Objectives

Large bone defect repair is a challenging clinical problem due to limited self-repair ability. A well-designed bone filling product should possess the ability to induce tissue in-growth and facilitate neovascularization and new bone formation. Puerarin has been used in clinics for a long time, and recently it was found to be able to promote osteogenesis. This study aimed to investigate a puerarin-based drug/delivery combination implant for promoting large bone defect repair.

Methods

Puerarin was incorporated into the poly (lactic-co-glycolic acid)/β-calcium phosphate (PLGA/TCP, PT) to form a porous PLGA/TCP/Puerarin (PTP) composite scaffold by low-temperature rapid prototyping technology. Its structural and degradation were analyzed in vitro. Then we employed a rat calvarial critical size defect model to assess the potency of the PTP scaffold. MC3T3-E1 cells and EA. hy 926 ​cells were used to investigate the underlying mechanism.

Results

PTP scaffold inherited all advantages of PT scaffold in structural, mechanical, and biodegradation, meanwhile puerarin stably and continuously released from PTP scaffold and lasted for 5 months in vitro. At 8 weeks after implantation, the PTP scaffold triggered new bone formation in the macro-pores of the scaffold and inside the scaffold accompanied by the degrading materials. The underlying mechanism revealed that the PTP scaffold induced vascular infiltration and recruit repair cells through stimulating vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2) expressions to promote angiogenesis and osteogenesis.

Conclusion

Puerarin-enriched porous PTP scaffold was a promising local delivery system with sustained release of puerarin for facilitating defect repair through getting synergistic angiogenic and osteogenic effects.

The Translational Potential of this Article

The PTP scaffold presents a potential drug/device combination medical implant for large bone defect repair, which also provides a new and innovative application for the “old drug” puerarin.

中文翻译：

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老药的新用途：葛根素局部给药通过促进血管生成和成骨促进大鼠临界尺寸缺陷修复

目标

由于自我修复能力有限，大骨缺损修复是一个具有挑战性的临床问题。精心设计的骨填充产品应具有诱导组织向内生长并促进新血管形成和新骨形成的能力。葛根素已在临床上使用了很长时间，最近发现它能够促进成骨。本研究旨在研究一种基于葛根素的药物/递送组合植入物，用于促进大骨缺损修复。

方法

通过低温快速成型技术将葛根素掺入聚乳酸-乙醇酸共聚物/β-磷酸钙（PLGA/TCP，PT）中形成多孔PLGA/TCP/葛根素（PTP）复合支架。对其结构和降解进行了体外分析。然后我们采用大鼠颅骨临界尺寸缺陷模型来评估 PTP 支架的效力。MC3T3-E1 细胞和 EA。hy 926 细胞用于研究潜在机制。

结果

PTP支架继承了PT支架在结构、力学、生物降解等方面的所有优势，同时葛根素从PTP支架中稳定、持续释放，在体外可持续5个月。在植入后 8 周，PTP 支架在支架的大孔和支架内部引发了新的骨形成，伴随着降解材料。其潜在机制表明，PTP 支架通过刺激血管内皮生长因子 (VEGF) 和骨形态发生蛋白 2 (BMP-2) 的表达来促进血管生成和成骨，从而诱导血管浸润和募集修复细胞。

结论

富含葛根素的多孔 PTP 支架是一种很有前途的局部递送系统，具有葛根素的持续释放，通过获得协同的血管生成和成骨作用促进缺损修复。

本文的转化潜力

PTP支架为大骨缺损修复提供了一种潜在的药物/器械组合医疗植入物，也为“老药”葛根素提供了新的创新应用。