# Intrasurgical tissue engineering of autologous grafts using irreversible electroporation for bladder reconstruction

> **NIH NIH R01** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2021 · $349,187

## Abstract

PROJECT SUMMARY
Bladder reconstruction (BR) is essential to restore urinary function in patients with neurogenic bladder,
congenital disorders, and as sequalae to the surgical treatment of bladder or pelvic malignancies. The current
standard of care is to use the patient's own intestinal tissue (ileal segment; IS) as graft material during BR to
create a neobladder or urinary diversion. While IS grafts are non-immunogenic and readily available, post-
surgical persistence of intestinal cells in the graft impedes regeneration into bladder wall, resulting in stone
formation, metabolic acidosis and risk of secondary cancers. Our objective is to develop new technology for
intrasurgical tissue engineering of the IS by knockdown of cellular components using irreversible
electroporation (IRE) and identify factors fundamental for regeneration of functional bladder wall. IRE is used in
patients for tumor ablation by inducing cell death with ultrashort electric pulses. Our proposed strategy builds
upon our preliminary data showing (i) IRE can knockdown intestinal cells in an IS graft, aiding repopulation
with urothelium in a rat model of BR, (ii) feasibility of new pulse application strategies for the focal knockdown
of mucosa, or decellularization while preserving vasculature and ECM in the IS, and (iii) phenotypic changes in
IRE treated IS following urothelialization, that were not observed in sham controls under physiologic conditions
of bladder filling and voiding. In specific aim 1, we will Define the impact of graft perfusion on bladder wall
regeneration by performing vasculature sparing IRE of the IS. In specific aim 2, Elucidate the role of IS
mucosa in post-BR complications by knockdown with IRE. In specific aim 3, Investigate the role of
mechanotransduction in bladder function development in IRE treated IS. Intrasurgical creation of a perfused,
histocompatible graft (Aim 1) and focal decellularization of the mucosa while sparing the underlying layers in
the IS (Aim 2) are the first examples of in vivo knockdown tissue engineering using IRE. The study and
application of mechanotransduction principles to augment urinary barrier function development in IS grafts
(Aim 3) is previously undescribed. Knowledge gained from proposed research will yield a simple intrasurgical
technique (mt-IRE or vs-IRE) that combines technology (IRE) and grafting technique (with IS) that are already
in the clinic, enabling rapid translation for the immediate benefit of patients undergoing BR. Eventually, we
anticipate our work to advance the concept of in vivo production of functionalized grafts using the patient as the
source of biomaterial and the bioreactor, with application to reconstructive surgery involving other tubular
organs such as the esophagus, trachea or large blood vessels.

## Key facts

- **NIH application ID:** 10277714
- **Project number:** 1R01DK129990-01
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Govindarajan Srimathveeravalli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $349,187
- **Award type:** 1
- **Project period:** 2021-07-12 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10277714

## Citation

> US National Institutes of Health, RePORTER application 10277714, Intrasurgical tissue engineering of autologous grafts using irreversible electroporation for bladder reconstruction (1R01DK129990-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10277714. Licensed CC0.

---

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