Hypoxia-Responsive Oxygen Nanobubbles for Tissues-Targeted Delivery in Developing Tooth Germs

Eun Jung Kim, Ji Eun Lee, Semi Yoon, Dong Joon Lee, Han Ngoc Mai, Hiroko Ida-Yonemochi, Jonghoon Choi, Han Sung Jung

Research output: Contribution to journalArticlepeer-review


Hypoxia is a state of inadequate supply of oxygen. Increasing evidence indicates that a hypoxic environment is strongly associated with abnormal organ development. Oxygen nanobubbles (ONBs) are newly developed nanomaterials that can deliver oxygen to developing tissues, including hypoxic cells. However, the mechanisms through which nanobubbles recover hypoxic tissues, such as developing tooth germs remain to be identified. In this study, tooth germs were cultured in various conditions: CO2 chamber, hypoxic chamber, and with 20% ONBs for 3 h. The target stages were at the cap stage (all soft tissue) and bell stage (hard tissue starts to form). Hypoxic tooth germs were recovered with 20% ONBs in the media, similar to the tooth germs incubated in a CO2 chamber (normoxic condition). The tooth germs under hypoxic conditions underwent apoptosis both at the cap and bell stages, and ONBs rescued the damaged tooth germs in both the cap and bell stages. Using kidney transplantation for hard tissue formation in vivo, amelogenesis and dentinogenesis imperfecta in hypoxic conditions at the bell stage were rescued with ONBs. Furthermore, glucose uptake by tooth germs was highly upregulated under hypoxic conditions, and was restored with ONBs to normoxia levels. Our findings indicate that the strategies to make use of ONBs for efficient oxygen targeted delivery can restore cellular processes, such as cell proliferation and apoptosis, glucose uptake, and hypomineralization in hypoxic environments.

Original languageEnglish
Article number626224
JournalFrontiers in Cell and Developmental Biology
Publication statusPublished - 2021 Feb 15

Bibliographical note

Funding Information:
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) and funded by the Korean government (MSIP&MOHW) (No. 2017M3A9E4048172). This research was financially supported by grants from the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIP) (NRF-2016R1A5A2008630 and NRF-2019R1A2C3005294).

Publisher Copyright:
© Copyright © 2021 Kim, Lee, Yoon, Lee, Mai, Ida-Yonemochi, Choi and Jung.

All Science Journal Classification (ASJC) codes

  • Developmental Biology
  • Cell Biology


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