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pH-sensitive materials responding to metabolic activities of cariogenic plaque

Award Number: R21DE029925
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: 07/27/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2023

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pH-sensitive materials responding to metabolic activities of cariogenic plaque - Abstract: In today’s microbiome era, it is well-recognized that dental caries, one of the most prevalent and costly chronic infectious diseases world-wide, results from dysbiosis of the oral microbiota and the oral environmental changes that cause tooth damage. Specifically, frequent intake of fermentable carbohydrates promotes a progressive shift in microbial composition toward acidogenic and acid-tolerant species. The continual acid- induced demineralization eventually overcomes the buffering capacity and anti-microbial properties of saliva, leading to irreversible tooth destruction. The goal of this proposed research is to develop pH-responsive materials capable of targeted treatment of acid-producing bacteria (t-TAB) and antifouling. Our central hypothesis is that the combination of pH-responsive protein adsorption and acid-enhanced antimicrobial (AM) efficacy will inhibit the attachment and growth of acid-producing bacteria, consequently prevent the accumulation of cariogenic plaque. We propose three specific aims to design, develop, and evaluate the pH-responsive materials capable of altering protein-adsorption and achieving t-TAB. In Specific Aim 1, we will design and prepare Azo-QPS-containing materials that have pH-responsive surface properties. The Azo-QPS compounds have pH-sensitive AM efficacy and t-TAB functions in solution. We will covalently bond Azo-QPS functional groups onto surfaces in the form of single-molecule monolayer or Azo-QPS-polymers, which will produce variant amount of Azo-QPS functional groups/surface area. In addition, by bonding Azo-QPS with a clinically tested AM agent, chlorhexidine (CHX), we will enhance the new materials’ pH-responsive AM efficacy. In Specific Aim 2, we will evaluate the new materials’ performance in terms of pH-responsive reversible protein-adsorption and antifouling. We will enhance our understanding of the correlation between the surface chemical and physical properties and the antifouling performance. Specifically, we will focus on the correlation of hydrophilicity and charge density with the protein-adsorption in response to the pH variation between pH 4-8, a biological relevant pH range in oral environments. In Specific Aim 3, we will assess on-site antifouling and t-TAB efficacy of the new materials in a multispecies biofilm model that simulates oral microbial community. These will be performed in the presence and absence of sucrose—the cariogenic dietary carbohydrate. Strategy will entail evaluating biomass, analyzing microbial profiles and determining environmental pH. The successful completion of the proposed research will yield pH-responsive materials that are antifouling and obtain t-TAB in response to environmental changes autonomously. The material design may find extended utility in dental resin-restoratives, denture, and implant. As an exploratory research, the knowledge/results gained from this study will serve as preliminary data for an R01 application.


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 = $0 )
2024	2021	ADA FORSYTH INSTITUTE, INC.	245 1ST ST 17TH FLOOR	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	2	5/28/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = -$33,527 )
2023	2020	ADA SCIENCE & RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	000	1	3/21/2023	NEW	-$33,527
														Subtotal = -$33,527

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	001	2	7/27/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$152,468
2022	2020	ADA SCIENCE AND RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	000	1	7/27/2022	NEW	-$152,468
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $248,750 )
2021	2021	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	001	2	8/16/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$248,750
2021	2020	ADA SCIENCE AND RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	000	1	8/13/2021	NEW	$0
														Subtotal = $248,750

Issue Date FY: 2020 ( Subtotal = $233,618 )
2020	2020	ADA SCIENCE AND RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	000	1	8/31/2020	NEW	$233,618
2020	2020	ADA SCIENCE AND RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	001	1	9/4/2020	NEW	-$233,618
2020	2020	ADA SCIENCE AND RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	002	1	9/11/2020	NEW	$233,618
														Subtotal = $233,618

Grand Total All Awards = $448,841

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pH-sensitive materials responding to metabolic activities of cariogenic plaque

Award Number: R21DE029925

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: 07/27/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2023

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