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

Kenny Zhuoran Wu1, Rockie Haiyao Ding1, Zixuan Zhao2

  • 1Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, Singapore, 119276, Singapore.

Advanced Materials (Deerfield Beach, Fla.)
|May 20, 2025
PubMed

Insights

New hyaluronan hydrogels improve patient-derived tumor explants (PDTE) for peritoneal metastases (PM) research. This advanced model better preserves tumor characteristics and predicts drug efficacy, aiding treatment development.

Area of Science:

  • Biomedical Engineering
  • Oncology
  • Drug Development

Background:

  • Peritoneal metastases (PM) lack effective clinical treatments, necessitating improved preclinical models.
  • Conventional patient-derived tumor explants (PDTE) often fail to accurately represent the original tumor's biology ex vivo.
  • Developing advanced models is crucial for accelerating drug discovery and personalized medicine in PM.

Purpose of the Study:

  • To develop hyaluronan (HA) hydrogel-supported PDTE for peritoneal metastases (PM) that better preserve tumor characteristics.
  • To investigate the role of hydrogel properties and ascites in enhancing ex vivo PDTE models.
  • To establish a more accurate platform for evaluating therapeutic efficacy in PM.

Main Methods:

  • Engineered hyaluronan (HA) hydrogels to embed patient-derived tumor explants (PDTE) from peritoneal metastases (PM).
  • Investigated hydrogel parameters (stiffness, degradation, 3D embedding) and HA's effect on PDTE maintenance.
  • Incorporated patient ascites into the ex vivo model to mimic the tumor microenvironment.

Main Results:

  • HA hydrogels significantly enhanced PDTE maintenance by preserving histological features, composition, and biological pathways.
  • Hydrogel embedding disrupted myosin II-mediated tissue contraction, improving PDTE viability.
  • The inclusion of ascites recapitulated the tumor microenvironment and revealed ascites-dependent drug efficacy.

Conclusions:

  • Bioengineered HA hydrogel-supported PDTE offer a superior platform for studying peritoneal metastases ex vivo.
  • This model accurately reflects tumor characteristics and predicts drug responses, crucial for therapeutic evaluation.
  • The developed model facilitates drug development and personalized treatment strategies for peritoneal metastases.
Keywords:
drug developmenthyaluronan hydrogelspatient‐derived tumor explantsperitoneal metastasespersonalized oncology

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