3D bioprinted microfluidic based osteosarcoma-on-a chip model as a physiomimetic pre-clinical drug testing platform for anti-cancer drugs

Abstract

Standard chemotherapeutic regimen for osteosarcoma (OS) treatment often leads to poor therapeutic outcome, primarily due to lack of an adequate representative model reflecting native OS structural and cellular complexity, posing a translational gap. Three-dimensional bioprinting (3D-BP) represents an efficient and advanced technique for precise recapitulation of the structural and cellular complexity of OS tumor microenvironment (TME). In the present study, we employed a dual extrusion-based 3D-BP method to develop an improved in vitro OS model consisting of both tumor and stromal components. Additionally, a human physiomimetic microfluidic bioreactor is introduced to mimic the dynamic TME and provide physiologically relevant mechanical stimulation to the cells. The model named TC-OS _Dynamic model, demonstrated close resemblance to native OS-TME, validated by in vitro studies. Continuous media flow provided mechanical stimulation in the form of shear stress, positively influencing the growth and aggressiveness of OS. Further, drug screening with the model anticancer drugs (doxorubicin, cis-platin, sorafenib) demonstrated enhanced sensitivity in TC-OS _Dynamic model as compared to TC-OS _Static model, emphasizing enhanced mass transfer, availability and distribution of anticancer drug due to continuous media flow. Overall, TC-OS _Dynamic model holds significant potential as a platform in future for high throughput pre-clinical screening of anticancer drugs.