Effects on bone remodeling by strontium-containing nanoparticles

In this thesis, research efforts focused on the development of a new nanosystem for the delivery of strontium to improve bone formation are reported. Strontium-substitute hydroxyapatite nanoparticles were synthesized and deeply physical-chemical characterize. The effect of nanoparticles on bone remodeling was evaluated using four different in vitro models that allowed investigations on every single bone cell type: bone marrow mesenchymal stem cells, osteoblasts, osteocytes and osteoclasts. Sr-containing nanoparticles enhanced osteoblasts differentiation by increasing in alkaline phosphatase activity, bone matrix deposition and mineralization and increasing gene expression of specific markers for osteogenesis. On the other hand, Sr-containing nanoparticles inhibited the differentiation of osteoclasts, the cells responsible for bone resorption, by reducing tartrate-resistant acid phosphatase activity and preventing cell fusion and adhesion with inhibition of multinucleated cell formation. Sr-containing nanoparticles affected also the osteocytes differentiation inducing more mature stages and improving their ability to deposit a mineralize bone matrix. Moving from in vitro to in vivo, a new material was developed made of gelatin sponge and enriched with Sr-hydroxyapatite and its effect on ectopic bone formation was evaluated in mice. Ectopic bone formation induced by Sr-hydroxyapatite resulted comparable, even greater in some cases, to Bone Morphogenetic Protein 2 (BMP2) effect. Histology analysis and gene expression revealed increased endochondrial ossification induced by Sr-hydroxyapatite. Moreover, Sr-hydroxyapatite enriched sponges improved bone formation enhancing osteogenic-associated gene expression and reducing those related to osteoclasts differentiation. The bone loss is one of the main problems for astronauts who spend long period on ISS. Besides, microgravity is an ideal model to study the inhibition of osteoblast differentiation. Sr-containing nanoparticles showed to be a useful countermeasure to the bone reduction induced by microgravity, with lower side effects than pharmacological treatments.