Abstract:

Organoid and organ-on-a-chip technologies are three-dimensional tissue structures that are cultivated in vitro from stem cells or tissue-derived primary cells. They replicate the functions and microenvironments of actual organs, allowing researchers to study biological processes and disease mechanisms more accurately. This offers new possibilities for establishing in vitro disease models, drug screening, and personalized medicine. In vitro-constructed organoids could potentially be used as anti-aging or regenerative therapies to replace diseased or aging tissues in the future. However, the current construction of organoid models still presents numerous problems and challenges. To simulate the microenvironment of human organs accurately and to understand the functional relationship between various components, constructing organoids face challenges in terms of cell complexity and diversity, tissue structure, geometrical morphology, and functional component integrity. This review proposes an integrated design strategy based on engineering principles to tackle these challenges and to optimize organoid technologies. The aim is to examine following five key bioengineering elements: integrating essential cell types, constructing macroscopic and microscopic structures, controlling and mimicking developmental processes, establishing cellular interactions, and designing for different functional purposes. The article establishes a systematic connection between biological elements and the technological interventions in organ and disease development. The optimization of organoids-on-a-chip technology involves multiple fields, including biology, medicine, mechanobiology, optics, materials science, biofabrication, and computational modeling. This allows for collaboration among teams with different areas of expertise, all focused on improving organoids and organ-on-a-chip technologies. Such collaboration is necessary to enhance in vitro culture, tissue development, functional acquisition, dynamic monitoring, and standardization. Furthermore, the integration of high-dimensional data sets in digital twin organoid systems can aid in the management, analysis, and tracking of big data in organoids and organ-on-a-chip. These advancements can lead to more accurate disease analysis, improved predictions, and early intervention strategies, ultimately advancing precision medicine into a new era of preemptive healthcare.

Key words: engineered organoids, organoids-on-a-chip, integrated design strategies, interdisciplinary, digitalized organoids

摘要：

类器官和类器官芯片技术是一种由干细胞或特定类型的细胞在体外培养而成的模拟真实器官功能和微环境的三维组织结构，帮助研究者更准确地研究生物过程、疾病机制，为体外疾病模型的建立、药物筛选和个性化医疗提供了新的可能性。然而，当前类器官模型的构建还存在无法全面、准确模拟体内生物过程的诸多问题。为应对这一挑战，本文将讨论利用基于工程化原理的整合设计策略，指导类器官与类器官芯片技术的进一步优化，并通过将器官发育和疾病发展中的生物要素与跨学科工程方法建立合理的系统性联系，实现类器官在时间维度和空间维度上高度模拟体内器官自组织过程、结构与形态构建、生物功能获取的目标。进一步，利用整合高维数据集的数字孪生类器官系统，实现对类器官与类器官芯片的大数据管理、分析、追踪，将有助于更准确地进行疾病分析、指导预测、提出提前干预方案，推动精准医疗向“治未病”时代的进步。

关键词: 工程化类器官, 类器官芯片, 整合设计策略, 跨学科, 数字化类器官