Evaluation of carbon nanotubes functionalized with sodium hyaluronate in the inflammatory processes for oral regenerative medicine applications

Clin Oral Investig. 2016 Sep;20(7):1607-16. doi: 10.1007/s00784-015-1639-5. Epub 2015 Nov 10.


Objectives: The objectives of this study were to assess the effects of hyaluronic acid (HY), multi-walled carbon nanotubes (MWCNT), and MWCNT functionalized with HY (HY-MWCNT) on the resolution of neutrophilic inflammation in the pleural cavity of LPS-challenged mice and to assess the influence of these materials in the inflammatory process of bone repair of tooth sockets of rats.

Materials and methods: C57Bl/6 mice were intra-pleurally injected with HY, MWCNT, HY-MWCNT, phosphate-buffered saline (PBS), or LPS. The animals were euthanized after 8 and 24 h, and cells were harvested for total and differential cell counting. The tooth sockets of Wistar rats were filled with HY, MWCNT, HY-MWCNT, or blood clot (control). After 1, 3, and 7 days, histological and morphometric analyses evaluated the number of cell nuclei and blood vessels, and bone trabeculae formation in the sockets. Myeloperoxidase (MPO) activity quantified neutrophil accumulation in the sockets.

Results: HY, MWCNT, and HY-MWCNT increased neutrophilic recruitment at 8 h and reduced the inflammatory process at 24 h in the pleural cavity. Histological and morphometric analyses and MPO activity showed no significant differences in the recruitment of inflammatory cells in the tooth sockets. HY increased the number of blood vessels, and HY and HY-MWCNT increased bone trabeculae formation at 7 days of tooth extraction.

Conclusions: HY, MWCNT, and HY-MWCNT resolved the neutrophilic inflammation in the pleural cavity of the mice. However, these materials did not modulate the inflammatory process in the early stages of bone repair of the tooth sockets, thereby excluding this action as a possible mechanism by which these biomaterials accelerate bone repair.

Clinical relevance: HY-MWCNT is capable of accelerating bone repair/regeneration without affecting the inflammatory phase during the bone healing process.

Keywords: Bone repair; Carbon nanotubes; Hyaluronic acid; Inflammation; Neutrophil.

MeSH terms

  • Animals
  • Cell Movement
  • Hyaluronic Acid / pharmacology*
  • Inflammation / metabolism
  • Leukocytes / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nanotubes, Carbon*
  • Peroxidase / metabolism
  • Rats
  • Rats, Wistar
  • Regenerative Medicine / methods*
  • Tooth Socket / drug effects*
  • Wound Healing / drug effects


  • Nanotubes, Carbon
  • Hyaluronic Acid
  • Peroxidase