iCELLS-CM aims to reinvent cellular and tissue mechanobiology and enhance its therapeutic applications through the development of a unique set of technologies for its research and efficient, safe, and sustainable implementation. The core of the project is the design, manufacture, testing, and validation of a unique set of modular and versatile mechanobiological labs-on-chips that facilitate a pioneering multiscale approach to mechanobiology, generate knowledge in this area, and decipher the potentially therapeutic effects of numerous mechanical stimuli on cells and tissues. To this end, the labs-on-chips will include inserts that address the study of the following levels: macro or tissular, using tissue engineering scaffolds or 3D/4D scaffolds inside them; meso or functional, using organoids as physiologically representative portions; and micro or cellular, thanks to bio-MEMS, with which to interrogate individual cells. For the first time, digital twins of these labs-on-chips will be obtained, with an approach that aims to become a reference for multiphysical and multiscale simulation. To achieve this, neural cellular automata (NCA) models will be programmed, adequately trained with experimental data from in vitro studies, which will allow modeling the behavior at the cellular level and predicting the responses of different cells to the microcosm of possible stimuli present in the cellular niche. These stimuli will be obtained through finite element simulations and will modulate the response of the NCA. The generated knowledge will be applied to the development of mechanobiological labs-on-chips for the study of three global health challenges:

1) Diabetes and its ulcerative processes.

2) Cancer and metastasis with an application to breast cancer.

3) Tissue engineering and regenerative medicine with applications to bone regeneration and angiogenesis.

These labs-on-chips for diabetes, cancer and metastasis, and tissue engineering, as well as their digital twins, will be shared as open resources as part of the open science strategy.

Open innovation actions will also be promoted, providing access to the unique technologies developed in iCELLS-CM and contributing to positioning the Community of Madrid as a global reference in mechanobiology. A «Synergy Grant» for the European Research Council and a set of R&D&I projects will be proposed to enhance the medium and long-term impacts of the project.