Hydrogel‐Mediated Preservation of Live Tumor Explants for Drug Development in Peritoneal Metastases
Abstract
AbstractClinically 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.
Article Details
Authors (17)
Kenny Zhuoran Wu
Department of Biomedical Engineering National University of Singapore 15 Kent Ridge Crescent Singapore 119276 Singapore
Rockie Haiyao Ding
Department of Biomedical Engineering National University of Singapore 15 Kent Ridge Crescent Singapore 119276 Singapore
Zixuan Zhao
Clara Yieh Lin Chong
Laboratory of Applied Human Genetics Division of Medical Sciences National Cancer Center Singapore 30 Hospital Boulevard Singapore 168583 Singapore
Ruochii You
Department of Biomedical Engineering National University of Singapore 15 Kent Ridge Crescent Singapore 119276 Singapore
Hengjia Zhou
Department of Biomedical Engineering National University of Singapore 15 Kent Ridge Crescent Singapore 119276 Singapore
Dong Hua Seah
Department of Biomedical Engineering National University of Singapore 15 Kent Ridge Crescent Singapore 119276 Singapore
Wei Qiang Leow
Department of Anatomical Pathology Division of Pathology Singapore General Hospital 20 College Road Singapore 169856 Singapore
Hong Kit Lim
School of Materials Science and Engineering Nanyang Technological University 50 Nanyang Avenue Singapore 639798 Singapore
Sukanya Shyamasundar
Department of Anatomy Yong Loo Lin School of Medicine National University of Singapore Singapore 117594 Singapore
Kanishka Fernando
Department of Biomedical Engineering National University of Singapore 15 Kent Ridge Crescent Singapore 119276 Singapore
Fathima Farzana Kuthubudeen
Department of Biomedical Engineering National University of Singapore 15 Kent Ridge Crescent Singapore 119276 Singapore
Gillian Ng
Laboratory of Applied Human Genetics Division of Medical Sciences National Cancer Center Singapore 30 Hospital Boulevard Singapore 168583 Singapore
Chor Yong Tay
School of Materials Science and Engineering Nanyang Technological University 50 Nanyang Avenue Singapore 639798 Singapore
Narayanan Gopalakrishna Iyer
Division of Surgical Oncology National Cancer Center Singapore 30 Hospital Boulevard Singapore 168583 Singapore
Chin‐Ann Johnny Ong
Laboratory of Applied Human Genetics Division of Medical Sciences National Cancer Center Singapore 30 Hospital Boulevard Singapore 168583 Singapore
Eliza Li Shan Fong
Department of Biomedical Engineering National University of Singapore 15 Kent Ridge Crescent Singapore 119276 Singapore