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Dissecting Mechanisms of Microvascular Function in Peri-Implantitis

Award Number: R01DE035479
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2031

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Dissecting Mechanisms of Microvascular Function in Peri-Implantitis - Project Summary Dental implants are a vital solution for edentulism, yet their success can be undermined by peri-implant diseases, including peri-implant mucositis and peri-implantitis, which impact around 20% of implant recipients. A hallmark clinical sign of these diseases is bleeding on probing (BOP), an indicator of endothelial inflammation in the peri-implant mucosa that reflects increased microvascular leakiness and tissue damage. The etiology of these conditions is multifactorial, involving bacterial biofilms and titanium particles (i-TiPs) released from implant degradation, both of which promote inflammation. Especially, i-TiPs amplify the peri-implant inflammatory response leading to further tissue damage. Thus, the need for early detection and intervention of peri-implantitis is essential. To address this need, the current study aims to deconvolute key spatiotemporal mechanisms involved in endothelial function in peri-implantitis. Particular emphasis of our study focus on identifying new mechanisms involved in regulation endothelial barrier function in response to peri-implant inflammatory cues, such as bacteria and i-TiPs. Our preliminary data provide a foundation for our hypothesis by revealing how inflammatory factors, such as i-TiPs and lipopolysaccharides (LPS), disrupt endothelial barrier integrity. We have identified paracrine signaling and cell adhesion mechanisms involved in regulating this function. Specifically, LPS impairs microvascular barrier function through Toll-like receptor 4 (TLR4) signaling in endothelial cells, while i-TiPs similarly disrupt barrier function and elevate TLR4 levels in gingival fibroblasts. Additionally, the presence of i-TiPs and LPS increases vascular endothelial growth factor (VEGF) levels in gingival fibroblasts, further contributing to barrier dysfunction. Alterations in endothelial barrier function are related to changes in intracellular adhesion molecules, such as the gap junction protein Connexin 43 (Cx43). This data serves as the basis to mechanistically investigate the role of peri-implant inflammatory cues, i-TiPs and bacteria on regulation of endothelial barrier function via TRL4/VEGF paracrine mechanisms (Aim 1). Next, we will test the hypothesis of how endothelial barrier function is modulated through Cx43 homotypic and heterotypic cell adhesion mechanisms (Aim 2). Finally, in collaboration with Dr. Kotsakis (Rutgers University) a clinician-scientist and board-certified periodontist with expertise in peri-implantitis, we will investigate whether i-TiPs alter endothelial barrier, induce endothelial inflammation and alter cell adhesion molecules related endothelial barrier function in a peri-implantitis rat model and human subjects (Aim 3). Given the recognized fundamental importance of the complexity in oral diseases, these studies may pave the way to identify novel targets for treatments against peri-implantitis.


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 = $559,869 )
2026	2026	GEORGETOWN UNIVERSITY	MAIN CAMPUS	WASHINGTON	DC	20057	DISTRICT OF COLUMBIA	USA	Oral Diseases and Disorders Research	000	1	8/13/2026	NEW	$559,869
														Subtotal = $559,869

Grand Total All Awards = $559,869

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Dissecting Mechanisms of Microvascular Function in Peri-Implantitis

Award Number: R01DE035479

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2031

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