Cellular and Functional Recuperation of Impaired Cavernous Nerve Mediated by a Personalized Cell-free Fibrous Bioimplant

Prostate cancer is one the most common cancer type worldwide, affecting more than 16% of men. Radical prostatectomy (RP) is the main curative treatment of localized cancer. However, 60-70% of the patients will suffer from postoperative erectile dysfunction (ED) due to the unintentional cavernous nerve (CN) damage. In this study, a personalized and specific bioactive cell-free fibrous implant was proposed for the permanent treatment of prostate cancer patients suffering from ED after being subject to RP. The bioactivity of the fibrous implant is conferred by the selectively bound nerve growth factor (NGF) present in the rat urine. The safety and efficacy profile of this implantable device to regenerate injured CN was investigated in vivo.

In the rat model, the personalized cell-free fibrous bioimplant improves recovery of the CN and restores erectile function within one month after bilateral CN crush. Such functional recovery was confirmed by: (i) a high score of penis glans exposure and erection; (ii) a 60% increase in the intracavernosal pressure; (iii) a low score of cavernous nerve atrophy and irregularity; (iv) a low score of fibroelastic tissue density and vascular lesion in corpus cavernosum tissue and (v) a low score of dorsal nerves demyelination and degeneration.

Our data suggests that the developed advanced bioimplant constitutes a neurodegenerative approach able to promote erectile functional recover. Therefore, this personalized regenerative strategy could overcome the recognized drawbacks of currently available treatments of CN injuries. This implantable device represents a new hope for prostate cancer patients suffering from ED after being subject to radical prostatectomy.

Acknowledgements: The authors would like to acknowledge the Portuguese Foundation for Science and Technology (FCT) for the PhD grant of M.R.C. (PD/BD/113797/2015) financed by the Doctoral Program on Advanced Therapies for Health (PATH) (FSE/POCH/PD/169/2013), and the projects PTDC/BTM-SAL/28882/2017, UIDB/04033/2020, PTDC/BTM-MAT/2844/2021 and NORTE-01-0145-FEDER-000055.