# Tailoring of cellular mechanical microenvironments to rescue age-related impairments in bone regeneration

> **NIH NIH R01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2022 · $779,768

## Abstract

Aging impairs both the responsiveness of bone cells to mechanical loading and the success of bone
healing following injury. Growing evidence indicates that these two phenomena are related: local
mechanical cues present in the cellular microenvironment (“mechanical microenvironment”) regulate
numerous aspects of bone healing, including recruitment and osteoblastic differentiation of marrow
stromal cells (MSCs). Importantly, studies by multiple groups of investigators have indicated that aged
cells remain mechanosensitive, but require higher stimulus magnitudes. Therefore, the focus of this
project is on directly manipulating the mechanical microenvironment during bone healing, via
customization of the architecture of additively manufactured (AM), osteoinductive, bioceramic
scaffolds, in order to identify how the cellular responses to local mechanical cues differ with age. The
hypothesis of this work is that tailoring of cellular mechanical microenvironments through advanced AM
scaffold design can rescue age-related impairments in bone regeneration. This work builds on
preliminary data demonstrating use of an innovative AM method to print mechanically robust ceramic
scaffolds of exceptionally tunable architectures with high porosity (>80%) and pore sizes large enough to
facilitate vascularization and osteogenesis in vivo. In Aim 1, we will compare the osteogenic responses
of young (12-week-old) vs. mature (77-week-old) vs. aged (104-week-old) murine MSCs to the
mechanical microenvironment within mechanically loaded scaffolds in vitro. The local mechanical cues
present in these scaffolds will be determined using finite element modeling and mechanical testing, and
the cellular responses evaluated using a novel combination of techniques including spatial assessment of
the progression of osteogenesis at the single-cell level. Aim 2 will leverage these analytical tools as well,
and will compare the bone regeneration responses to tailored mechanical microenvironments within
scaffolds implanted in young and aged mice. Together, these two aims address an area of high clinical
need and will fill critical gaps in knowledge regarding age-related changes in bone mechano-
responsiveness during healing. The outcomes of this work will lay the foundation for a new generation
of bone repair technologies that can accommodate alterations in cell behavior with aging and harness
cell mechano-sensitivity to promote osteogenic differentiation, bone tissue formation, and ultimately,
restoration of bone function following injury.

## Key facts

- **NIH application ID:** 10520754
- **Project number:** 1R01AG073671-01A1
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Elise F Morgan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $779,768
- **Award type:** 1
- **Project period:** 2022-09-30 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10520754

## Citation

> US National Institutes of Health, RePORTER application 10520754, Tailoring of cellular mechanical microenvironments to rescue age-related impairments in bone regeneration (1R01AG073671-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10520754. Licensed CC0.

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