Orchestrating the Parkinson's disease microenvironment in 3D for pathogenesis study and therapeutic development.

Abstract

The incidence of Parkinson's disease (PD) has been steadily increasing globally, while traditional two-dimensional cell cultures and animal models face significant challenges in effectively elucidating its complex pathological mechanisms and screening potential drugs. Advanced<i>in vitro</i>models that incorporate patient-specific characteristics and three-dimensional (3D) microenvironments have emerged as powerful alternatives. This review first outlines current perspectives on PD etiology and pathogenesis, highlighting their implications for 3D modeling systems. A systematic comparison evaluates organoid, microfluidic, and 3D bioprinting platforms by leveraging their recent applications in PD mechanistic studies and therapeutic screening. The utilization of these cutting-edge technologies in PD model development not only deepens mechanistic insights but also streamlines therapeutic innovation, paving the way for effective treatments against this debilitating neurodegenerative disorder.