Abstract

Traditional cell culture is experiencing a revolution moving toward physiomimetic approaches aiming to reproduce healthy and pathological cell environments as realistically as possible. There is increasing evidence demonstrating that biophysical and biochemical factors determine cell behavior, in some cases considerably. Alongside the explosion of these novel experimental approaches, different bioengineering techniques have been developed and improved. Increased affordability and popularization of 3D bioprinting, fabrication of custom-made lab-on-a chip, development of organoids and the availability of versatile hydrogels are factors facilitating the design of tissue-specific physiomimetic in vitro models. However, lower oxygen diffusion in 3D culture is still a critical limitation in most of these studies, requiring further efforts in the field of physiology and tissue engineering and regenerative medicine. During recent years, novel advanced 3D devices are introducing integrated biosensors capable of monitoring oxygen consumption, pH and cell metabolism. These biosensors seem to be a promising solution to better control the oxygen delivery to cells and to reproduce some disease conditions involving hypoxia. This review discusses the current advances on oxygen biosensors and control in 3D physiomimetic experimental models.

Highlights

  • Traditional cell culture is experiencing a revolution moving toward physiomimetic approaches aiming to reproduce healthy and pathological cell environments as realistically as possible

  • In addition to the ethical concerns that arise from their use in research, animal models often give a poor prediction for the responses of subsequent human clinical trials [1]

  • In spite of efforts focused on mimicking the native extracellular matrix (ECM), especially with biomaterials developed from decellularized tissues and organs, using the current technologies it is not possible to build a functional complex organ which can be used for transplantation [12]

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Summary

Physiomimetic In Vitro Models

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The use of animal models has the advantage that all real-life cell interactions are included, but it has the limitations inherent to being carried out in species other than human. On the other hand, do not generally reflect the complexity of the cellular microenvironment found in vivo: two-dimensional plastic cultures, which historically have been the first choice for in vitro assays, are known to present a nonphysiological microenvironment for the cells, potentially leading to abnormal cellular function and limiting the applicability of the obtained results [2]. In vitro tests usually are carried out under nonphysiological conditions and without the interactions with other cell types experienced in the organism. There is a current need for the development of physiomimetic in vitro models that permit the analysis of intercellular and tissue interactions in a more relevant organ context [3].

Extracellular Matrix Scaffolds for Experimental Models
Physioxia
Hypoxia and Oxidative Stress
Oxygenation in 3D Experimental Models
Spatiotemporal
Bioreactors and Oxygen Control
Findings
Conclusions and Perspectives

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