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3D 打印平台多负载生物活性、磁性纳米粒子和抗生素,用于再生骨组织。

3D-printed platform multi-loaded with bioactive, magnetic nanoparticles and an antibiotic for re-growing bone tissue.

机构信息

Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Avenida Prof. Gama Pinto, 1649-003 Lisboa, Portugal.

Laboratory for Bone Metabolism and Regeneration - Faculty of Dental Medicine, U. Porto, Portugal; REQUIMTE/LAQV - Universidade do Porto, Porto, Portugal.

出版信息

Int J Pharm. 2021 Jan 25;593:120097. doi: 10.1016/j.ijpharm.2020.120097. Epub 2020 Nov 17.

Abstract

Polymeric platforms obtained by three-dimensional (3D) printing are becoming increasingly important as multifunctional therapeutic systems for bone treatment applications. In particularly, researchers aim to control bacterial biofilm on these 3D-platforms and enhance re-growing bone tissue, at the same time. This study aimed to fabricate a 3D-printed polylactic acid platform loaded with hydroxyapatite (HA), iron oxide nanoparticles (IONPs) and an antibiotic (minocycline) with tuneable properties and multistimuli response. IONPs were produced by a facile chemical co-precipitation method showing an average diameter between 11 and 15 nm and a superparamagnetic behaviour which was preserved when loaded into the 3D-platforms. The presence of two types of nanoparticles (IONPs and HA) modify the nanomorphological/nanotopographical feature of the 3D-platforms justifying their adequate bioactivity profile and in vitro cellular effects on immortalized and primary osteoblasts, including cytocompatibility and increased osteogenesis-related gene expression (RUNX2, BGLAP and SPP1). Disk diffusion assays and SEM analysis confirmed the effect of the 3D-platforms loaded with minocycline against Staphylococcus aureus. Altogether results showed that fabricated 3D-platforms combined the exact therapeutic antibiofilm dose of the antibiotic against S. aureus, with the enhanced osteogenic stimulation of the HA and IONPs nanoparticles which is a disruptive approach for bone targeting applications.

摘要

通过三维(3D)打印获得的聚合物平台作为用于骨治疗应用的多功能治疗系统变得越来越重要。特别是,研究人员旨在控制这些 3D 平台上的细菌生物膜,并同时增强再生骨组织。本研究旨在制造一种 3D 打印的聚乳酸平台,该平台负载有羟基磷灰石(HA)、氧化铁纳米粒子(IONP)和一种抗生素(米诺环素),具有可调特性和多刺激响应。IONP 通过简单的化学共沉淀方法制备,平均直径在 11 到 15nm 之间,具有超顺磁性,当负载到 3D 平台上时仍保持其超顺磁性。两种类型的纳米粒子(IONP 和 HA)的存在改变了 3D 平台的纳米形态/纳米形貌特征,证明了其适当的生物活性谱和对永生化和原代成骨细胞的体外细胞效应,包括细胞相容性和增加与成骨相关的基因表达(RUNX2、BGLAP 和 SPP1)。圆盘扩散试验和 SEM 分析证实了载有米诺环素的 3D 平台对金黄色葡萄球菌的抑制作用。总的来说,结果表明,所制造的 3D 平台将抗生素针对金黄色葡萄球菌的精确治疗抗菌剂量与 HA 和 IONP 纳米粒子的增强成骨刺激结合在一起,这是一种针对骨靶向应用的颠覆性方法。

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