# Bioengineered Composite for the Treatment of Peripheral Arterial Disease

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $441,377

## Abstract

PROJECT SUMMARY
Peripheral artery disease (PAD) affects 8-10 million people in the US. Clinical trials evaluating stem cell, growth
factor, or gene therapy systems for the treatment of PAD have shown some promising results. Use of biomaterial
matrices either to enhance therapies or as a standalone treatment are just beginning to be explored in small
animal models of PAD, with promising findings indicating that a biomaterial strategy can enhance the efficacy of
intramuscular cell therapies in treating the effects of leg ischemia. There are important requirements for optimal
delivery, retention, and performance of a bioengineered composite in the mechanically, histologically, and
biochemically dynamic intramuscular environment of the PAD leg. The material should: (a) undergo minimal
swelling once inside the target tissue; (b) have proper mechanical properties with high resilience to tolerate
repeated compressive strain during muscle contraction for its long-term intramuscular retention; (c) be porous
enough to facilitate the exchange of trophic factors with the surrounding environment and to permit recruitment
of host progenitor and endothelial cells; and (d) have antioxidative and angiogenic properties that can be
beneficial to the management of the myopathy of PAD.
The objective of the current proposal is to characterize and optimize a biomaterial-based treatment for PAD. We
have recently developed an injectable, angiogenic, nanofiber-hydrogel composite with unique interfacial bonding
between the hydrogel matrices and the fibers, and successfully applied the composite for the regeneration of
soft tissue defects in a rabbit model. We have further modified the hydrogel to have antioxidant properties with
minimal swelling and optimized mechanical characteristics to mimic skeletal muscle. Testing in a rat model of
PAD, the hydrogel reduced lipid oxidation, enhanced local blood flow in the muscle, and improved running
capacity of the treated rats. In addition, we have developed and validated a porcine model of hindlimb ischemia
(iliofemoral artery ligation/excision), which recapitulates key aspects of the pathophysiology of human
PAD/claudication and can be a platform for the development of therapies for PAD. We are now primed to develop
and test our novel therapies for PAD in our porcine model.
We have all of the tools in place to address the central hypothesis that a nanofiber-hydrogel composite with
optimized mechanical, angiogenic, and antioxidative characteristics will improve hemodynamic,
histologic, and physiological endpoints of the ischemic hindlimb in rat and porcine models of PAD.
Successful completion of this project will deliver the first off-the-shelf synthetic composite matrix for the treatment
of PAD patients. As providing local therapy for the ischemic leg is critical to prevent myopathy and to improve
the performance of the affected lower limbs in PAD patients, this study will provide an important advancement
over other currently ava...

## Key facts

- **NIH application ID:** 10817161
- **Project number:** 5R01HL168513-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Xiaowei Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $441,377
- **Award type:** 5
- **Project period:** 2023-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817161

## Citation

> US National Institutes of Health, RePORTER application 10817161, Bioengineered Composite for the Treatment of Peripheral Arterial Disease (5R01HL168513-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10817161. Licensed CC0.

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