Shenzhen University General Hospital, Shenzhen 518060, China; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen 518060, China.
College of life science and technology, Huazhong university of science and technology. Wuhan 430074, China.
J Adv Res. 2023 Dec;54:239-249. doi: 10.1016/j.jare.2023.01.019. Epub 2023 Jan 24.
Scaffolds loaded with antibacterial agents and osteogenic drugs are considered essential tools for repairing bone defects caused by osteomyelitis. However, the simultaneous release of two drugs leads to premature osteogenesis and subsequent sequestrum formation in the pathological situation of unthorough antibiosis.
In this study, a spatiotemporal drug-release polydopamine-functionalized mesoporous silicon nanoparticle (MSN) core/shell drug delivery system loaded with antibacterial silver (Ag) nanoparticles and osteogenic dexamethasone (Dex) was constructed and introduced into a poly-l-lactic acid (PLLA) scaffold for osteomyelitis therapy.
MSNs formed the inner core and were loaded with Dex through electrostatic adsorption (MSNs@Dex), and then polydopamine was used to seal the core through the self-assembly of dopamine as the outer shell (pMSNs@Dex). Ag nanoparticles were embedded in the polydopamine shell via an in situ growth technique. Finally, the Ag-pMSNs@Dex nanoparticles were introduced into PLLA scaffolds (Ag-pMSNs@Dex/PLLA) constructed by selective laser sintering (SLS).
The Ag-pMSNs@Dex/PLLA scaffold released Ag at the 12th hour, followed by the release of Dex starting on the fifth day. The experiments verified that the scaffold had excellent antibacterial performance against Escherichia coli and Staphylococcus aureus. Moreover, the scaffold significantly enhanced the osteogenic differentiation of mouse bone marrow mesenchymal stem cells.
The findings suggested that this spatiotemporal drug release scaffold had promising potential for osteomyelitis therapy.
载有抗菌剂和成骨药物的支架被认为是修复由骨髓炎引起的骨缺损的重要工具。然而,在抗生素未彻底作用的病理情况下,两种药物的同时释放会导致过早成骨和随后的死骨形成。
在这项研究中,构建了一种时空药物释放的聚多巴胺功能化介孔硅纳米颗粒(MSN)核/壳药物输送系统,该系统负载有抗菌银(Ag)纳米颗粒和成骨地塞米松(Dex),并将其引入聚-l-乳酸(PLLA)支架中用于骨髓炎治疗。
MSNs 形成内核,并通过静电吸附负载 Dex(MSNs@Dex),然后使用多巴胺自组装作为外壳(pMSNs@Dex)来密封内核。Ag 纳米颗粒通过原位生长技术嵌入聚多巴胺壳中。最后,将 Ag-pMSNs@Dex 纳米颗粒通过选择性激光烧结(SLS)引入到 PLLA 支架(Ag-pMSNs@Dex/PLLA)中。
Ag-pMSNs@Dex/PLLA 支架在第 12 小时释放 Ag,随后在第 5 天开始释放 Dex。实验验证了该支架对大肠杆菌和金黄色葡萄球菌具有优异的抗菌性能。此外,该支架显著增强了小鼠骨髓间充质干细胞的成骨分化。
这些发现表明,这种时空药物释放支架在骨髓炎治疗方面具有广阔的应用前景。