A ferroelectric living interface for fine-tuned exosome secretion toward physiology-mimetic neurovascular remodeling

Establishing vascular neural networks is critical for tissue regeneration. However, none of the existing approaches can replicate the physiological processes that varying extracellular cues sequentially play parts in different phases, thus hindering synergistic neurovascular remodeling. Here, we report a ferroelectric living interface for fine-tuned exosome secretion (LIFES) that harnesses unique topographical and electric (piezoelectric and photopyroelectric) signals and sustained generation of bioactive exosomes by rationally constructing a ferroelectric layer and a living cell layer. The LIFES exhibits physiology-mimicking paracrine effects, including sustained (∼192 h), phase-specific exosome secretion with tunable contents (∼8-fold increases) and programmable microRNA (miRNA) cargoes (initially pro-angiogenic and later pro-neurogenic), which overcome the limitations of the existing exosome delivery systems, such as short lifetime (∼24–48 h), difficult-to-preserve bioactivity, and non-changeable cargoes. LIFES allows for enhanced effectiveness in promoting neurovascular remodeling both in vitro and in challenging diabetic wound models, opening new avenues for next-generation intelligent materials and biomedical devices.