Evaluation of Drug Combinations for Aging-Related Multimorbidity Management Using a 3D Printed Human Multi-Organ Microphysiological System

IF 11.6 1区工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY

Engineering Pub Date : 2025-08-26 DOI:10.1016/j.eng.2025.08.026

Jing Wang, Yuxiu Wang, Yakun Wang, Yueyang Qu, Bingcheng Lin, Xiuli Zhang, Yong Luo

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引用次数: 0

Abstract

Polypharmacy presents a critical challenge in the management of age-related multimorbidity, in which empirical combination therapies may inadvertently exacerbate drug toxicity through complex pharmacokinetic interactions. To address this issue, a three-dimensional (3D) printed human multi-organ microphysiological system (HMOMPS) was developed featuring induced pluripotent stem cell (iPSC) differentiation, 3D cell spheroids, and a multi-drug scoring system. This engineered platform simulated co-occurring cancer and cardiomyopathy and systematically evaluated single-agent and combination therapies through dynamic toxicity monitoring. The system provided quantitative comparisons of mechanistically distinct drug combinations to support the clinical demand of multi-target interventions. Recognizing the interplay between polypharmacy and aging, we induced cellular senescence to establish a geriatric 3D HMOMPS model, which revealed significant age-dependent variations in pharmacodynamics across identical drug regimens. Experimental validation demonstrated the capacity of the 3D HMOMPS to maintain preserved cellular viability and functionality while recapitulating inter-organ communication. These findings advance the use of microphysiological systems in personalized anti-aging pharmacotherapy for multimorbid conditions.

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使用3D打印人体多器官微生理系统对衰老相关多疾病管理的药物组合进行评估

多种药物治疗在治疗与年龄相关的多种疾病中提出了一个关键的挑战，在这种情况下，经验性联合治疗可能会通过复杂的药代动力学相互作用无意中加剧药物毒性。为了解决这一问题，研究人员开发了一个三维（3D）打印的人体多器官微生理系统（HMOMPS），该系统具有诱导多能干细胞（iPSC）分化、3D细胞球体和多药物评分系统。这个工程平台模拟癌症和心肌病的共同发生，并通过动态毒性监测系统地评估单药和联合治疗。该系统提供了机制上不同的药物组合的定量比较，以支持多靶点干预的临床需求。认识到多药与衰老之间的相互作用，我们诱导细胞衰老建立了一个老年3D HMOMPS模型，该模型揭示了相同药物方案中药效学的显着年龄依赖性变化。实验验证表明，3D HMOMPS能够在再现器官间通信的同时保持细胞活力和功能。这些发现促进了微生理系统在多种疾病的个体化抗衰老药物治疗中的应用。

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来源期刊

Engineering Environmental Science-Environmental Engineering

自引率

1.60%

发文量

335

审稿时长

35 days

期刊介绍： Engineering, an international open-access journal initiated by the Chinese Academy of Engineering (CAE) in 2015, serves as a distinguished platform for disseminating cutting-edge advancements in engineering R&D, sharing major research outputs, and highlighting key achievements worldwide. The journal's objectives encompass reporting progress in engineering science, fostering discussions on hot topics, addressing areas of interest, challenges, and prospects in engineering development, while considering human and environmental well-being and ethics in engineering. It aims to inspire breakthroughs and innovations with profound economic and social significance, propelling them to advanced international standards and transforming them into a new productive force. Ultimately, this endeavor seeks to bring about positive changes globally, benefit humanity, and shape a new future.