Chemical engineering methods in analyses of 3D cancer cell cultures: Hydrodinamic and mass transport considerations

Abstract

A multidisciplinary approach based on experiments and mathematical modeling was used in biomimetic system development for three-dimensional (3D) cultures of cancer cells. Specifically, two cancer cell lines, human embryonic teratocarcinoma NT2/D1 and rat glioma C6, were immobilized in alginate microbeads and microfibers, respectively, and cultured under static and flow conditions in perfusion bioreactors. At the same time, chemical engineering methods were applied to explain the obtained results. The superficial medium velocity of 80 μm s-1 induced lower viability of NT2/D1 cells in superficial microbead zones, implying adverse effects of fluid shear stresses estimated as ∼67 mPa. On the contrary, similar velocity (100 μm s-1) enhanced the proliferation of C6 glioma cells within microfibers compared to static controls. An additional study of silver release from nanocomposite Ag/honey/alginate microfibers under perfusion indicated that the medium partially flows through the hydrogel (interstitial velocity of ∼10 nm s-1). Thus, a diffusion-advection-reaction model described the mass transport to immobilized cells within microfibers. Substances with diffusion coefficients of ∼10-9-10-11 m2 s-1 are sufficiently supplied by diffusion only, while those with significantly lower diffusivities (∼10-19 m2 s-1) require additional convective transport. The present study demonstrates the selection and contribution of chemical engineering methods in tumor model system development.

Keywords

• tumor engineering
• alginate hydrogel
• perfusion bioreactor
• mathematical modeling
• glioma c6 cell line
• embryonic teratocarcinoma nt2/d1 cell line