Implantable Deferoxamine-Hyaluronic Acid Nanoparticle Promotes Angiogenesis and Accelerates Bone Regeneration
Deshpande, Samir S.
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Deferoxamine (DFO), an angiogenic stimulant, has shown great promise in the development of a new vasculature, a prerequisite to new bone growth. Unfortunately, as a treatment for radiation-related bone morbidities, it has numerous drawbacks including patient discomfort and increased opportunity for infection. In this experiment, DFO was bound to an implantable, hyaluronic acid (HA) based nanoparticle (LDFO) to avoid the disadvantages of frequent injections. Nanoparticle structure and breakdown were confirmed by NMR and enzymatic degradation experiments. Nanoparticle efficacy was tested both in vitro and in vivo. In vitro investigation utilized Human Umbilical Vascular Endothelial Cells in Matrigel exposed to DFO, low dose LDFO, and high dose LDFO. In vivo, four groups of Sprague-Dawley rats underwent external fixator placement and fracture osteotomy. Three groups received radiotherapy; one of these groups received DFO treatment while another received LDFO treatment. After 40 days, rats imaged to calculated micro-CT and biomechanical metrics. In vitro, microtubule formation assays demonstrate that LDFO successfully promotes the proliferation of microtubules, a measure of angiogenic potential. In vivo, across all metrics, LDFO animals performed significantly better than radiated rats receiving no therapy; no significant difference was observed between LDFO animals and DFO animals. These data suggest that DFO conjugated to a HA-based nanoparticle represents a viable alternative to injectable DFO in the fight to ameliorate radiation-related bone morbidities.