Organoids in concert: engineering in vitro models toward enhanced fidelity

Organoids have emerged as a powerful platform for studying complex biological processes and diseases in vitro. However, most studies have focused on individual organoids, overlooking the inter-organ interactions in vivo and limiting the physiological relevance of the models. To address this limitation, the development of a multi-organoid system has gained considerable attention. This system aims to recapitulate inter-organ communication and enable the study of complex physiological processes. This review provides a comprehensive overview of the recent advancements in organoid engineering and the emerging strategies for constructing a multi-organoid system. First, we highlight the critical mechanical, structural, and biochemical factors involved in designing suitable materials for the growth of different organoids. Additionally, we discuss the incorporation of dynamic culture environments to enhance organoid culture and enable inter-organoid communication. Furthermore, we explore techniques for manipulating organoid morphogenesis and spatial positioning of organoids to establish effective inter-organoid communication networks. We summarize the achievements in utilizing organoids to recapitulate inter-organ communication in vitro, including assembloids and microfluidic multi-organoid platforms. Lastly, we discuss the existing challenges and opportunities in developing a multi-organoid system from its technical bottlenecks in scalability to its applications toward complex human diseases.