# Nitric oxide-releasing hyaluronic acid therapeutics for treating periodontal disease

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $475,349

## Abstract

SUMMARY
Microbial plaque biofilms that form at and below the gum line are the perpetrators of periodontal diseases,
which are a class of diseases associated with non-resolving inflammation that results in soft and hard tissue
destruction. Periodontitis is characterized by an unending cycle of chronic inflammation which leads to tissue
destruction and prevents wound healing but cannot control the biofilms microbial dysbiosis. Under conditions
of systemic inflammation, these host factors are amplified leading to more severe and refractory periodontal
disease conditions. As such, periodontal diseases are affected by and can be risk factors for a number of systemic
health issues such as diabetes. Current treatment of periodontitis involves mechanical removal of supra- and
sub-gingival bacterial plaque and calculus and is often accompanied by the use of locally administered
adjunctive therapies aimed at restoring microbial homeostasis. Current adjunctive therapies do not address the
need to break the unending cycle of chronic inflammation and restore tissue homeostasis. Thus, there is a
profound need to develop an adjunctive therapeutic that: a) possesses broad-spectrum activity against biofilms
with minimal toxicity to mammalian cells; b) provides anti-inflammatory activity; and, c) promotes tissue
healing.
Due to its antibacterial and immunomodulatory functions, nitric oxide (NO) is an attractive adjunctive agent in
the treatment of periodontal diseases. In the proposed research program, we will synthesize, characterize and
evaluate nitric oxide-releasing hyaluronic acid (HA) as a multi-action NO-release system. Upon release, the
NO will serve as a broad-spectrum antibacterial and pro-wound healing agent. The macromolecule that remains
(HA) will then further serve to mitigate immunmodulation and wound healing. We will evaluate the efficacy
and associated mechanisms of this multi-action therapeutic (e.g., NO: antibacterial, HA and NO:
immunomodulatory, and NO and HA: pro-wound healing). We propose this approach will reduce the
frequency of and/or augment clinical interventions and promote improved resolution of disease. We aim to: 1)
synthesize nitric oxide-releasing hyaluronic acid nanomaterials and formulations, showing the influence of NO-
releasing HA on antibacterial and antibiofilm action, mammalian cell cytotoxicity, and inflammation in various
oral delivery formulations; 2) delineate the mechanisms modulating microbial dysbiosis, immune dysfunction
and tissue-stasis; and, 3) test in vivo therapeutic efficacy in preventing and/or halting periodontal disease
progression.

## Key facts

- **NIH application ID:** 10831096
- **Project number:** 5R01DE032060-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Mark H Schoenfisch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $475,349
- **Award type:** 5
- **Project period:** 2023-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10831096

## Citation

> US National Institutes of Health, RePORTER application 10831096, Nitric oxide-releasing hyaluronic acid therapeutics for treating periodontal disease (5R01DE032060-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10831096. Licensed CC0.

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