Porous nanofibrous scaffold incorporated with S1P loaded mesoporous silica nanoparticles and BMP-2 encapsulated PLGA microspheres for enhancing angiogenesis and osteogenesis
Porous nanofibrous scaffold incorporated with S1P loaded mesoporous silica nanoparticles and BMP-2 encapsulated PLGA microspheres for enhancing angiogenesis and osteogenesis
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多孔纳米纤维支架与负载 S1P 的介孔二氧化硅纳米颗粒和 BMP-2 封装的 PLGA 微球相结合，用于增强血管生成和成骨
DOI：
10.1039/c8tb02138d
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发表时间：
2018
影响因子：
7
通讯作者：
He Chuanglong
中科院分区：
文献类型：
--
作者：
Zhang Qianqian;Qin Ming;Zhou Xiaojun;Nie Wei;Wang Weizhong;Li Lei;He Chuanglong
骨缺损的修复仍然是一个主要的临床挑战，因为骨代用品中的血管化不充分或异常，这通常导致骨形成不良或骨不愈合。因此，骨缺损的愈合需要血管生成和成骨生成的协调过程。本研究首先将鞘氨醇-1-磷酸（S1P）装载到介孔二氧化硅纳米颗粒（MSNs）中形成血管生成微载体，随后通过热诱导相分离（TIPS）过程将其嵌入多孔纳米纤维聚l -乳酸（PLLA）支架中，而将骨形态发生蛋白-2 （BMP-2）包裹到聚乳酸-羟基乙酸（PLGA）微球中获得成骨微载体。然后通过后播种方法将其集成到MSNs/PLLA纳米纤维支架上。在体外和体内对所制备的含双生物活性因子支架的成骨和血管生成活性进行了评价。模拟药物释放研究表明，这两种生物活性因子将从制备的复合支架中同时连续释放。此外，异位骨形成结果表明，复合支架中S1P和BMP-2的持续释放对血管形成和骨再生具有协同作用。综上所述，双生物活性因子负载纳米纤维支架在增强骨再生方面具有广阔的应用前景。
Repair of bone defects remains a major clinical challenge due to inadequate or abnormal vascularization in bone substitutes, which commonly leads to inferior bone formation or bone nonunion. Therefore, healing of bone defects requires the coordinated processes of angiogenesis and osteogenesis. In this study, sphingosine-1-phosphate (S1P) was initially loaded into mesoporous silica nanoparticles (MSNs) to form angiogenic microcarriers, which were subsequently embedded into porous nanofibrous poly-L-lactide (PLLA) scaffolds during a thermally induced phase separation (TIPS) process, while bone morphogenetic protein-2 (BMP-2) was encapsulated into poly(lactic-co-glycolic acid) (PLGA) microspheres to obtain osteogenic microcarriers, which were then integrated onto a MSNs/PLLA nanofibrous scaffold by a post seeding method. The osteogenic and angiogenic activities of the resulting dual-bioactive factor containing scaffolds were evaluated both in vitro and in vivo. The simulated drug release studies indicated that both bioactive factors will be released simultaneously and continuously from the fabricated composite scaffold. Moreover, the ectopic bone formation results showed that the sustained release of S1P and BMP-2 from the composite scaffold resulted in a synergistic effect on blood vessel formation and bone regeneration. Taken together, the results showed the promising application of the dual-bioactive factor loaded nanofibrous scaffold for enhanced bone regeneration.