Multiphysics-Driven Assembly of Biomimetic Vesicles.

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.