Latest developments of microphysiological systems (MPS) in aging-related and geriatric diseases research: a review.

Aging is a gradual and irreversible process accompanied by the decline in tissue function and a significantly increased risk of various aging-related and geriatric diseases. Especially in the paradoxical context of accelerated global aging and the widespread emergence of pandemics, aging-related and geriatric diseases have become leading causes of individual mortality and disability, drawing increasing attention from researchers and investors alike. Despite the utility of current in vitro systems and in vivo animal models for studying aging, these approaches are limited by insurmountable inherent constraints. In response, microphysiological systems (MPS), leveraging advances in tissue engineering and microfluidics, have emerged as highly promising platforms. MPS are capable of replicating key features of the tissue microenvironment within microfabricated devices, offering biomimetic tissue culture conditions that enhance the in vitro simulation of intact or precise human body structure and function. This capability improves the predictability of clinical trial outcomes while reducing time and cost. In this review, we focus on recent advancements in MPS used to study age-related and geriatric diseases, with particular emphasis on the application of organoids and organ-on-a-chip technologies in understanding cardiovascular diseases, cerebrovascular diseases, neurodegenerative diseases, fibrotic diseases, locomotor and sensory degenerative disorders, and rare diseases. And we aim to provide readers with critical guidelines and an overview of examples for modeling age-related and geriatric diseases using MPS, exploring mechanisms, treatments, drug screening, and other subsequent applications, from a physiopathological perspective, emphasizing the characteristic of age-related and geriatric diseases and their established correlations with the aging process. We also discuss the limitations of current models and propose future directions for MPS in aging research, highlighting the potential of interdisciplinary approaches to address unresolved challenges in the field.