# Hybrid Synthetic and Biologic Shear Thinning Hydrogels for Diabetic Wound Healing

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2020 · $474,007

## Abstract

PROJECT SUMMARY:
 Nonhealing skin wounds are a major source of morbidity worldwide and becoming more of a burden due to
an increase in health care costs, an aging population, and growing incidence of diabetes. Non-healing skin
wounds occur in nearly 25% of diabetic patients, and ~6% are admitted to the hospital for wound-related
treatment, which if not successful, can lead to limb amputation or death. While more advanced treatments are
needed, cutting edge, multi-component technologies such as hydrogels or scaffolds loaded either with cells
and/or drugs have not achieved clinical impact. Failure of new candidate treatments is often due to poor tissue
integration, insufficient drug release profiles, and loss of biological (cell or growth factor) activity upon delivery
into a hostile wound microenvironment characterized by high concentrations of cytokines, proteases, and
cytotoxic reactive oxygen species (ROS).
 The overall goal of the current project is to develop and apply a next generation, shear-thinning, and ROS
scavenging hydrogel that comprises a hybrid of ROS responsive nanoparticles (NPs) and hyaluronic acid (HA),
a natural extracellular matrix component. The shear thinning hydrogel mechanical properties will be achieved
through guest-host chemistry based on adamantane (AD) and beta-cyclodextrin (CD), which form reversible,
mechanically-stabilizing inclusion complexes. NPs will be surface functionalized with AD, and HA polymers will
be modified with CD; when these two components are mixed, they form shear-thinning solutions that rapidly self-
heal to form stable hydrogels within the tissue defect. The HA component is included because of its precedent
for efficacious use in wound healing devices/dressings, while the NP is designed to have ROS reactivity (making
it inherently antioxidant). The NPs can also be “pre-loaded” with drugs prior to hydrogel formation, providing a
mechanism for sustained drug release to the wound site.
 The first aim of this project will be to optimize the proposed NP/HA hydrogel system by tuning polymer
molecular weight and AD/CD modification density on the NP and HA components, respectively. The second aim
will involve testing of lead candidate hydrogels in vivo to assess tissue response, sustained model drug release,
and ROS scavenging / protection of therapeutic stem cells loaded into the device. In the third aim, we will
compare the leading NP/HA hydrogel formulation to a HA-based, clinical control material for healing benefit alone
on in combination with either stem cells or a small molecule drug that activates the pro-healing transcription
factor HIF1alpha. These studies, designed to establish proof of concept for clinical efficacy, will be completed in
extremely challenged (ischemic and genetically-driven enhanced ROS phenotype) diabetic wound models. Our
multidisciplinary team, including a bioengineer, chemist, wound healing expert, and stem cell expert, is poised
to achieve the proposed goals toward establ...

## Key facts

- **NIH application ID:** 10005338
- **Project number:** 5R01EB028690-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Craig Lewis Duvall
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $474,007
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10005338

## Citation

> US National Institutes of Health, RePORTER application 10005338, Hybrid Synthetic and Biologic Shear Thinning Hydrogels for Diabetic Wound Healing (5R01EB028690-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10005338. Licensed CC0.

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