# Partial Bladder Outlet Obstruction: Mechanisms of Injury and Novel Repair Strategies

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $316,198

## Abstract

PROJECT SUMMARY/ABSTRACT
 Functional and anatomical obstruction of the urinary bladder from congenital and acquired urologic
abnormalities results in reduced bladder capacity, diminished compliance, urothelial dysfunction, and
incontinence. Enterocystoplasty is utilized as the primary strategy to increase bladder capacity and decrease
high intravesical pressures to preserve renal function in patients with obstructive bladder disease. However, the
presence of absorptive intestinal epithelium in autologous gastrointestinal grafts frequently leads to serve
complications such as chronic urinary tract infection, mucus production, and metabolic abnormalities once
integrated into the urinary tract. Silk fibroin (SF) biomaterials provide an exceptional combination of physical
characteristics including high tensile strength and elasticity, diverse processing flexibility, controllable
degradability, and low immunogenicity to create “off-the-shelf” scaffolds for treatment of obstructive bladder
disease. Novel bladder reconstructive strategies employing bi-layer (BL) SF scaffolds impregnated with SF
hydrogels capable of targeted intravesical delivery of anti-fibrotic therapeutics, halofuginone, ABT-263, and pan-
TGF-β neutralizing antibodies will be developed and investigated for their ability to restore normal urodynamic
parameters and promote superior constructive remodeling in a newly developed, large animal model of partial
bladder outlet obstruction (pBOO). In this proposal, we will challenge the overall hypothesis that: composite
BLSF matrices loaded with SF hydrogels capable of intravesical release of anti-fibrotic compounds will provide
a superior approach for restoring normal bladder function in chronically obstructed bladders in comparison to
enterocystoplasty. The specific aims of the application are: Specific Aim 1: Evaluate the impact of chronic
pBOO on bladder regenerative processes following augmentation cystoplasty with BLSF scaffolds. Specific Aim
2: Develop composite BLSF grafts impregnated with SF hydrogels with the capacity for intravesical delivery of
anti-fibrotic agents and compare their efficacy for reconstruction of chronically obstructed bladders to
enterocystoplasty.

## Key facts

- **NIH application ID:** 10130517
- **Project number:** 5R01DK119240-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Carlos R Estrada
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $316,198
- **Award type:** 5
- **Project period:** 2019-12-18 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130517

## Citation

> US National Institutes of Health, RePORTER application 10130517, Partial Bladder Outlet Obstruction: Mechanisms of Injury and Novel Repair Strategies (5R01DK119240-04). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10130517. Licensed CC0.

---

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