关键词: Biomimetics High throughput Microphysiological system Multidimensional drug screening Organ-on-a-chip

来  源:   DOI:10.1016/j.bioactmat.2024.05.019   PDF(Pubmed)

Abstract:
Spheroids and organoids have attracted significant attention as innovative models for disease modeling and drug screening. By employing diverse types of spheroids or organoids, it is feasible to establish microphysiological systems that enhance the precision of disease modeling and offer more dependable and comprehensive drug screening. High-throughput microphysiological systems that support optional, parallel testing of multiple drugs have promising applications in personalized medical treatment and drug research. However, establishing such a system is highly challenging and requires a multidisciplinary approach. This study introduces a dynamic Microphysiological System Chip Platform (MSCP) with multiple functional microstructures that encompass the mentioned advantages. We developed a high-throughput lung cancer spheroids model and an intestine-liver-heart-lung cancer microphysiological system for conducting parallel testing on four anti-lung cancer drugs, demonstrating the feasibility of the MSCP. This microphysiological system combines microscale and macroscale biomimetics to enable a comprehensive assessment of drug efficacy and side effects. Moreover, the microphysiological system enables evaluation of the real pharmacological effect of drug molecules reaching the target lesion after absorption by normal organs through fluid-based physiological communication. The MSCP could serves as a valuable platform for microphysiological system research, making significant contributions to disease modeling, drug development, and personalized medical treatment.
摘要:
类球体和类器官作为疾病建模和药物筛选的创新模型已经引起了极大的关注。通过使用各种类型的球体或类器官,建立提高疾病建模精度和提供更可靠、更全面的药物筛选的微生理系统是可行的。支持可选的高通量微生理系统,多种药物的并行测试在个性化医疗和药物研究中具有广阔的应用前景。然而,建立这样一个系统非常具有挑战性,需要多学科的方法。这项研究介绍了具有多功能微结构的动态微生理系统芯片平台(MSCP),这些微结构涵盖了上述优点。我们开发了高通量肺癌球体模型和肠-肝-心-肺癌微生理系统,对四种抗肺癌药物进行平行测试,证明了MSCP的可行性。这种微生理系统结合了微观和宏观生物模拟物,可以对药物疗效和副作用进行全面评估。此外,微生理系统能够评估药物分子通过基于流体的生理通讯被正常器官吸收后到达靶病变的真实药理作用。MSCP可以作为微生理系统研究的有价值的平台,为疾病建模做出了重大贡献,药物开发,和个性化医疗。
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