Department of Chemistry "Giacomo Ciamician", University of Bologna, via Selmi 2, 40126 Bologna, Italy.
Laboratory of Preclinical and Surgical Studies, Codivilla-Putti Research Institute, Rizzoli Orthopaedic Institute, via di Barbiano 1/10, 40136 Bologna, Italy.
Eur J Pharm Biopharm. 2018 Jun;127:120-129. doi: 10.1016/j.ejpb.2018.02.018. Epub 2018 Feb 15.
The development of new biomaterials able to favor bone formation and to inhibit bone abnormal resorption is mandatory to face the increasing number of age-related musculo-skeletal disorders. Moreover, the increasing antibiotic resistance of clinically important bacteria, which is among the main causes of implant failure, requires new antimicrobial systems. In this study, we prepared multifunctional materials consisting of hydroxyapatite-zoledronate composite crystals decorated with Ag Nanoparticles (AgNPs). Zoledronate, a potent bisphosphonate widely applied for the treatment of pathologies associated to abnormal bone loss, was incorporated into hydroxyapatite up to about 8 wt%. Loading of poly(ethylenimine) - stabilized AgNPs onto the crystals was promoted by zoledronate functionalization and provoked a significant variation of the values of zeta potential. The results of in vitro tests demonstrate that the multifunctional materials combine the beneficial actions of zoledronate and AgNPs. In fact, they improve osteoblast differentiation and activity, whereas they inhibit osteoclastogenesis and osteoclast differentiation, and significantly hinder the growth of multi-drug resistant Gram positive and Gram negative bacteria. As a consequence, they can be exploited both as antiresorptive agents and as antimicrobial materials able to prevent the development of bone-associated infections.
开发能够促进骨形成和抑制骨异常吸收的新型生物材料对于应对日益增多的与年龄相关的肌肉骨骼疾病至关重要。此外，临床重要细菌对抗生素的耐药性不断增加，这是植入物失败的主要原因之一，因此需要新的抗菌系统。在本研究中，我们制备了由羟基磷灰石-唑来膦酸复合晶体修饰的载银纳米粒子（AgNPs）组成的多功能材料。唑来膦酸是一种广泛应用于治疗与骨丢失异常相关疾病的强效双膦酸盐，其在羟基磷灰石中的负载量约为 8wt%。通过唑来膦酸的功能化促进了载 Poly(ethylenimine) - 稳定化 AgNPs 到晶体上的负载，从而导致了zeta 电位值的显著变化。体外试验结果表明，多功能材料结合了唑来膦酸和 AgNPs 的有益作用。事实上，它们可以促进成骨细胞的分化和活性，同时抑制破骨细胞的生成和分化，并显著抑制多药耐药的革兰阳性和革兰阴性菌的生长。因此，它们既可以用作抗吸收剂，也可以用作抗菌材料，以防止与骨骼相关的感染的发生。
