Controlled release of odontogenic exosomes from a biodegradable vehicle mediates dentinogenesis as a novel biomimetic pulp capping therapy.
Controlled release
Dentin
Exosome
Pulpotomy
Tissue engineering
Journal
Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908
Informations de publication
Date de publication:
10 08 2020
10 08 2020
Historique:
received:
31
01
2020
revised:
04
06
2020
accepted:
08
06
2020
pubmed:
14
6
2020
medline:
22
6
2021
entrez:
14
6
2020
Statut:
ppublish
Résumé
Mineralized enamel and dentin provide protection to the dental pulp, which is vital tissue rich with cells, vasculature, and nerves in the inner tooth. Dental caries left untreated threaten exposure of the dental pulp, providing facile access for bacteria to cause severe infection both in the pulp and systemically. Dental materials which stimulate the formation of a protective dentin bridge after insult are necessary to seal the pulp chamber in an effort to maintain natural dentition and prevent pulpal infection. Dental materials to date including calcium hydroxide paste, mineral trioxide aggregate, and glass ionomer resin, are used with mixed results. Herein we exploited the cell-cell communicative properties of exosomes, extracellular vesicles derived from both mineralizing primary human dental pulp stem cells (hDPSCs) and an immortalized murine odontoblast cell line (MDPC-23), to catalyze the formation of a reactionary dentin bridge by recruiting endogenous stem cells of the dental pulp, through an easy-to-handle delivery vehicle which allows for their therapeutic controlled delivery at the pulp interface. Exosomes derived from both hDPSCs and MDPCs upregulated odontogenic gene expression and increased mineralization in vitro. We designed an amphiphilic synthetic polymeric vehicle from a triblock copolymer which encapsulates exosomes by polymeric self-assembly and maintains their biologic integrity throughout release up to 8-12 weeks. The controlled release of odontogenic exosomes resulted in a reparative dentin bridge formation, superior to glass-ionomer cement alone in vivo, in a rat molar pulpotomy model after six weeks. We have developed a platform for the encapsulation and controlled, tunable release of cell-derived exosomes, which maintains their advantageous physiologic properties reflective of the donor cells. This platform is used to modulate downstream recipient cells towards a designed dentinogenic trajectory in vitro and in vivo. Additionally, we have demonstrated the utility of an immortalized cell line to produce a high yield of exosomes with cross-species efficacy.
Identifiants
pubmed: 32534011
pii: S0168-3659(20)30340-0
doi: 10.1016/j.jconrel.2020.06.006
pmc: PMC7429296
mid: NIHMS1607567
pii:
doi:
Substances chimiques
Delayed-Action Preparations
0
Drug Combinations
0
Oxides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
679-694Subventions
Organisme : NIDCR NIH HHS
ID : F30 DE029359
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE022327
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE027662
Pays : United States
Organisme : NIDCR NIH HHS
ID : T32 DE007057
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
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