Biomimetic delivery of chemokines and growth factors based on stem cell recruitment and endochondral ossification, as the key steps in natural regenerative process, has been an area of intense research in recent years. An inflammatory chemokine, interleukin-8 (IL-8), was recently reported with high recruitment efficiency of bone marrow stem cells, chondrogenic inductivity and immune regulatory functions. In this study, the effect of IL-8 action duration on bone morphogenetic protein-2 (BMP-2)-induced bone regeneration was studied to achieve an optimal synergism of these two proteins. Herein, a mesoporous bioactive glass (MBG)-based scaffold with BMP-2 entrapment and IL-8-loaded chitosan microspheres (CMs) was developed. The MBG scaffold with size-matched mesopores was adopted for the long-term sustained delivery of BMP-2; and CMs with different sizes, prepared using a modified ionotropic gelation method, were customized to match the optimal action time of IL-8. The results indicated that CMs of 100 μm diameter and medium crosslinking density exhibited an 85% release of IL-8 in 7 days and the MBG substrate exhibited a long-term sustained release of BMP-2. Furthermore, the binary delivery system exhibited excellent biocompatibility and synergistically enhanced osteoinductivity. In an in situ bone regeneration model of a rabbit radius large segmental defect, the system efficiently accelerated the whole regenerative process, with the highest bone formation amount from an early stage and the highest degree of regenerative completion. Since delivery systems for multiple cytokines have been in great demand due to the requirement of complicated biological processes, we believe that this new binary delivery system could be customized to design other dual delivery systems for improving bone-repairing biomaterials with higher regenerative efficiency.

中文翻译：

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含壳聚糖微球的MBG支架，用于IL-8和BMP-2的二元递送，用于骨骼再生†

近年来，基于自然再生过程的关键步骤，基于干细胞募集和软骨内骨化的趋化因子和生长因子的仿生传递已成为研究的热点。最近报道了一种炎症趋化因子白细胞介素8（IL-8），具有骨髓干细胞的高募集效率，软骨诱导性和免疫调节功能。在这项研究中，研究了IL-8作用持续时间对骨形态发生蛋白2（BMP-2）诱导的骨再生的影响，以实现这两种蛋白的最佳协同作用。本文中，开发了具有BMP-2包埋和负载IL-8的壳聚糖微球（CMs）的中孔生物活性玻璃（MBG）基支架。具有大小匹配的中孔的MBG支架被用于BMP-2的长期持续递送。使用改良的离子型凝胶法制备的不同大小的CM可以进行定制，以匹配IL-8的最佳作用时间。结果表明，直径为100μm和中等交联密度的CM在7天内表现出85％的IL-8释放，而MBG底物表现出BMP-2的长期持续释放。此外，二元递送系统表现出优异的生物相容性和协同增强的骨诱导性。在 该二元递送系统表现出优异的生物相容性并协同增强了骨诱导性。在 该二元递送系统表现出优异的生物相容性并协同增强了骨诱导性。在在兔radius骨大段缺损的原位骨再生模型中，该系统有效地加速了整个再生过程，从早期开始就形成了最高的骨形成量，并且完成了最高程度的再生。由于由于复杂的生物过程的需求，对多种细胞因子的递送系统的需求很大，因此我们认为，可以定制这种新的二元递送系统，以设计其他双重递送系统，以提高骨修复生物材料的再生效率。