed, can be chemically modified and used as a promising ink material for 3D bioprinting.

2024

  1. Ryotaro Kazama, Satoshi Fujita, Shinji Sakai, Shinji Sakai, Cell Dome-Based Transfection Array for Non-adherent Suspension Cells, Biochemical Engineering Journal, 213, January 2025, 109554 (2024). DOI:10.1016/j.bej.2024.109554].
    This paper reports on our Cell Dome technology, which enables efficient gene introduction to non-adherent cells that proliferate without adhering to the substrate. This is a collaborative work with Dr. Fujita from AIST (Osaka Photonics Center).
  2. Ayari Miyawaki, Shinji Sakai, Immobilization of laccases on mechanically ground silk fibroin nanofibers for enhanced stability, International Journal of Biological Macromolecules, 282 (1), 136745 (2024).[DOI:10.1016/j.ijbiomac.2024.136745].
    The paper demonstrates that silk nanofibers obtained by mechanically grinding silk fibers contribute to enhancing the stability of laccase when used as an immobilization carrier, allowing long-term use as a catalytic immobilization membrane in continuous reactors.
  3. Colin Zhang, Kelum Chamara Manoj Lakmal Elvitigala, Wildan Mubarok, Yasunori Okano, Shinji Sakai, Machine learning-based prediction and optimization framework for as-extruded cell viability in extrusion-based 3D bioprinting, Virtual and Physical Prototyping, 19(1), e2400330 (2024).[DOI:10.1080/17452759.2024.2400330].
    This research demonstrates the capability of predicting the load exerted on various types of cells within inks flowing through the nozzle during bioprinting and the subsequent reduction in viability, achieved through machine learning. This study was conducted in collaboration with Dr. Okano.
  4. Ryota Goto, Shinji Sakai, Cédric Delattre, Emmanuel Petit, Redouan El Boutachfaiti, Masaki Nakahata, Enzymatically cross-linkable sulfated bacterial polyglucuronic acid as an affinity-based carrier of FGF-2 for therapeutic angiogenesis, Journal of Bioscience and Bioengineering, 138 (6), 541-547 (2024).[DOI:10.1016/j.jbiosc.2024.08.011].
    This study, conducted in collaboration with a French research group, involves the development of an angiogenesis-promoting gel by chemically modifying polyglucuronic acid with sulfate groups to enhance its affinity with the cytokine bFGF and cross-linking it enzymatically.
  5. Mitsuyuki Hidaka, Masaru Kojima, Shinji Sakai, Micromixer driven by bubble-induced acoustic microstreaming for multi-ink 3D bioprinting, Lab on a Chip, 24, 4571-4580 (2024).[DOI:10.1039/D4LC00552J].
    This paper details the development of a 3D bioprinting nozzle equipped with a micromixer that stirs using bubbles oscillated by sound waves, an innovation by Hidaka. The method is slightly noisy when operating (earplugs solve this issue), and cell viability is not compromised.
  6. Wildan Mubarok, Kelum Chamara Manoj Lakmal Elvitigala, Hiroto Nakaya, Tomoki Hotta, Shinji Sakai, Cell cycle modulation through physical confinement in micrometer-thick hydrogel sheaths, Langmuir, 40 (35), 18717-18726 (2024).[DOI:10.1021/acs.langmuir.4c02434].
    This study reports on how the cell cycle is affected by a micrometer-thick gel membrane formed on the cell surface via peroxidase enzymatic reaction. This research, initiated by Hotta during his master’s studies, was further developed by Wildan, Kelum, and Nakaya.
  7. Mitsuyuki Hidaka, Masaru Kojima, Colin Zhang, Yasunori Okano, Shinji Sakai, Experimental and Numerical Approaches for Optimizing Conjunction Area Design to Enhance Switching Efficiency in Single-Nozzle Multi-Ink Bioprinting Systems, International Journal of Bioprinting, 10 (5), 4091 (2024).[DOI:10.36922/ijb.4091].
    This paper presents research on the design of nozzles for multi-ink 3D bioprinting, aiming to enhance ink switching within a single nozzle using experimental methods and simulations.
  8. Masaki Nakahata, Ai Sumiya, Yuka Ikemoto, Takashi Nakamura, Anastasia Dudin, Julius Schwieger, Akihisa Yamamoto, Shinji Sakai, Stefan Kaufmann, Motomu Tanaka, Hyperconfined Bio-Inspired Polymers in Integrative Flow-Through Systems for Highly Selective Removal of Heavy Metal Ions, Nature Communications, 15(1) 5824 (2024)[DOI:10.1038/s41467-024-49869-8].
    This paper discusses the development of a new polymer material inspired by proteins that selectively capture heavy metal ions in plants. The material achieves enhanced ion capture efficiency through ultra-high density and is applied to flow-through water purification systems.
  9. Kelum Chamara Manoj Lakmal Elvitigala, Wildan Mubarok, Shinji Sakai, Hydrogels with ultrasound-treated hyaluronic acid regulate CD44-mediated angiogenic potential of human vascular endothelial cells in vitro, Biomolecules, 14 (5), 604 (2024)[DOI:10.3390/biom14050604].
    This study shows that low-molecular-weight hyaluronic acid with phenolic hydroxyl groups introduced through ultrasound treatment controls capillary-like network formation mediated by CD44 expression on the surface of vascular cells.
