Wireless mechano-electrical stimulation of pudendal nerve using piezoelectric platform for stress urinary incontinence

利用压电平台无线机电刺激阴部神经治疗压力性尿失禁

• 批准号: 10629570
• 负责人: Metin Uz
• 金额: $ 43.52万
• 依托单位: CLEVELAND STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10629570
• 关键词: Action Potentials; Affect; Anatomy; Anxiety; Brain-Derived Neurotrophic Factor; Cell Survival; Cells; Clinic; Clinical; Cues; Denervation; Deterioration; Discipline; Economic Burden; Economics; Electric Stimulation; Electrodes; Engineering; Exercise; Exposure to; Feasibility Studies; Generations; Health; Home; Hour; Human; Human Resources; Implant; In Vitro; Incontinence; Injury; Kegel exercise; Life; Mechanics; Mental Depression; Metals; Methods; Microfluidics; Modeling; Motor Neurons; Movement; Muscle; Natural regeneration; Nerve; Nerve Entrapment; Nerve Regeneration; Neuronal Injury; Neurons; Operative Surgical Procedures; Patients; Pelvic floor structure; Penetration; Performance; Physical activity; Polymers; Population; Postoperative Period; Pregnant Women; Prevalence Study; Property; Quality of life; Rattus; Recovery; Recovery of Function; Rehabilitation therapy; Reporting; Research; Risk; Running; Safety; Schwann Cells; Site; Social isolation; Sphincter; Stress Urinary Incontinence; Stretching; Symptoms; Testing; Therapeutic; Time; Tissues; Toxic effect; Treatment Efficacy; Urethral sphincter; Urinary Incontinence; Urology; Vaginal delivery procedure; Woman; biomaterial compatibility; blind; clinical translation; cytokine; design; electric field; exercise rehabilitation; experience; flexibility; implantation; in vivo; injured; innovation; mechanical force; mechanical properties; nerve injury; neurotrophic factor; prototype; regenerative; reinnervation; response; simulation; stem cell therapy; success; technology platform; translational approach; urinary; wireless

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.

项目摘要 /摘要 压力尿失禁（SUI）是许多女性阴道后经历的常见尿疾病 送货。据报道，约有55％的孕妇患有尿失禁症状。而约20-45％ 这种人口经验在阴道分娩后持续存在的SUI，其余的人口仍处于发展的风险 尽管自发恢复，但生活中的尿失禁。阴道后造成损害对底膜神经（PN）的损害 递送导致再生细胞因子和神经营养蛋白的表达降低（即脑源性 神经营养因子（BDNF）），然后随后对外部尿道括约肌（EUS）进行修饰。它有 已显示使用直接电刺激（ES）对PN的特定靶向可以提供PN再生 通过神经营养蛋白分泌（即BDNF）受伤的神经元和内源性schwann细胞（SC），可以是 被认为是SUI治疗的潜在替代方法。但是，这种方法的临床翻译可能是 由于以下原因而挑战：（1）由于其解剖学课程导致PN很难找到PN 固定电极的困难。 （2）在手术期间只能在术中应用ES（仅一次 〜1小时）。 （3）由于电极的侵入性和盲渗透，术后多个ES很难应用 缺乏精确，准确和局部治疗。 （4）通过金属电极的ES需要专业人员，并且 不允许按需自我治疗。在这个项目中，基于压电材料的生物降解和 提议植入平台作为启用无线，本地和按需机械的替代方法 PN的电刺激（MES）用于术后SUI治疗。为此，将追求三个目标 完成可行性研究。在AIM 1中，灵活的袖口电极集成的压电平台将是 设计，制造和特征。产生的压电反应和体外降解曲线 将确定控制MES条件。在AIM 2中，压电平台的体外性能将 根据生物相容性，安全性和治疗功效进行评估。体内研究的试点也将是 进行用于评估平台的手术程序和植入的进行 生物相容性和生物降解性。在AIM 3中，植入的MES产生的MES的治疗性能 平台将在RAT SUI模型上进行验证。将确定子阈值MES值，并体内 压电平台的治疗功效将通过跑步锻炼和详细评估 组织化学和功能恢复测试。这些目标的成功完成将引入 创新的设计压电平台可实现PN的本地，无线和术后MES。长时间 术语，此压电平台可以与Kegel练习协同结合，以提供本地MES 康复的凯格尔运动以促进PN再生和加剧，这是一种开创性和创新的 可以在SUI治疗的泌尿外科领域发生范式转移的策略。