Cells comprising biological tissues are surrounded by a structure known as the stroma, and their behavioradapts in response to stimuli generated by flow and transport phenomena. Despite its importance, ourunderstanding of how cells respond to their surrounding microenvironment remains limited, hindering thedevelopment of effective disease prevention and treatment strategies. A significant challenge has been thedifficulty in observing cellular behavior while simultaneously controlling the local culture environment.Although microfluidic devices have become increasingly prevalent in recent years, they have not fullyaddressed the need for comprehensive environmental control. To overcome this limitation, we developed the"stromal function chip," which focuses on three critical environmental factors within the stroma: oxygenconcentration, pH, and interstitial flow. This innovative platform enables precise and rapid manipulation ofthese parameters while facilitating real-time observation of both individual cellular responses and complexcell-cell interactions.

Traditionally, stage incubators mounted on microscopes have been employed to maintain culture conditionsduring time-lapse observations of cellular behavior. However, these conventional systems present significantlimitations in actively and rapidly controlling localized changes within the culture microenvironment. Whilerecent advances in microfluidic devices and organ-on-a-chip technologies have enhanced our ability toobserve cellular responses under controlled conditions, these approaches still exhibit considerable constraintsin achieving comprehensive environmental regulation. In contrast, our newly developed chip providesprecise, dynamic, and immediate control over the culture microenvironment during cellular experiments,enabling high-fidelity visualization and quantification of complex cellular dynamics in response to environmental stimuli.

• The stromal function chip features sophisticated architecture comprising cell culture channels with multiplegas channels strategically positioned in vertical alignment above them. Through the controlled delivery ofprecisely mixed gases containing specific oxygen and carbon dioxide concentrations to these gas channels,the chip facilitates gas exchange that enables exquisite regulation of both oxygen concentration and pHwithin the cell culture microenvironment. This approach represents a significant advancement overconventional chemical reaction-based methods, as it eliminates potential cellular toxicity while providinghighly flexible and dynamic control over oxygen concentration and pH. Furthermore, the chip's innovativedesign allows for the precise modulation of interstitial flow—achieved by embedding hydrogel within theculture channels and establishing controlled hydrostatic pressure gradients between inlet and outlet ports. Bysimultaneously manipulating these three critical environmental factors—oxygen concentration, pH, andinterstitial flow—researchers can systematically investigate cellular response mechanisms and characterizehow cells adapt to specific stromal microenvironmental conditions, thereby advancing our understanding oftissue physiology and pathophysiology.

By precisely recapitulating the hypoxic and acidic microenvironmental conditions that characterize tumorniches and inflammatory sites, this innovative chip serves as a powerful platform for pre-clinical evaluationof therapeutic efficacy, enabling researchers to determine optimal drug candidates and dosage regimens priorto in vivo studies. Moreover, the system serves as a platform/tool for fundamental medical and biologicalinvestigations, allowing for high-resolution cellular observation and analysis under rigorously controlled andphysiologically relevant culture conditions.

Cells comprising biological tissues are surrounded by a structure known as the stroma, and their behavioradapts in response to stimuli generated by flow and transport phenomena. Despite its importance, ourunderstanding of how cells respond to their surrounding microenvironment remains limited, hindering thedevelopment of effective disease prevention and treatment strategies. A significant challenge has been thedifficulty in observing cellular behavior while simultaneously controlling the local culture environment.Although microfluidic devices have become increasingly prevalent in recent years, they have not fullyaddressed the need for comprehensive environmental control. To overcome this limitation, we developed the"stromal function chip," which focuses on three critical environmental factors within the stroma: oxygenconcentration, pH, and interstitial flow. This innovative platform enables precise and rapid manipulation ofthese parameters while facilitating real-time observation of both individual cellular responses and complexcell-cell interactions.

Traditionally, stage incubators mounted on microscopes have been employed to maintain culture conditionsduring time-lapse observations of cellular behavior. However, these conventional systems present significantlimitations in actively and rapidly controlling localized changes within the culture microenvironment. Whilerecent advances in microfluidic devices and organ-on-a-chip technologies have enhanced our ability toobserve cellular responses under controlled conditions, these approaches still exhibit considerable constraintsin achieving comprehensive environmental regulation. In contrast, our newly developed chip providesprecise, dynamic, and immediate control over the culture microenvironment during cellular experiments,enabling high-fidelity visualization and quantification of complex cellular dynamics in response to environmental stimuli.

• The stromal function chip features sophisticated architecture comprising cell culture channels with multiplegas channels strategically positioned in vertical alignment above them. Through the controlled delivery ofprecisely mixed gases containing specific oxygen and carbon dioxide concentrations to these gas channels,the chip facilitates gas exchange that enables exquisite regulation of both oxygen concentration and pHwithin the cell culture microenvironment. This approach represents a significant advancement overconventional chemical reaction-based methods, as it eliminates potential cellular toxicity while providinghighly flexible and dynamic control over oxygen concentration and pH. Furthermore, the chip's innovativedesign allows for the precise modulation of interstitial flow—achieved by embedding hydrogel within theculture channels and establishing controlled hydrostatic pressure gradients between inlet and outlet ports. Bysimultaneously manipulating these three critical environmental factors—oxygen concentration, pH, andinterstitial flow—researchers can systematically investigate cellular response mechanisms and characterizehow cells adapt to specific stromal microenvironmental conditions, thereby advancing our understanding oftissue physiology and pathophysiology.

