Toward Dynamic Biointerface Toxicology of Micro- and Nanoplastics Using Organoids and Organ-on-a-Chip Models

Abstract Micro- and nanoplastic (MNP) toxicity depends on the exposure conditions under which particles encounter biological tissues, yet nominal material descriptors alone do not resolve these conditions. Environmental transformation, biomolecular adsorption, aggregation, and chemical release can alter particle delivery and biological interactions. This Review evaluates these processes alongside evidence from organoids and organ-on-a-chip models, distinguishing direct MNP findings from analogue studies and demonstrations of platform capability. We propose exposure identity as an analytical framework connecting particle history and state with tissue encounter and subsequent processing over time. The synthesis examines what available studies establish about tissue access, barrier responses, distal relay, and susceptibility, and where interpretation remains constrained by exposure characterization or unresolved mechanisms. Human-derived models provide opportunities to investigate tissue-specific responses, but neither biological complexity nor perfusion establishes environmental representativeness or predictive validity. We identify measurement and control requirements for separating particle transfer from chemical release and tissue-derived signaling, interpreting absent effects, and evaluating heterogeneous exposures. Priorities include traceable delivered-dose measurements, synchronized exposure and response sampling, targeted mechanistic tests, and independent validation for a defined use. The proposed framework organizes evidence and testable relationships while retaining uncertainty about generalization to human exposure and health outcomes.