# Rejuvenating aged bone regeneration by innovative nanomaterials-mediated drug delivery

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2021 · $351,577

## Abstract

PROJECT SUMMARY
Scaffold-mediated exogenous cells transplantation and growth factors/hormones delivery are
two widely-studied alternatives to conventional autologous grafts, the "gold standard." For
therapeutic translation, however, both approaches encounter various barriers, including safety
concerns. Compared to use of exogenous cells/proteins, strategies that promote tissue
regeneration by leveraging endogenous cells/signals in situ are more intriguing. Nonetheless,
changes in tissue associated with aging (iron accumulation and chronic inflammation) challenge
bone regeneration and repair, particularly in older populations. Emerging evidence suggests
that the hypoxia-induced factor-1α (HIF-1α) signaling pathway is a central driver of regeneration
and angiogenesis. Findings also show sustained activation of HIF-1α by an iron chelator (e.g.,
Deferoxamine, DFO) is a promising strategy to improve the capacity of regeneration in aged
bones where HIF-1α is markedly inhibited by elevated iron levels. Preliminary work by the Sun
lab has found that another small molecule, phenamil, shows strong anti-inflammatory ability in
addition to playing a powerful role in promoting bone formation by targeting BMP signaling. A
locally and sustained drug delivery system and a bio-mimicking scaffold are critical for
successful translational application of these promising small molecular drugs. The primary goal
of this study is to develop an innovative translational tissue engineering strategy to improve
aged large bone regeneration by rejuvenating endogenous signals and reparative cells. Our
central hypothesis is that novel bio-mimicking 3D nanofibrous (NF) scaffold-mediated dual-
release of small molecules, DFO and phenamil, can improve critical-sized bone defect repair in
aged mice through locally: (1) scavenging for detrimental aged-related factors, i.e., excessive
iron and inflammatory cytokines; and (2) activating HIF1α and BMP signaling pathways, thereby
promoting production of endogenous angiogenic and osteogenic factors, and recruitment of
reparative cells (e.g., MSCs, endothelial cells) in situ, for bone regeneration with a primary focus
on non-load-bearing bone defects. In Aim 1, we will develop novel, biomimetic 3D NF scaffolds,
using our innovative technique of thermally induced nanofiber self-agglomeration (TISA). In Aim
2, we will develop the dual-release system of DFO and phenamil from a 3D NF scaffold to
modulate both angiogenesis and osteogenesis in aged cells in vitro. In Aim 3, we will investigate
the contribution of local and controlled release of DFO and phenamil from scaffolds for critical-
sized cranial bone defect repair in aged mice. The success of this project will establish a novel
strategy for challenged bone repair by improving endogenous tissue regeneration.

## Key facts

- **NIH application ID:** 10194462
- **Project number:** 5R01DE029159-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Hongli Sun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $351,577
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10194462

## Citation

> US National Institutes of Health, RePORTER application 10194462, Rejuvenating aged bone regeneration by innovative nanomaterials-mediated drug delivery (5R01DE029159-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10194462. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*