Computational and experimental studies of a cell-imprinted-based integrated microfluidic device for biomedical applications

Abstract

It has been proved that cell-imprinted substrates molded from template cells can be used for the re-culture of that cell while preserving its normal behavior or to differentiate the cultured stem cells into the template cell. In this study, a microfluidic device was presented to modify the previous irregular cell-imprinted substrate and increase imprinting efficiency by regular and objective cell culture. First, a cell-imprinted substrate from template cells was prepared using a microfluidic chip in a regular pattern. Another microfluidic chip with the same pattern was then aligned on the cell-imprinted substrate to create a chondrocyte-imprinted-based integrated microfluidic device. Computational fluid dynamics (CFD) simulations were used to obtain suitable conditions for injecting cells into the microfluidic chip before performing experimental evaluations. In this simulation, the effect of input flow rate, number per unit volume, and size of injected cells in two different chip sizes were examined on exerted shear stress and cell trajectories. This numerical simulation was first validated with experiments with cell lines. Finally, chondrocyte was used as template cell to evaluate the chondrogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs) in the chondrocyte-imprinted-based integrated microfluidic device. ADSCs were positioned precisely on the chondrocyte patterns, and without using any chemical growth factor, their fibroblast-like morphology was modified to the spherical morphology of chondrocytes after 14 days of culture. Both immunostaining and gene expression analysis showed improvement in chondrogenic differentiation compared to traditional imprinting methods. This study demonstrated the effectiveness of cell-imprinted-based integrated microfluidic devices for biomedical applications.

Integrative lymph node-mimicking models created with biomaterials and computational tools to study the immune system

“…By using in silico models to inform the processes from initial seeding of organoid models to maturation and organization, spatiotemporal predictions of organoid properties can be improved [ 301 ]. Computational methods can also provide insight when developing microfluidic devices, such as informing constructing microstructures based on organ-tissue specific architectures and features, as well as predicting fluid flow profile in the microchannels [ 302 , 303 ]. For example, through combining micro-computed tomography scan, artificial intelligence approach and high-resolution bioprinting, high accurate on-a-chip platforms which can mimic tiny complex organs are possible to be created [ 304 ].…”

Molecular imprinting as a simple way for the long-term maintenance of the stemness and proliferation potential of adipose-derived stem cells: an in vitro study

“…After centrifuging the homogenate at 2000 rpm for five minutes, the deposited cell pellet was suspended and cultured in DMEM supplemented with 10% FBS and 1% Pen/Strep under common cell culture conditions (37 °C, 5% CO 2 , in a humidified atmosphere). 2,47,59…”

“…Then the mold was peeled off from the tissue culture plate and rinsed thoroughly with 1 M NaOH solution for 30 minutes to eliminate any residual cell debris and existing chemicals from the imprinted substrates. 2,49,54,55,59…”

3D bioprinting of articular cartilage: Recent advances and perspectives

“…The material flow can be simulated to interconnect biomaterial properties (rheology, density), printing parameters (speed, temperature), needle geometry and length, extrusion-related mechanical forces and predict the mechanical stress applied on the cells during printing [120]. Simulation results have been validated with experimental results in a study using a cell-imprinted-based microfluidic device [121]. The study shows that parameters such as injection speed, size and number of cells, notably MSCs and chondrocytes, as well as channel dimensions can be selected to define the experimental conditions without wasting time and materials.…”