Yoon Jeong-Kee, Kim Hong Nam, Bhang Suk Ho, Shin Jung-Youn, Han Jin, La Wan-Geun, Jeong Gun-Jae, Kang Seokyung, Lee Ju-Ro, Oh Jaesur, Kim Min Sung, Jeon Noo Li, Kim Byung-Soo
1 School of Chemical and Biological Engineering, Seoul National University , Seoul, Republic of Korea.
2 Center for BioMicrosystems, Brain Science Institute, Korea Institute of Science and Technology (KIST) , Seoul, Republic of Korea.
Tissue Eng Part A. 2016 Apr;22(7-8):654-64. doi: 10.1089/ten.TEA.2015.0417. Epub 2016 Mar 31.
The rapid recruitment of osteoblasts in bone defects is an essential prerequisite for efficient bone repair. Conventionally, osteoblast recruitment to bone defects and subsequent bone repair has been achieved using growth factors. Here, we present a methodology that can guide the recruitment of osteoblasts to bone defects with topographically defined implants (TIs) for efficient in vivo bone repair. We compared circular TIs that had microgrooves in parallel or radial arrangements with nonpatterned implants for osteoblast migration and in vivo bone formation. In vitro, the microgrooves in the TIs enhanced both the migration and proliferation of osteoblasts. Especially, the microgrooves with radial arrangement demonstrated a much higher efficiency of osteoblast recruitment to the implants than did the other types of implants, which may be due to the efficient guidance of cell migration toward the cell-free area of the implants. The expression of the intracellular signaling molecules responsible for the cell migration was also upregulated in osteoblasts on the microgrooved TIs. In vivo, the TI with radially defined topography demonstrated much greater bone repair in mouse calvarial defect models than in the other types of implants. Taken together, these results indicate that implants with physical guidance can enhance tissue repair by rapid cell recruitment.
骨缺损部位成骨细胞的快速募集是高效骨修复的重要前提。传统上,利用生长因子可实现成骨细胞向骨缺损部位的募集及随后的骨修复。在此,我们提出一种方法,可通过具有拓扑结构定义的植入物(TIs)引导成骨细胞向骨缺损部位募集,以实现高效的体内骨修复。我们将具有平行或径向排列微槽的圆形TIs与无图案植入物进行比较,观察成骨细胞迁移及体内骨形成情况。在体外,TIs中的微槽增强了成骨细胞的迁移和增殖。特别是,具有径向排列的微槽在引导成骨细胞向植入物募集方面比其他类型的植入物效率高得多,这可能是由于其能有效地引导细胞向植入物的无细胞区域迁移。负责细胞迁移的细胞内信号分子在微槽TIs上的成骨细胞中表达也上调。在体内,具有径向拓扑结构的TI在小鼠颅骨缺损模型中显示出比其他类型植入物更好的骨修复效果。综上所述,这些结果表明具有物理引导作用的植入物可通过快速细胞募集增强组织修复。