Advancing tumor organoid 3D culture with functionalized hydrogels: Applications in precision medicine and technological challenges

Abstract

Traditional tumor models are limited by short in vitro survival, pronounced interspecies differences, and inadequate recapitulation of tumor heterogeneity. This review systematically classifies hydrogels into matrix-supporting, signal-regulating, and stimulus-responsive categories based on functional characteristics, and summarizes the fabrication strategies of natural, synthetic, and composite hydrogels. Tumor organoids preserve the genotype and phenotype of primary tumors; their integration with hydrogels provides complementary advantages, enabling the reconstruction of biomimetic tumor microenvironments, long-term in vitro culture, and personalized tumor modeling. Hydrogel-tumor organoid systems therefore demonstrate substantial value in tumor model development, high-throughput drug screening, and the investigation of drug resistance mechanisms. However, several challenges remain, including insufficient matching of mechanical properties, batch-to-batch variability of hydrogels, stringent organoid culture requirements, and the lack of standardized protocols—among which the standardization of natural hydrogels represents a major barrier to clinical translation. Finally, this review highlights emerging technological directions, including intelligent hydrogels and 3D bioprinting, outlines trends in interdisciplinary integration, and discusses future clinical application prospects. Addressing issues related to standardization and cost will be critical for fully unlocking the potential of hydrogel-organoid platforms in precision oncology.

Keywords

Hydrogels / Tumor organoids / Tumor models / Precision medicine

References

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