The effects of insulin-like growth factor-1 and basic fibroblast growth factor on the proliferation of chondrocytes embedded in the collagen gel using an integrated microfluidic device.

This work presents an integrated microfluidic device on which the proliferation of rabbit chondrocytes was investigated in the presence of insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (bFGF), and their combinations. The microfluidic device was mainly composed of an upstream concentration gradient generator and a downstream perfusion-based three-dimensional cell culture module. The rabbit articular chondrocytes were cultured for 2 weeks at the different concentrations of growth factors generated by concentration gradient generator. IGF-1, up to 57.14 ng/mL, had the ability to promote the proliferation of chondrocytes in a dose-dependent manner, and there were no further promotions at higher concentrations. bFGF increased chondrocyte proliferation dose dependently up to 5.72 ng/mL, and then the proliferation rate decreased when the concentration was increased. The combination of IGF-1 and bFGF could synergistically promote the proliferation, and the group of 85.73 ng/mL IGF-1 and 1.43 ng/mL bFGF presented an optimal effect (up to 4.76-fold), which had statistically significant differences compared with IGF-1 and bFGF, respectively. Moreover, the proliferation test using the conventional method was performed simultaneously and revealed similar results. The results obtained in this study demonstrated that the microfluidic device is an effective platform for cartilage tissue engineering. With this device, experimental conditions are flexible and can be optimized by changing either the category of growth factors or the concentration of input growth factor. Further, the small number of cells (1-100) required, with which parallel experiments could be performed simultaneously, makes it an attractive platform for the high-through screening at the cellular level in autologous chondrocyte implantation.