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A Novel Implantable Angiogenic Nanotechnology Improves Bone Mineralization, Biomechanical Strength, and Union Rates In Irradiated Fractures
Russell E. Ettinger, MD1, Alexis Donneys, MD1, Noah S. Nelson, BS1, Jose J. Rodriguez, MD1, Alicia E. Snider, MD1, Kavitha Ranganathan, MD1, Sagar S. Deshpande, BS1, M. Laird Forrest, PhD2, Mark S. Cohen, MD1, Steven R. Buchman, MD1.
1University of Michigan, Ann Arbor, MI, USA, 2University of Kansas, Lawrence, KS, USA.

Purpose: Pathologic fractures and associated non-unions arising in irradiated bone are complex management dilemmas for reconstructive surgeons. We developed an implantable, sustained-release nanoparticle formulation of a known angiogenic small molecule, Deferoxamine (DFO) which obviates the need for serial injections of standard DFO. Here we investigate the efficacy of nano-DFO as compared to standard DFO, in its ability to improve metrics of mineralization, mechanical strength, and bony union.
Methods: Rats (n=44) were divided into 4 groups. Fracture, radiated fracture, radiated fracture with standard DFO and radiated fracture with nano-DFO. Radiated groups received radiotherapy 2 weeks prior to mandibular osteotomy. The nano-DFO group received implantation of the drug at the time of surgery. Following a 40-day healing period, mandibles were assessed for bony-union, imaged with µCT, and mechanically tested to failure. ANOVA was used for comparison (p<0.05).
Results: We observed decreases in all metrics for the radiation group that were remediated with the addition of both DFO and nano-DFO therapies. For metrics of bone mineral density (BMD), total mineral density (TMD), bone volume fraction (BVF), Stiffness, and Failure Load, there was no difference between the two treatments. However, there was a clinically relevant increase in Bony Unions with nano-DFO therapy that was 24% higher than standard DFO (67%vs.91%).
Conclusions: Our data demonstrate in vivo efficacy for the mineralization and biomechanical properties of implanted nano-DFO when compared to normal DFO. We support the continued investigation of this promising treatment in its translation for the management of pathologic fractures and associated non-unions after radiotherapy.


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