# Mineralized collagen composite to accelerate craniofacial bone regeneration

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2021 · $479,938

## Abstract

ABSTRACT
Defects in craniofacial bones of the skull occur congenitally, after high-energy impacts, and during the course of
treatment for stroke and cancer. Autologous bone or alloplastic implants are the current gold-standards for
surgical reconstruction. However, limited quantities and time-intensive intraoperative fitting of autologous bone,
the non-regenerative nature of alloplastic implants, and surgical challenges that stem from irregular defect
margins and the quality of the surrounding bone all contribute to poor healing and high complication rates. A
biomaterial that could be shaped precisely and quickly like an alloplastic implant but that works in a regenerative
fashion like autologous bone would be transformative for craniofacial reconstruction. The objective of this
proposal is to potentiate regeneration of the structure, composition, and mechanical properties of craniofacial
bone using an innovative scaffold-mesh composite biomaterial. We have generated extensive proof-of-principle
data for a surgically-practical composite biomaterial for craniofacial bone regeneration. Our core technology is a
porous mineralized collagen scaffold to expand MSCs in vivo. We have identified microstructural features of this
material to activate mechanotransduction and BMP receptor signaling to accelerate MSC osteogenicity and
secretion of osteoprotegerin (OPG), a soluble glycoprotein and endogenous inhibitor of osteoclast activity. As a
result, this material increases osteogenicity and transiently inhibits osteoclast activity to accelerate regenerative
healing of craniofacial bone defects osteogenic supplements or exogenously-seeded stem cells. We have
independently developed a millimeter-scale polymeric mesh that can be integrated into the scaffold, à la rebar
in concrete, to form a modular composite that can be shaped intraoperatively to conformally fit irregular defects.
Excitingly, prototype scaffold-mesh composites generated using a mesh printed from an advanced Hyperelastic
Bone® material increases MSC OPG secretion. These findings suggest the exciting possibility to co-optimize
scaffold microstructural properties as well as the composition and architecture of the integrated polymer mesh
to both passively aid surgical-practicality and actively accelerate regenerative healing. Our central hypothesis is
that a multi-scale scaffold-mesh composite will accelerate MSC recruitment and retention, increase osteogenesis
while inhibiting osteoclast activity, and facilitate vascular remodeling to improve regeneration. To do this we will
first define the contribution of scaffold anisotropy on the recruitment and activity of osteoprogenitors and
endothelial cells (Aim 1). We will establish topology parameters of a scalable mesh to aid surgical practicality
and regenerative potential (Aim 2). Lastly, we will demonstrate in vivo efficacy of a scaffold-mesh composite in
a confined calvarial defect model (Aim 3). Our unified effort to develop craniofacial regene...

## Key facts

- **NIH application ID:** 10185367
- **Project number:** 1R01DE030491-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Brendan A. Harley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $479,938
- **Award type:** 1
- **Project period:** 2021-05-03 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10185367

## Citation

> US National Institutes of Health, RePORTER application 10185367, Mineralized collagen composite to accelerate craniofacial bone regeneration (1R01DE030491-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10185367. Licensed CC0.

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