Calvarial Defect Healing Induced by Small Molecule Smoothened Agonist

Soonchul Lee, Jia Shen, Hsin Chuan Pan, Swati Shrestha, Greg Asatrian, Alan Nguyen, Carolyn Meyers, Vi Nguyen, Min Lee, Chia Soo, Kang Ting, Aaron W. James

Research output: Contribution to journalArticle

Abstract

Hedgehog (Hh) signaling positively regulates both endochondral and intramembranous ossification. Use of small molecules for tissue engineering applications poses several advantages. In this study, we examined whether use of an acellular scaffold treated with the small molecule Smoothened agonist (SAG) could aid in critical-size mouse calvarial defect repair. First, we verified the pro-osteogenic effect of SAG in vitro, using primary neonatal mouse calvarial cells (NMCCs). Next, a 4 mm nonhealing defect was created in the mid-parietal bone of 10-week-old CD-1 mice. The scaffold consisted of a custom-fabricated poly(lactic-co-glycolic acid) disc with hydroxyapatite coating (measuring 4 mm diameter × 0.5 mm thickness). Treatment groups included dimethylsulfoxide control (n = 6), 0.5 mM SAG (n = 7) or 1.0 mM SAG (n = 7). Evaluation was performed at 4 and 8 weeks postoperative, by a combination of high-resolution microcomputed tomography, histology (H & E, Masson's Trichrome), histomorphometry, and immunohistochemistry (BSP, OCN, VEGF). In vivo results showed that SAG treatment induced a significant and dose-dependent increase in calvarial bone healing by all radiographic parameters. Histomorphometric analysis showed an increase in all parameters of bone formation with SAG treatment, but also an increase in blood vessel number and density. In summary, SAG is a pro-osteogenic, provasculogenic stimulus when applied locally in a bone defect environment.

Original languageEnglish (US)
Pages (from-to)1357-1366
Number of pages10
JournalTissue Engineering - Part A
Volume22
Issue number23-24
DOIs
StatePublished - Dec 1 2016

Keywords

  • Osteogenesis
  • bone healing
  • hedgehog signaling
  • small molecule
  • smoothened agonist
  • vasculogenesis

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

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  • Cite this

    Lee, S., Shen, J., Pan, H. C., Shrestha, S., Asatrian, G., Nguyen, A., Meyers, C., Nguyen, V., Lee, M., Soo, C., Ting, K., & James, A. W. (2016). Calvarial Defect Healing Induced by Small Molecule Smoothened Agonist. Tissue Engineering - Part A, 22(23-24), 1357-1366. https://doi.org/10.1089/ten.tea.2016.0167