Bone tissue regeneration in critical-size defects is possible after implantation of a 3D scaffold and can be additionally enhanced once the scaffold is enriched with drugs or other factors supporting bone remodelling and healing. Sodium alendronate (Aln), a widely used anti-osteoporosis drug, exhibits strong inhibitory effect on bone resorption performed by osteoclasts. Thus, we propose a new approach for the treatment of bone defects in craniofacial region combining biocompatible titanium dioxide scaffolds and poly(l-lactide-co-glycolide) microparticles (MPs) loaded with Aln. The MPs were effectively attached to the surface of the scaffolds’ pore walls by human recombinant collagen. Drug release from the scaffolds was characterized by initial burst (24 ± 6% of the drug released within first 24 h) followed by a sustained release phase (on average 5 µg of Aln released per day from Day 3 to Day 18). In vitro tests evidenced that Aln at concentrations of 5 and 2.5 µg/ml was not cytotoxic for MG-63 osteoblast-like cells (viability between 81 ± 6% and 98 ± 3% of control), but it prevented RANKL-induced formation of osteoclast-like cells from macrophages derived from peripheral blood mononuclear cells, as shown by reduced fusion capability and decreased tartrate-resistant acid phosphatase 5b activity (56 ± 5% reduction in comparison to control after 8 days of culture). Results show that it is feasible to design the scaffolds providing required doses of Aln inhibiting osteoclastogenesis, reducing osteoclast activity, but not affecting osteoblast functions, which may be beneficial in the treatment of critical-size bone tissue defects.

中文翻译：

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阿仑膦酸钠装入聚（升-lactide-共-glycolide）固定在用于局部治疗骨缺损的陶瓷支架微粒

植入3D支架后，可能会在关键尺寸缺损中进行骨骼组织再生，并且一旦支架中富含支持骨骼重塑和愈合的药物或其他因素，就可以进一步增强骨骼组织。阿仑膦酸钠（Aln）是一种广泛使用的抗骨质疏松药物，对破骨细胞进行的骨吸收表现出强烈的抑制作用。因此，我们提出了一种结合生物相容性二氧化钛支架和聚（l-丙交酯-co）联合治疗颅面部骨缺损的新方法。-乙交酯）微粒（MPs）负载Aln。MP通过人类重组胶原蛋白有效地附着在支架孔壁表面。从支架释放的药物的特征在于最初的爆发（最初24小时内释放药物的24±6％），然后是持续释放阶段（从第3天到第18天每天平均释放5μgAln）。体外实验证明，浓度为5和2.5 µg / ml的Aln对MG-63成骨细胞样细胞没有细胞毒性（生存力在对照组的81±6％和98±3％之间），但它阻止了RANKL诱导的破骨细胞形成。融合能力降低和抗酒石酸酸性磷酸酶5b活性降低（与培养8天后的对照相比降低了56±5％）表明，这种细胞类似于来自外周血单核细胞的巨噬细胞所产生的细胞。结果表明，设计提供所需剂量的Aln抑制破骨细胞生成，降低破骨细胞活性但不影响成骨细胞功能的支架是可行的，这可能对关键尺寸的骨组织缺损的治疗有益。