# Osteoclast modulatory biomaterials for skull regeneration

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $368,648

## Abstract

PROJECT SUMMARY/ABSTRACT
Skull defects occur secondary to trauma, stroke, cancer, and congenital anomalies resulting in significant
neurological, psychological, social, and vocational burdens. Current clinical options for cranioplasty, or calvarial
reconstruction, are limited by availability and morbidity in autologous bone grafts and complications and cost in
alloplastic materials. Such drawbacks provide an opportunity to develop methods that specifically target
calvarial bone regeneration. Despite decades of research, contemporary regenerative strategies consisting of
expanded stem cells and growth factor cocktails delivered by scaffolding materials have not attained clinical
translation due to surgical impracticality, cost, time consumption, and safety concerns. The increasing
knowledge of instructive capabilities of the extracellular matrix (ECM) in cell fate determination has provided an
alternative paradigm for regeneration. We demonstrated that an ECM-inspired material composed of
nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) regenerates up to 60% the mineralization
and biomechanical properties of native calvarium without ex vivo progenitor cell loading or exogenous growth
factor supplementation. Simultaneously, MC-GAG inhibits osteoclast activation and resorption without affecting
the paracrine osteoinductive properties offered by osteoclasts via direct material to cell interactions as well as
indirectly by inducing osteoprogenitors to secrete osteoprotegerin (OPG), an endogenous inhibitor for
osteoclast activation. With the addition of exogenous OPG, this uncoupling of osteogenesis from
osteoclastogenesis is augmented. In combination, these data provided a proof of principle that a composite
material of MC-GAG and OPG (MCGO) delivered in a temporospatially-limited manner may be a potential
material for calvarial regeneration. In order to develop the MCGO material for clinical translation, three
questions must be answered: 1. What are the mechanisms activated in osteoclasts by direct interactions with
MC-GAG? 2. As the resorptive abilities of osteoclasts are necessary for remodeling and maturation of bone,
how long should OPG exist in the system? 3. Should OPG be eluted or anchored to the material? To answer
these questions, we have developed two MCGO materials via non-covalent and covalent incorporation of OPG
resulting in a high concentration, fast release and a low concentration, extended release MCGO material,
respectively. In Aim 1, we will elucidate the anti-osteoclastogenic mechanisms induced by MC-GAG and
MCGO materials. We hypothesize that MC-GAG and the two MCGO materials will differentially affect hOC
activation and resorption. In Aim 2, we will evaluate the two MCGO materials compared to MC-GAG in rabbit
calvarial regeneration to generate preclinical efficacy, safety, and performance data for MCGO materials
compared to MC-GAG. Our proposed studies are unified in the goal of calvarial regenerative technology
d...

## Key facts

- **NIH application ID:** 10451692
- **Project number:** 5R01DE029234-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Justine Chia Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $368,648
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10451692

## Citation

> US National Institutes of Health, RePORTER application 10451692, Osteoclast modulatory biomaterials for skull regeneration (5R01DE029234-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10451692. Licensed CC0.

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