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The effect of age-related changes in macrophage polarization and the post-injury immune response on fracture healing

Award Number: R03AG095801
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2025
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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The effect of age-related changes in macrophage polarization and the post-injury immune response on fracture healing - Project Abstract Aging is associated with an increased incidence of fracture, subsequent increased morbidity and mortality, increased rates of nonunion and delayed bone healing. Aging is thought to result in an increased baseline inflammatory state, known as “inflamm-aging”. Strategies to improve fracture healing in these patients must start with a clear understanding of why fracture repair is inhibited with age so targeted interventions can be developed. Fracture triggers a robust inflammatory response to initiate healing. Following this initial inflammatory phase, an anti-inflammatory response is initiated that drives tissue regeneration. Disruption of this transition may result in decreased fracture healing. Macrophages are thought to play a vital role in this process, with classically activated (M1) macrophages driving early inflammation, followed by a transition to an anti-inflammatory alternatively activated (M2) macrophage response. Aging is associated with an increased baseline inflammatory state, known as “inflamm-aging”. This imbalance may drive the delayed healing observed in geriatric fracture patients. However, work in human subject has been minimal, and the role of aging in fracture healing remains a poorly understood area of study. We hypothesize that this imbalance drives the impaired geriatric fracture healing response and expect that elderly patients have an increased initial inflammatory response at the time of fracture with a decreased ability to mount the subsequent anti-inflammatory response required for initiation of the regenerative phase of fracture healing and derangements in macrophage polarization. Two primary aims well assist in quantifying the differences in the fracture microenvironments between young and elderly patients. AIM1: To determine if geriatric fracture patients have altered macrophage polarization and an increased inflammatory response at the site of acute fracture compared to younger individuals. AIM2: to determine if geriatric fracture patients have an altered transition to M2 polarization and a delay in the production of anti-inflammatory cytokines at the fracture site during fracture healing compared to younger individuals. This innovative study would be the first to critically examine the role of macrophage polarization in human subjects, bridging the gap between animal and human models and identifying potential therapeutic targets for further study.


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 = $393,750 )
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Aging Research	000	1	8/6/2025	NEW	$393,750
														Subtotal = $393,750

Grand Total All Awards = $393,750

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The effect of age-related changes in macrophage polarization and the post-injury immune response on fracture healing

Award Number: R03AG095801

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2025

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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