# Synthesis of Hydrogel-Based Microgels and Nanogels Toward Therapeutic and Biomedical Applications
## 5 Therapeutic and Biomedical Applications of Micro- and Nano-Hydrogels
### Advanced Drug Screening  
Drug screening is a critical step in pharmaceutical development that identifies and evaluates potential therapeutic compounds [258]. Traditional drug screening models such as in vitro 2D cell culture or animal models often fail to mimic the complexity of human tissues and their microenvironment, which contributes to the extremely low success rate of drug development. Recent advances in the three-dimensional scaffolds specialized in mimicking human tissue environments, also known as organoids, have been highlighted for their ability to emulate physiological conditions of complex tissue or even organs [13; 14; 259; 260]. Hydrogel is an essential element to realize complex environments of ECM or tumor sites, enabling high-throughput, multiplexed platforms for drug screening.  
From the material perspective, PEG and polysaccharides have been widely adapted for this application. PEG-based hydrogels are particularly valued for the facile tunability of their properties and intrinsic biocompatibility, which enables controllability over the stiffness, porosity, or degradation kinetics of hydrogels. Polysaccharides can mimic the native ECM effectively while exhibiting essential features such as antimicrobial activity or pH sensitivity [176]. Although the application of microgels and nanogels in drug screening remains in its early stages, the focus on their unique advantages for drug delivery systems has been growing with the advances in organoid technologies. The synergistic combinationsof hydrogels as drug carriers and diverse organoid models such as brains, intestines, and cancer pose an eminent potential to bridge the gap between in vitro and in vivo models, ultimately toward a significant advancement in preclinical drug development.  
PEG-based hydrogel 3D matrices consisting of alkoxysilane-modified PEG reported by [PERSON] et al. compared the impacts of 3D and 2D environments to drug resistance evaluation, where a 3D model supported A2058 melanoma spheroid formation and showed an increased survival rate and higher resistance to daunorubicin treatment (Figure 7a) [261]. [PERSON] et al. utilized a polysaccharide-based bioink, VitroGel, to develop 3D tumor scaffolds for chemotherapeutic agent screening. The resulting system remained stable in physiological settings and successfully formed spheroids from non-small-cell lung cancer-derived xenograft cells. A drug sensitivity study revealed that the 3D-printed scaffolds showed significantly higher IC50 values for docetaxel, DOX, and erlotinib than 2D culture, highlighting the enhanced resistance associated with 3D TME (Figure 7b) [176]. [PERSON] and [PERSON] developed a 2D-3D hybrid co-culture platform based on alginate to encapsulate HepG2 liver cells and MCF-7 breast cancer cells. Ionically crosslinked hydrogel showed acceptable cell viability of >80% over 3 days without diffusion-limited nutrient deficiency. Overall, 3D models showed greater correlation with in vivo LD50 values and successfully demonstrated simultaneous hepatotoxicity and drug evaluations [98].