Advanced in vitro cell culture systems or microphysiological systems (MPSs), including microfluidic organ‐on‐a‐chip (OoC), are breakthrough technologies in biomedicine. These systems recapitulate features of human tissues outside of the body. They are increasingly being used to study the functionality of different organs for applications such as drug evolutions, disease modeling, and precision medicine. Currently, developers and endpoint users of these in vitro models promote how they can replace animal models or even be a better ethically neutral and humanized alternative to study pathology, physiology, and pharmacology. Although reported models show a remarkable physiological structure and function compared to the conventional 2D cell culture, they are almost exclusively based on standard passive polymers or glass with none or minimal real‐time stimuli and readout capacity. The next technology leap in reproducing in vivo‐like functionality and real‐time monitoring of tissue function could be realized with advanced functional materials and devices. This review describes the currently reported electronic and optical advanced materials for sensing and stimulation of MPS models. In addition, an overview of multi‐sensing for Body‐on‐Chip platforms is given. Finally, one gives the perspective on how advanced functional materials could be integrated into in vitro systems to precisely mimic human physiology.

New cell-imprint surface modification techniques based on direct-cell photolithography and optical soft lithography using poly­(dimethylsiloxane) (PDMS) cell imprints are presented for enhanced cell-based studies. The core concept of engineering materials for cell-based studies is the material’s ability to redesign the physicochemical characteristics of the cellular niche. There is a growing interest in direct molding from cells (cell imprinting). These negative copies of cell surface topographies have been shown to affect cell shape and direct mesenchymal stem cells’ differentiation. Analyzing the results is however challenging as cells seeded on these substrates do not always end up in a cell pattern, which leads to decreased effectiveness and biased quantification. To gain control over cell seeding into the patterns and avoid unwanted cell population outside of the patterns, the cell-imprinted surface needs to be modified. From this perspective, the standard optical contact lithography process was modified and cells were introduced to the cleanroom. Direct-cell photolithography was used for a single-step PDMS cell-imprint (chondrocytes as the molding template) surface modification down to single-cell (approximately 5 μm in diameter) resolution. As cells come in a variety of shapes, sizes, and optical profiles, a complementary optical soft lithography-based photomask fabrication technique is also reported. The simplicity of the fabrication process makes this cell-imprint surface modification technique compatible with any adherent cell type and leads to efficient cell-based studies.

There is little evidence demonstrating the effects of electromagnetic fields (EMFs) generated within the biological entity and the effect of extrinsic fields on cellular programing. Taking the path of the more studied stimuli into attention, mechanical forces, it could be understood that nonchemical factors play a consequential role in transcriptional regulatory networks. Cartilaginous tissue consists of collagen protein that is considered as a piezoelectric substrate and is influenced by electric fields making chondrogenic specific genes an exciting candidate for bioelectromagnetic studies. As electromagnetic properties highly depend on the frequencies applied, this study delves into the ability of two EMFs with the frequency of 25 Hz and 50 Hz in inducing SOX9 and COL2 gene expressions in a three-dimensional (3D) mesenchymal stem cell (MSC)-alginate construct. Cell-alginate beads were divided into six groups and treated for a time period of 21 days. To determine the results, qualitative and quantitative data were both reviewed. On observation of real-time polymerase chain reaction (PCR) data, it was apparent that TGF-β1 treatment had a greater COL2 and SOX9 gene expression impact on MSCs compared to pulsed electromagnetic field (PEMF) treatments alone. COL2 was shown to have a greater transcriptional tendency to PEMF, whereas under defined electromagnetic parameters applied in this study, no significant difference was detected in SOX9 gene expressions compared to the control group. PEMF co-treatments enhanced the deposition of extracellular matrix molecules, as the matrix-rich beads were positively stained by Alcian blue. This genre of study is the venue for the control and healing of connective tissue defects.

Electroporation is defined as cell membrane permeabilization under the application of electric fields. The mechanism of hydrophilic pore formation is not yet well understood. When cells are exposed to electric fields, electrical stresses act on their surfaces. These electrical stresses play a crucial role in cell membrane structural changes, which lead to cell permeabilization. These electrical stresses depend on the dielectric properties of the cell, buffer solution, and the applied electric field characteristics. In the current study, the effect of electric field frequency on the electrical stresses distribution on the cell surface and cell deformation is numerically and experimentally investigated. As previous studies were mostly focused on the effect of electric fields on a group of cells, the present study focused on the behavior of a single cell exposed to an electric field. To accomplish this, the effect of cells on electrostatic potential distribution and electric field must be considered. To do this, Fast immersed interface method (IIM) was used to discretize the governing quasi-electrostatic equations. Numerical results confirmed the accuracy of fast IIM in satisfying the internal electrical boundary conditions on the cell surface. Finally, experimental results showed the effect of applied electric field on cell deformation at different frequencies.