A high-throughput, 28-day, microfluidic model of gingival tissue inflammation and recovery.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
23 01 2023
23 01 2023
Historique:
received:
11
06
2021
accepted:
05
01
2023
entrez:
23
1
2023
pubmed:
24
1
2023
medline:
26
1
2023
Statut:
epublish
Résumé
Nearly half of American adults suffer from gum disease, including mild inflammation of gingival tissue, known as gingivitis. Currently, advances in therapeutic treatments are hampered by a lack of mechanistic understanding of disease progression in physiologically relevant vascularized tissues. To address this, we present a high-throughput microfluidic organ-on-chip model of human gingival tissue containing keratinocytes, fibroblast and endothelial cells. We show the triculture model exhibits physiological tissue structure, mucosal barrier formation, and protein biomarker expression and secretion over several weeks. Through inflammatory cytokine administration, we demonstrate the induction of inflammation measured by changes in barrier function and cytokine secretion. These states of inflammation are induced at various time points within a stable culture window, providing a robust platform for evaluation of therapeutic agents. These data reveal that the administration of specific small molecule inhibitors mitigates the inflammatory response and enables tissue recovery, providing an opportunity for identification of new therapeutic targets for gum disease with the potential to facilitate relevant preclinical drug efficacy and toxicity testing.
Identifiants
pubmed: 36690695
doi: 10.1038/s42003-023-04434-9
pii: 10.1038/s42003-023-04434-9
pmc: PMC9870913
doi:
Substances chimiques
Cytokines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
92Informations de copyright
© 2023. The Author(s).
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