Cao Huijuan, Li Lingli, Li Ling, Meng Xiangbo, Liu Yanzhi, Cheng Wenxiang, Zhang Peng, Gao Yongbo, Qin Ling, Wang Xinluan
Centre for Translational Medicine Research & Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, PR China.
University of Chinese Academy of Sciences, Beijing, PR China.
J Orthop Translat. 2022 Jul 31;36:52-63. doi: 10.1016/j.jot.2022.05.003. eCollection 2022 Sep.
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.
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 . 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.
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 . 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.
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 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.
由于自身修复能力有限，大骨缺损修复是一个具有挑战性的临床问题。设计良好的骨填充产品应具备诱导组织向内生长、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很长时间，最近发现它能够促进成骨作用。本研究旨在研究一种基于葛根素的药物/递送组合植入物，以促进大骨缺损修复。
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-磷酸三钙（PLGA/TCP，PT）中，形成多孔PLGA/TCP/葛根素（PTP）复合支架。分析其结构和降解情况。然后，我们采用大鼠颅骨临界尺寸缺损模型来评估PTP支架的效能。使用MC3T3-E1细胞和EA.hy 926细胞来研究其潜在机制。
PTP支架继承了PT支架在结构、力学和生物降解方面的所有优点，同时葛根素从PTP支架中稳定持续释放，持续时间长达5个月。植入后8周，PTP支架在支架的大孔内和支架内部引发新骨形成，同时伴有材料降解。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）的表达来诱导血管浸润并募集修复细胞，从而促进血管生成和成骨作用。
富含葛根素的多孔PTP支架是一种有前景的局部递送系统，可通过协同血管生成和成骨作用促进缺损修复，实现葛根素的持续释放。
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”葛根素提供了一种新的创新性应用。
