Monday, January 19, 2026 1/19/2026

Investigate the mechanisms underlying microRNA-146a activity in regulation of foreign body response to biomaterials

Award Number: R01AI172086
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/10/2017
PERIOD OF PERFORMANCE END DATE: 05/31/2027

Group Awards By:

View Award Description

Investigate the mechanisms underlying microRNA-146a activity in regulation of foreign body response to biomaterials - Project Summary Implantation of biomaterials and devices often leads to the development of a foreign body response (FBR), a chronic inflammatory condition that can ultimately lead to implant failure, which may cause harm to or death of the patient. The molecular mechanisms underlying the FBR remain poorly understood. Improved understanding of the molecular mechanisms underlying the generation of FBR is the most important step for the development of novel and effective therapeutic strategies that eliminate or reduce the FBR. Macrophages are central to development and progression of the FBR. They participate in the expression of inflammatory proteins, formation of destructive foreign body giant cells (FBGCs), remodeling of the extracellular matrix, and encapsulation of the implant. Emerging data support a critical role for a mechanical signal, e.g., matrix stiffness, in macrophage activation. MicroRNAs (miRs) are endogenous, small, non-coding RNAs that have emerged as powerful regulators of gene expression in numerous cellular processes including macrophage activation, cell fusion, inflammation, and fibrosis. The function of specific miRs in regulation of FBR to biomaterials is uncertain; specifically, it remains an open question whether matrix stiffness regulates miR expression to drive FBR. These gaps pose a significant barrier to progress in the FBR field. In recent, exciting preliminary data, we obtained evidence that miR-146a may be a negative regulator of FBR to biomaterials. Specifically, we found that: 1) miR-146a expression levels decreased in the implant-adhered tissues in a subcutaneous (s.c) implantation model, which correlated with increased macrophage accumulation, FBGC formation, and collagen accumulation; 2) miR-146a deletion in mice exacerbated FBR processes in a s.c implantation model; 3) the severity of the in vivo macrophage accumulation at the tissue-implant interface was dependent on the stiffness of the implant; 4) genetic ablation of miR-146a augmented macrophage adhesion and spreading on stiff matrix, FBGC formation, and inflammation in macrophages, and 5) genetic ablation of TRPV4, an ion channel in the transient receptor potential vanilloid family, inhibited development of implant-adhered tissue stiffness under FBR as determined by Atomic Force Microscopy. Further preliminary data suggested an association between matrix stiffness, miR-146a activity, and TRPV4, under FBR conditions. The objective of this proposal is to define the role of miR-146a in the FBR, and to elucidate the underlying molecular mechanisms. Based on our preliminary data, our central hypothesis is that miR-146a modulates the FBR to biomaterials by regulating macrophage activation and fibrogenesis in a manner dependent on implant-induced change in tissue stiffness. We will test our hypothesis through molecular gain- or loss-of-function studies. We expect that the results of this study may provide invaluable information and insight regarding the molecular mechanisms mediating the FBR to biomaterials, which may lead to the development of a novel and effective microRNA-based therapeutic strategy for the amelioration of the poorly understood FBR to biomaterials.


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: 2026 ( Subtotal = $0 )
2026	2025	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	8	12/9/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $690,817 )
2025	2025	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	8	4/28/2025	NON-COMPETING CONTINUATION	$690,817
														Subtotal = $690,817

Issue Date FY: 2024 ( Subtotal = $703,177 )
2024	2024	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	7	5/16/2024	NON-COMPETING CONTINUATION	$703,177
														Subtotal = $703,177

Issue Date FY: 2023 ( Subtotal = $750,691 )
2023	2023	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	001	6	5/18/2023	NON-COMPETING CONTINUATION	$717,801
2023	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	5	5/12/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$32,890
														Subtotal = $750,691

Issue Date FY: 2022 ( Subtotal = $736,942 )
2022	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	5	6/8/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$736,942
														Subtotal = $736,942

Grand Total All Awards = $2,881,627

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigate the mechanisms underlying microRNA-146a activity in regulation of foreign body response to biomaterials

Award Number: R01AI172086

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/10/2017

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