Friday, July 4, 2025 7/4/2025

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

Award Number: R01AG073671
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

Group Awards By:

View Award Description

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $605,631 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	000	4	5/1/2025	NON-COMPETING CONTINUATION	$556,192
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	001	4	6/20/2025	NON-COMPETING CONTINUATION	$49,439
														Subtotal = $605,631

Issue Date FY: 2024 ( Subtotal = $703,034 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	000	3	4/29/2024	NON-COMPETING CONTINUATION	$703,034
														Subtotal = $703,034

Issue Date FY: 2023 ( Subtotal = $733,122 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	001	2	5/25/2023	NON-COMPETING CONTINUATION	$733,122
2023	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	000	1	11/1/2022	NEW	$0
														Subtotal = $733,122

Issue Date FY: 2022 ( Subtotal = $779,768 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	000	1	9/21/2022	NEW	$779,768
														Subtotal = $779,768

Grand Total All Awards = $2,821,555

Top

All Categories

About

Search

Reports

Data Submission

Award Information

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

Award Number: R01AG073671

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/30/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer