"Design and Control of Multicellular Adaptivity with Biotechnology and Materials Technology -Development of Multicellular Materials Systems-" is a research and development strategy to promotes a combination of biotechnology and materials technology for controlling multicellular behaviors. Thereby, novel materials systems, named "multicellular materials systems", will be developed, which enable various advanced functions, such as structural formation, transformation of substances or energy, information processing or learning, and adaptivity to the uses and usage conditions.

A variety of technologies has been developed by engineering biological (biologically-derived) materials or controlling them via artificial materials. Such technologies have aimed to realize novel materials' properties and functions beyond or compensating existing artificial and biological materials. Recently, progress of both biotechnology and materials technology has demonstrated potential for controlling multicellular behaviors such as the complex dynamics and functions through interactions between (engineered) multiple cells and artificial materials.

The adaptivity of multicellular materials systems will provide various technological solutions beyond the scopes of biotechnology or materials technology so far. For example, maximizing the functions under a specific condition and properties of self-repairing or self-growth will lead to optimal material manufacturing and circular systems in a society. Further applications will be also expected including artificial biological systems to reconstruct individual physiological responses for medical treatment and drug development, systems for environmental monitoring and remediation, healthcare devices and soft robots which response to human physical and mental conditions, and so on. Development of such technologies contributes to establishing sustainable social systems, conversing global environment and biodiversity, and realizing individual well-being. Moreover, related novel markets will be pioneered, bringing economic advantages of Japanese industry.

Currently, various applied studies which incorporate multiple cells into materials or systems have been reported. However, its performance and adaptability are not sufficiently controlled, and social implementation has been limited. This is due to the lack of understanding for the complex behavior among composited multiple cells and artificial materials, resulted in difficulties of rational design and construction.

Therefore, aiming to realize advanced functions and adaptivity based on controlled multicellular behaviors, we propose to promote understanding of the various dynamics (spatiotemporal state changes) derived from complex multiple cells-materials interactions, and to establish reliable methodology for designing and constructing multicellular materials systems. Herein, the R&D subjects are proposed as follows.

[R&D subject 1] Understand complex dynamics of multiple cells and materials

Understandings of complex dynamics derived from interactions between multiple cells and artificial materials must be enhanced. The followings sub-subjects need to be co-progressed: (A) Perturbations (inputs): materials technology to precisely stimulate cells and arrange extracellular environment, and biological techniques to induce cell-cell interactions, (B) Measurements of output responses or related parameters: measurement technologies for compositions and physical properties of multiple cells and extracellular substances, (C) Modeling: developing models or theories to correlate inputs and outputs quantitatively. Particularly, such perturbation and measurement techniques must be applicable to various ranges of spatio-temporal scales, and the models need to connect phenomena on different spatio-temporal scales.

[R&D subject 2] Create multicellular materials systems

Development of multicellular materials systems which enable specific advanced functions and adaptivity must be progressed. Based on the models or theories demonstrated in R&D subject 1, desired multicellular materials systems need to be (A) designed and (B) constructed. Firstly, for (A) designing the systems, components called modules are to be defined with correlations between the inputs and outputs. Then, the systems will be designed based on the combination of modules. Standardization of modules and development of system simulation tools are also required. Furthermore, for (B) constructing the systems, fabrication and assembly techniques must be advanced to make and integrate modules. Moreover, monitoring and feedback techniques are required to modulate the systems continually.

To promote these R&D subjects, cooperation among engineering applications, approaches via biotechnology and materials technology, and fundamental physicochemical interpretation is required. Therefore, we propose the following actions.

[Action 1] Establish a leading research community and discuss continuously beyond disciplines and stakeholders

A leading research community involving relevant academic and industrial communities need to be established. Active discussions in the community should promote the R&D subjects. Also, the community will function as an organizer for technology governance toward social implementation.

[Action 2] Launch long-term projects based on team collaboration

Research projects must be conducted involving several teams comprised of researchers from diverse disciplines. The projects promote R&D subject 1 and 2, coordinating within and across the subjects. Through a sufficient R&D period (~10 years), research findings and products should be led to social implementation seamlessly.

[Action 3] Found a research center

A research center needs to be found for promoting interdisciplinary research collaboration, developing and securing human resources, and constructing research infrastructure such as databases and platform for research tools.

Through these actions, the R&D subjects will be executed efficiently, and research outcome will be maximized in the medium- to long-term. Furthermore, these actions will encourage new entry of researchers, incubate unique research ideas, and develop human resources for the next generation. Thereby, research environment for this new research field will be established toward the long-time sustainable progress.