# Pathways underlying recovery of injured urethral sphincter and a novel regenerative biomaterial intervention

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $557,778

## Abstract

PROJECT SUMMARY
Dysfunction of the striated external urethral sphincter is the strongest predictor of stress urinary incontinence,
defined as involuntary loss of urine due to increased intraabdominal pressure in the absence of bladder
contraction. Stress urinary incontinence affects approximately 1 in 2 women at some point in their lives. The
primary inciting event behind the development of chronic stress urinary incontinence has been unequivocally
identified as injury to the urinary continence mechanism sustained by women during vaginal deliveries. This
astoundingly prevalent condition dramatically decreases quality of life, causes significant morbidity, and is
associated with large economic burden to the individuals and society. Despite this, preventative strategies are
almost non-existent, and the available treatments are delayed and compensatory as they do not directly target
the underlying pathophysiology. The above is largely due to the fact that our understanding of the pathways that
lead to failure of the intrinsic muscular components of the external urethral sphincter following birth injury remains
limited. Furthermore, the prevailing preclinical studies do not utilize biologically relevant pregnant animal model
of birth injury. To address the existing unmet clinical need and knowledge gaps, we assembled a cross-
disciplinary team with diverse but complimentary expertise to execute the current project at the interface between
basic science, biomaterial development, and translational medicine. We will use a validated and biologically
relevant pregnant pre-clinical model to investigate structural, molecular, and cellular events at multiple time
points across a recovery continuum of the striated external urethral sphincter following birth injury. These basic
processes will inform the development of and the critical time to deliver new, minimally invasive tissue-
engineered therapy for the prevention and treatment of urethral muscle dysfunction. Specifically, we will test a
novel pro-regenerative skeletal muscle-specific injectable extracellular matrix hydrogel, derived from
decellularized porcine skeletal muscles, in preventing and reversing maladaptive recovery of the external urethral
sphincter following birth injury. Collectively, this innovative study will provide fundamental knowledge of the
biological processes involved in the regulation of external urethral sphincter muscle regeneration, and
comprehensive functionally relevant assessments of the role of low-cost acellular minimally invasive
regenerative therapy to counteract the existing epidemic of urinary incontinence.

## Key facts

- **NIH application ID:** 10186348
- **Project number:** 1R01DK128639-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Marianna Alperin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $557,778
- **Award type:** 1
- **Project period:** 2021-07-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10186348

## Citation

> US National Institutes of Health, RePORTER application 10186348, Pathways underlying recovery of injured urethral sphincter and a novel regenerative biomaterial intervention (1R01DK128639-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10186348. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*