Dynamic negative pressure enhances MSC-derived exosomes treatment for vessel injury-related erectile dysfunction by facilitating cavernous diffusion

Exosomes (Exos) have demonstrated significant efficacy in the treatment of erectile dysfunction (ED). However, their clinical application is limited by immediate dilution and rapid release upon entry into the bloodstream, reducing targeted delivery efficiency. Moreover, there is a dearth of research on the use of exosomes for vessel injury-related erectile dysfunction (VI-ED). A dynamic negative pressure (DNP) system was developed to validate the facilitative effect of DNP on targeted Exos infiltration into the corpus cavernosum. Using a high-fat diet and surgical intervention, we established a VI-ED model and employed DNP for exosomes delivery to VI-ED rats to validate the efficacy of Exos in ameliorating erectile dysfunction and elucidate their specific mechanisms both in vivo and in vitro. Negative pressure can facilitate the infiltration of MSC-derived Exos into the penile corpus cavernosum. Compared with sustained negative pressure, DNP exhibits twofold greater delivery efficiency (p < 0.05), thereby enhancing the targeted delivery efficiency of Exos. Moreover, Exos delivered by DNP promote vascular remodeling and inhibit phenotypic transformation through the modulation of the PTEN/PI3K/AKT signaling pathway. The findings of this study demonstrate that DNP, as a noninvasive delivery modality, facilitates the targeted infiltration of Exos and augments the therapeutic efficacy of VI-ED.