FTY720 promotes local microvascular network formation and regeneration of cranial bone defects

Caren E.Petrie Aronin, Lauren S. Sefcik, Sunil S. Tholpady, Ashok Tholpady, Karim W. Sadik, Timothy L. MacDonald, Shayn M. Peirce, Brian R. Wamhoff, Kevin R. Lynch, Roy C. Ogle, Edward A. Botchwey

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

The calvarial bone microenvironment contains a unique progenitor niche that should be considered for therapeutic manipulation when designing regeneration strategies. Recently, our group demonstrated that cells isolated from the dura are multipotent and exhibit expansion potential and robust mineralization on biodegradable constructs in vitro. In this study, we evaluate the effectiveness of healing critical-sized cranial bone defects by enhancing microvascular network growth and host dura progenitor trafficking to the defect space pharmacologically by delivering drugs targeted to sphingosine 1-phosphate (S1P) receptors. We demonstrate that delivery of pharmacological agonists to (S1P) receptors S1P1 and S1P3 significantly increase bone ingrowth, total microvessel density, and smooth muscle cell investment on nascent microvessels within the defect space. Further, in vitro proliferation and migration studies suggest that selective activation of S1P3 promotes recruitment and growth of osteoblastic progenitors from the meningeal dura mater.

Original languageEnglish (US)
Pages (from-to)1801-1809
Number of pages9
JournalTissue Engineering - Part A
Volume16
Issue number6
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

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