Abstract

Abstract Hypoxia and acidity are key characteristics of the tumor microenvironment (TME). Gelatin methacryloyl (GelMA) is a versatile biomaterial extensively utilized in various biomedical fields. Studies have shown that during the photocrosslinking process of GelMA hydrogel, the commonly used photoinitiator Irgacure 2959 consumes oxygen and induces an acidic and hypoxia environment. However, there is currently limited research on its involvement in the three-dimensional (3D) culture of tumor cells. Therefore, we constructed a 3D culture system utilizing GelMA hydrogel and investigated its influence on the growth and drug response of lung cancer cells (A549). The results demonstrated that the GelMA hydrogel-based 3D culture system exhibited excellent biocompatibility and robust mechanical properties and provided an acidic microenvironment conducive to tumor cell proliferation. Furthermore, the cancer cells exhibited heightened sensitivity to chemotherapeutics in this 3D culture model. These results suggest that the GelMA hydrogel-based 3D culture system can serve as a perfect model for in vitro study of tumor cells.

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