Development of Biomimetic In-Vitro Cell Culture Models Integrating Mechanobiology and Mechanotransduction for Tissue Engineering and Theranostics

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Background

In the past decade, it has been found that multiple physico-chemical properties of the cellular microenvironment are impacting cells in a critical manner. Local architecture, geometry, composition, mechanics, surface chemistry and dynamic modifications of local adhesions between cells and matrix greatly influence cell shape, phenotype, function and even fate. In particular, it has been discovered that the cells are mechanosensitive units, capable of sensing and reacting rapidly to elastic and viscoelastic properties of their environment. Thanks to a complex stress-transmission chain from focal adhesions down to their nucleus, cells are affected by mechanics as much as by soluble molecules. Cell mechanotransduction and signalling are critical to study, especially when the objective is to construct in vitro biomimetic culture platforms for tissue engineering and theranostics. Furthermore, new models are needed in order to help us understand better the cell response to mechanics and to continue improving cellular models.

Recent research works in biomimetism, 3D microfabrication and bioprinting have led to important progress in materials science and microtechnology for possible applications in the development of biomedical solutions, especially in the field of cell culture platforms, where biomimetism is now sought. Although mechanotransduction processes at the extra- and intracellular levels are still not fully understood, the impact of apparent stiffness (elastic or nonlinear modules, viscoelastic relaxation effects and dynamic changes of mechanical properties while cells are cultured) suggests that common culture substrates are now obsolete, as the natural environment of the cells needs to be better imitated to offer meaningful results in tissue engineering and theranostics applications. In particular, from simple well plates to complex cell scaffolds and organ-on-chips, culture platforms require a proper integration of tailor-made mechanical cues. This will help to build better models that would enable the study of diseases that are related directly to mechanics, such as fibrosis, cancer or even aging for instance. Depending on the biological problem that needs to be studied or modeled in vitro, it is critical to develop platforms with specific physical properties of the microenvironment materials such as elastic stiffness, nonlinear viscoelastic dissipation and dynamic softening/stiffening. Efforts in materials science and engineering, including fabrication techniques, are needed to open the road to the construction of structures dedicated to mechanobiology studies (traction force microscopy, protein micro and nanopatterning, dynamic mechanical stress on chip, etc).

This Research Topic aspires to concentrate research papers, current opinions and reviews that will help a broad range of researchers and developers (biologists, medical doctors, engineers, physicists, chemists, materials scientists) to better understand all the processes that need to be taken into account in the design, fabrication and validation of biomimetic in vitro models, with applications in tissue engineering, diagnostics, drug testing and development before pre-clinical tests, personalized medicine and organ on chip development. We hope that this Topic becomes a toolbox for multidisciplinary teams that are discussing these important topics in order to design and validate new platforms and models for fundamental basic research and translational biotechnology applications such as drug testing, precision medicine and biosensing.

Keywords: mechanobiology, organ-on-chip, co-culture, biochip, microfluidics, biomimetics

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