# Effect of Hesperidin on Craniofacial Bone Regeneration

> **NIH NIH R03** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $155,500

## Abstract

Abstract
A predictable means of regenerating bone in the craniofacial area is critical. Typical surgical therapies to
reconstruct bone include the use of combined osteoconductive and osteoinductive materials. However, there is
wide variation in results of currently implemented bone regeneration therapies due to a combination of factors
such as variable remodeling rates of the scaffold, bioavailability of growth factors, triggering of unwanted side
effects such as inflammation, fibrous encapsulation and even ectopic ossification. One of the most potent
inductive biologic is bone morphogenetic protein, BMP, but it is a high cost therapy making its use prohibitive
for a large portion of the population specifically for dental care. We have in vitro preliminary data showing that
the natural flavonoid compound extracted from citrus fruits, hesperidin (HE), up-regulates expression of key
osteoblast differentiation markers, enhances the quality of the collagen matrix and mineral-to-matrix ratio in
vitro, and prevents osteoclast formation. Further, we have in vivo data showing that HE promotes bone
formation in a critical-sized craniofacial bone defect (CSCBD) and the growth of bone forming cells is
stimulated in an HE-based scaffold. Previous reports have shown that this compound can prevent loss of bone
density in ovariectomized rats. Our central hypothesis is that HE increases and accelerates the rate of bone
formation by favoring osteoblast vs. osteoclast function, promoting wound healing and positively affecting
quality of extracellular matrix formation in a CSCBD as compared to a well-known bone promoting factor such
as BMP2. This proposal will utilize a CSCBD in the mandible of rats which will be treated with an HE-collagen
scaffold while addressing the following specific aims: 1) We will characterize the bone healing profile of HE-
treated defects in early post-surgical stages of the mandible osteotomy model (3 and 7 days) by analyzing
wound healing, osteogenic and osteoclastic markers as well as associated signaling pathways; 2) We will
characterize bone vascularity and kinetics of bone formation during early and mid-healing stages (14 and 30
days) of the osteotomy sites treated with HE by functionalized micro-computed tomography (µCT) and
fluorochrome-aided histological studies; 3) We will characterize the quality of the fully regenerated bone in
response to HE (matured up to 60 days) as compared to exogenous BMP2 by imaging, biomechanics and
histology. Preliminary data is very promising on the effect of HE on bone regeneration and potential
mechanisms. The results of our studies could have a major impact on regenerative medicine/dentistry by
means of introducing a simple, cost-effective, alternative and predictable bone inducing therapy for bone
defects. This proposal will contribute to the fulfillment of NIDCR's mission of improving craniofacial health as
it will lead to the discovery and characterization of the effects of a novel agent for tr...

## Key facts

- **NIH application ID:** 9954017
- **Project number:** 5R03DE028035-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Patricia Miguez
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $155,500
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954017

## Citation

> US National Institutes of Health, RePORTER application 9954017, Effect of Hesperidin on Craniofacial Bone Regeneration (5R03DE028035-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9954017. Licensed CC0.

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