MBG scaffolds containing chitosan microspheres for binary delivery of IL-8 and BMP-2 for bone regeneration
MBG scaffolds containing chitosan microspheres for binary delivery of IL-8 and BMP-2 for bone regeneration
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DOI：
10.1039/c8tb00875b
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发表时间：
2018-07-21
影响因子：
7
通讯作者：
Liu, Changsheng
中科院分区：
文献类型：
--
作者：
Cai, Lisha;Lin, Dan;Liu, Changsheng
作为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递送已成为近年来的热门研究领域。最近报道了一种炎症趋化因子白细胞介素-8 (IL-8)，其具有高骨髓干细胞募集效率、软骨形成诱导性和免疫调节功能。在本研究中，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。在此，开发了一种基于介孔生物活性玻璃（MBG）的支架，具有 BMP-2 包埋和负载 IL-8 的壳聚糖微球（CM）。采用具有尺寸匹配介孔的MBG支架用于BMP-2的长期持续递送；并定制不同尺寸的 CM，使用改进的离子凝胶法制备，以匹配 IL-8 的最佳作用时间。结果表明，直径100 m、中等交联密度的CM在7天内释放出85%的IL-8，MBG底物则表现出长期持续释放的BMP-2。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。在兔桡骨大节段缺损原位骨再生模型中，该系统有效加速了整个再生过程，早期骨形成量最高，再生完成度最高。由于复杂的生物过程的要求，对多种细胞因子的递送系统的需求量很大，我们相信这种新的二元递送系统可以定制以设计其他双重递送系统，以提高具有更高再生效率的骨修复生物材料。
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 m 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.