Hydrogel 3D in vitro tumor models for screening cell aggregation mediated drug response

Area of Science:

• Biomaterials Science
• Cancer Research
• Drug Discovery

Background:

• Hydrogel-based 3D in vitro models using tumor ECM-mimetic biomaterials show promise for preclinical drug testing.
• The optimal cellular arrangement (cell-laden vs. spheroid-embedded) within these hydrogels for anti-cancer therapeutics evaluation is unclear.

Purpose of the Study:

• To investigate the impact of cellular arrangement on cancer cell behavior and drug response within ECM-mimetic hydrogels.
• To compare the performance of 3D spheroid microtumors versus cell-laden MG-63 osteosarcoma platforms in hydrogel scaffolds.

Main Methods:

• Developed 3D spheroid microtumors and cell-laden MG-63 osteosarcoma platforms embedded in GelMA and Matrigel hydrogels.
• Utilized liquid overlay technique for spheroid assembly, ensuring reproducible size, morphology, and necrotic core formation.
• Screened lorlatinib drug performance on both model types after in vitro maturation.

Main Results:

• MG-63 spheroids within hydrogel scaffolds demonstrated significantly higher invasion and drug resistance compared to cell-laden hydrogel counterparts.
• The study revealed distinct physiological and drug response variations between randomly distributed cells and 3D spheroid microtissues in hydrogels.
• Spheroid assembly via liquid overlay successfully mimicked native tumor characteristics, including necrotic cores.

Conclusions:

• Cellular aggregation state significantly influences in vitro tumor modeling outcomes and drug response.
• Evaluating different cellular arrangements is essential for designing effective ECM-mimetic hydrogels for preclinical drug screening.
• 3D spheroid microtumor models offer a more physiologically relevant platform for anti-cancer drug evaluation.