Hydrogel-Mediated Preservation of Live Tumor Explants for Drug Development in Peritoneal Metastases.

Abstract

Clinically effective treatments for peritoneal metastases (PM) remain a significant unmet need. To expedite drug development in PM, hyaluronan (HA) hydrogel-supported PM patient-derived tumor explants (PDTE) that better preserve histological features, composition, and biological pathways of the original tumor, as compared to conventional PDTE culture methods are developed. Hydrogel modulation shows that stiffness, degradation, three-dimensional embedding, and HA itself are key parameters that enhance PDTE maintenance ex vivo. Further, HA hydrogels effectively preserve PDTE viability by disrupting myosin II-mediated tissue contraction, a phenomenon that occurs in the absence of hydrogel embedding. Lastly, the addition of ascites into PM PDTE not only recapitulates changes to the tumor microenvironment as observed in patients but also ascites-dependent drug efficacy, highlighting the importance of incorporating ascites into ex vivo PM models for accurate therapeutic evaluation. The bioengineered PM PDTE models in this study serve as a valuable platform for drug development and treatment personalization.