# Engineering nitric oxide releasing polymer with immobilized thrombin inhibitor for blood contacting applications

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2022 · $370,870

## Abstract

Project Summary/Abstract
Currently, clinical applications of intravascular catheters suffer from major challenges: 1) platelet activation and
surface-induced thrombosis, 2) biofouling of surfaces with proteins and bacteria, and 3) infection. Thrombus
formation can further lead to obstruction of blood vessels, catheter malfunction, or even life-threatening situations
such as embolism. Bacterial contamination of catheters causes more than 28,000 deaths per year in the United
States, as well as costing the healthcare industry a staggering $2.3 billion. Commercial catheters with heparin-
bonded surfaces are available to prevent clotting, but do little to prevent infections. In additions, catheters coated
with antiseptics or antibiotics decrease the risk of bacterial infection, but do not prevent biofilm formation that
shields bacteria from antibiotics. Therefore, there is a necessity and opportunity to combine strategies for
preventing thrombosis and infection into single implantable device coatings for enhanced patency and safety.
Our work and others have demonstrated that nitric oxide (NO) release from polymer surfaces can prevent platelet
activation and bacterial infection. This technology mimics the vascular endothelial cells lining the blood vessels,
as well as other cells in our bodies, producing NO locally to prevent clotting and bacterial biofilm and subsequent
infections. Recently we discovered that all of the positive effects can be achieved from polymers impregnated
with the NO donor molecule S-nitroso-N-acetylpenicillamine (SNAP), which is nontoxic, inexpensive, and easy
to synthesize. Active NO release from the NO donor functionalities in the polymer reduces thrombosis and
bacterial infection polymer-blood interface; however, the NO-release strategy alone is limited by the finite
reservoir of NO donor functionalities within the polymer that limit the duration of the NO availability at the polymer-
blood interface and inability to prevent fibrin formation on the surface. Our recent work has shown the potential
of combining active NO-release with catalytic NO-generating mechanism in a single polymer. The goal of this
proposal is to develop a polymer comprised of a NO donor impregnated in the polymer to provide active
NO-release in combination with immobilized selenocystamine-heparin moieties to provide long-term NO-
generation and resist fibrin formation, resulting in a new generation of polymers that possess potent
broad-spectrum antimicrobial properties and reduce thrombosis by inhibiting platelet
adhesion/activation. The new polymers will be applicable to any blood-contacting device; however, this
proposal will focus on studying the combined NO-releasing, catalytic NO generation, and immobilized heparin
strategy in long-term (up to 30 d) intravascular catheters on clotting and infection. Successful completion of this
project will allow progression to early clinical trials and development of a new generation of catheters that can
reduce ...

## Key facts

- **NIH application ID:** 10367198
- **Project number:** 2R01HL134899-05
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Hitesh Handa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $370,870
- **Award type:** 2
- **Project period:** 2017-03-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367198

## Citation

> US National Institutes of Health, RePORTER application 10367198, Engineering nitric oxide releasing polymer with immobilized thrombin inhibitor for blood contacting applications (2R01HL134899-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10367198. Licensed CC0.

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