Impact of hydrogel biophysical properties on tumor spheroid growth and drug response

Abstract

The extracellular matrix (ECM) plays a critical role in regulating cell-matrix interactions during tumor progression. These interactions are due in large part to the biophysical properties responding to cancer cell interactions. Within in vitro models, the ECM is mimicked by hydrogels, which possess adjustable biophysical properties that are integral to tumor development. This work presents a systematic and comparative study on the impact of the biophysical properties of two widely used natural hydrogels, Matrigel and collagen gel, on tumor growth and drug response. The biophysical properties of Matrigel and collagen including complex modulus, loss tangent, diffusive permeability, and pore size, were characterised. Then the spheroid growth rates in these two hydrogels were monitored for spheroids with two different sizes (140 μm and 500 μm in diameters). An increased migratory growth was observed in the lower concentration of both the gels. The effect of spheroid incorporation within the hydrogel had a minimal impact on the hydrogel's complex modulus. Finally, 3D tumor models using different concentrations of hydrogels were applied for drug treatment using paclitaxel. Spheroids cultured in hydrogels with different concentrations showed different drug response, demonstrating the significant effect of the choice of hydrogels and their concentrations on the drug response results despite using the same spheroids. This study provides useful insights into the effect of hydrogel biophysical properties on spheroid growth and drug response and highlights the importance of hydrogel selection and in vitro model design.

Keywords: Biophysical properties; Cancer; Drug response; Extracellular matrix; Hydrogel; Spheroid.