Additive Manufacturing for Extracellular Vesicle Therapeutics: Engineering Strategies for Production, Isolation, and Delivery.

Abstract

Despite the therapeutic promise of extracellular vesicles (EVs) in regenerative medicine, immunotherapy, and targeted drug delivery, translation to the clinic remains constrained by persistent manufacturing bottlenecks, including low yields, poor purity-recovery trade-offs, inconsistent cargo composition, variable product quality, and limited scalability. Additive manufacturing (AM) technologies present new strategies to overcome these hurdles by enabling precise control over biomaterial composition, microarchitecture, and spatial organization across three pipeline areas: EV production, isolation and purification, and scaffold-based delivery. This review examines AM applications across those EV production pipeline nodes. We analyze how AM variables - matrix stiffness, scaffold geometry, shear conditions, and crosslinking chemistry - affect EV yield, cargo composition, membrane integrity, and functional potency. By linking engineering approaches with biological considerations, we highlight AM's potential to unify manufacturing efficiency with therapeutic performance, while addressing limitations in throughput, standardization, and translational readiness.