Tuning microenvironment for multicellular spheroid formation in thermo-responsive anionic microgel scaffolds

Tumor spheroids are considered to be effective in drug screening and evaluation. Three-dimensional scaffold-based cell culture becomes very promising in producing multicellular spheroids. Different from other approaches, 3D scaffolds mimic in vivo cellular microenvironment which encourages intercellular and extracellular interactions. The properties of the cellular microenvironment include the surface wettability, chemistry, and charge of the scaffolds which may influence cell attachment, proliferation as well as migration and these properties are essential for multicellular spheroids formation. Through co-polymerization with different carboxylic acids, we demonstrate that the surface charge density and hydrophobicity of the microenvironment have a great impact on the tumor spheroids formation progress and their size distribution. Our results show that a scaffold with a moderate negative charge density and a highly hydrophilic surface promotes cell proliferation, resulting in quicker and larger spheroids formation. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2899-2909, 2018.