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.
