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Controlled release of odontogenic exosomes from a biodegradable vehicle mediates dentinogenesis as a novel biomimetic pulp capping therapy

Swanson, W. Benton ; Gong, Ting ; Zhang, Zhen ; Eberle, Miranda ; Niemann, David ; Dong, Ruonan ; Rambhia, Kunal J. ; Ma, Peter X.

Journal of controlled release, 2020-08, Vol.324, p.679-694 [Periódico revisado por pares]

Netherlands: Elsevier B.V

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  • Título:
    Controlled release of odontogenic exosomes from a biodegradable vehicle mediates dentinogenesis as a novel biomimetic pulp capping therapy
  • Autor: Swanson, W. Benton ; Gong, Ting ; Zhang, Zhen ; Eberle, Miranda ; Niemann, David ; Dong, Ruonan ; Rambhia, Kunal J. ; Ma, Peter X.
  • Assuntos: Animals ; Biomimetics ; Controlled release ; Delayed-Action Preparations ; Dental Caries - therapy ; Dental Pulp Capping ; Dentin ; Dentinogenesis ; Drug Combinations ; Exosome ; Exosomes ; Mice ; Oxides ; Pulpotomy ; Rats ; Tissue engineering
  • É parte de: Journal of controlled release, 2020-08, Vol.324, p.679-694
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    This work was carried out in the Polymeric Biomaterials and Tissue Engineering Laboratory at the University of Michigan. WBS and TG contributed overall equally to this work and drafted the manuscript. TG did mainly the biological and animal experiments including exosome isolation, cell culture, molecular and biochemical characterizations, subcutaneous implantation, pulp capping, and histological analysis. WBS did mainly the biomaterials and controlled release studies, including polymer synthesis, scaffold and microsphere fabrication, controlled release, and physical characterizations. ZZ, RD, and KJR participated in animal and biological studies. ME and DN participated in biomaterials and controlled release experiments. PXM organized and supervised the project, trained study participants, obtained funding, analyzed and interpreted data with trainees, revised and finalized the manuscript, and is the corresponding author.
    Current Address: Hospital of Stomatology, Zunyi Medical University, Zunyi, 563000, China
    These two authors contributed equally to this work.
    Current Address: Department of Orthopedic Surgery, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China
    CRediT author statement
  • Descrição: 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. [Display omitted] •Exosomes from dental pulp stem cells and odontoblast cells upregulate odontogenic genes.•Triblock copolymer is able to deliver exosomes with tunable dose and duration.•Sustained exosome release induces dental pulp stem cell migration and dentin regeneration.•Exosome-loaded dental pulp capping materials facilitate dentin bridge formation and protect pulp tissue.
  • Editor: Netherlands: Elsevier B.V
  • Idioma: Inglês
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