Abstract
Artificial extracellular vesicles (AEVs) are programmable, biomimetic materials that combine the structural and biological complexity of naturally secreted extracellular vesicles (NEVs) with the design flexibility of synthetic nanomaterials. A multiphysics-driven microfluidics is developed to efficiently integrate the nanoknife-assisted membrane rupture with flow dynamics and acoustothermal modulation for the reproducible, high-yield, scalable, and standardized production of AEVs. Compared to empirical mechanical processes, this integrated microfluidic workflow, which exploits physical and biological insights for EV production, enables multiphysics-based predictions for a precise control of material inputs, flow dynamics, and cell-knife interactions within the channel. The biomimetic AEVs developed through this integrated, optimized single-flow platform, with a sustained and efficient therapeutic encapsulation process, preserve native protein architectures to conduct biomimetic mechanisms of immune modulation and homologous targeting. The standardizable microfluidic platform paves the way for a structure-process-function design strategy, enabling the formation of scalable, adaptive biomaterials for the development of bioinspired interfacial engineering and biomedicine.