  10. Mitsuyuki Hidaka, Masaru Kojima, Shinji Sakai, Cédric Delattre, Characterization of Chitosan Hydrogels Obtained through Phenol and Tripolyphosphate Anionic Crosslinking, Polymers, 16 (9), 1274 (2024)[DOI:10.3390/polym16091274/].
    The gel preparation of chitosan with phenolic hydroxyl groups was performed by using a ruthenium complex catalyst to form crosslinks between the phenolic hydroxyl groups and between the amino groups of sodium tripolyphosphate and chitosan. The properties of the double crosslinked gel were evaluated. This is the result of joint research with Cedric from Universite Clermont Auvergne (France).
  11. Kelum Chamara Manoj Lakmal Elvitigala, Lakshimi Mohan, Wildan Mubarok, Shinji Sakai, Photo-tuning of hyaluronic acid-based hydrogel properties to control network formation in human vascular endothelial cells, Advanced Healthcare Materials, 2303787 (2024)[DOI:10.1002/adhm.202303787].
    This research result shows that the network formation of human vascular cells can be controlled by controlling the crosslinking and decomposition of hyaluronic acid derivatives through photoreaction. This result will contribute to the development of screening for drugs targeting angiogenesis and the development of technologies related to angiogenesis in tissue engineering. The research was conducted together with Lakshmi Mohan of UCLA.
  12. Wildan Mubarok, Colin Zhang, Shinji Sakai, 3D Bioprinting of Sugar Beet Pectin Through Horseradish Peroxidase-Catalyzed Crosslinking, ACS Applied Bio Materials, 7(5), 3506-3514 (2024)[DOI:10.1021/acsabm.4c00418].
    Sugar beet pectin can be made into a gel from its aqueous solution through a reaction catalyzed by horseradish peroxidase without chemical modification. Taking advantage of this property, we have reported that it is possible to bioprint three-dimensional structures containing living human cells using an ink whose main component is sugar beet pectin.
  13. Kotoko Furuno, Keiichiro Suzuki, Shinji Sakai, Transduction and Genome Editing of the Heart with Adeno-Associated Viral Vectors Loaded on Electrospun Polydioxanone Nonwoven Fabrics, Biomolecules, 14(4), 506 (2024). [DOI:10.3390/biom14040506].
    Polydioxanone is a highly biocompatible material that forms elastic threads. This paper demonstrates that by carrying an adeno-associated virus vector on a nanofiber nonwoven fabric made from this material using electrostatic spinning and attaching it to the surface of the heart, gene transfer and genome editing can be performed on the heart. This is the result of joint research with the Suzuki Laboratory.
  14. Shinji Sakai, Shota Yamamoto, Ryo Hirami, Mitsuyuki Hidaka, Kelum Chamara Manoj Lakmal Elvitigala, Enzymatically Gellable Chitosan Inks with Enhanced Printability by Chitosan Nanofibers for 3D Printing of Wound Dressings,European Polymer Journal, 210, 112960.(2024) [DOI:10.1016/j.eurpolymj.2024.112960/].
    Aqueous solutions containing chitosan are generally difficult to gel under mild conditions for living organisms and cells, and when used as ink, the concentration must be increased considerably in order to achieve sufficient viscosity for good printing. Therefore, by using chitosan nanofibers as an additive and chitosan that gels through an enzyme reaction, this paper demonstrates that good modeling can be achieved and that the gel obtained by 3D printing has excellent performance as a wound dressing.
  15. Ryotaro Kazama, Shinji Sakai, Effect of cell adhesiveness of Cell Dome’s shell on enclosed HeLa cells, Journal of Bioscience and Bioengineering, 137(4), 313-320 (2024). [DOI:10.1016/j.jbiosc.2024.01.002].
    The cell adhesiveness of the Cell Dome can be controlled by controlling the composition of the gel film that constitutes it. For example, cell adhesiveness can be imparted by adding a gelatin derivative to the film. In this paper, it was revealed that when HeLa cells were cultured in a Cell Dome made of a gel film with cell adhesive properties, the cell cycle and proliferation characteristics were different from those when the cells were cultured in a Cell Dome made of a gel film without cell adhesive properties.
  16. Kotoko Furuno, Kelum Chamara Manoj Lakmal Elvitigala, Keiichiro Suzuki, Shinji Sakai, Local Delivery of Adeno-associated Viral Vectors with Electrospun Gelatin Nanofiber Mats, ournal of Biomedical Materials Research: Part B - Applied Biomaterials, 112(1), e35345 (2024). [DOI:10.1002/jbm.b.35345].
    This is the result of research into a new treatment method in which a gelatin nanofiber nonwoven fabric carrying an adeno-associated virus vector, obtained by electrostatic spinning, is attached to the surface of an organ using an endoscope, allowing site-selective gene introduction and genome editing. This was conducted as a collaborative research project with the Suzuki Laboratory.

