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多功能 pH 敏感的 3D 支架用于治疗和预防骨感染。

Multifunctional pH sensitive 3D scaffolds for treatment and prevention of bone infection.

机构信息

Departamento de Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain.

Departamento de Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.

出版信息

Acta Biomater. 2018 Jan;65:450-461. doi: 10.1016/j.actbio.2017.11.009. Epub 2017 Nov 8.

Abstract

UNLABELLED

Multifunctional-therapeutic three-dimensional (3D) scaffolds have been prepared. These biomaterials are able to destroy the S. aureus bacterial biofilm and to allow bone regeneration at the same time. The present study is focused on the design of pH sensitive 3D hierarchical meso-macroporous 3D scaffolds based on MGHA nanocomposite formed by a mesostructured glassy network with embedded hydroxyapatite nanoparticles, whose mesopores have been loaded with levofloxacin (Levo) as antibacterial agent. These 3D platforms exhibit controlled and pH-dependent Levo release, sustained over time at physiological pH (7.4) and notably increased at infection pH (6.7 and 5.5), which is due to the different interaction rate between diverse Levo species and the silica matrix. These 3D systems are able to inhibit the S. aureus growth and to destroy the bacterial biofilm without cytotoxic effects on human osteoblasts and allowing an adequate colonization and differentiation of preosteoblastic cells on their surface. These findings suggest promising applications of these hierarchical MGHA nanocomposite 3D scaffolds for the treatment and prevention of bone infection.

STATEMENT OF SIGNIFICANCE

Multifunctional 3D nanocomposite scaffolds with the ability for loading and sustained delivery of an antimicrobial agent, to eliminate and prevent bone infection and at the same time to contribute to bone regeneration process without cytotoxic effects on the surrounding tissue has been proposed. These 3D scaffolds exhibit a sustained levofloxacin delivery at physiological pH (pH 7.4), which increasing notably when pH decreases to characteristic values of bone infection process (pH 6.7 and pH 5.5). In vitro competitive assays between preosteoblastic and bacteria onto the 3D scaffold surface demonstrated an adequate osteoblast colonization in entire scaffold surface together with the ability to eliminate bacteria contamination.

摘要

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已经制备了多功能治疗性三维(3D)支架。这些生物材料能够同时破坏金黄色葡萄球菌细菌生物膜并允许骨再生。本研究集中于设计基于 MGHA 纳米复合材料的 pH 敏感 3D 分级中孔-大孔 3D 支架,该纳米复合材料由具有嵌入羟基磷灰石纳米颗粒的介孔玻璃状网络形成,其介孔中装载有左氧氟沙星(Levo)作为抗菌剂。这些 3D 平台表现出受控制且依赖 pH 的 Levo 释放,在生理 pH(7.4)下持续时间长,在感染 pH(6.7 和 5.5)下显著增加,这是由于不同 Levo 物种与二氧化硅基质之间的不同相互作用速率所致。这些 3D 系统能够抑制金黄色葡萄球菌的生长并破坏细菌生物膜,同时对人成骨细胞无细胞毒性作用,并允许前成骨细胞在其表面进行适当的定植和分化。这些发现表明这些分级 MGHA 纳米复合材料 3D 支架在治疗和预防骨感染方面具有广阔的应用前景。

意义声明

已经提出了具有负载和持续输送抗菌剂能力的多功能 3D 纳米复合材料支架,以消除和预防骨感染,同时有助于骨再生过程,而对周围组织无细胞毒性作用。这些 3D 支架在生理 pH(pH 7.4)下表现出持续的左氧氟沙星释放,当 pH 降低到骨感染过程的特征值(pH 6.7 和 pH 5.5)时,释放显著增加。3D 支架表面上的前成骨细胞与细菌之间的竞争测定表明,在整个支架表面上都有足够的成骨细胞定植,并且能够消除细菌污染。

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