Organ-on-a-chip technology has gained great interest in recent years given its ability to control the spatio-temporal microenvironments of cells and tissues precisely. While physical parameters of the respective niche such as microchannel network sizes, geometric features, flow rates, and shear forces, as well as oxygen tension and concentration gradients, have been optimized for stem cell cultures, little has been done to improve cell-matrix interactions in microphysiological systems. Specifically, detailed research on the effect of matrix elasticity and extracellular matrix (ECM) nanotopography on stem cell differentiation are still in its infancy, an aspect that is known to alter a stem cell’s fate. Although a wide range of hydrogels such as gelatin, collagen, fibrin, and others are available for stem cell chip cultivations, only a limited number of elasticities are generally employed. Matrix elasticity and the corresponding nanotopography are key factors that guide stem cell differentiation. Given this, we investigated the addition of gold nanowires into hydrogels to create a tunable biointerface that could be readily integrated into any organ-on-a-chip and cell chip system. In the presented work, we investigated the matrix elasticity (Young’s modulus, stiffness, adhesive force, and roughness) and nanotopography of gold nanowire loaded onto fibrin hydrogels using the bio-AFM (atomic force microscopy) method. Additionally, we investigated the capacity of human amniotic mesenchymal stem cells (hAMSCs) to differentiate into osteo- and chondrogenic lineages. Our results demonstrated that nanogold structured-hydrogels promoted differentiation of hAMSCs as shown by a significant increase in Collagen I and II production. Additionally, there was enhanced calcium mineralization activity and proteoglycans formation after a cultivation period of two weeks within microfluidic devices.

We present a combination of micromachined optofluidic platforms equipped with a fiber-optic sensing configuration based on a three-path Mach–Zehnder interferometer (MZI) for simultaneous measurement of the refractive index of liquids and the autocalibration in dynamic regime. The sensing principle is based on the low-coherence interferometry, characterized by a generation of Gaussian enveloped interferograms, for which the position of its maximum depends on the optical path difference (OPD) between the sensing and reference arm of the MZI. When liquid flows through the central microchannel of the optofluidic platform it crosses the light beam between the two optical fibers in the sensing arm causing the OPD change. An algorithm has been applied for the calculation of the refractive index of liquids out of the raw interference signals. We obtained a very good agreement between the experimental results and literature data of refractive indices of subjected fluids. The accuracy of refractive index measurement is approximately 1%, predominantly determined by the accuracy of reading the position of the mechanical scanner. The proposed sensor is attractive for the label-free biological, biochemical, and chemical sensing owing autocalibration and high sensitivity yet consuming a very small sample volume of 1 µL. It is capable to measure the refractive index of various liquids and/or gases simultaneously in the process.

As centre of energy production and key regulators of metabolic and cellular signaling pathways, the integrity of mitochondria is essential for mesenchymal stem cell function in tissue regeneration. Alterations in the size, shape and structural organization of mitochondria are correlated with the physiological state of the cell and its environment and could be used as diagnostic biomarkers. Therefore, high-throughput experimental and computational techniques are crucial to ensure adequate correlations between mitochondrial function and disease phenotypes. The emerge of microfluidic technologies can address the shortcomings of traditional methods to determine mitochondrial dimensions for diagnostic and therapeutic use. This review discusses optical detection methods compatible with microfluidics to measure mitochondrial dynamics and their potential for clinical stem cell research targeting mitochondrial dysfunction.