Fully synthetic nanofibrillar hydrogel for the growth and enzyme-free release of patient-derived ovarian tumor organoids.

Abstract

Patient-derived tumor organoids (PTOs) closely recapitulate the histopathology, gene expression, and drug response of patient tumor tissues, thereby making them highly reliable in vitro models in preclinical cancer research. Currently, basement membrane extracts (BME or Matrigel) dominate the in vitro culture of PTO models, although BME hydrogels suffer from batch-to-batch variability, possible contamination of murine host cells, and non-tunable mechanical properties. Here, we design and prepare fully synthetic thermoreversible nanofibrillar hydrogels (TNHs) for the growth and enzyme-free release of ovarian PTOs. PTOs cultured in TNHs exhibit morphological, histological, and gene expression similarities to organoids grown in Matrigel and their corresponding tumor tissues. In addition, the on-demand release of PTOs without loss of cell viability and organoid integrity is achieved upon cooling. The released PTOs show a strong tumorigenic ability by xenografts of PTOs in mice. The results show that the fully synthetic TNHs is a highly promising alternative to BME for the establishment of ovarian PTOs in vitro.