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Low Temperature Plasma as an Approach for the Treatment of Peri-Implantitis

Award Number: R21DE028929
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: 08/01/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2023

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Low Temperature Plasma as an Approach for the Treatment of Peri-Implantitis - Biofilm formed around dental implants trigger inflammation, which plays a leading role into promoting osteoclast mediated bone resorption and inhibiting bone formation, resulting in net bone loss around implants referred to as peri-implantitis. Once established, peri-implantitis progresses and leads to implant loss. The use of low temperature plasma (LTP) as a co-adjuvant to treat peri-implantitis is promising, as unlike current peri-implantitis treatment strategies and demonstrated by our preliminary data, has the unique potential to simultaneously (i) decontaminate infected surfaces while (ii) allowing for the creation of a suitable environment for bone regrowth around the implant (iii) without damaging peri-implant related tissues. Advantages of LTP over traditional antimicrobial applications are that LTP can be used for site-specific treatment, provides an almost instantaneous bactericidal response, antimicrobial resistance is less likely to occur, and there are minimal side effects. Our hypothesis is that LTP, coupled with surgical debridement, is a unique efficacious approach for treatment of peri-implantitis. To address our hypothesis, the following specific aims are proposed: Aim 1) To determine the LTP protocol most disruptive to in vitro multispecies peri-implantitis related biofilms, while maintaining low cytotoxicity. Biofilms in several levels of maturation comprising of Streptococcus oralis, Actinomyces naeslundii, Veillonela dispar, and Porphyromonas gingivalis will be treated with LTP in different conditions and compared to controls, which includes gas flow, 0.12% Chlorhexidine, 14 µg/mL of amoxycillin and 140 µg/mL metronidazole, individually or in combination. Efficacy, in the absence of toxicity, will be confirmed using in vitro reconstituted oral (ROE) and gingival epithelium (RGE) infected or not with P. gingivalis; Aim 2) To evaluate the effect of LTP treatment on peri-implantitis using a Gottingen minipig model. Ligature induced peri-implantitis will be developed in the jaws of miniature swine. These will be surgically treated coupled with two LTP regimens or with appropriate controls, allowed to heal, and the level of both soft and hard tissue reattachment evaluated by histology assays and three-dimensional image reconstruction. Anabolic and catabolic events will also be assessed. The proposed project will expand on our preliminary experiments and refine a unique approach for the treatment of emerging problem of peri-implantitis, using LTP’s synergistic effects to decontaminate and/or detoxify the infected peri- implantitis site, and create a suitable environment for bone regrowth around the implant, all of this in a single and short time application (minutes) and low-toxicity to the mucosa. Furthermore, our proposed experiments will test LTP in a large preclinical animal model that is remarkably similar to humans allowing direct translation of findings toward clinical practice.


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: 2024 ( Subtotal = -$26,238 )
2024	2020	ADA SCIENCE & RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	000	3	4/11/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$26,238
														Subtotal = -$26,238

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Oral Diseases and Disorders Research	002	2	6/9/2023	NON-COMPETING CONTINUATION	$0
2023	2020	ADA SCIENCE AND RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	001	3	12/12/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$81,836
2023	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Oral Diseases and Disorders Research	000	2	12/9/2022	NON-COMPETING CONTINUATION	-$81,836
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Oral Diseases and Disorders Research	000	2	11/18/2021	NON-COMPETING CONTINUATION	$0
2022	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Oral Diseases and Disorders Research	001	2	9/1/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $236,716 )
2020	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Oral Diseases and Disorders Research	001	2	7/31/2020	NON-COMPETING CONTINUATION	$236,716
2020	2019	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Oral Diseases and Disorders Research	000	1	5/28/2020	NEW	$0
														Subtotal = $236,716

Issue Date FY: 2019 ( Subtotal = $211,716 )
2019	2019	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Oral Diseases and Disorders Research	000	1	7/29/2019	NEW	$211,716
														Subtotal = $211,716

Grand Total All Awards = $422,194

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Low Temperature Plasma as an Approach for the Treatment of Peri-Implantitis

Award Number: R21DE028929

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: 08/01/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2023

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