Division of Surgery, Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
Division of Microbiology, Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
Int J Pharm. 2024 Dec 5;666:124826. doi: 10.1016/j.ijpharm.2024.124826. Epub 2024 Oct 12.
Chronic osteomyelitis presents significant treatment challenges, necessitating an efficient system for infection elimination and bone repair. This study developed a natural hydrogel scaffold using silk fibroin (SF) and chitosan thiourea (CST), incorporating vancomycin (VC) and quercetin (QC) loaded PLGA nanoparticles (NPs) for dual-purpose treatment. SF/CST hydrogel scaffolds exhibited homogeneous porosity and smaller interconnected pore size than pure SF and pure CST hydrogel scaffolds. Optimal PLGA/QC NPs measured 206 nm in size, displayed spherical morphology, had uniform distribution, and achieved 87 % QC loading. The release study showed sustained long-term release of VC and QC from the hydrogel scaffolds for over 20 days. Biocompatibility tests indicated that hydrogel scaffolds promoted osteoblast adhesion without cytotoxicity, with QC-containing scaffolds enhancing osteoblast growth. Antibacterial tests confirmed retained VC activity against methicillin-resistant Staphylococcus aureus (MRSA) in SF/CST. An experimental study assessed the efficacy of the hydrogel scaffolds in a MRSA-infected rat osteomyelitis model. Radiographic scores demonstrated a significant reduction for SF/CST-VC-PLGA/QC NPs compared to control, indicating reduced osteomyelitis effects. Macroscopic evaluations showed notable reductions in gross pathological effects for VC-containing groups. Histopathological assessments revealed significantly lower osteomyelitis scores and higher healing scores in the SF/CST-VC-PLGA/QC NPs, with reduced inflammatory cell infiltration and more organized connective tissue formation. In conclusion, SF/CST-VC-PLGA/QC NPs is an effective dual drug delivery system for osteomyelitis treatment, demonstrating significant antibacterial activity, enhanced bone regeneration, and reduced infection rate.
慢性骨髓炎的治疗极具挑战性，需要建立一种高效的感染消除和骨修复系统。本研究开发了一种使用丝素蛋白（SF）和壳聚糖硫脲（CST）的天然水凝胶支架，其中包含载万古霉素（VC）和槲皮素（QC）的 PLGA 纳米颗粒（NPs），用于双重治疗。SF/CST 水凝胶支架的比纯 SF 和纯 CST 水凝胶支架具有更均匀的孔隙率和更小的连通孔尺寸。最佳 PLGA/QC NPs 的尺寸为 206nm，呈球形形态，分布均匀，QC 负载率达到 87%。释放研究表明，VC 和 QC 从水凝胶支架中持续释放 20 多天。生物相容性试验表明，水凝胶支架促进成骨细胞黏附而无细胞毒性，含 QC 的支架促进成骨细胞生长。抗菌试验证实 SF/CST 中保留了 VC 对耐甲氧西林金黄色葡萄球菌（MRSA）的活性。一项实验研究评估了水凝胶支架在 MRSA 感染大鼠骨髓炎模型中的疗效。放射学评分表明 SF/CST-VC-PLGA/QC NPs 组与对照组相比，显著降低了骨髓炎的影响，表明降低了骨髓炎的效果。宏观评估显示 VC 组的大体病理影响明显降低。组织病理学评估显示 SF/CST-VC-PLGA/QC NPs 组骨髓炎评分显著降低，愈合评分显著升高，炎症细胞浸润减少，结缔组织形成更有序。总之，SF/CST-VC-PLGA/QC NPs 是一种有效的骨髓炎治疗双重药物输送系统，具有显著的抗菌活性、增强的骨再生和降低的感染率。
