A microbially-induced inflammatory periodontal disease is the main initiator to disrupt the periodontium. It is desirable to develop a newly guided bone regeneration (GBR) scaffold to accomplish the periodontal tissue regeneration for the concurrent control of inflammation. A novel therapeutic solution for GBR based on 3D multifunctional scaffolds, which combines the merits of osseous regeneration and local anti-inflammatory drug delivery, has been developed. The 3D dual-drug delivery scaffold (DDDS) loaded with parthenolide and naringin was successfully developed by thermally-induced phase separation techniques. The DDDS was hierarchically interconnected to the porous PLLA scaffold loaded with the hydrophobic parthenolide. In addition, the hydrophilic naringin loaded in chitosan microspheres was embedded in the scaffold. In vitro drug release profile results revealed that the DDDS showed an efficient sequential controlled release pattern with parthenolide delivered rapidly, followed by naringin delivered in a more sustained manner. Cell viability of MC3T3-E1 showed a combined effect of dual-drug delivery. Hemolysis of the DDDS was 1.84 ± 0.44%, which is less than that of the pure PLLA scaffold. To further evaluate the in vivo guided bone regeneration effect of the DDDS, a rat fenestration defect model was generated. The defects were harvested after 4 and 8 weeks for micro-CT and histological observation. The results suggested that the DDDS group had significantly increased the regenerated bone volume fraction compared to both the control and PLLA groups at 8 weeks, which was in parallel with the reduced expression of IL-6. This DDDS, as a GBR scaffold, might be utilized as a novel adjunctive treatment in periodontitis.

中文翻译：

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在大鼠开窗缺损模型中用于骨再生的顺序控释双药支架

微生物引起的炎性牙周疾病是破坏牙周的主要引发剂。期望开发新引导的骨再生（GBR）支架以完成牙周组织再生以同时控制炎症。已开发出一种基于3D多功能支架的GBR新型治疗方案，该解决方案结合了骨再生和局部消炎药物递送的优点。通过热诱导相分离技术成功开发了装载有小白菊内酯和柚皮苷的3D双药输送支架（DDDS）。DDDS分层互连至装载有疏水性偏苯二酚的多孔PLLA支架。另外，将负载在壳聚糖微球中的亲水性柚皮苷嵌入支架中。体外药物释放曲线结果表明，DDDS表现出高效的顺序控制释放模式，其中小白菊内酯被快速递送，随后柚皮苷以更持续的方式被递送。MC3T3-E1的细胞生存能力显示了双重药物递送的综合作用。DDDS的溶血率为1.84±0.44％，低于纯PLLA支架的溶血率。进一步评估体内在DDDS的骨再生作用的指导下，生成了大鼠开窗缺损模型。在第4和第8周后收集缺损以进行显微CT和组织学观察。结果表明，与对照组和PLLA组相比，DDDS组在第8周时均显着增加了再生骨体积分数，这与IL-6的表达降低平行。DDDS作为GBR支架，可作为牙周炎的新型辅助治疗方法。