From organ to system: multiorgan-on-a-chip platforms as next-generation biomedical simulators

Abstract Organs in the human body exist within a highly integrated and dynamically interacting environment, and their interactions are critical for maintaining normal physiological processes. Traditional cell culture models and animal models fail to meet the needs of preclinical research, as they struggle to fully recapitulate in vivo physiology and pathology. Thus, innovative in vivo platforms are urgently needed to bridge the gaps between preclinical research and clinical translation. Multiorgan-on-a-chip (multi-OoC), an emerging field in bioengineering, offers precise control over cellular microenvironments and recapitulates organ-level functions and interorgan crosstalk. By mimicking complex human physiology and pathophysiology, multi-OoC systems provide novel opportunities for disease modeling, drug discovery, and personalized medicine. This paper will systematically elaborate on the necessity of developing multi-OoC systems, delve into their structural design and biomanufacturing strategies, and highlight their recent applications in biomedical research. Additionally, it will analyze key challenges such as the establishment of standardized operating procedures and the validation of model outputs, and envision their application prospects in the field of personalized medicine. The aim is to provide a reference for promoting the standardization and clinical translation of this technology.