# Small molecule microenvironment design for craniofacial bone regeneration

> **NIH NIH R01** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2021 · $1

## Abstract

Over 30,000 people per year undergo craniofacial resective surgery and approximately
15% of the US population suffers from periodontal disease severe enough to warrant surgery
(Marolt 2015). Currently, craniofacial and periodontal bone tissue engineering faces unique
challenges due to the exposure of cranial and periodontal bones to continuous and varying
loads (Rah 2000). The effect of continuous loads onto the engineered construct necessitates a
gradual augmentation of an engineered regenerate rather than the en bloc insertion of a
mechanically inert replacement tissue. In contrast to long bones, which are formed through
endochondral ossification, cranial vault and periodontal bones are characterized by their unique
mode of intramembranous ossification, which is accomplished through the stepwise
mineralization of a specialized extracellular protein matrix rich in collagen and proteoglycans.
When cranial and/or periodontal bones are lost due to trauma or disease, this loss not only
affects osteoblasts, progenitors, and other bone cells, but also the unique extracellular bone
matrix that maintains the instructive signaling environment for continuous bone regeneration
and replacement. In the present application we have focused on a recently described small
molecule mediator, the SETD7 histone lysine methyltransferase inhibitor PFI-2 that in our
preliminary studies has induced osteoblasts to secrete a typical bone-like extracellular matrix
enriched in collagen, fibronectin and osteocalcin. In animal studies, PFI-2 has demonstrated
extraordinary potential to induce bone regeneration, including alveolar bone regeneration over
half of a tooth root’s length and more than 50% new bone coverage of critical size cranial
defects. Providing a possible mechanism for these exciting new findings, we have
demonstrated that PFI-2 inhibited SETD7 mediated -catenin methylation, resulting in nuclear
-catenin translocation and bone matrix protein transcription activation in addition to the
stimulation of other processes related to new bone formation, such as cell proliferation and
differentiation. In the present application, we seek to exploit PFI-2’s potential for cranial and
periodontal bone regeneration, define the mechanism(s) by which PFI-2 triggers new bone
extracellular matrix deposition, and engineer scaffolds of sufficient stability to provide a template
for PFI-2 nanosphere controlled release toward future applications in clinical use and patient
care.

## Key facts

- **NIH application ID:** 10190888
- **Project number:** 5R01DE019463-07
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** Xianghong Luan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1
- **Award type:** 5
- **Project period:** 2009-07-20 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190888

## Citation

> US National Institutes of Health, RePORTER application 10190888, Small molecule microenvironment design for craniofacial bone regeneration (5R01DE019463-07). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10190888. Licensed CC0.

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