Development of perfusion-based microbioreactor platform capable of providing tunable dynamic compressive loading to 3-D cell culture construct: Demonstration study of the effect of compressive stimulations on articular chondrocyte functions

Mechanical compression plays an important role in modulating cell physiology. To precisely investigate the cellular response to compression, a stable culture condition is required. In this study, we developed a microbioreactor platform capable of providing dynamic compressive loading to the 3-D cell culture constructs under a steady environment. The mechanism of generating compression stimulation to cells is based on the pneumatically-driven deformation of a polydimethylsiloxane (PDMS) membrane, which then exerts compressive loading to the cultured cells through a micropillar. By modulating the magnitude and frequency of the applied pneumatic pressure, the compressive loading can be generated in a tunable manner. In this study, the quantitative relationship between the applied pneumatic pressure and the generated compressive strain on the culture construct was established. Moreover, the effects of compression on the cell viability and the metabolic and biosynthetic activities of articular chondrocytes were investigated. The results disclosed that the dynamic compressive loading (51.3% strain, 1 Hz) might up-regulate the metabolic activity and glycosaminoglycan biosynthesis of articular chondrocytes after 5 day culture. Overall, this study presents a micro cell culture device that is capable of exploring the effects of compressive loading on cell physiology in a precise, high-throughput, low-cost, and user-friendly manner.