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Rapid initiation of guided bone regeneration driven by spatiotemporal delivery of IL-8 and BMP-2 from hierarchical MBG-based scaffold.
Biomaterials ( IF 14.0 ) Pub Date : 2017-11-17 , DOI: 10.1016/j.biomaterials.2017.11.011
Dan Lin 1 , Yanjun Chai 2 , Yifan Ma 2 , Bing Duan 1 , Yuan Yuan 3 , Changsheng Liu 4
Affiliation  

Initiation of endogenous repair mechanisms, including key steps of stem cell recruitment and cartilage intermediate formation in endochondral ossification, is vital to regeneration of large bone defects. To biomimetically promote a rapid initiation and ensuing osteogenic stimulation, exogenous chemokine IL-8 and growth factor BMP-2 were orchestrated in a mesoporous bioactive glass (MBG)-based spatiotemporal delivery system, to achieve a rapid release of IL-8 followed by a long-term sustained release of BMP-2. The synergistic effect of IL-8 and BMP-2 on initiation stage of bone healing and underlying mechanism were thoroughly investigated in vitro and in vivo. Intriguingly, apart from its superiority in stem cell recruitment to BMP-2, IL-8 not only endowed a histological "prep-state" of endochondral ossification by up-regulating chondrogenic genes and inducing the formation of extensive cartilage tissues, facilitating rapid bone transformation by BMP-2, but also triggered a cellular "prep-state" with high expression of BMP receptors, enhancing the osteoinductivity of BMP-2. With the spatiotemporal delivery system, orchestrated signal stimuli of IL-8 and BMP-2 induced a rapid initiation including efficient stem cell recruitment and a "chondrogenic/osteogenic balance" at the first stage of endochondral ossification, and the scaffold facilitated sufficient osteoconductivity, together resulting in early extensive bone mineralization and an advanced regeneration throughout the repair of large bone defect. We believe this new idea could provide insights toward designing bone-repairing biomaterials with higher regenerative efficiency.

中文翻译:

从基于MBG的支架中IL-8和BMP-2的时空传递驱动快速启动引导的骨再生。

内源性修复机制的启动,包括软骨内骨化中干细胞募集和软骨中间形成的关键步骤,对于大骨缺损的再生至关重要。为了仿生地促进快速启动和随后的成骨刺激,在基于介孔生物活性玻璃(MBG)的时空传递系统中精心设计了外源趋化因子IL-8和生长因子BMP-2,以实现IL-8的快速释放,然后快速释放。 BMP-2的长期持续释放。IL-8和BMP-2对骨愈合起始阶段和潜在机制的协同作用已在体内和体外进行了深入研究。有趣的是,除了干细胞向BMP-2募集方面的优势外,IL-8不仅具有组织学上的“准备状态” 上调软骨形成基因并诱导广泛的软骨组织形成,促进软骨内骨化的发生,促进BMP-2快速骨转化,但也触发了BMP受体高表达的细胞“预备状态”,增强了BMP- 2。通过时空传递系统,IL-8和BMP-2的协调信号刺激在软骨内骨化的第一阶段诱导了快速启动,包括有效的干细胞募集和“软骨/成骨平衡”,并且支架促进了充分的骨电导性。导致早期大范围的骨矿化和整个大骨缺损修复过程中的高级再生。
更新日期:2018-11-29
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