Agarose-collagen I hydrogels: impact of the matrix stiffness on the
growth of breast cancer cell lines spheroids and on drug penetration
Abstract
Three-dimensional (3D) cell culture systems mimic the structural
complexity of the tissue microenvironment that includes the
extracellular matrix (ECM) in addition to the cellular components Thus,
3D culture systems are increasingly important as they resemble the
ECM-cell and cell-cell physical interactions occurring in vivo. So far,
several scaffold-based culture systems and techniques have been proposed
as valuable approaches for large-scale production of spheroids, but
often suffering of poor reproducible conditions or high costs of
production. In this work we present a reliable 3D culture system based
on collagen I-blended agarose hydrogels and show how the variation of
the agarose weight percentage affects the physical and mechanical
properties of the resulting hydrogel, being that with a lower amount of
agarose more permeable, softer and more prone to degradation compared to
hydrogels with higher agarose concentrations. We have also evaluated the
effect of the different physical and mechanical properties of the
agarose hydrogels on the growth, size, morphology and cell motility of
spheroids obtained by culturing three different breast cancer cell lines
(MCF-7, MDA-MB-361and MDA-MB-231). As proof of concept, the cisplatin
penetration and its cytotoxic effect on the tumor spheroids was
evaluated as function of the hydrogel stiffness. Noteworthy, the
possibility to recover the spheroids from the hydrogels for further
processing and other biological studies has been also considered.