# Pulmonary Valved Graft with Regeneration Potential for Pediatric Patients

> **NIH NIH R44** · ANNOVIANT, INC · 2024 · $833,493

## Abstract

Congenital heart diseases (CHD) refer to abnormalities present in the heart and the great vessels at birth.
CHD is the most commonly diagnosed birth defect and the leading cause of birth-related mortality. These
abnormalities can be a single defect or a combination of multiple defects that can alter the blood flow to and/or
from the heart to the body. CHD affects approximately 40,000 newborns annually in the US and 1.35 million
globally. The prevalence of CHD in the US population has been estimated to be close to 2.9 million patients,
which represents about 25% of the total number of CHD cases worldwide. Among patients with CHD, around
22% of the total critical CHDs are affected by anomalies that impact the right ventricular outflow tract (RVOT),
such as tetralogy of Fallot (ToF), pulmonary atresia, truncus arteriosus, and transposition of the great vessels.
Replacement valves and conduits are needed to replace structures that are congenitally absent or hypoplastic
in these conditions and restore normal blood flow.
The choice of materials for RVOT reconstruction in CHD patients remains a controversial and inadequate area
of study. Although glutaraldehyde-fixed bovine jugular vein (BJV) (Contegra) is a commonly used material due
to its unlimited availability and lack of antigenic reaction, complications such as stenosis at the distal
anastomosis of the conduit, aneurysm, or pseudoaneurysm have been reported in 6-50% of patients, with an
increased risk of infection after implantation. The glutaraldehyde crosslinking process results in a stiff and
calcification-prone tissue material, leading to early failure of the bioprosthetic device. Recent studies have
highlighted that the early failure of bioprosthetic valves may not only be attributed to calcification but also to
non-calcification mechanisms such as accumulation of advanced glycation end products (AGEs), altered
collagen microstructure, and elevated tissue crosslinking. Glutaraldehyde treatment also prevents cellular
repopulation of the tissues, making them incapable of cell-mediated remodeling and leading to the
accumulation of AGE-related products. Pediatric patients with a higher metabolism have a higher risk of
structural valve failure, which results in multiple re-operations throughout their lifetime. There is, therefore, an
urgent need to develop more durable pulmonary valved grafts that are resistant to calcification,
inflammation, thrombosis, and accumulation of AGEs, and that have regenerative potential, as a safe
reconstructive device for pediatric patients.
We propose to develop a pulmonary valved graft (PVG) from a decellularized and pentagalloyl glucose (PGG)
treated (Also referred to as TxGuardTM) bovine jugular vein. TxGuardTM PVG will be non-thrombogenic,
infection- and calcification-resistant, prevent accumulation of AGEs, and have a potential to remodel
and grow. Based on reproducible pre-clinical data during STTR Phase 1 and SBIR Phase II, we firmly believe
that the new devi...

## Key facts

- **NIH application ID:** 10796422
- **Project number:** 2R44HL147771-04
- **Recipient organization:** ANNOVIANT, INC
- **Principal Investigator:** Ajay Houde
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $833,493
- **Award type:** 2
- **Project period:** 2019-05-24 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10796422

## Citation

> US National Institutes of Health, RePORTER application 10796422, Pulmonary Valved Graft with Regeneration Potential for Pediatric Patients (2R44HL147771-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10796422. Licensed CC0.

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