Wu Kenny Zhuoran, Ding Rockie Haiyao, Zhao Zixuan, Chong Clara Yieh Lin, You Ruochii, Zhou Hengjia, Seah Dong Hua, Leow Wei Qiang, Lim Hong Kit, Shyamasundar Sukanya, Fernando Kanishka, Kuthubudeen Fathima Farzana, Ng Gillian, Tay Chor Yong, Iyer Narayanan Gopalakrishna, Ong Chin-Ann Johnny, Fong Eliza Li Shan
Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, Singapore, 119276, Singapore.
The N.1 Institute for Health, National University of Singapore, 28 Medical Drive, Singapore, 117456, Singapore.
Adv Mater. 2025 Aug;37(33):e2418647. doi: 10.1002/adma.202418647. Epub 2025 May 20.
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.
腹膜转移（PM）的临床有效治疗方法仍然存在重大未满足需求。为了加快PM的药物开发，与传统的患者来源肿瘤外植体（PDTE）培养方法相比，开发了透明质酸（HA）水凝胶支持的PM患者来源肿瘤外植体，其能更好地保留原始肿瘤的组织学特征、组成和生物学途径。水凝胶调节表明，硬度、降解、三维包埋和HA本身是增强PDTE体外维持的关键参数。此外，HA水凝胶通过破坏肌球蛋白II介导的组织收缩有效保持PDTE活力，这种现象在没有水凝胶包埋的情况下会发生。最后，向PM PDTE中添加腹水不仅重现了患者中观察到的肿瘤微环境变化，还重现了腹水依赖性药物疗效，突出了将腹水纳入体外PM模型以进行准确治疗评估的重要性。本研究中的生物工程PM PDTE模型是药物开发和治疗个性化的宝贵平台。
