# Biomimetics for craniofacial regeneration

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $370,500

## Abstract

Abstract
In young healthy individuals minor insults to bone heal with minimal compromise. In an aging
population, in chronic disease, and with large reconstructive needs, the process often fails
leaving compromised form and function. Work in the previous project period as well as work
from others has identified actions of the anabolic agent parathyroid hormone (PTH) to drive
osteoclastogenesis and localization of macrophages on the endosteal surface. Such osteal
macrophages are essential for normal osseous healing where they act to increase bone
formation through various mechanisms. A vital function of macrophages is in the clearance of
dead and dying cells, a process termed efferocytosis. Upon efferocytosis, macrophages
produce factors which facilitate resolution and regeneration. Based on findings of cellular
actions of calcium and drug delivery modalities in the previous funding period, the project team
proposes a new strategy for bone regeneration. Biomimicry based on developing calcium
loaded biodegradable microspheres with surface signals that macrophages recognize as dying
cells triggers efferocytosis and the secretion of factors to evoke wound healing. The overall
hypothesis of this proposal is that apoptotic cell mimicry enhances bone regeneration via
macrophage efferocytosis. Three aims will dissect the mechanisms involved, optimize
microsphere properties, and translate to clinically relevant models that will move this novel
approach forward. Specifically, aim one will utilize apoptotic mimicry microspheres to elucidate
the role of the macrophage derived chemokine CCL2 in mesenchymal stem cell (MSC)
migration and osteogenesis. Aim two will develop optimal apoptosis-mimicry microspheres to
drive MSC migration by modulating the size, composition, and surface signals. Aim three will
determine the osseous regenerative capacity of calcium loaded apoptotic cell mimicry
microspheres using a clinically relevant animal model. At the completion of this project, a new
strategy that does not require cell transplantation but builds upon the innate capacity of
macrophages to regenerate bone will be mechanistically validated, characterized and optimized
for translation to a clinical application.

## Key facts

- **NIH application ID:** 10130486
- **Project number:** 5R01DE022327-09
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Laurie K. McCauley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $370,500
- **Award type:** 5
- **Project period:** 2012-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130486

## Citation

> US National Institutes of Health, RePORTER application 10130486, Biomimetics for craniofacial regeneration (5R01DE022327-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10130486. Licensed CC0.

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