# Local Delivery of Neurogenic Factors via Polymeric Microparticles for Enhanced Endochondral Bone Repair in the Mandible

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $40,112

## Abstract

Project Summary/Abstract
There are approx. 15 million bone fractures annually and the mandible sustains the vast majority of craniofacial
bone fractures. Currently clinical approaches, such as maxillofacial fixation, are exceedingly invasive and the
prevalence of impaired healing remains. Therefore, the objective of this grant is to address the clinical need for
a translational and clinically relevant approach to mandibular fractures. Accomplishing this goal requires cross-
disciplinary methods that harness expertise in biomaterials and drug delivery coupled with an understanding of
the mechanisms that drive functional bone repair. The mandible primarily heals through endochondral
ossification, in which a cartilage intermediate forms and is later replaced by bone. In recent years, many
groups, including ours, have published significant evidence to show that chondrocytes transdifferentiate into
osteoblasts during bone development and fracture healing. The mechanisms underlying chondrocyte
transdifferentiation have thus far not been thoroughly explored. However, my preliminary data, along with
previously published work, indicate that β-catenin signaling is a critical mediator of chondrocyte-derived
osteoblastogenesis. Activation of β-catenin by NGF/TrkA signaling has been observed in various cell types and
interestingly; our preliminary data show an increase in NGF and TrkA expression in fracture calluses. Finally,
our preliminary data show that NGF administration onto fractures during the cartilaginous phase accelerates
bone repair. During this fellowship I aim to understand the role of NGF in chondrocyte transdifferentiation, and
develop a therapeutic delivery system for local and sustained release of a “painless” NGF, NGFR100W. The
central hypothesis for this project is that sustained release of NGFR100W via PEGDMA microparticles will
accelerate endochondral fracture healing by activating β-catenin signaling in hypertrophic chondrocytes.
In the first Aim I will build on our preliminary data of enhanced bone repair in NGF-treated mice by engineering
NGFR100W-eluting PEGDMA microparticles to accelerate healing. NGFR100W-loaded PEGDMA microparticles will
be injected percutaneously onto fracture calli followed by assessment of tissue composition, biomechanical
strength, and rate of healing by using histology, microCT imaging, three-point bending tests, and stereology.
In the second Aim, I will determine the mechanism by which NGF stimulates osteogenesis. I will use an ex vivo
system of fracture callus-derived cartilage cultured with NGF to measure downstream markers of
osteogenesis, angiogenesis, and candidate pathways including β-Catenin, Sox2, and hedgehog by RT-qPCR
and western blot. In vivo I will conditionally delete TrkA from chondrocytes by crossing the TrkAfl/fl and
aggrecan-CreER transgenic mice to test if NGF is required for chondrocyte transdifferentiation during fracture
healing using the same functional outcome measures described in Aim...

## Key facts

- **NIH application ID:** 9895427
- **Project number:** 5F31DE028485-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Kevin Omar Rivera
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,112
- **Award type:** 5
- **Project period:** 2019-03-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895427

## Citation

> US National Institutes of Health, RePORTER application 9895427, Local Delivery of Neurogenic Factors via Polymeric Microparticles for Enhanced Endochondral Bone Repair in the Mandible (5F31DE028485-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9895427. Licensed CC0.

---

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