2023

  1. Ryota Goto, Masaki Nakahata, Cédric Delattre, Emmanuel Petit, Redouan El Boutachfaiti, Shinji Sakai, Fabrication of cell-laden microbeads and microcapsules composed of bacterial polyglucuronic acid, International Journal of Biological Macromolecules, 244, 125481 (2023) [DOI:10.1016/j.ijbiomac.2023.125481].
    The French group has discovered that polyglucuronic acid is useful for cosmetic applications, and has demonstrated that it is also useful as a material for producing cell-encapsulating capsules, a material that has been used frequently with alginic acid up until now. This material has different properties from alginic acid, and future applications are expected to be developed.
  2. Wildan Mubarok, Kelum Chamara Manoj Lakmal Elvitigala, Takashi Kotani, Shinji Sakai, Visible light photocrosslinking of sugar beet pectin for 3D bioprinting applications, Carbohydrate Polymers, 316(15), 121026 (2023) [DOI:10.1016/j.carbpol.2023.121026].
    This paper is the first to demonstrate that sugar beet pectin can be used as an ink material for bioprinting that crosslinks with visible light without chemical modification. It was successfully incorporated into 3D printed structures without impairing cell viability.
  3. Ikki Horiguchi, Hotaka Nagate, Yasuyuki Sakai: Particle-tracking-based strategy for the optimization of agitation conditions in a suspension culture of human induced pluripotent stem cells in a shaking vessel, Journal of Bioscience and Bioengineering, 135(5), (2023).  [DOI: 10.1016/j.jbiosc.2023.02.007]
    We proposed a method to optimize the operating conditions of suspension culture of human iPS cells by tracking the movement of cell aggregates in the suspension culture with a high-speed camera and calculating the time average of acceleration.
  4. Ryotaro Kazama, Ryuta Sato, Hiroyuki Fujiwara, Yanfei Qu, Masaki Nakahata, Masaru Kojima, Satoshi Fujita, Shinji Sakai,Development of non-adherent cell-enclosing domes with enzymatically cross-linked hydrogel shell, Biofabrication, 15(1),015002 (2023) [DOI: 10.1088/1758-5090/ac95ce].
    We proposed a new microdevice called cell dome for culturing suspension cells and reported its fabrication method.
  5. Kelum Chamara Manoj Lakmal Elvitigala, Wildan Mubarok, Shinji Sakai, Tuning the crosslinking and degradation of hyaluronic acid/gelatin hydrogels using hydrogen peroxide for muscle cell sheet fabrication, Soft Matter, 19, 5880 (2023) [DOI:10.1039/D3SM00560G].【Selected as Back Cover】
    The properties of a hyaluronic acid/gelatin composite gel sheet, which is used as a culture substrate for creating muscle cell sheets, are controlled by crosslinking and polymerizing the polymer using hydrogen peroxide.
  6. Takashi Kotani, Wildan Mubarok, Takehito Hananouchi, Shinji Sakai, Horseradish peroxidase-mediated bioprinting via bioink gelation by alternately extruded support material, ACS Biomaterials Science & Engineering, 9(10) 5804–5812 (2023). [DOI:10.1021/acsbiomaterials.3c00996].【Selected as Cover】
    The results are based on a new method for bioprinting soft structures containing cells using an enzymatic reaction with horseradish peroxidase to gel the ink.

[Review article, etc...]

  1. Thaaranni Bashkeran, Shinji Sakai, Retno Wahyu Nurhayati, Minh Hong Nguyen, Wildan Mubarok, Ryota Goto, Dinda Shezaria Hardy Lubis, Auzan Luthfi, Masrina Mohd Nadzirm, Microbial Exopolysaccharides Production and Applications (Edited By Shashi Kant Bhatia, Parmjit Singh Panesar, Sanjeet Mehariya, CRC Press) [DOI: 10.1201/9781003342687], Chapter 4: Biomedical applications of exopolysaccharides
    An explanation of the biomedical applications of microbial exopolysaccharides secreted by microorganisms.
  2. Ayari Miyawaki, Shinji Sakai, Bioprinting using enzyme-gelling ink, Japanese Society of Imaging Science and Technology, Vol. 63, No. 4, 2024 p. 388-396　[DOI: 10.11370/isj.63.388],
    An explanation of 3D bioprinting using enzyme-gelling ink.