PURPOSE: Osteoporosis is a severe health problem with social and economic impacts on society. The standard treatment consists of the systemic administration of drugs such as bisphosphonates, with alendronate (ALN) being one of the most common. Nevertheless, complications of systemic administration occur with this drug. Therefore, it is necessary to develop new strategies, such as local administration. METHODS: In this study, emulsion/dispersion scaffolds based on W/O emulsion of PCL and PF68 with ALN, containing hydroxyapatite (HA) nanoparticles as the dispersion phase were prepared using electrospinning. Scaffolds with different release kinetics were tested in vitro on the co-cultures of osteoblasts and osteoclast-like cells, isolated from adult osteoporotic and control rats. Cell viability, proliferation, ALP, TRAP and CA II activity were examined. A scaffold with a gradual release of ALN was tested in vivo in the bone defects of osteoporotic and control rats. RESULTS: The release kinetics were dependent on the scaffold composition and the used system of the poloxamers. The ALN was released from the scaffolds for more than 22 days. The behavior of cells cultured in vitro on scaffolds with different release kinetics was comparable. The difference was evident between cell co-cultures isolated from osteoporotic and control animals. The PCL/HA scaffold show slow degradation in vivo and residual scaffold limited new bone formation inside the defects. Nevertheless, the released ALN supported bone formation in the areas surrounding the residual scaffold. Interestingly, a positive effect of systemic administration of ALN was not proved. CONCLUSION: The prepared scaffolds enabled tunable control release of ALN. The effect of ALN was proved in vitro and in in vivo study supported peri-implant bone formation.

BIOFABICS Lda Porto Portugal

Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Applied Biology Institute for Nanomaterials Advanced Technologies and Innovation Technical University of Liberec Liberec Czech Republic

Department of Chemistry Faculty of Science Humanities and Education Technical University of Liberec Liberec Czech Republic

Department of Pathological Physiology Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Tissue Engineering Institute of Experimental Medicine the Czech Academy of Sciences Prague Czech Republic

Institute of Anatomy 1st Faculty of Medicine Charles University Prague Czech Republic

Institute of Dental Medicine 1st Faculty of Medicine and General University Hospital Prague Czech Republic

Institute of Histology and Embryology 1st Faculty of Medicine Charles University Prague Czech Republic

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Electrospun Poly(L-lactide-co-ε-caprolactone) Nanofibers with Hydroxyapatite Nanoparticles Mimic Cellular Interplay in Bone Regeneration