# Drug Eluting Silk Fibroin Grafts for Repair of Long Urethral Strictures

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $625,761

## Abstract

PROJECT SUMMARY/ABSTRACT
 Pediatric and adult disorders of the urethra including hypospadias, trauma, and stricture disease
represent significant health care burdens which require surgical intervention to replace developmentally absent
or damaged tissue to preserve urinary tract function. Autologous tissue grafts derived from extragenital skin
flaps or buccal mucosa are primarily utilized to restore urethral continuity in cases where end-to-end anastomosis
is not feasible. However, these approaches have been associated with adverse side effects including stricture
recurrence, diverticulae and fistula formation. 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 urethral stricture
disease. Novel urethral reconstructive strategies employing bi-layer (BL) SF scaffolds impregnated with SF
hydrogels capable of targeted urethral delivery of stem cell homing factors, MCP1/CCL2 or SDF1α/CXCL12, will
be developed and investigated for their ability to restore normal micturition and promote superior constructive
remodeling in newly developed, large animal models of long urethral strictures in males and females. In this
proposal, we will challenge the overall hypothesis that: composite BLSF matrices loaded with SF hydrogels
capable of controlled release of MCP1/CCL2 or SDF1α/CXCL12 will provide a superior approach for restoring
function of long urethral strictures in comparison to buccal mucosal grafts. The specific aims of the proposal
are: Specific Aim 1: Determine the impact of CXCR4-SDF1α/CXCL12 and CCR2-MCP1/CCL2 signaling axes
on scaffold-mediated, urethral tissue regeneration in a rabbit model of urethral stricture repair. Specific Aim 2:
Create MCP-1/CCL2 and SDF1α/CXCL12 releasing, composite BLSF grafts with the capacity to promote
superior functional urethral regeneration in novel male and female porcine models of long urethral strictures.

## Key facts

- **NIH application ID:** 10774304
- **Project number:** 5R01DK131211-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Joshua Robert Mauney
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $625,761
- **Award type:** 5
- **Project period:** 2023-02-15 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10774304

## Citation

> US National Institutes of Health, RePORTER application 10774304, Drug Eluting Silk Fibroin Grafts for Repair of Long Urethral Strictures (5R01DK131211-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10774304. Licensed CC0.

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