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In vitro 3D human gingival tissue model to study oral microbiome

Award Number: R03DE030224
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: 07/15/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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In vitro 3D human gingival tissue model to study oral microbiome - PROJECT SUMMARY The oral cavity contains different microenvironments, i.e. the non-shedding surface of the teeth and the epithelial mucosa, where oral barriers and microbial communities coexist. The interactions and balances between these two communities are responsible for oral tissue homeostasis or dysbiosis, that ultimately dictate health or disease. Disruption of this equilibrium is the first necessary step towards chronic inflammation and permanent tissue damage in the case of chronic periodontitis. Current experimental animal and in vitro models do not fully resemble the human condition. To improve clinical outcomes and design effective treatments, new humanized experimental tools are needed to further elucidate these initial host-pathogens unbalances. Previously developed in vitro systems have been used to test irritant responses of new dental materials, dentifrices, and oral care consumer products, but are unable to maintain the complexity of the oral pathogen community organization, due to the lack of the native oxygen and metabolic conditions. In addition, host saliva contributes to the maintenance of the overall oral system stability by buffering the oral environment, providing nutrition to the different communities and delivering antimicrobial features. Therefore, the recapitulation of physiological oral conditions, including oxygen gradients, physiological shear stress, and buffering from saliva will enhance the functions of a humanized sustained gingival tissue model to study initial host-pathogen interactions in vitro. We are proposing to design a physiological culture system based on artificial saliva in order to support long-term culture after inoculation with oral microbiota derived from healthy patients. We will replicate the stability of the ecosystem and evaluate the contribution of host saliva to buffer and provide nutrition to the oral community, as well as physiological shear stress that contributes to the maturation and maintenance of a healthy epithelium. The 3D anatomical gingival tissue model has been shown to modulate the production of a range of cytokines and chemokines in response to interactions with inoculated plaque samples from healthy patients. To assess the clinical relevance of this response, we will study the production of selected cytokines under different conditions; response to the addition of plaque derived from healthy and diseased (gingivitis) patients in comparison to crevicular fluid extracted from the same pool of patients. The efforts will elucidate the initial interactions and balances between these two communities that are responsible for the oral tissue homeostasis or dysbiosis, that ultimately dictates healthy or diseased tissue states. The interdisciplinary team involved in the project has established collaborative activities and includes material scientists, tissue engineers, microbiologists, and periodontists. They are experts in host-material interactions, advanced in vitro tissue and culture models, microbial pathogenesis, host defense, periodontal immunology, and periodontal inflammation.


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 = -$2,551 )
2025	2023	UNIVERSITY OF MASSACHUSETTS LOWELL	220 PAWTUCKET ST STE 400	LOWELL	MA	01854	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	2	5/5/2025	SUPPLEMENT FOR EXPANSION	-$2,551
														Subtotal = -$2,551

Issue Date FY: 2023 ( Subtotal = $154,142 )
2023	2023	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 212	LOWELL	MA	01854	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	2	7/14/2023	SUPPLEMENT FOR EXPANSION	$154,142
														Subtotal = $154,142

Issue Date FY: 2022 ( Subtotal = $233,291 )
2022	2022	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	Oral Diseases and Disorders Research	007	2	7/18/2022	SUPPLEMENT FOR EXPANSION	-$143,242
2022	2022	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	Oral Diseases and Disorders Research	004	2	6/22/2022	NON-COMPETING CONTINUATION	$160,286
2022	2022	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	Oral Diseases and Disorders Research	006	2	7/14/2022	SUPPLEMENT FOR EXPANSION	$154,142
2022	2022	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	Oral Diseases and Disorders Research	005	2	6/23/2022	SUPPLEMENT FOR EXPANSION	$62,105
2022	2021	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	Oral Diseases and Disorders Research	001	1	4/22/2022	NEW	$174,223
2022	2021	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	Oral Diseases and Disorders Research	003	1	5/25/2022	SUPPLEMENT FOR EXPANSION	$45,092
2022	2021	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	1	4/20/2022	NEW	-$174,223
2022	2021	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	Oral Diseases and Disorders Research	002	1	5/23/2022	SUPPLEMENT FOR EXPANSION	-$45,092
														Subtotal = $233,291

Issue Date FY: 2021 ( Subtotal = $219,315 )
2021	2021	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	1	6/14/2021	NEW	$174,223
2021	2021	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	Oral Diseases and Disorders Research	001	1	8/2/2021	SUPPLEMENT FOR EXPANSION	$45,092
														Subtotal = $219,315

Grand Total All Awards = $604,197

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In vitro 3D human gingival tissue model to study oral microbiome

Award Number: R03DE030224

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: 07/15/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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