Music-inspired acoustic-piezoelectric stimulation accelerates extracellular vesicle production and programs...

Area of Science:

• Biomaterials Science
• Cell Biology
• Regenerative Medicine

Background:

• Macrophage small extracellular vesicles (sEVs) show therapeutic potential for immunomodulation and regeneration.
• Current limitations include low sEV production rates and inadequate control over their function.
• Macrophage phenotype (M1/M2) influences sEV cargo and bioactivity.

Purpose of the Study:

• To develop a novel method for enhancing macrophage sEV biogenesis and controlling their therapeutic function.
• To investigate the use of acoustic stimulation via a piezoelectric nanofiber substrate (PES) for sEV production and macrophage polarization.

Main Methods:

• Fabrication of a music-activated piezoelectric nanofiber substrate (PES).
• Application of programmable electrical stimulation derived from audible sound to macrophage cultures.
• Tuning acoustic parameters (frequency, dissonance/consonance) to modulate macrophage polarization and sEV yield.
• Characterization of sEV cargo and bioactivity based on macrophage phenotype.

Main Results:

• Adjusting acoustic parameters significantly increased sEV yield.
• Specific sound stimuli (low-frequency, dissonant vs. higher-frequency, consonant) biased macrophages towards M1-like (inflammatory) or M2-like (regenerative) phenotypes, respectively.
• Distinct sEV cargo and bioactivities were observed corresponding to the induced macrophage phenotypes.
• Optimized acoustic stimulation maximized both sEV production and M2-like polarization, yielding sEVs with enhanced regenerative potential.

Conclusions:

• A programmable acoustic-piezoelectric strategy effectively enhances macrophage sEV production.
• This method allows for precise tuning of macrophage phenotypes and sEV bioactivity for therapeutic applications.
• The developed platform offers a scalable approach for producing tailored sEVs for immunomodulation and regeneration.