# Repair by Local Infusion of Sulfides (ReLIS™) for Treatment of Disadvantaged Surgical Incisions

> **NIH NIH R43** · EXHALIX, LLC · 2022 · $300,396

## Abstract

Project Summary/Abstract
The proposed effort addresses the need for a novel therapeutic tool that improves the recovery of at-risk surgical incisions.
There are 48.3 million surgical procedures performed in the United States each year, 1/3 of which are performed on
individuals older than 65. Among this population, a significant number suffer from endothelial dysfunction and impaired
blood flow leading to peripheral artery disease and chronic limb threatening ischemia (CLTI), thus requiring lower limb
revascularization. Despite a recent surge in the number of percutaneous and endovascular interventions, open surgery is
still a preferred method of revascularization for a large number of CLTI cases due to long term durability, lower rate of
restenosis and better hemodynamic efficiency in certain anatomies. Given the high cost of readmission related to post-
operative healing complications, there is a critical need for development of advanced techniques to address the at-risk
and disadvantaged incision healing failure. Hydrogen sulfide (H2S), an endogenous VOC and recently recognized as a
gasotransmitter, has been shown to promote angiogenesis-related behavior in endothelial cells through activation of
pathways that include nitric oxide signaling and the canonical HIF-1 and VEGF-A-mediated angiogenesis cascade. There
is also significant evidence linking deficiency in endogenous H2S to endothelial dysfunction and consequently
microvascular disorder and poor perfusion. Systemic administration of (exogenous) H2S donors have been shown to
markedly improve the rate of regeneration in ischemic tissue. However, systemic and widespread delivery of H2S can lead
to unintended consequences including hypotension, hepatotoxicity, and malignant angiogenesis. This leaves a significant
opportunity for individualizing patient care through targeted, precision delivery of H2S. In the proposed SBIR Phase I study,
we intend to demonstrate a unique therapeutic system that locally delivers a precisely controlled exogenous amount
needed to sustain the concentration of H2S at the target location within a therapeutic window by transdermally detecting
the local endogenous and exogenous H2S levels. In this collaborative effort between Exhalix and the University of New
Mexico School of Medicine, we will show the feasibility and merits of this sustained ReLIS™ therapeutic approach for
treatment of surgical incisions on small animal models. We anticipate that the proposed feasibility study will last 12
months and success in reaching our objectives will lead to a Phase II effort for development of prototypes and
demonstration on larger animals.

## Key facts

- **NIH application ID:** 10474641
- **Project number:** 1R43AG076027-01A1
- **Recipient organization:** EXHALIX, LLC
- **Principal Investigator:** Reza Shekarriz
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $300,396
- **Award type:** 1
- **Project period:** 2022-08-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474641

## Citation

> US National Institutes of Health, RePORTER application 10474641, Repair by Local Infusion of Sulfides (ReLIS™) for Treatment of Disadvantaged Surgical Incisions (1R43AG076027-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10474641. Licensed CC0.

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