Wireless mechano-electrical stimulation of pudendal nerve using piezoelectric platform for stress urinary incontinence - PROJECT SUMMARY / ABSTRACT Stress urinary incontinence (SUI) is a common urinary condition that many women experience after vaginal delivery. It is reported that ~55% of pregnant women have symptoms of urinary incontinence. While ~20-45% of this population experience persistent SUI after vaginal delivery, the remaining population is still at risk to develop incontinence later in life despite the spontaneous recovery. The damage to the pudendal nerve (PN) after vaginal delivery causes decreased expression of regenerative cytokines and neurotrophins (i.e., brain-derived neurotrophic factor (BDNF)) followed by subsequent denervation of the external urethral sphincter (EUS). It has been shown that the specific targeting of PN using direct electrical stimulation (ES) can provide PN regeneration via neurotrophin secretion (i.e., BDNF) of injured neurons and endogenous Schwann Cells (SC) and can be considered as a potential alternative for SUI treatment. However, clinical translation of this approach may be challenging due to the following reasons: (1) PN is difficult to locate because of its anatomical course leading to difficulties in fixing the electrodes. (2) ES can only be applied intraoperatively during the surgery (only once for ~1 hour). (3) Postoperative multiple ES is difficult to apply due to invasive and blind penetration of electrodes lacking precise, accurate, and local treatment. (4) ES via metal electrodes requires professional personnel and does not allow on-demand self-treatment. In this project, a piezoelectric material-based biodegradable and implantable platform is proposed as an alternative approach to enable wireless, local, and on-demand mechano- electrical stimulation (MES) of PN for postoperative SUI treatment. For this purpose, three aims will be pursued to complete the feasibility studies. In Aim 1, flexible cuff electrode-integrated piezoelectric platform will be designed, fabricated, and characterized. The generated piezoelectric response and in vitro degradation profile will be determined to control MES conditions. In Aim 2, the in vitro performance of the piezoelectric platform will be evaluated in terms of biocompatibility, safety, and therapeutic efficacy. A pilot in vivo study will also be conducted for evaluating the surgical procedure and implantation of the platform along with the in vivo biocompatibility and biodegradability. In Aim 3, therapeutic performance of generated MES by the implanted platform will be validated on rat SUI model. The subthreshold MES value will be determined, and the in vivo therapeutic efficacy of piezoelectric platform will be evaluated by running wheel exercise and detailed histochemical and functional recovery tests. The successful completion of these aims will introduce an innovatively engineered piezoelectric platform enabling local, wireless, and postoperative MES of PN. In the long term, this piezoelectric platform can be synergistically combined with Kegel exercise to provide local MES upon rehabilitative Kegel movements to promote PN regeneration and reinnervation, a pioneering and innovative strategy that can generate a paradigm shift in the urology field for SUI treatment.
