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Music-Inspired Acoustic-Piezoelectric Stimulation Accelerates Extracellular Vesicle Production and Programs
Biorxiv : the Preprint Server for Biology
|April 10, 2026
Summary
We developed a music-activated substrate to boost macrophage small extracellular vesicle (sEV) production. This strategy precisely controls sEV function for enhanced immunomodulation and tissue regeneration therapies.
Area of Science:
- Biomaterials Science
- Cell Biology
- Regenerative Medicine
Background:
- Macrophage small extracellular vesicles (sEVs) show therapeutic potential in immunomodulation and regeneration.
- Current limitations include low sEV yield and poor control over their functional properties.
Purpose of the Study:
- To develop a novel method for enhancing macrophage sEV production and function.
- To investigate the use of acoustic stimulation to control macrophage polarization and sEV bioactivity.
Main Methods:
- Utilized a music-activated piezoelectric nanofiber substrate (PES) to convert sound into electrical stimulation.
- Manipulated acoustic parameters (frequency, dissonance/consonance) to influence macrophage polarization (M1/M2).
- Analyzed sEV cargo and bioactivity based on induced macrophage phenotypes.
Main Results:
- Adjusting acoustic parameters significantly increased sEV yield.
- Low-frequency, dissonant stimuli promoted M1-like inflammatory sEVs.
- Higher-frequency, consonant stimuli favored M2-like regenerative sEVs with enhanced therapeutic potential.
- Customized music stimuli maximized both sEV production and M2-like regenerative properties.
Conclusions:
- Acoustic-piezoelectric stimulation is a viable strategy to enhance macrophage sEV biogenesis.
- This method allows for programmable tuning of macrophage polarization and sEV bioactivity.
- The developed strategy holds promise for scalable production of potent regenerative sEVs.

