4.1. Drug Discovery Allowing cells to acquire a more natural phenotype when grown in 3D as opposed to 2D is a great advantage. This is especially true for the field of drug discovery where countless examples have been shown of the mismatch between in vitro drug effect and in vivo drug efficacy. 4.1.1. Cancer Already in 1990 an alginate culture method was used to test the effects of vincristine and 5‑fluorouracil on HT-29 human colon carcinoma cells [130]. Creating a more clinically relevant model of tumor biology has been a prime impetus for developing 3D culture systems. Burdett et al. [131] described the superiority of 3D over 2D cell culture where mimicking tumor behavior and drug resistance often seen in vivo is important. AlgiMatrix® is a commercial alginate-based product for 3D cell culture. Godugu et al. [110] demonstrate the possibility of using this culture system as an in vitro tumor model for anticancer drug screening. They treated several human non-small cell lung cancer cell lines (A549, H460, and H1650) with several anticancer drugs used in the clinic. 4.1.2. Safety and Toxicology HepG2 liver cells have been encapsulated in sterile alginate hydrogels and used to demonstrate their capability to metabolize a coumarin pro-drug in a manner similar to in vivo hepatic metabolic activity [132]. Another hepatic cell line, Huh-7, cultured in an alginate hydrogel showed cellular organization and hepatocyte architecture with respect to cell polarity, cell junctions and the appearance of bile canaliculi. The alginate-encapsulated Huh-7 cells also expressed specific hepatitis C virus receptors indicating that this 3D culture system may be useful in viral studied and liver tissue engineering [133]. Alginate encapsulation of hepatocytes provides protection from shear stress for hepatocyte aggregates in a 3D bioreactor cultures system [134]. In addition, the alginate hydrogel seems to provide the cells with a good support for extracellular matrix deposition.