American Association of Plastic Surgeons

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Quantifying Type H Vasculature in Irradiated Distraction Osteogenesis as a Marker for Enhanced Bone Healing
Melissa Daniel, MD1, Nathan Sheppard, BArch2, Noah Nelson, MPH3, Alex Donneys, MD3, Steven Buchman, MD3
1University of Oklahoma- Tulsa, Tulsa, OK, USA, 2University of Tenessee, Tennessee, TN, USA, 3University of Michigan, Ann Arbor, MI, USA

Introduction: Within bone defects, the injured vasculature and loss of hemodynamic stimulates vascular and upregulates sprouting of type H vessels (HV). However the HV response remains inadequate to overcome radiation injury. We posit that the destruction of HV plays a role in precluding distraction osteogenesis (DO)ís effectiveness in irradiated bone defect healing and localized application of deferoxamine (DFO) will enhance HV formation and promote healing in irradiated DO defects.Methods: Three groups: DO, Radiation with DO (xDO), and xDO + localized DFO (xDODFO). Samples were immunofluorescently stained for endomucin, CD31, Hoechst and Osterix. Images were acquired analyzed. HV osteoprogenitor quantify is represented by the area fraction of CD31+/EMCN+ vessel and Osterix+/ CD31+ inside the regenerate sample.Results: There was a 6-fold increase in the HV area fraction in the DO group than the xDO group. Abundance of HV was 15-fold higher in xDODFO compared to xDO (p= 0.00133531). HV mediated recruitment of osteoprogenitor cells mimicked the described HV formation trend in our study groups. xDO groups contained three-fold less osteoprogenitor cells compared to DO controls. The xDODFO group revealed a 12-fold increase in Osterix+ cells, highlighting significant remediation of radiation damage.Conclusions: Radiation severely decreased HV formation along with an associated significant diminution of new bone formation and non-union. DFO administration, however, resulted in vascular replenishment and the restoration of high quantities of HV and osteoprogenitor cells, recapitulating the normal process of bone regeneration and holding promise for clinical translation.


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