Application of high throughput perfusion micro 3-D cell culture platform for the precise study of cellular responses to extracellular conditions -effect of serum concentrations on the physiology of articular chondrocytes

Mammalian cells are sensitive to extracellular microenvironments. In order to faithfully explore the physiological responses of cells to extracellular conditions, a steady, homogenous, and three-dimensional (3-D) culture environment is required because it can provide a more quantifiable and biologically-relevant culture condition. To achieve this, this study reports a perfusion micro cell culture platform encompassing 22 microbioreactor units for high throughput 3-D cell culture. The cell culture platform structurally consisting of a plug and a microbioreactor chamber module was simply fabricated by replica molding of polydimethylsiloxane (PDMS) polymer. The platform features in the proposed plug module with multiple molds incorporated, facilitating the preparation of cell encapsulated 3-D hydrogel constructs in a precise and efficient manner. This trait is found particularly useful for high-precision and high-throughput micro 3-D cell culture-based assay. In this study, the real value of the proposed platform to maintain a stable and homogenous culture condition was discussed. Besides, the application of the presented platform for precisely investigating the effect of serum concentration on the metabolic activities and biosynthetic abilities of articular chondrocytes was also demonstrated. As a whole, the proposed device has paved an alternative route to carry out high throughput micro-scale 3-D perfusion cell culture in a simple, cost-effective and precise manner. The promising applications include 3-D cell culture-based high throughput drug or toxicity testing/screening, or other investigations on the cell biology, where the precise quantification of the links between the cellular responses and extracellular conditions is required.