By precisely recapitulating the hypoxic and acidic microenvironmental conditions that characterize tumorniches and inflammatory sites, this innovative chip serves as a powerful platform for pre-clinical evaluationof therapeutic efficacy, enabling researchers to determine optimal drug candidates and dosage regimens priorto in vivo studies. Moreover, the system serves as a platform/tool for fundamental medical and biologicalinvestigations, allowing for high-resolution cellular observation and analysis under rigorously controlled andphysiologically relevant culture conditions.

By applying nanoscale surface modification to individually designed 3D-printed titanium implants based on CT data, a biomimetic microenvironment is recreated, enabling regeneration of periodontal ligament-like tissue through host stem cell induction. This provides a novel treatment approach without cell transplantation for cases where existing implants are difficult to adapt.

Conventional implant treatment assumes direct bonding with bone, thus disregarding the regeneration of periodontal tissues such as the periodontal ligament. Furthermore, some patients avoid treatment due to concerns about bone-cutting surgery and multiple invasive procedures. This technology utilizes a nano-surface to induce stem cells, forming periodontal tissues similar to natural teeth. This enables the restoration of natural occlusal sensation through a single minimally invasive procedure.

• Custom-designed for each patient's root morphology, it reproduces natural force transmission and chewing sensation. Furthermore, by utilizing nanostructures to control cell adhesion and differentiation, it enables periodontal tissue reconstruction without the need for cell transplantation or regenerative factor administration.

In the future, we aim to collaborate with implant manufacturers to advance mass-production prototyping and quality evaluation, targeting practical application as a medical device. We also seek partnerships with companies and management talent who can jointly undertake strategic planning and clinical deployment for commercialization.

Cells comprising biological tissues are surrounded by a structure known as the stroma, and their behavioradapts in response to stimuli generated by flow and transport phenomena. Despite its importance, ourunderstanding of how cells respond to their surrounding microenvironment remains limited, hindering thedevelopment of effective disease prevention and treatment strategies. A significant challenge has been thedifficulty in observing cellular behavior while simultaneously controlling the local culture environment.Although microfluidic devices have become increasingly prevalent in recent years, they have not fullyaddressed the need for comprehensive environmental control. To overcome this limitation, we developed the"stromal function chip," which focuses on three critical environmental factors within the stroma: oxygenconcentration, pH, and interstitial flow. This innovative platform enables precise and rapid manipulation ofthese parameters while facilitating real-time observation of both individual cellular responses and complexcell-cell interactions.

Traditionally, stage incubators mounted on microscopes have been employed to maintain culture conditionsduring time-lapse observations of cellular behavior. However, these conventional systems present significantlimitations in actively and rapidly controlling localized changes within the culture microenvironment. Whilerecent advances in microfluidic devices and organ-on-a-chip technologies have enhanced our ability toobserve cellular responses under controlled conditions, these approaches still exhibit considerable constraintsin achieving comprehensive environmental regulation. In contrast, our newly developed chip providesprecise, dynamic, and immediate control over the culture microenvironment during cellular experiments,enabling high-fidelity visualization and quantification of complex cellular dynamics in response to environmental stimuli.

• The stromal function chip features sophisticated architecture comprising cell culture channels with multiplegas channels strategically positioned in vertical alignment above them. Through the controlled delivery ofprecisely mixed gases containing specific oxygen and carbon dioxide concentrations to these gas channels,the chip facilitates gas exchange that enables exquisite regulation of both oxygen concentration and pHwithin the cell culture microenvironment. This approach represents a significant advancement overconventional chemical reaction-based methods, as it eliminates potential cellular toxicity while providinghighly flexible and dynamic control over oxygen concentration and pH. Furthermore, the chip's innovativedesign allows for the precise modulation of interstitial flow—achieved by embedding hydrogel within theculture channels and establishing controlled hydrostatic pressure gradients between inlet and outlet ports. Bysimultaneously manipulating these three critical environmental factors—oxygen concentration, pH, andinterstitial flow—researchers can systematically investigate cellular response mechanisms and characterizehow cells adapt to specific stromal microenvironmental conditions, thereby advancing our understanding oftissue physiology and pathophysiology.

By precisely recapitulating the hypoxic and acidic microenvironmental conditions that characterize tumorniches and inflammatory sites, this innovative chip serves as a powerful platform for pre-clinical evaluationof therapeutic efficacy, enabling researchers to determine optimal drug candidates and dosage regimens priorto in vivo studies. Moreover, the system serves as a platform/tool for fundamental medical and biologicalinvestigations, allowing for high-resolution cellular observation and analysis under rigorously controlled andphysiologically relevant culture conditions.

• To generate a rice plant suitable for efficient biofuel production from its straw, we examined effects of overexpression of cellulase on saccharification of straw. The transgenic plant constitutively overexpressing cellulase showed enhanced saccharification, but various physiological and morphological abnormalities were also observed. To overcome this problem, a senescence-inducible promoter was used to express the cellulase. The plants successfully avoided the problem and showed enhanced saccharification after senescence.

Rice straw will be an efficient material for biofuel production. This method can be applied to other plants. In combination with highly engineered microorganisms for saccharification and fermentation, this method will contribute to efficient production of biofuels.